RxPG News : Cardiology

Two-hit model may explain loss in barrier function of endothelial cells

Mon, 01 Mar 2010 12:34:08 PST

( from http://www.rxpgnews.com ) Researchers at Albany Medical College are releasing results of a study this week that they say will help refocus the search for new drug targets aimed at preventing or reversing the devastating tissue inflammation that results after heart attack and stroke.

In the March 5 issue of the Journal of Biological Chemistry, lead author Alejandro P. Adam and his colleagues at the college's Center for Cardiovascular Science are reporting that vascular cells' ability to properly regulate fluid movement is not necessarily affected solely by the activity of an enzyme that for years has been in the crosshairs of scientists and pharmaceutical developers.

"Learning the mechanisms of inflammation is a key step in the development of new and better therapies to improve the outcome of widespread pathologies, such as stroke, heart attack, septic shock and pulmonary edema," said Adam, a postdoctoral fellow at the cardiovascular center. "To determine which are the best targets for treatment, we need to understand exactly what role each molecule is playing in the regulation of the vessel walls, and we found that the enzyme Src may be needed to get changes in barrier function but by itself is not sufficient."

Blood vessels, which form a tight barrier between blood and the surrounding tissues, are composed of endothelial cells that act as gatekeepers, controlling how, when and where molecules of water, solutes and blood cells pass through them into the body's tissues.

Previous studies have shown blocking the enzyme Src altered the structure of a protein known to hold the endothelial cells together, thus, keeping their barriers tight and limiting tissue damage caused by fluid accumulation, or edema.

"We found that Src indeed adds several phosphates to this protein, but this addition of the phosphates did not alter barrier function of the endothelial cells," explained professor Peter A. Vincent, who oversaw the team's research. "These findings suggest other pathways are needed for Src to change permeability and open the door to future studies to determine what these other signals are."

There are many "adhesion molecules" involved in holding endothelial cells together and many signaling molecules that tell the adhesion molecules when to hold onto or release each other. Vincent's team is moving forward with what he calls a "two-hit model" – the idea that endothelial cells require two different signals to open up cell-cell connections and allow the passage of fluids.

"Many factors lead to a complex array of signals inside the endothelial cells to promote this loss of barrier function," Adam said. "A two-hit model would explain much better than a single-hit model the regulation of the vascular permeability. On the pharmacological side, it would allow us to propose other drug targets to prevent or reverse inflammation and edema."

By being named a "Paper of the Week" by the Journal of Biological Chemistry, the article by Adam and Vincent, graduate student Amy L. Sharenko and associate professor Kevin Pumiglia has been categorized in the top 1 percent of papers reviewed by the journal's editorial board in terms of significance and overall importance.

Blacks more likely to have undiagnosed key stroke risk factor, have higher stroke incidence

Fri, 26 Feb 2010 04:59:36 PST

( from http://www.rxpgnews.com ) Blacks are more likely to have an undiagnosed key risk factor for stroke and are more likely to have a stroke than whites, according to two studies presented at the American Stroke Association's International Stroke Conference 2010.

In two separate reports using data from the REGARDS (REasons for Geographic and Racial Differences in Stroke) study, researchers found significant racial and geographic disparities in stroke incidence and in receiving the recommended treatment to prevent stroke.

The REGARDS study enrolled 30,239 participants across the United States, age 45 or older, between January 2003 and October 2007 and continues to follow them for health events.

In the first analysis (Meschia, Abstract P160), researchers found that among 432 study participants (88 blacks; 344 whites) who had atrial fibrillation (AF), blacks were two-thirds less likely to know they had the disorder and three-fourths less likely to be treated with the gold standard of care, the blood thinner warfarin.

These disparities are a problem, said James F. Meschia, M.D., the study's lead author and a neurologist at the Mayo Clinic in Jacksonville, Fla. For patients who are able to take warfarin, it makes a huge difference. Stroke trials have shown that warfarin reduces the risk of stroke by 60 percent.

Meschia notes that warfarin is not for everyone, because of the risk of bleeding. AF, which affects more than 2.2 million Americans, occurs when one of the heart's upper chambers quivers and doesn't effectively pump blood out, which allows blood to pool and clot. These dangerous clots can cause stroke if they lodge in an artery in or leading to the brain. This research is also simultaneously published in Stroke: Journal of the American Heart Association.

Because atrial fibrillation is such a powerful risk factor for stroke, these findings suggest that lower awareness of atrial fibrillation and reduced likelihood of treatment among blacks may place blacks at higher risk of a stroke, which in turn could contribute to the higher stroke mortality among blacks, Meschia said.

The healthcare system needs to better screen for and inform people about whether they have AF, and more study is needed to shed light on the causes of the disparity in warfarin treatment, he said.

In the second analysis (Howard, abstract P158), researchers provide the first national data describing racial and regional disparities in stroke incidence. Researchers reviewed data on about 26,580 REGARDS participants who had not had a stroke at baseline and documented 299 strokes during the almost five-year period.

Total fat, trans fat linked to higher incidence of ischemic stroke

Wed, 24 Feb 2010 04:59:36 PST

( from http://www.rxpgnews.com ) Post-menopausal women who reported consuming the most daily dietary fat had a 40 percent higher incidence of clot-caused strokes compared to women who ate the least amount, according to research presented at the American Stroke Association's International Stroke Conference 2010.

The incidence of ischemic stroke also increased by 30 percent in the quartile of women consuming the highest daily amount of trans fat (average intake 7 grams per day) compared to those who consumed the least (average 1 gram/day). Two common sources of trans fat are processed foods and fried foods.

Ischemic strokes are caused by blockages in blood vessels in or leading to the brain.

We found positive associations between total fat intake and ischemic stroke incidence and between trans fat intake and ischemic stroke incidence, said Sirin Yaemsiri, M.S.P.H., a doctoral student in the department of epidemiology in the Gillings School of Global Public Health at the University of North Carolina in Chapel Hill.

The study is the first to examine the associations of different fats and different subtypes of ischemic stroke in post-menopausal women, who face a higher stroke risk than men of a similar age.

Evidence from other studies shows that different types of fat have different effects on the incidence of coronary heart disease (CHD), with trans fat implicated in the development of CHD. However, studies of ischemic stroke and fat have been inconclusive, possibly because earlier studies had small numbers of ischemic stroke cases.

Before menopause, women have a lower risk of stroke compared to men of similar age, a situation that reverses after menopause, Yaemsiri said.

The analysis included data on 87,230 post-menopausal women ages 50 to 79 who participated in the Women's Health Initiative (WHI) Observational Study, a project sponsored by the National Institutes of Health and the National Heart, Lung and Blood Institute. The women answered a food frequency questionnaire when they entered the study and were followed for an average of 7.6 years, the researchers said. During that time, 1,049 ischemic strokes occurred.

Researchers looked for links between dietary fat intake and four ischemic stroke subtypes, which were characterized by their size or point of origin. However, the data on ischemic stroke subtypes fell short of statistical significance, perhaps because strokes are difficult to characterize and 43 percent (445 cases) of the ischemic strokes in the study were of unknown type, Yaemsiri said.

Researchers divided the women into quartiles based on the amount of total dietary fat and types of fat (saturated fat, monounsaturated fat, polyunsaturated fat and trans fat) they reported consuming per day.

Variables included age, race, smoking status, physical activity, alcohol or aspirin use, body mass index, hormone therapy, heart disease history, diabetes, systolic blood pressure and whether the women took medication for high blood pressure or to reduce cholesterol, vitamin E supplementation, fruit/vegetable intake, total calories and dietary fiber.

Women in the top quartile for total fat intake had an average intake of 86 grams of total fat per day. Those in the lowest quartile consumed an average of 26 grams a day.

I think our findings support the American Heart Association recommendations for keeping trans fat intake at less than 1 percent of energy, said Ka He, M.D., Sc.D., M.P.H., senior author of the study and associate professor of nutrition and epidemiology at the UNC Gillings School of Global Public Health.

Vitamin B3 shows early promise in treatment of stroke

Wed, 24 Feb 2010 04:59:36 PST

( from http://www.rxpgnews.com ) An early study suggests that vitamin B3 or niacin, a common water-soluble vitamin, may help improve neurological function after stroke, according to Henry Ford Hospital researchers.

When rats with ischemic stroke were given niacin, their brains showed growth of new blood vessels, and sprouting of nerve cells which greatly improved neurological outcome.

Now research is underway at Henry Ford to investigate the effects of an extended-release form of niacin on stroke patients. Henry Ford is the only site nationally conducting such a study.

If this proves to also work well in our human trials, we'll then have the benefit of a low-cost, easily-tolerable treatment for one of the most neurologically devastating conditions, Michael Chopp, Ph.D., scientific director of the Henry Ford Neuroscience Institute.

Dr. Chopp will present results from the animal model study at the International Stroke Conference in San Antonio.

According to the National Stroke Association, stroke is the third-leading cause of death in America and a leading cause of disability.

Ischemic strokes occur as a result of an obstruction within a blood vessel supplying blood to the brain. Ischemic stroke accounts for about 87 percent of all cases. One underlying condition for this type of obstruction is the development of fatty cholesterol deposits lining the vessel walls.

Niacin is known to be the most effective medicine in current clinical use for increasing high-density lipoprotein cholesterol (HDL-C), which helps those fatty deposits.

Dr. Chopp and his colleagues found that in animals niacin helps restore neurological function in the brain following stroke.

In 2009, stroke physicians at Henry Ford Hospital published research which showed that HDL-C is abnormally low at the time stroke patients arrive at the hospital.

Dr. Chopp's research found that in animals, niacin increased good cholesterol (HDL-C), which increased blood vessels in the brain and axonal and dendritic growth leading to a substantial improvement in neurological function.

Niacin essentially re-wires the brain which has very exciting potential for use in humans, says Dr. Chopp. The results of this study may also open doors in other areas of neurological medicine, including brain injury.

Andrew Russman, D.O., is the principal investigator of the team at Henry Ford Hospital who will evaluate in clinical trials whether niacin improves recovery for human stroke patients.

If we are able to prove that treating patients with niacin helps to restore neurological function after stroke, we're opening a whole new avenue of treatment for the leading cause of serious long-term disability in adults, says Dr. Russman.

Changes during menopause increases risk of heart disease and stroke

Tue, 23 Feb 2010 04:59:36 PST

( from http://www.rxpgnews.com ) CHICAGO- When women hear the word menopause, they often think about hot flashes, hormone shifts and mood swings. But what about heart disease? Studies show a woman's risk of heart disease intensifies drastically around the time of natural menopause, which for most women is around the age of 50. This news may come as a surprise, but experts explain that understanding risk factors is an important first step, and reassure women that there are ways to lower your risk.

Many women younger than 50 have not yet gone through menopause and still have high levels of the female hormone estrogen in their blood, which is thought to help protect the heart. After menopause, however, the levels of estrogen in a woman's body drop significantly and can contribute to the higher risks of cardiovascular disease, explains Vera Rigolin,MD, associate director of the Center for Women's Cardiovascular Health in the Bluhm Cardiovascular Institute of Northwestern Memorial Hospital.

Weight gain is also a factor that may play a role in postmenopausal risk of heart disease. Maintaining a healthy weight often becomes difficult after your body experiences a change in hormone levels. Extra mass can take a toll on the body causing physical inactivity, high blood pressure, diabetes, and high cholesterol, all risk factors that can lead to heart attack and stroke.

Detecting heart disease in women can be difficult. Many women are unaware that symptoms of the disease may differ from those of men. Although women often experience chest discomfort when presenting with a heart attack, they commonly have other, more subtle symptoms, including fatigue, nausea, shortness of breath, jaw pain and general discomfort in the chest and abdominal area.

In some women, plaque can build in the smallest blood vessels called the microvascular circulation. These blockages do not show up in an angiogram, says Rigolin. In these cases, we often use Magnetic Resonance Imaging (MRI) with medication to visualize blood flow within the small blood vessels when other standard tests do not provide us answers.

Women, especially those who are menopausal can reduce the risk of heart disease by adopting a healthy lifestyle.

If you are a smoker, quit immediately and avoid second hand smoke. Eat a diet rich in fruits and vegetables and exercise at least three times per week to maintain a healthy body weight, says Rigolin.

Rigolin also recommends visiting your health care provider at least once per year to have your blood pressure, blood sugar and cholesterol levels checked.

Silver nanoparticles may one day be key to devices that keep hearts beating strong and steady

Tue, 16 Feb 2010 04:59:12 PST

( from http://www.rxpgnews.com ) BUFFALO, N.Y. -- Diamonds and gold may make some hearts flutter on Valentine's Day, but in a University at Buffalo laboratory, silver nanoparticles are being designed to do just the opposite.

The nanoparticles are part of a new family of materials being created in the laboratory of SUNY Distinguished Professor and Greatbatch Professor of Advanced Power Sources Esther Takeuchi, PhD, who developed the lithium/silver vanadium oxide battery. The battery was a major factor in bringing implantable cardiac defibrillators (ICDs) into production in the late 1980s. ICDs shock the heart into a normal rhythm when it goes into fibrillation.

Twenty years later, with more than 300,000 of these units being implanted every year, the majority of them are powered by the battery system developed and improved by Takeuchi and her team. For that work she has earned more than 140 patents, believed to be more than any other woman in the United States. Last fall, she was one of four recipients honored in a White House ceremony with the National Medal of Technology and Innovation.

ICD batteries, in general, now last five to seven years. But she and her husband and co-investigator, SUNY Distinguished Teaching Professor of Chemistry Kenneth Takeuchi, PhD, and Amy Marschilok, PhD, UB research assistant professor of chemistry, are exploring even-better battery systems, by fine-tuning bimetallic materials at the atomic level.

Their research investigating feasibility for ICD use is funded by the National Institutes of Health, while their investigation of new, bimetallic systems is funded by the U.S. Department of Energy.

So far, their results show that they can make their materials 15,000 times more conductive upon initial battery use due to in-situ (that is, in the original material) generation of metallic silver nanoparticles. Their new approach to material design will allow development of higher-power, longer-life batteries than was previously possible.

These and other improvements are boosting interest in battery materials and the revolutionary devices that they may make possible.

We may be heading toward a time when we can make batteries so tiny that they -- and the devices they power -- can simply be injected into the body, Takeuchi says. Right now, her team is exploring how to boost the stability of the new materials they are designing for ICDs. The materials will be tested over weeks and months in laboratory ovens that mimic body temperature of 37 degrees Celsius.

What's really exciting about this concept is that we are tuning the material at the atomic level, says Takeuchi. So the change in its conductivity and performance is inherent to the material. We didn't add supplements to achieve that, we did it by changing the active material directly.

She explains that new and improved batteries for biomedical applications could, in a practical way, revolutionize treatments for some of the most persistent diseases by making feasible devices that would be implanted in the brain to treat stroke and mental illness, in the spine to treat chronic pain or in the vagal nerve system to treat migraines, Alzheimer's disease, anxiety, even obesity.

And even though batteries are an historic technology, they are far from mature, Takeuchi notes. This spring, she is teaching the energy storage course in UB's School of Engineering and Applied Sciences and the class is filled to capacity. I've never seen interest in batteries as high as it is now, she says.

High prevalence of AF found among cross-country skiers

Tue, 09 Feb 2010 04:59:36 PST

( from http://www.rxpgnews.com ) Next month, in the Norwegian town of Rena, 12,000 elite cross-country skiers will line up for this year's Birkebeiner ski marathon, an annual endurance race which will take them through 54 kilometres of snow-covered countryside to the winter sports resort of Lillehammer. The race has been run almost every year since 1932, and in 1976 almost 150 participants were invited to take part in a long-term study designed to discover the extent of latent heart disease in these elite cross-country skiers. Now, after some 30 years, the results of the follow-up study have been published and suggest that long-distance competition skiers - as well as other endurance athletes - are at an unusually high risk of atrial fibrillation, the most common abnormality of the heart's beating rhythm.(1)

Results showed that participants in the study are at a high risk of atrial fibrillation (AF) without known structural heart disease or other known causes (a condition termed lone AF). A prevalence of 12.8% found among the skiers who completed the study's investigations in 1976, 1981 and 2004-2006, when echocardiographic (ECG) and heart rate tests were performed at rest and at exercise. In the general population studies have found the prevalence of AF to be as low as 0.5%, with rates only rising to around 15% in men over the age of 75.

When the study began in 1976 participants were classified according to age - group I 26-33 years, group II 43-50 years, and group III 58-64 years; all had been competing in long-distance skiing events and were in the top 25% for age related performance. When the final follow-up examinations were performed during 2004-2006, a large proportion from group III (28/39) had died, leaving 78 of the original 122 available for further tests and questioning.

This analysis showed that 13 of those 78 skiers (16.7%) had experienced AF at some time during the 28-30 years of follow-up, with a current prevalence of 12.8% AF with no other known heart disease. The latter, say the investigators, is the highest prevalence yet described in long-term endurance sport practitioners. In age group I the prevalence was found to be 18.2%. The mean age at which the AF occurred was 58 years.

The study also detected two characteristics in the skiers which may predict their risk of AF: a slow heart rate at rest (known as bradycardia) and a large left atrium of the heart.(2) Both have been suggested in previous studies as common findings in the hearts of endurance athletes. However, the study found no association between the years of training in cross-country skiing (an average of 36 years in this study) and the occurrence of AF. As a result, the authors advise that there is still not enough evidence to recommend a specific age to reduce training volume and/or intensity. However, they do recommend that after the appearance of AF practice should be stopped or reduced until rhythm control is attained.

Disturbances in heart rhythm, which are the most common cause of sudden cardiac death, represent one of the major cardiovascular reasons for hospital admission. Professor Josep Brugada, President of the European Heart Rhythm Association of the ESC (and Medical Director at the Hospital Clinic in Barcelona), has described their impact as enormous, noting that around 5% of all medical expenditure in Europe is related to atrial fibrillation, the most common arrhythmic condition.

So far, only three case-control studies have found a higher prevalence of AF in athletes than in controls. However, a population-based study from 2009 showed that those with the highest level of endurance training also had the highest prevalence of AF.

Studies aiming to find an explanation for a higher AF prevalence have also found that the size of the heart muscle and chambers was larger in athletes than in controls, and this seemed a predictor for AF.

Commenting on the findings from the Birkebeiner study, principal investigator Dr Jostein Grimsmo from the Feiring Heart Clinic in Norway, agreed that enlargement of the heart's left atrium - along with bradycardia - appeared to be an important risk factor for AF among long-term endurance cross-country skiers. This atrial enlargement, he said, is the heart's adaptation to endurance training.

As many as 20% of young competitive athletes have been found to have an enlarged left atrium in some studies, said Dr Grimsmo. But we are not aware of any documentation of such a high prevalence as we have found either in athletes or in controls under the age of 75!

But despite our findings, he added, we still can't say why some athletes end up with AF and others don't. Genetic factors predisposing to 'athlete's heart', with enlarged cardiac dimensions and a slow heart rate, may be important as risk factors. And while it may be that prolonged endurance training over many years may not always be good for the heart, we do not yet have sufficient evidence to make specific recommendations.

Virus-free technique enables Stanford scientists to easily make stem cells pluripotent

Sun, 07 Feb 2010 04:59:36 PST

( from http://www.rxpgnews.com ) STANFORD, Calif. - Tiny circles of DNA are the key to a new and easier way to transform stem cells from human fat into induced pluripotent stem cells for use in regenerative medicine, say scientists at the Stanford University School of Medicine. Unlike other commonly used techniques, the method, which is based on standard molecular biology practices, does not use viruses to introduce genes into the cells or permanently alter a cell's genome.

It is the first example of reprogramming adult cells to pluripotency in this manner, and is hailed by the researchers as a major step toward the use of such cells in humans. They hope that the ease of the technique and its relative safety will smooth its way through the necessary FDA approval process.

This technique is not only safer, it's relatively simple, said Stanford surgery professor Michael Longaker, MD, and co-author of the paper. It will be a relatively straightforward process for labs around the world to begin using this technique. We are moving toward clinically applicable regenerative medicine.

The Stanford researchers used the so-called minicircles - rings of DNA about one-half the size of those usually used to reprogram cell - to induce pluripotency in stem cells from human fat. Pluripotent cells can then be induced to become many different specialized cell types. Although the researchers plan to first use these cells to better understand - and perhaps one day treat-human heart disease, induced pluripotent stem cells, or iPS cells, are a starting point for research on many human diseases.

Imagine doing a fat or skin biopsy from a member of a family with heart problems, reprogramming the cells to pluripotency and then making cardiac cells to study in a laboratory dish, said cardiologist Joseph Wu, MD, PhD. This would be much easier and less invasive than taking cell samples from a patient's heart. Wu is the senior author of the research, which will be published online Feb. 7 in Nature Methods. Research assistant Fangjun Jia, PhD is the lead author of the work.

Longaker is the deputy director of Stanford's Institute for Stem Cell Biology and Regenerative Medicine and director of children's surgical research at Lucile Packard Children's Hospital. Wu is an assistant professor of cardiology and of radiology, and a member of Stanford's Cardiovascular Institute. A third author, Mark Kay, MD, PhD, is the Dennis Farrey Family Professor in Pediatrics and professor of genetics.

The finding brings together disparate areas of Stanford research. Kay's laboratory invented the minicircles several years ago in a quest to develop suitable gene therapy techniques. At the same time, Longaker was discovering the unusual prevalence and developmental flexibility of stem cells from human fat. Meanwhile, Wu was searching for ways to create patient-specific cell lines to study some of the common, yet devastating, heart problems he was seeing in the clinic.

About three years ago Mark gave a talk and I asked him if we could use minicircles for cardiac gene therapy, said Wu. And then it clicked for me, that we should also be able to use them for non-viral reprogramming of adult cells.

The minicircle reprogramming vector works so well because it is made of only the four genes needed to reprogram the cells (plus a gene for a green fluorescent protein to track minicircle-containing cells). Unlike the larger, more commonly used DNA circles called plasmids, the minicircles contain no bacterial DNA, meaning that the cells containing the minicircles are less likely than plasmids to be perceived as foreign by the body. The expression of minicircle genes is also more robust, and the smaller size of the minicircles allows them to enter the cells more easily than the larger plasmids. Finally, because they don't replicate they are naturally lost as the cells divide, rather than hanging around to potentially muck up any subsequent therapeutic applications.

The researchers chose to test the reprogramming efficiency of the minicircles in stem cells from human fat because previous work in Wu and Longaker's lab has shown that the cells are numerous, easy to isolate and amenable to the iPS transformation, probably because of the naturally higher levels of expression of some reprogramming genes. They found that about 10.8 percent of the stem cells took up the minicircles and expressed the green fluorescent protein, or GFP, versus about 2.7 percent of cells treated with a more traditional DNA plasmid.

When the researchers isolated the GFP-expressing cells and grew them in a laboratory dish, they found that the minicircles were gradually lost over a period of four weeks. To be sure the cells got a good dose of the genes, they reapplied the minicircles at days four and six. After 14 to 16 days, they began to observe clusters of cells resembling embryonic stem cell colonies - some of which no longer expressed GFP.

They isolated these GFP-free clusters and found that they exhibited all of the hallmarks of induced pluripotent cells: they expressed embryonic stem cell genes, they had similar patterns of DNA methylation, they could become multiple types of cells and they could form tumors called teratomas when injected under the skin of laboratory mice. They also confirmed that the minicircles had truly been lost and had not integrated into the stem cells' DNA.

Altogether, the researchers were able to make 22 new iPS cell lines from adult human adipose stem cells and adult human fibroblasts. Although the overall reprogramming efficiency of the minicircle method is lower than that of methods using viral vectors to introduce the genes (about 0.005 percent vs. about 0.01-0.05 percent, respectively), it still surpasses that of using conventional bacterial-based plasmids. Furthermore, stem cells from fat, and, for that matter, fat itself, are so prevalent that a slight reduction in efficiency should be easily overcome.

This is a great example of collaboration, said Longaker. This discovery represents research from four different departments: pediatrics, surgery, cardiology and radiology. We were all doing our own things, and it wasn't until we focused on cross-applications of our research that we realized the potential.

We knew minicircles worked better than plasmids for gene therapy, agreed Kay, but it wasn't until I started talking to stem cell people like Joe and Mike that we started thinking of using minicircles for this purpose. Now it's kind of like 'why didn't we think of this sooner?'

NHLBI funds preclinical tests on devices for infants and children with congenital heart defects

Thu, 04 Feb 2010 04:59:36 PST

( from http://www.rxpgnews.com ) The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, has awarded four contracts totaling $23.6 million to begin preclinical testing of devices to help children born with congenital heart defects or those who develop heart failure. The four-year program is called Pumps for Kids, Infants, and Neonates (PumpKIN).

Each year in the United States, nearly 1,800 infants die as a result of congenital heart defects and another 350 develop heart disease, which leads to heart failure for many. Approximately 60 infants and children under 5 years old who are placed on the heart transplant waiting list die each year before receiving one. Mechanically assisted circulatory support could be used to sustain these young patients as they seek to recover or wait to receive a heart transplant.

This research seeks to develop technologies to expand life-saving options for infants and children born with congenital heart defects or those who develop heart failure, said NHLBI Acting Director Susan B. Shurin, M.D., a pediatrician. The NHLBI is committed to saving the lives of our youngest patients. Well-designed circulatory support devices are expected to substantially improve the outcomes of the infants and young children who need them as they seek to recover or wait to receive a heart transplant.

The options for chronic circulatory support devices for infants and young children are limited, and all have substantial risks for serious adverse events such as infection, stroke, and device failure. With this in mind, the NHLBI launched the Pediatric Circulatory Support Program in 2004 by funding the development of five novel circulatory support devices for infants and young children with congenital and acquired cardiovascular disease.

The PumpKIN program is the next phase of NHLBI support for the development and clinical realization of these devices. The program's goal is to complete the needed animal studies and other tests in artificial environments for the most promising devices in order to gain approval from the FDA to begin clinical testing.

Devices in the program will provide suitable circulatory support for newborns, older infants, and children less than 55 pounds who experience heart failure due to congenital and acquired cardiovascular disease. They are designed to supply adequate blood flow to prevent organ damage while minimizing the risk of blood vessel damage, infection, breakdown of red blood cells, excessive bleeding, brain damage, and dangerous blood clots. The devices are intended to support circulation in pediatric patients for one to six months, be sufficiently small and reasonably portable, and be able to be routinely positioned and functioning in less than one hour, among other specifications.

Similar devices are used in adults, Shurin noted. As an adult, your heart is normally about the size of your fist; devices for small children require radically different designs from adult devices to adapt to the differences in the size of the patients.

The program will test ventricular assist devices (VADs) and advanced extracorporeal membrane oxygenator (ECMO) devices. The VADs in the PumpKIN program are very small rotary pumps which are implanted to provide circulatory support for extended periods of use. They work by drawing blood from the heart and pumping it to the body. ECMO devices circulate and supply oxygen to the blood, and are commonly used for patients who need both heart and lung support. For ECMO devices, tubes connecting the patient to the device are placed directly into large blood vessels near the base of the neck. Blood is drawn from the right side of the heart, pumped through the oxygenator, and then returned to the body on the left side of the heart so the oxygen-rich blood can be delivered throughout the body.

The contractors will conduct all preclinical animal testing and analysis in the first three years of the contract. During the third year, they will partner with a data coordinating center (the contract for which is still to be awarded) to complete the necessary activities to seek FDA approval to begin the clinical trial.

Further research findings on cholesterol and atherosclerosis

Tue, 02 Feb 2010 14:20:11 PST

( from http://www.rxpgnews.com ) By considering molecular-level events on a broader scale, researchers now have a clearer, if more complicated, picture of how one class of immune cells goes wrong when loaded with cholesterol. The findings reported in the February 3rd issue of Cell Metabolism, a Cell Press publication, show that, when it comes to the development of atherosclerosis and heart disease, it's not about any one bad actor—it's about a network gone awry.

The new findings also highlight a pretty remarkable thing, Heinecke says: "Despite 30 years of study, we still don't know how cholesterol causes heart disease." But, with the new findings, scientists are getting closer.

Earlier studies had shown that heart disease is about more than just high LDL ("bad") cholesterol. Cells known as macrophages also play a critical role. Macrophages are part of the innate immune system that typically gobble up pathogens and clear away dead cells. But they also take up and degrade cholesterol derivatives. When they get overloaded with those lipoproteins, they take on a foamy appearance under the microscope to become what scientists aptly refer to as foam cells. Those foam cells are the ones that seem to have critical importance in the development of atherosclerosis.

People had typically thought about this problem in terms of linear pathways, Heinecke explained. In essence, macrophages end up with too much cholesterol going in and not enough coming out. The macrophages get overwhelmed and trapped in the artery wall, and somehow plaques form as a result.

But the new results show that it isn't really about simple paths in and out; rather, there is an integrated network of macrophage proteins involved. When that network gets disrupted, as it does when too much cholesterol comes in, atherosclerosis forms. "It's definitely a different way to think about what is going on," Heinecke says.

Heinecke's group applied sophisticated technologies and statistical tools to get a global view of what happens to macrophage proteins when they turn into foam cells. Their analysis revealed what they call a macrophage sterol-responsive network (MSRN), including proteins already known to work together. Most of them are also found in one place, within microvesicles outside the macrophage cells.

The researchers further found that drugs used to lower cholesterol and inflammation, including statins and rosiglitazone, restore the macrophage network to almost normal, even in mice that don't have the LDL receptors that are considered the usual targets of the drugs. On the other hand, mice lacking single proteins in the network, including APOE and so-called complement proteins of the immune system, have macrophages that look like foam cells even when they aren't loaded with cholesterol.

The findings suggest that anything that sends the macrophage network off kilter could promote heart disease, Heinecke said. They also change the way researchers should think about how heart disease is treated. The key may be how to best restore the function of an integrated network rather than to lower cholesterol levels or ratchet individual proteins up or down.

"We propose that the atherogenic actions of cholesterol-loaded macrophages are an emergent property that results when the normal balance of MSRN proteins in microvesicles is perturbed," the researchers conclude. "We further suggest that certain dietary factors or genetic variations can disturb this network, thereby promoting vascular disease. By integrating mouse and human data, we hope to better understand the MSRN's role in foam cell formation, with the long-term goal of identifying therapeutic interventions for targeting networks rather than individual proteins."

Study prompts calls for Europe-wide salt legislation

Tue, 26 Jan 2010 04:59:36 PST

( from http://www.rxpgnews.com ) This study provides excellent ammunition both to convince patients about the benefits of reducing their individual salt intakes and also to persuade the EU of the urgent need to introduce legislation to restrict the salt content of processed foods, said ESC spokesman Professor Frank Ruschitzka, a cardiologist and hypertension specialist from the University of Zurich, Switzerland.

This study represents the evidence that a reduction of salt intake not only lowers blood pressure but also prevents cardiovascular events. The case for population-wide salt reduction is now compelling, he added.

In the paper, Kirsten Bibbins-Domingo and colleagues, from the University of California, San Francisco, USA, undertook a computer simulation showing the effects of population wide reductions of dietary salt intakes in all adults aged 35 to 85 years in the USA. Reducing dietary salt intake by 3 g per day (1200mg less sodium per day) could result in 60,000 to 120,000 fewer cases of heart disease , 32,000 to 66,000 fewer strokes and 54,000 to 100,000 fewer heart attacks.

A reduction in dietary salt of 3g per day, the authors went on to say, would have approximately the same effect on reducing cardiac events as a 50 % reduction in tobacco use, a 5% reduction in body mass index among obese adults or the use of statins to treat people at low or intermediate risk for CHD events. Furthermore, reducing dietary salt intakes by 3g per day would save $10 billion to $ 24 billion in annual health care costs.

ESC spokesperson Professor Giuseppe Mancia, from the University of Milano-Bicocca, St. Gerardo Hospital (Milan, Italy), said the annual health cost savings outlined in the study would be likely to prove a persuasive argument for both the EU and individual European governments.

Recent studies clearly show that salt reduction reduces cardiovascular deaths.4

Epidemiological studies have also firmly established that increased intakes of salt directly increase blood pressure. High salt intakes are believed to exert their detrimental effects by influencing fluid retention, which in turn increases blood pressure. But it's important for patients to appreciate that not all cardiovascular problems relating to salt are mediated through hypertension. Salt can have an adverse effect on cardiovascular health, even among people with normal blood pressure, said Ruschitzka.

Salt intakes across Europe are known to vary widely, ranging from 8.6 g of salt per day in the UK, to around 12 g salt in Croatia. Even the best intakes, however, are falling widely short of the ESC Clinical Practice Guidelines for the Management of Arterial Hypertension(2), based on WHO data, that recommend that only 5g of salt should be consumed per day. This amounts to just one teaspoonful.

While individuals may use salt sparingly at home, around 75 % of the salt we eat is already in the food we buy. This, says the ESC, underlines the need for legislation to lay down guidelines. The reality of international food production in Europe means that such public health initiatives need to be tackled on a European wide basis, rather than an individual country basis, said Ruschitzka.

Furthermore, added Mancia, concerted action is usually more effective. It has the advantage of preventing country to country inequalities and furthermore prevents the reinvention of the wheel in each individual country, he said.

But calls for legislation do not mean that physicians should stop their efforts to persuade patients to introduce individual changes in lifestyle. Patients, they stress, need to be taught about the importance of reducing salt in their cooking and also for the need to check food labels. People need to learn to appreciate that the salt contents can vary widely even in the same product. Take bread, for example. Recent research from Consensus Action on Salt and Health (a charity lobbying food manufacturers in the UK) has shown that the highest salt content was 3g salt per 100 g of bread, while the lowest was 0.7 g salt per 100g.

To improve cardiovascular health, salt reduction cannot be undertaken in isolation. It needs to be remembered that lifestyle measures such as smoking cessation, weight reduction, increased physical exercise, and eating plenty of fruit and vegetables are also important for reducing cardiovascular disease, said Mancia.

Salt will again be on the agenda with World Salt Awareness Week 2010 , which runs from February 1- 7 (3). The week is being run by World Action on Salt and Health (WASH), a global group that works with governments to highlight the need for widespread introduction of population based salt reduction strategies.

Much can be done to reduce salt intakes through public health policy, say WASH. They cite the success of Consensus Action on Salt and Health (CASH), launched in 1996 to encourage food manufacturing companies in the UK to make voluntary reductions in their salt content. Since the start of the policy salt intakes among UK adults (calculated from 24-hour urine samples) have fallen from 9.5 to 8.6 g per day.

In July 2009, WASH surveyed over 260 food products available around the world from food manufacturers such as KFC, McDonalds, Kellogg's, Nestle, Burger King and Subway, finding surprisingly wide spread variations. For example, Kellogg's All Bran for sale in France, Norway, Sweden and the Netherlands contains 1.30 g salt per 100 g compared to salt levels of 0.65 g per 100g for the product in the US. Such data underlines the urgent need to eradicate country to country inequalities, and bring everyone up to the highest possible standards.

The paper by Bibbins-Domingo and colleagues is an urgent call to action. Policy makers in the European Community need to implement public health interventions that result in reductions in salt intake now. Reducing the salt content of our unneccesarily oversalted ,processed food is an inexpensive, yet highly effective public health intervention that we can't afford to miss, concluded Ruschitzka.

Antioxidants aren't always good for you and can impair muscle function, study shows

Tue, 26 Jan 2010 04:59:36 PST

( from http://www.rxpgnews.com ) Antioxidants increasingly have been praised for their benefits against disease and aging, but recent studies at Kansas State University show that they also can cause harm.

Researchers in K-State's Cardiorespiratory Exercise Laboratory have been studying how to improve oxygen delivery to the skeletal muscle during physical activity by using antioxidants, which are nutrients in foods that can prevent or slow the oxidative damage to the body. Their findings show that sometimes antioxidants can impair muscle function.

Antioxidant is one of those buzz words right now, said Steven Copp, a doctoral student in anatomy and physiology from Manhattan and a researcher in the lab. Walking around grocery stores you see things advertised that are loaded with antioxidants. I think what a lot of people don't realize is that the antioxidant and pro-oxidant balance is really delicate. One of the things we've seen in our research is that you can't just give a larger dose of antioxidants and presume that there will be some sort of beneficial effect. In fact, you can actually make a problem worse.

David C. Poole and Timothy I. Musch, K-State professors from both the departments of kinesiology and anatomy and physiology, direct the Cardiorespiratory Exercise Laboratory, located in the College of Veterinary Medicine complex. Researchers in the lab study the physiology of physical activity in health and disease through animal models. Copp and Daniel Hirai, an anatomy and physiology doctoral student from Manhattan working in the lab, have conducted various studies associated with how muscles control blood flow and the effects of different doses and types of antioxidants.

Abnormalities in the circulatory system, such as those that result from aging or a disease like chronic heart failure, can impair oxygen delivery to the skeletal muscle and increase fatigability during physical activity, Copp said. The researchers are studying the effects antioxidants could have in the process.

If you have a person trying to recover from a heart attack and you put them in cardiac rehab, when they walk ona treadmill they might say it's difficult, Poole said. Their muscles get sore and stiff. We try to understand why the blood cells aren't flowing properly and why they can't get oxygen to the muscles, as happens in healthy individuals.

Copp said there is a potential for antioxidants to reverse or partially reverse some of those changes that result from aging or disease. However, K-State's studies have shown that some of the oxidants in our body, such as hydrogen peroxide, are helpful to increase blood flow.

Bypass procedure used during infant heart surgery does not impair later neurological outcomes

Tue, 26 Jan 2010 04:59:36 PST

( from http://www.rxpgnews.com ) Congenital heart defects (CHD) are the most common birth defects in humans, affecting 8 per 1000 live births with one third of affected children requiring intervention in early infancy. Increasing numbers of survivors combined with developmental expectations for independence, behavioral self-regulation and academic achievement have led to a growing identification of neurobehavioral symptoms in some survivors. A study now suggests that a cooling technique often used in heart operations does not impair neurological outcomes.

Congenital heart disease and its treatment were originally thought to potentially increase neurologic injury in these patients. The technique of deep hypothermic circulatory arrest (DHCA) is used in order to repair these congenital cardiac defects by providing a bloodless surgical field, which may facilitate completion of the best physiologic repair, and decrease the duration of blood exposure to the bypass circuit. However, it involves a period of reduced blood flow in the brain. Cooling is a protective mechanism to reduce metabolism of the brain and other organs during periods of low blood flow.

Stephanie Fuller, M.D., a cardiothoracic surgeon at The Children's Hospital of Philadelphia, presented these research findings yesterday in the prestigious J. Maxwell Chamberlain Lecture at the annual meeting of the Society of Thoracic Surgeons in Fort Lauderdale, Fla. According to the study, DHCA does not impair language skills, attention, and other neurocognitive abilities in school-age children.

Dr. Fuller and colleagues from Children's Hospital and the University of Washington assessed the use of DHCA as a predictor of neurodevelopmental outcomes in children who had cardiac surgery as infants. The infants were enrolled in a prospective study of apolipoprotein-E (APOE) polymorphisms and neurodevelopmental outcome after cardiac surgery and underwent formal neurodevelopmental testing at four years of age.

Neurodevelopmental testing was completed in 238 out of 307 eligible patients. The surgeons used DHCA in 92 of those infants as deemed necessary to provide better operative exposure with a bloodless and less cluttered surgical field and therefore a shorter total cardiopulmonary support time. Use of DHCA was not predictive of worse performance for any neurodevelopmental outcome. Significant predictors of worse outcome included lower socioeconomic status, preoperative mechanical ventilation and babies that were younger and smaller at the time of first operation. Neurodevelopmental assessment included cognition, language skills, attention, impulsivity, executive function, social competence, and visual-motor and fine-motor skills.

Selective use of DHCA during cardiac surgery in infancy may facilitate operative repair and is not associated with impaired neurodevelopmental outcomes, said Dr. Fuller. Despite added risk factors, the selective use of DHCA during infancy for repair of congenital heart disease without an obstruction in the aorta was not predictive of worse performance at four years of age.

Dr. Fuller added use of DHCA as a support technique during cardiac surgery in infancy has many advantages; it is not necessary to sacrifice these advantages merely to avoid use of DHCA. Our study adds to the growing literature showing no adverse influence of limited periods of DHCA. New support techniques must be carefully evaluated prior to wide-spread acceptance to confirm they are not inferior to conventional management strategies.

Hypertension: Beta-blockers effective in combination therapies

Tue, 19 Jan 2010 04:59:36 PST

( from http://www.rxpgnews.com ) Using beta-blockers as a second-line therapy in combination with certain anti-hypertensive drugs significantly lowers blood pressure in patients with hypertension, according to a systematic review by Cochrane Researchers. This review also goes some way to explaining the differences in the way that patients respond to beta-blockers and other classes of blood pressure lowering drugs.

Beta-blockers are commonly used in the treatment of hypertension (high blood pressure) to help reduce the risk of stroke and cardiovascular disease. They can be used alone or as a second-line therapy in combination with a wide range of anti-hypertensive drugs. The idea behind combining two different drugs to treat hypertension is that each has a different mechanism of action and thus may help tackle different mechanisms involved in causing the condition. In this way, greater decreases in blood pressure may be achieved than with single drug therapy.

The review included 20 trials involving a total of 3,744 patients. Overall, the researchers found that adding beta-blockers as the second-line drug, in combination with thiazide diuretics or calcium channel blockers, caused an additional blood pressure reduction. The reduction was around 30% greater when the dose was doubled.

This data was compared with a Cochrane Review published in Issue 4, 2009 that examined the blood pressure lowering effect of second-line thiazide diuretics. They concluded that the two drugs produced different patterns of blood pressure lowering. Second-line beta-blockers were found to be more effective at reducing diastolic blood pressure (the minimum pressure in the arteries between beats when the heart relaxes to fill with blood) but had little or no effect on pulse pressure, while second-line thiazides significantly decreased pulse pressure in a dose-related manner.

We feel that these findings are generalisable to most patients being treated for hypertension where a beta-blocker is added as a second-line drug to a first-line thiazide, said lead researcher, Jenny Chen, who works in Pharmacology and Therapeutics at the University of British Columbia in Vancouver, Canada. The finding that beta-blockers produce a different pattern of blood pressure lowering to thiazides when used as second-line drugs certainly deserves further attention as it might explain why beta-blockers appear to be less effective than thiazide diuretics at reducing adverse cardiovascular outcomes, particularly in older individuals.

The major limitation of this work is that we only know what happens when you add beta-blockers to thiazides and calcium channel blockers. It is possible that adding beta-blockers to other classes of drugs might produce a different result, said Chen.

Nanoparticles - possible alternative to drug eluting stents

Mon, 18 Jan 2010 14:00:58 PST

( from http://www.rxpgnews.com ) Researchers at MIT and Harvard Medical School have built targeted nanoparticles that can cling to artery walls and slowly release medicine, an advance that potentially provides an alternative to drug-releasing stents in some patients with cardiovascular disease.

The particles, dubbed "nanoburrs" because they are coated with tiny protein fragments that allow them to stick to target proteins, can be designed to release their drug payload over several days. They are one of the first such particles that can precisely home in on damaged vascular tissue, says Omid Farokhzad, associate professor at Harvard Medical School and an author of a paper describing the nanoparticles in the Jan. 18 issue of the Proceedings of the National Academy of Sciences.

Farokhzad and MIT Institute Professor Robert Langer, also an author of the paper, have previously developed nanoparticles that seek out and destroy tumors.

The nanoburrs are targeted to a specific structure, known as the basement membrane, which lines the arterial walls and is only exposed when those walls are damaged. Therefore, the nanoburrs could be used to deliver drugs to treat atherosclerosis and other inflammatory cardiovascular diseases. In the current study, the team used paclitaxel, a drug that inhibits cell division and helps prevent the growth of scar tissue that can clog arteries.

"This is a very exciting example of nanotechnology and cell targeting in action that I hope will have broad ramifications," says Langer.

The researchers hope the particles could become a complementary approach that can be used with vascular stents, which are the standard of care for most cases of clogged and damaged arteries, or in lieu of stents in areas not well suited to them, such as near a fork in the artery.

The particles, which are spheres 60 nanometers in diameter, consist of three layers: an inner core containing a complex of the drug and a polymer chain called PLA; a middle layer of soybean lecithin, a fatty material; and an outer coating of a polymer called PEG, which protects the particle as it travels through the bloodstream.

The drug can only be released when it detaches from the PLA polymer chain, which occurs gradually by a reaction called ester hydrolysis. The longer the polymer chain, the longer this process takes, so the researchers can control the timing of the drug's release by altering the chain length. So far, they have achieved drug release over 12 days, in tests in cultured cells.

In tests in rats, the researchers showed that the nanoburrs can be injected intravenously into the tail and still reach their intended target — damaged walls of the left carotid artery. The burrs bound to the damaged walls at twice the rate of nontargeted nanoparticles.

Because the particles can deliver drugs over a longer period of time, and can be injected intravenously, patients would not have to endure repeated and surgically invasive injections directly into the area that requires treatment, says Juliana Chan, a graduate student in Langer's lab and lead author of the paper.

How they did it: The researchers screened a library of short peptide sequences to find one that binds most effectively to molecules on the surface of the basement membrane. They used the most effective one, a seven-amino-acid sequence dubbed C11, to coat the outer layer of their nanoparticles.

Next steps: The team is testing the nanoburrs in rats over a two-week period to determine the most effective dose for treating damaged vascular tissue. The particles may also prove useful in delivering drugs to tumors.

"This technology could have broad applications across other important diseases, including cancer and inflammatory diseases where vascular permeability or vascular damage is commonly observed," says Farokhzad.

Researchers revisit pulmonary arterial hypertension survival

Wed, 06 Jan 2010 04:59:12 PST

( from http://www.rxpgnews.com ) Setting out to determine the survival of patients with pulmonary arterial hypertension (PAH), researchers at the University of Chicago Medical Center and their colleagues also discovered that an equation used for more than 20 years to predict survival is outdated. Accordingly, they developed and recently published a new survival prediction equation that will impact clinical practice and the drug development process.

In PAH, the pulmonary arteries, which carry blood from the heart to the lungs to pick up oxygen, become restricted, forcing the lower right chamber of the heart to pump harder. This leads to shortness of breath, limited exercise capacity, fatigue, heart failure and death. Often the condition goes undetected until it is advanced. Untreated, patients with PAH have a very poor prognosis.

That prognosis is determined using an equation developed by a landmark National Institutes of Health study published in 1987, well before there were any Food and Drug Administration approved therapies for PAH. The first such therapy was approved in 1995; today there are seven.

Since 1987, great progress has been made in understanding and treating PAH, so a few years ago we decided that it was time to study contemporary survival, said Mardi Gomberg-Maitland, MD, MSc, Associate Professor of Medicine and Director of Pulmonary Hypertension at the University of Chicago Medical Center. Our results show that survival is vastly improved today. That led us to rework the NIH equation, which has been a standard measuring stick for more than 22 years.

Gomberg and her colleagues at the Medical Center and Northwestern University's Feinberg School of Medicine studied the survival of 576 PAH patients in their registry. Of these patients, 282 had idiopathic, familial, and anorexigen-associated PAH, which matches the conditions of the 187 patients in the pioneering NIH study.

Using the NIH equation, these 282 patients would have been expected to have one-, three- and five-year survival rates of 65%, 43% and 32%, respectively. In fact, their survival rates were much higher: 92%, 75% and 66%, respectively.

This new formula is important for patients who want to know what, on average, to expect from their disease and for doctors who want to give accurate advice, said Stephen L. Archer, MD, Harold Hines Jr. Professor and Chief of Cardiology at the University of Chicago Medical Center and co-author of the study. We hope others will test our work. If it is validated by others it could be a very useful tool.

Renal sympathetic nerve ablation may cure high blood pressure

Mon, 28 Dec 2009 16:19:50 PST

( from http://www.rxpgnews.com ) British medical scientists have demonstrated a revolutionary new operation that can effectively 'cure' persistent high blood pressure and takes under an hour to carry out.

The surgery, described as relatively straightforward and cheap, could reduce the risk of a major heart attack or stroke in those patients on whom medication has no effect.

Although doctors say there is no substitute for diet and exercise, one in 10 of the 15 million Britons suffering from high blood pressure - also known as hypertension - either do not respond to medication or cannot tolerate drugs.

The new procedure, called renal sympathetic-nerve ablation, involves placing tiny burns in the nerve responsible for hypertension in some people.

It disrupts signals from the brain telling the kidneys to keep blood pressure raised. Initial tests suggest it can be effective within three months, scientists said.

'This is the most exciting development in hypertension since the advent of anti-hypertensive medication 50 years ago. It is hard to forecast the limitations and it could eventually be compared to medication,' said Mel Lobo, a doctor and specialist in clinical hypertension with Britain's National Health Service.

The Daily Telegraph said its reporter watched the operation being performed on a 68-year-old London chef, who is diabetic and has already suffered a stroke and a deep vein thrombosis.

The patient was awake throughout the procedure carried out at the London Chest Hospital - the first such in Britain and part of an international clinical trial.

Although the patient was kept in the hospital overnight, once greater experience is gained with the technique, patients will be able to go home the same day.

His blood pressure has come down just two weeks after the operation and it is thought most patients will see an improvement within three months, the paper said.

Martin Rothman, the cardiologist who performed the operation said: 'This relatively trivial procedure has the potential to make a serious improvement in the quality of life for the patient. It is very efficient and can lower the blood pressure enough to reduce stroke mortality by 50 percent.'

Paul Sobotka, chief medical officer of Ardian, a company which has developed the equipment for the surgery, said: 'For the first time we can think of a cure for hypertension.'

David Collier, a doctor and senior clinical trials fellow at the Biomedical Research Unit at Queen Mary University London, told the paper the operation offers real hope of an alternative to a life on pills for patients whose blood pressure is difficult to control.

However, he warned that it was not the 'lazy person's answer' to diet and exercise.

Researchers to investigate the genetics of congenital heart disease

Tue, 22 Dec 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Researchers at Children's Hospital Boston and Brigham and Women's Hospital have received funding from the National Heart, Lung, and Blood Institute (NHLBI) to support their search for undiscovered gene defects that cause congenital heart disease. The $4.19 million, 6-year grant is part of the Pediatric Cardiac Genomics Consortium (PCGC), which seeks to identify genetic and epigenetic causes of human congenital heart disease, and relate genetic variants present in the congenital heart disease patient population to clinical outcomes.

Though individual congenital heart defects are rare, together they affect 35,000-40,000 U.S. infants born annually, making congenital heart disease the most common group of birth defects. The ultimate goal of the PCGC, part of the newly established Bench to Bassinet initiative at NHLBI, is to identify preventive strategies, targets for treatment, and better diagnostic and prognostic information for families.

Too many young lives are lost each year due to congenital heart defects, said Susan B. Shurin, MD, acting director of the National Heart, Lung, and Blood Institute at the National Institutes of Health. To help give these children a chance at a healthier life, the Bench to Bassinet program will delve into how the cardiovascular system develops and help translate the best research findings into clinical practice.

We are thrilled to be part of this ground-breaking new endeavor, says Jane Newburger, MD, MPH, Associate Chief for Academic Affairs in the Department of Cardiology at Children's, Commonwealth Professor of Pediatrics at Harvard Medical School, and Principal Investigator on the grant together with Christine E. Seidman, MD, Director of the Cardiovascular Genetics Center at Brigham and Women's Hospital and Thomas W. Smith Professor of Medicine at Harvard Medical School. Jonathan Seidman, PhD, Henrietta B. and Frederick H. Bugher Foundation Professor of Genetics at Harvard Medical School, is also a key co-investigator. The other PCGC institutions are Yale University, Mt. Sinai School of Medicine, Columbia University, and Children's Hospital of Philadelphia.

Although a few genetic causes of congenital heart disease are already known, the researchers hope to zero in on novel, undiscovered genes. Because gene discovery research requires a high number of patient samples, a collaborative consortium such as the PCGC will propel research forward by allowing scientists to share patient samples, data and technology. Everybody recognizes that no one center alone can do this research, Newburger says.

Several other Children's Hospital Boston researchers are co-investigators in the PCGC. Steven Colan, MD, Associate Chief for Clinical Operations in the Department of Cardiology and Professor of Pediatrics at Harvard Medical School, will lead the echocardiography and other cardiac imaging studies which are essential to characterize the exact form or phenotype of the patients' heart conditions. Roger Breitbart, MD, Assistant Professor of Pediatrics at Harvard Medical School, will serve as an important liaison between the clinical effort and research laboratory. Amy Roberts, MD, Assistant Professor in Pediatrics at Harvard Medical School, will lead the recruitment of new patients and collection of DNA.

Competition inspires people to work quickly, but this particular area of research begs for collaboration, says Roberts, who is Director of the Cardiovascular Genetics Research Program at Children's. The collaborative effort is the only way we have a chance of making big discoveries in a short period of time.

Members of the European Parliament discuss achieving heart health in Europe

Wed, 09 Dec 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Brussels, 9 December 2009 - Members of the European Parliament Heart Group (MEP HG) meet today, in Brussels, with the Cardiology profession and representatives of national Heart Foundations to evaluate the achievements at EU level in combating Cardiovascular Disease (CVD), and to reveal the need for further action.

With the title 'Achieving Heart Health in Europe: Why the European Parliament Matters', the meeting is the first since the European elections in June this year. During the 2004-2009 term, the MEP Heart Group was the largest forum on health in the European Parliament. The group resumes now its activities which endeavour to raise heart health as a priority on the EU political agenda. CVD is the number one killer in Europe, accounting for over 2 million deaths in the EU alone and costing the EU over 190 billion Euros each year. (1)

Mr Dirk Sterckx MEP, Co-chair of the MEP HG, believes that the European Union has a major role to play in fostering heart health promotion and developing wide-ranging prevention strategies. The European Parliament has set the example with the 2007 Resolution on action to tackle cardiovascular disease (2). However, the recent declining trends in CVD deaths in Europe are now slowing down. This is very worrying; it represents an alarm call to the European Commission and the Council.

The EU cannot turn its back on CVD, agrees Linda McAvan MEP, Co-chair of the MEP HG. Evidence does exist that prevention brings significant health gains. It is therefore the task of decision makers at European and national level to ensure that effective policies supporting prevention are put in place.

CVD is currently THE public health challenge in Europe, says Prof. Simon Capewell, Professor of Clinical Epidemiology, Liverpool University, UK. There are widening gaps both between and within Member States. CVD mortality rates have been decreasing in the past 30 years but they are now flattening. This is extremely frustrating because 80% of premature CVD deaths can be prevented by tackling the major risk factors, diet and smoking. A comprehensive European heart health strategy addressing health promotion and disease prevention is a moral responsibility for policymakers.

Significant policy developments addressing cardiovascular disease have taken place in Europe in the last decade. These include the Council Conclusions to promote heart health (adopted in 2004), the European Heart Health Charter (launched in 2007), and the European Parliament Resolution on action to tackle cardiovascular disease (adopted with a large majority in July 2007). Despite this, a tangible European strategy to address CVD is still non-existent. The MEP HG is calling for action from the European Commission and Member States to fill the gap. We urgently need to address what should be the Number 1 public health priority in Europe.

Think again about keeping little ones so squeaky clean

Tue, 08 Dec 2009 04:59:36 PST

( from http://www.rxpgnews.com ) EVANSTON, Ill. --- A new Northwestern University study suggests that American parents should ease up on antibacterial soap and perhaps allow their little ones a romp or two in the mud --- or at least a much better acquaintance with everyday germs.

The study is the first to look at how microbial exposures early in life affect inflammatory processes related to diseases associated with aging in adulthood.

Most provocatively, the Northwestern study suggests that exposure to infectious microbes early in life may actually protect individuals from cardiovascular diseases that can lead to death as an adult.

Contrary to assumptions related to earlier studies, our research suggests that ultra-clean, ultra-hygienic environments early in life may contribute to higher levels of inflammation as an adult, which in turn increases risks for a wide range of diseases, said Thomas McDade, lead author of the study, associate professor of anthropology in Northwestern's Weinberg College of Arts and Sciences and a faculty fellow at the Institute for Policy Research.

Relatively speaking, humans only recently have lived in such hyper-hygienic environments, he stressed.

The research suggests that inflammatory systems may need a higher level of exposure to common everyday bacteria and microbes to guide their development. In other words, inflammatory networks may need the same type of microbial exposures early in life that have been part of the human environment for all of our evolutionary history to function optimally in adulthood, said McDade, also a member of Northwestern's Cells to Society (C2S).

The Northwestern study is the first research on microbial effects on inflammatory systems in infancy that relate in later life to diseases associated with aging. Advancing the scientific literature on the developmental origins of disease, the study arguably is the most significant research on long-term effects of early environments on human physiological function and health in adulthood.

The research took advantage of a longitudinal study of Filipinos, following participants in utero through 22 years of age, to get a better understanding of how environments early in life affect production of C-reactive protein (CRP) production in adulthood.

Levels of the protein rise in the blood due to inflammation, an integral part of the immune system's fight against infection. CRP research mostly has centered on the protein as a predictor of heart disease, independent of lipids, cholesterol and blood pressure, though researchers still dispute that association. Researchers have been looking at excess body fat as a primary source of pro-inflammatory cytokines that produce CRP and behavioral factors related to diet, exercise and smoking. And the CRP research largely has been conducted in relatively affluent settings, such as in the United States, with low levels of infectious diseases.

The Northwestern researchers were interested in what CRP production looks like in the Philippines, a population with a high level of infectious diseases in early childhood compared to Western countries. Relative to Western countries, the Philippines also has relatively low rates of obesity and cardiovascular diseases, consistent with the Northwestern research findings.

Blood tests showed that C-reactive protein was at least 80 percent lower for study participants in the Philippines when they reached young adulthood, relative to their American counterparts, though the Filipinos suffered from many more infectious diseases as infants and toddlers. Filipino participants in their early 20s had average CRP concentrations of .2 milligrams per liter -- five to seven times lower than average CRP levels for Americans. CRP concentrations for Americans in their early 20s were on average around 1 to 1.5 milligram per liter.

Early Origins of Inflammation: Microbial Exposures in Infancy Predict Lower Levels of C-reactive Protein in Adulthood, will be published online December 9 in the journal

Therapeutic Hypothermia - Cooling therapy protects brain after cardiac arrest

Mon, 07 Dec 2009 15:20:49 PST

( from http://www.rxpgnews.com ) Revival of the heart after it stops may save a patient's life, but it permanently damages the brain. Cooling the patient for some time is known to mitigate this harmful effect and improve survival, under a procedure known as therapeutic hypothermia.

Cardiac arrest interrupts the blood supply, depriving cells of oxygen and causing the body to release toxic compounds, that can overwhelm the organs and result in long-term brain injury.

Therapeutic hypothermia slows the body's production of these compounds, reducing risk for brain injury. The therapy has been used successfully in adult cardiac arrest patients, and has been beneficial for newborns, who have received insufficient oxygen at birth.

Now, in the first large-scale multicentre study, physician-scientists are evaluating the effectiveness of the technique in infants and children.

'Cardiac arrest can occur in children either as a complication from a serious medical condition or due to an accident or sudden illness,' warns Charles Schleien, paediatrician and anesthesiologist at New York-Presbyterian Morgan Stanley Children's Hospital.

'While arrest in children is rare, currently no therapies have been shown to improve their chances of recovering,' adds Schleien, who is also the executive vice-chairman of paediatrics at Columbia University College of Physicians and Surgeons.

'In this new study, we aim to show that therapeutic hypothermia can give these children a better chance at survival and long-term quality of life,' says Schleien.

Those receiving hypothermia will have their body temperature reduced to between 89.6 degrees and 93.2 degrees Fahrenheit - for two days, then slowly increased to a normal body temperature and maintained for another three days, says a New York-Presbyterian release.

Co-led by Frank W. Moler at the University of Michigan C.S. Mott Children's Hospital and Michael Dean at the University of Utah, the six-year study involves a total of 16 study sites in North America.

New technology to identify compounds that triggers heart failure

Sat, 28 Nov 2009 13:52:27 PST

( from http://www.rxpgnews.com ) A breakthrough will help identify compounds implicated in heart failure more rapidly, says a new study.

The technology, developed by University of Minnesota's David Thomas and Razvan Cornea and Celladon Corporation's Krisztina Zsebo, allows for quicker screening of compounds linked with proteins implicated in heart failure.

Chronic heart failure is the leading medical cause of hospitalisation and is expected to cost the US healthcare system $ 37.2 billion in 2009 alone.

About 5.7 million people in the US have heart failure, and it contributes to or causes some 290,000 deaths annually.

Fluorescence resonance energy transfer - is used to measure disruption of the calcium regulatory system, which has long been implicated in cardiovascular disease.

This will provide key information on a particular drugs' likelihood of success early in the screening process.

'Dr. Cornea and I, along with our students, have worked for more than a decade developing methods for preparing membranes from purified components, and using FRET to detect changes in protein interactions,' Thomas said, according to a Minnesota release.

'Scientists from Celladon saw the potential for drug discovery, and this resulted in a breakthrough that has added an exciting new dimension to our research programme.'

However, developing new treatments is an extremely costly and time-consuming process, taking nearly a decade to gain regulatory approval and requiring hundreds of millions of dollars, the release added.

Engineers, doctors at UCLA develop novel material that could help fight arterial disease

Wed, 25 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) A fortuitous discovery that grew out of a collaboration between UCLA engineers and physicians could potentially offer hope to the nearly 10 million Americans who suffer from peripheral arterial disease.

Also known as hardening of the arteries, peripheral arterial disease, or PAD, is a common circulatory problem in which narrowed arteries reduce blood flow to the limbs. The condition is considered a red flag for vascular disease, heart attack and stroke, and its progression can result in the loss of limbs or death.

While there are currently several treatments for PAD, including balloon angioplasty, stenting and bypass surgery, devices used in the latter two can frequently cause thrombosis, in which clots form inside blood vessels, obstructing blood flow and leading to serious complications.

Now, a team from the UCLA Henry Samueli School of Engineering and Applied Science, in collaboration with researchers from the David Geffen School of Medicine at UCLA, is working to develop a PAD treatment device that can prevent thrombosis in small-diameter blood vessels.

Their research centers on stents that incorporate a material known as Nitinol, a superelastic nickel and titanium alloy that has the ability to be deformed and to recover its original shape upon heating.

In recognition of the potential of the research, the National Institutes of Health's National Heart, Lung and Blood Institute recently awarded the team a $1 million Challenge Grant.

What we've been doing at UCLA for the last five to 10 years now is working with thin-film Nitinol, said Greg Carman, a professor of mechanical and aerospace engineering and lead investigator for the multidisciplinary research team, which was organized under the umbrella of the UCLA Center for Advanced Surgical and Interventional Technologies.

Nitinol, discovered back in the 1960s, is a shape-memory material. They thought it was going to revolutionize the engineering field. It wasn't until 1985 that people began to think this material would probably be great to use in a stent, Carman said. The reason they liked it for a stent is because you could bend the material a very large distance and it would return back to its original shape. Other metals, such as surgical steel, do not allow such a large shape recovery and, as such, cannot be used in many stenting devices.

In the early 2000s, Carman's group started looking into making thin-film Nitinol and accidently stumbled across a way to fabricate what they believed was very high-quality, uniform-composition Nitinol.

That's when we started producing thin-film Nitinol. We weren't sure where the applications for this novel, very low-profile material would go until we ran into someone in the medical school, Carman said.

I immediately saw the promise that thin-film Nitinol had for intravascular and cardiac applications, said Dr. Daniel Levi, a pediatric cardiologist at Mattel Children's Hospital UCLA and a principal investigator on the team. Greg and I started working together immediately on stents and a heart valve.

University of Minnesota invention will help speed development of drug treatments for heart failure

Mon, 23 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Research conducted by University of Minnesota scientists, in collaboration with Celladon Corporation, has led to the invention of technology to more rapidly identify compounds for the treatment of heart failure.

Chronic heart failure is an increasingly important health problem. It is the leading medical cause of hospitalization and is expected to result in an estimated direct and indirect cost to the health care system of $37.2 billion in 2009 alone. About 5.7 million people in the United States have heart failure, and it contributes to or causes some 290,000 deaths annually. However, developing new treatments is an extremely costly and time-consuming process, taking nearly a decade to gain regulatory approval and requiring hundreds of millions of dollars.

The technology, developed by the universitys David Thomas and Razvan Cornea and Celladon Corporations Krisztina Zsebo, allows for increased screening efficiency of compounds capable of disrupting the interactions of proteins implicated in the development of heart failure. Fluorescence resonance energy transfer (FRET) is used to measure disruption of the calcium regulatory system, which has long been implicated in cardiovascular disease. This will provide key information on a particular drugs likelihood of success early in the screening process, since compounds that decrease FRET are good candidates for further development.

Dr. Cornea and I, along with our students, have worked for more than a decade developing methods for preparing membranes from purified components, and using FRET to detect changes in protein interactions, Thomas said. Scientists from Celladon saw the potential for drug discovery, and this resulted in a breakthrough that has added an exciting new dimension to our research program.

The high-throughput assay, developed by the university team, is based on a reconstituted membrane system composed of purified lipid and protein components. This technique is especially important because the interactions of integral membrane proteins are more complex than soluble proteins, making it very difficult to produce a synthetic system that recapitulates the cellular interactions in a large-scale and reproducible manner.

Celladon, based in La Jolla, Calif., has acquired an exclusive license for the technology from the University of Minnesota for the development of molecular therapies for cardiovascular diseases. Celladon also provided funding for the research that allowed Thomas to further refine the assay.

This technology is very important to the efficient selection and advancement of compounds with the potential to increase cardiac contractility and potentially accelerates product opportunities that will ultimately benefit patients and development partners alike, said Krisztina M. Zsebo, Ph.D., president and chief executive officer of Celladon Corporation. Celladon's investigation and development of first-in-class CDN small molecules as intravenous and oral drugs for the treatment of acute and chronic heart failure sets us apart in the cardiovascular field and presents multiple partnering opportunities.

Study on contribution of genetic variation on plasma lipoprotein profile

Sun, 22 Nov 2009 09:57:05 PST

( from http://www.rxpgnews.com ) Using highly precise measurements of plasma lipoprotein concentrations determined by nuclear magnetic resonance spectroscopy (NMR), researchers led by Daniel Chasman at Brigham and Women's Hospital and Harvard Medical School in Boston, MA, the Framingham Heart Study in Framingham, and the PROCARDIS consortium in Stockholm, Sweden and Oxford, England performed genetic association analysis across the whole genome among 17,296 women of European ancestry from the Women's Genome Health Study. This large scale analysis of the effects of common genetic variation on plasma lipoprotein profile, a critical component of cardiovascular risk, identified 43 genetic loci contributing to lipoprotein metabolism, including 10 loci not previously recognized in other whole genome analyses. The findings are published on November 20 in the open-access journal PLoS Genetics.

The findings were validated among additional populations of both men and women. The research also quantifies the contribution of common genetic variation to the concentration of plasma lipoproteins according to class, that is low-density lipoprotein (LDL), high-density lipoprotein (HDL), or very low density lipoprotein (VLDL), as well as size and cholesterol or triglyceride content.

The balance of LDL, HDL, and VLDL particle concentration is firmly established as a measure of cardiovascular risk. These major classes of lipoprotein particles are composed of sub-species that can be categorized according to size. While the overall concentration of each of the major classes can be estimated by the clinical measures of LDL-cholesterol, HDL-cholesterol, and triglycerides, the determinations of the concentration of the sub-species by NMR methodology in the current study provide a more precise picture of lipoprotein profile. Clinical research is engaged in determining the contribution of each of the sub-species to cardiovascular risk.

"This current genetic analysis complements clinical analysis of cardiovascular risk by evaluating the genetic contribution to the concentration of each lipoprotein sub-species and helps to delineate genes and metabolic pathways that might be targeted for interventional strategies," noted Dr. Chasman. He continued "the research can be placed in the larger context of studies that are leveraging knowledge of the human genome to dissect the molecular basis of common diseases, particularly cardiovascular disease, through large scale, genome-wide genetic analysis."

Carvedilol has additional benefit for cardiac patients

Sun, 22 Nov 2009 09:17:35 PST

( from http://www.rxpgnews.com ) A study, which appears in the journal Circulation Research, found that beta-blockers that target both the alpha- and beta-receptors on the heart muscle offer the most benefit to cardiac patients, while those that target only the beta-receptors can actually undermine the structure and function of the heart.

Circulation Research is published by the American Heart Association.

Heart disease is the leading cause of death in the United States. Patients with heart disease usually have higher levels of catecholamines – hormones that activate the beta-adrenergic receptors to stimulate cardiac muscle contraction. In this process, the heart initially grows to become a more efficient pump. Unfortunately, the researchers found, this growth also predisposes the heart to eventual failure.

Traditionally, beta-blockers targeting the beta-adrenergic receptors have been utilized as a long-term therapy for heart failure.

Interestingly, blocking adrenergic receptors has been widely used clinically for nearly 50 years without a full understanding of the molecular consequences of these drugs, said co-author and graduate student David Cervantes. Kevin Xiang, a professor of molecular and integrative physiology at the University of Illinois led the study. The research team also included researcher Catherine Crosby.

A previous study in 2003 showed that the beta-blocker carvedilol produced a greater survival benefit than another drug, metoprolol tartrate. Carvedilol targets both the beta- and alpha-adrenergic receptors.

The new study unveiled an elegant intracellular signaling system in which beta-receptor activation modulates alpha-adrenergic signaling. It showed that blocking the beta-receptor alone promotes cardiac remodeling via growth of cardiac fibroblasts induced by alpha-adrenergic receptor signaling. The growth of fibroblasts in the heart further damages the integrity and function of the heart.

This observation suggests that the use of carvedilol in combination with inhibitors of angiotensin-converting enzyme (ACE inhibitors) may be of the greatest benefit to cardiac patients, and has significant clinical implications on which beta-blockers patients should take.

"I think this is really good stuff," Xiang says. "It's a surprise project. It's not what we initially intended looking into. But it's a very nice, elegant study and a very beautiful cellular mechanism. It definitely will help people along the way to understand how to further manipulate this system. Beta blockers are still the most commonly used drug for heart disease."

Your own stem cells can treat heart disease

Tue, 17 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) CHICAGO --- The largest national stem cell study for heart disease showed the first evidence that transplanting a potent form of adult stem cells into the heart muscle of subjects with severe angina results in less pain and an improved ability to walk. The transplant subjects also experienced fewer deaths than those who didn't receive stem cells.

In the 12-month Phase II, double-blind trial, subjects' own purified stem cells, called CD34+ cells, were injected into their hearts in an effort to spur the growth of small blood vessels that make up the microcirculation of the heart muscle. Researchers believe the loss of these blood vessels contributes to the pain of chronic, severe angina.

This is the first study to show significant benefit in pain reduction and improved exercise capacity in this population with very advanced heart disease, said principal investigator Douglas Losordo, M.D., the Eileen M. Foell Professor of Heart Research at the Northwestern University Feinberg School of Medicine and a cardiologist and director of the program in cardiovascular regenerative medicine at Northwestern Memorial Hospital, the lead site of the study.

Losordo, also director of the Feinberg Cardiovascular Research Institute, said this study provides the first evidence that a person's own stem cells can be used as a treatment for their heart disease. He cautioned, however, that the findings of the 25-site trial with 167 subjects, require verification in a larger, Phase III study.

He presented his findings Nov. 17 at the American Heart Association Scientific Sessions 2009.

Out of the estimated 1 million people in the U.S. who suffer from chronic, severe angina -- chest pain due to blocked arteries -- about 300,000 cannot be helped by any traditional medical treatment such as angioplasty, bypass surgery or stents. This is called intractable or severe angina, the severity of which is designated by classes. The subjects in Losordo's study were class 3 or 4, meaning they had chest pain from normal to minimal activities, such as from brushing their teeth or even resting.

The stem cell transplant is the first therapy to produce an improvement in severe angina subjects' ability to walk on a treadmill. Twelve months after the procedure, the transplant subjects were able to double their improvement on a treadmill compared to the placebo group. It also took twice as long until they experienced angina pain on a treadmill compared to the placebo group, and, when they felt pain, it went away faster with rest. In addition, they had fewer overall episodes of chest pain in their daily lives.

In the trial, the CD34+ cells were injected into 10 locations in the heart muscle. A sophisticated electromechanical mapping technology identifies where the heart muscle is alive but not functioning, because it is not receiving enough blood supply.

Migraine raises risk of most common form of stroke

Mon, 16 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Pooling results from 21 studies, involving 622,381 men and women, researchers at Johns Hopkins have affirmed that migraine headaches are associated with more than twofold higher chances of the most common kind of stroke: those occurring when blood supply to the brain is suddenly cut off by the buildup of plaque or a blood clot.

The risk for those with migraines is 2.3 times those without, according to calculations from the Johns Hopkins team, to be presented Nov. 16 at the American Heart Association's (AHA) annual Scientific Sessions in Orlando. For those who experience aura, the sighting of flashing lights, zigzag lines and blurred side vision along with migraines, the risk of so-called ischemic stroke is 2.5 times higher, and in women, 2.9 times as high.

Study participants, mostly in North America and Europe, were between the ages 18 and 70, and none had suffered a stroke prior to enrollment.

Senior study investigator and cardiologist Saman Nazarian, M.D., says the team's latest analysis, believed to be the largest study of its kind on the topic, reinforces the relationship between migraine and stroke while correcting some discrepancies in previous analyses. For examples, a smaller combination study in 2005 by researchers in Montreal showed a bare doubling of risk, yet mixed together different mathematical measures of risk, while the Hopkins study kept them separate, pooling together only like measures. As well, another half dozen recent and smaller studies from Harvard University yielded mixed results, some showing a link between migraines and ischemic stroke, while one did not show a tie-in.

Nazarian says that while nearly 1,800 articles have been written about the relationship between migraine and ischemic stroke, the Hopkins review was more selective, combining only studies with similar designs and similar groups of people, and more comprehensive, including analysis of unpublished data.

Identifying people at highest risk is crucial to preventing disabling strokes, says Nazarian, an assistant professor at the Johns Hopkins University School of Medicine and its Heart and Vascular Institute. Based on this data, physicians should consider addressing stroke risk factors in patients with a history or signs of light flashes and blurry vision associated with severe headaches.

Prevention and treatment options for migraine, he says, range from smoking cessation and taking anti-blood pressure or blood-thinning medications, such as aspirin. In women with migraines, stopping use of oral contraceptives or hormone replacement therapy may be recommended.

Such widespread use of hormone-controlling drugs is what Nazarian says may explain why women with migraines have such high risk of ischemic stroke. Contraceptives and other estrogen therapies are both known to contribute to long-term risk factors for cardiovascular diseases and stroke, such as high blood pressure and increased reactivity by clot-forming blood platelets.

Nazarian says the researchers' next steps are to evaluate if preventive therapies, especially aspirin, offset the risk of ischemic stroke in people with migraines.

An often overlooked protein actually a potent regulator of cardiac hypertrophy

Mon, 16 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) (PHILADELPHIA) A protein long thought to be a secondary regulator in the heart's response to stressors like hypertension actually appears to be a primary regulator according to researchers from the Center for Translational Medicine at Thomas Jefferson University. The data will be presented in the Late Breaking Science session at the American Heart Associations Scientific Sessions in Orlando, Fla.

According to Thomas Force, M.D., the James C. Wilson Professor of Medicine at Jefferson Medical College of Thomas Jefferson University, glycogen synthase kinase-3 (GSK-3) proteins include the isoforms GSK-3beta and GSK-3alpha. GSK-3beta has always been thought to be the regulator of cardiac hypertrophy, and GSK-3alpha has been largely ignored. But the ignored isoform is actually quite powerful.

We found that knocking out GSK-3beta did not do much at all, but knocking out of GSK-3alpha caused a huge increase in hypertrophy, said Dr. Force, who led the study. The standard theory was that beta is more potent than alpha, but alpha was far more important at regulating this process.

Hypertrophy is the heart's response to stressors such as hypertension. In hypertrophy, the heart muscle cells get larger, as does the heart itself. This process is a predictor of heart failure and death. The concept, according to Dr. Force, is to understand the pathways through which this happens, which would allow physicians to intervene and possibly prevent the heart failure.

In addition to regulating hypertrophy, the researchers also found that GSK-3alpha is a potent positive regulator of the beta-adrenergic system, which allows the heart to respond to stresses and helps failing hearts pump better. But when GSK-3alpha was knocked out in the mice models, the heart systems simply failed and were not able to stand up to the pressure of stressors like hypertension.

GSK-3 is targeted by a number of drugs in development for several diseases, including bipolar disorder, Alzheimer's disease and diabetes.

If these inhibitors make it to clinical trials, patients being treated with them would need to be closely watched, especially if they have diseases like hypertension or underlying heart disease, Dr. Force said. They could run into trouble if their hearts are unable to respond to stressors due to the inhibition of GSK-3alpha.

Lastly, the researchers also found that when GSK-3beta was knocked out, the heart progenitor cells started to proliferate. This could potentially serve as the basis for a regenerative therapy approach for patients with heart failure, according to Dr. Force. Inhibiting GSK-3beta increased the proliferation of myocytes in the heart by five- to 10-fold.

Exercise-linked ventricular tachycardia is not a risk to healthy older adults

Mon, 16 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Healthy, older adults free of heart disease need not fear that bouts of rapid, irregular heartbeats brought on by vigorous exercise might increase short- or long-term risk of dying or having a heart attack, according to a report by heart experts at Johns Hopkins and the U.S. National Institute on Aging (NIA).

Researchers say such fears surfaced after previous studies found that episodes of errant heart rhythms, more formally known as non-sustained ventricular tachycardia, more than double the chance of sudden death in people who have already suffered a heart attack.

In a study to be presented Nov. 16 at the American Heart Association's (AHA) annual Scientific Sessions in Orlando, the research team monitored for on average 12 years the medical records of 2,234 initially healthy men and women, ages 21 to 96, and participating in the NIA's Baltimore Longitudinal Study of Aging. In adults with no earlier signs of heart disease, researchers found no adverse effects resulting from brief episodes of exercise-induced ventricular tachycardia.

In the study, each volunteer participant had a least one exercise stress test performed before 2001. The test assesses the heart's pumping ability, requiring participants, whose average age at testing was 52, to walk or jog on a treadmill at increasing speeds and inclines until they felt exhausted, about 10 minutes for most.

Eighty-one (roughly 4 percent, 65 men and 16 women, mostly older participants) experienced short periods of rapid, irregular heartbeats during exercise, typically lasting from three to six heartbeats, and at a rate hovering around 175 beats per minute.

Researchers say overall death rates were higher in the tachycardia group than in the nontachycardia group (at 29 percent and 16 percent, respectively). But when they adjusted their analysis to account for differences in age, gender, and those who developed known risk factors for heart disease early on, they found no measureable increased risk of overall death, death from heart disease, or suffering a heart attack between the tachycardia and nontachycardia groups.

Lead study investigator and cardiologist Joseph Marine, M.D., says the study results should provide reassurance among apparently healthy middle-age and older people that such short episodes of ventricular tachycardia provoked on exercise testing do not have long-term consequences to health.

So long as a medical examination shows no underlying heart disease or other serious health condition, then people should continue to live a normal lifestyle, including a return to exercise after clearance from their physician, says Marine, an associate professor at the Johns Hopkins University School of Medicine and its Heart and Vascular Institute. Our results suggest that brief, non-sustained ventricular arrhythmia during exercise testing should, generally, not cause undue alarm in patients or physicians.

When suspicious about heart disease, Marine says, care providers should investigate further for any signs of ischemia, arterial blockages, heart muscle disease or inherited risk of arrhythmia. But if everything checks out negative for heart disease, then restrictions on exercise are not needed. Indeed, he says, regular exercise has long been known to cut down on the risk of developing heart disease.

Study co-investigator and Hopkins cardiologist Gary Gerstenblith, M.D., adds that the latest study results should help physicians better triage which patients to treat after incidents of exercise-induced tachycardia.

Most people who experience erratic heart rhythms during exercise and who have no underlying heart condition can be left alone, they do not need to be treated, and they can continue to exercise, says Gerstenblith, a professor at Johns Hopkins School of Medicine. However, patients with erratic heartbeats who are later found to have underlying coronary heart disease should refrain from arduous exercise until consulting with their physician about treatment with drugs and/or an implantable device to improve their heart function and to decrease the risk of dying from a potentially fatal heart rhythm.

Marine says the next steps in their research are to determine whether other arrhythmias brought on by exercise, such as atrial tachycardia, have any impact on future death or heart-attack rates or lead to other arrhythmias.

Protein changes in heart strengthen link between Alzheimer's disease and chronic heart failure

Sun, 15 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) A team of U.S., Canadian and Italian scientists led by researchers at Johns Hopkins report evidence from studies in animals and humans supporting a link between Alzheimer's disease and chronic heart failure, two of the 10 leading causes of death in the United States.

The international team of biochemists and cardiologists say they have identified three changes in the chemical make-up of a key structural protein, called desmin, in heart muscle cells in dogs. The changes led to the formation of debris-like protein clusters, or amyloid-like oligomers containing desmin, in heart muscle, similar to the amyloid plaques seen in the brain tissue of Alzheimer's patients. The protein alterations, which were reversed by surgically repairing the heart, occurred at the onset of heart failure. Further experiments by the Hopkins scientists found the same chemical modifications to desmin in the heart muscle in four people already diagnosed with the disease.

Misshaped desmin proteins and amyloid-like debris had been previously reported in 2005 in mice genetically altered to develop chronic heart failure, providing the first biological link between the two chronic diseases. Studies since have also reported desmin changes in failing animal hearts, but none detailed what the chemical changes were or how they might affect organ function.

Researchers say their latest analysis, to be presented Nov. 15 at the American Heart Association's (AHA) annual Scientific Sessions in Orlando, is believed to be the first to tie common underlying structural changes in desmin to malformations observed in the heart as it weakens, strains to pump blood and starts to fail. Their results are also believed to be the first to suggest that toxic, desmin-like amyloids could form in response to stress placed on the heart.

Our study leads us to believe that desmin plays a key role in heart failure, says lead study investigator and protein biochemist Giulio Agnetti, Ph.D. Now we have a chemical target to research further and help us investigate what could be the underlying biological cause of heart failure and if it is like Alzheimer's, an amyloid-related disease.

Just as significantly, our study raises the prospect of testing new treatment options for heart failure by moving beyond treating symptoms of the disease and getting to the root of the matter, preventing these desmin amyloids from forming and impairing heart function from the start, says Agnetti, a postdoctoral research fellow at both the Johns Hopkins University School of Medicine and its Heart and Vascular Institute, and the University of Bologna and its National Institute for Cardiovascular Research, in Italy. Symptoms of heart failure may include fatigue, shortness of breath and enlargement of the heart.

Agnetti's work has been recognized at the heart meeting, where he is a finalist for the inaugural Functional Genomics and Translational Biology Council's Young Investigator Award.

The team's latest investigation began with an analysis of proteins contained in heart tissue samples collected from a group of dogs whose hearts had been surgically altered to beat irregularly, become stressed and fail. Additional tissue samples were taken from another group of healthy controls.

Researchers compared these samples, looking for structural and chemical changes in desmin, which is found in all heart muscle cells and is a key component of the intermediate filaments that make up the scaffolding, or muscle cell support structure. They say this is the same muscle structure that becomes disorganized in heart failure.

The team's analysis yielded at least three chemical differences in each desmin protein in response to heart failure. Further tests showed that phosphate molecules had attached at two spots within the protein's structure. They also found accumulating amyloid-like debris, containing desmin, in the damaged heart tissue.

When researchers performed surgery restoring the dogs' heart pumping function to normal, they found phosphorylated sites mostly reverted to normal. The amlyoid-like oligomers also began to disappear. Tissue samples from four people with heart failure showed similar desmin modifications.

Senior study investigator Jennifer Van Eyk, Ph.D., says that it is not surprising these changes in the so-called scaffolding structure of the heart can produce toxic debris. But what is most interesting about our findings is that we have shown that these chemical changes and debris are related to impaired heart function, which, ultimately, may explain how and why the heart can fail, says Van Eyk, a Johns Hopkins professor and director of Hopkins' NHLBI Proteomics Group and the Proteomics Center at Johns Hopkins Bayview Medical Center, where the protein analysis took place.

Researchers next plan to analyze each of the desmin modifications to determine the subsequent biological impact of each chemical change.

Agnetti points out that the team's protein analysis was only made possible in the last 15 years, and with the development of technologies for detailed chemical analysis, such mass spectrometry and gel electrophoresis. Previously, he says, scientists had mostly focused on genetic changes and their relationship to disease, as opposed to disease-causing alterations to proteins that occur after proteins are made.

Statins may worsen symptoms in some cardiac patients

Tue, 03 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Although statins are widely used to prevent heart attacks, strokes, and other cardiovascular disorders, new research shows that the class of drugs may actually have negative effects on some cardiac patients. A new study presented at CHEST 2009, the 75th annual international scientific assembly of the American College of Chest Physicians (ACCP), found that statins have beneficial effects on patients with systolic heart failure (SHF), but those with diastolic heart failure (DHF) experienced the opposite effect, including increased dyspnea, fatigue, and decreased exercise tolerance.

Systolic heart failure is most often due to coronary artery disease and appears to have more of an inflammatory component than diastolic heart failure, said Lawrence P. Cahalin, PhD, PT, Northeastern University, Boston, MA. It is possible that statins would help patients with systolic heart failure more than patients with diastolic heart failure due to the cholesterol-lowering and antiinflammatory effects of statins.

Researchers from Northeastern University and Massachusetts General Hospital, Boston, MA, retrospectively reviewed the charts of 136 patients with heart failure in order to examine the effect of statins on pulmonary function (PF) and exercise tolerance (ET) in patients with DHF vs. SHF. A non-statin group (82 percent of patients had DHF) of 75 patients was compared with a statin group (72 percent of patients had DHF) of 61 patients. Atorvastatin was prescribed in 75 percent of the patients on statins.

Results of the analysis showed that overall PF and ET of patients in the statin group were significantly lower than patients in the non-statin group. Further subgroup analyses revealed that PF measures in the DHF statin group were 12 percent lower than PF measures in the DHF non-statin group. Furthermore, the amount of exercise performed by patients with DHF who were on a statin was almost 50 percent less than patients with DHF not on a statin.

Some patients with diastolic heart failure may be more prone to the adverse effect of statins on muscle. It may be that patients with particular preexisting factors will experience unfavorable results from statin therapy, including exercise intolerance, dyspnea, and fatigue, said Dr. Cahalin.

Although the PF and ET measures in the SHF statin group were not significantly greater than in the SHF non-statin group, the PF measures were 11 percent to 14 percent higher, and the peak ET measures were 2 percent to 7 percent higher than the PF and ET measures of the SHF non-statin group, suggesting that statins did benefit patients with SHF.

Not all statins are alike and not all patients are alike. Some statins are stronger than others and are likely to act differently, given particular patient characteristics, and produce different degrees of wanted and unwanted effects, said Dr. Cahalin. In our continuing study, we hope to identify patient characteristics that are associated with favorable and less than favorable results from statin therapy.

Although the new data suggest that statins may actually worsen symptoms in patients with DHF, researchers feel that the benefits of using statins in patients with SHF and DHF outweigh the risks.

Due to beneficial effects on lipids and other cardiovascular factors, statins are becoming a standard treatment for many patients with or without systolic or diastolic heart failure. It is likely that the use of statins for these conditions will continue to increase, said Dr. Cahalin. However, if patients taking a statin are short of breath, fatigued, and unable to exercise or perform functional tasks, then exams of muscle strength and endurance, as well as pulmonary function and exercise tolerance, are warranted.

Statins provide significant benefits for patients with cardiovascular disease, said Kalpalatha Guntupalli, MD, FCCP, President of the American College of Chest Physicians. However, as for any new medication prescribed, clinicians should closely monitor the effects that different types of statins have on individual patients.

Gladstone and Stanford in collaboration to develop iPS cells for cardiac therapies

Mon, 02 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Scientists at the Gladstone Institute of Cardiovascular Disease (GICD) and Stanford University School of Medicine will collaborate in a new consortium funded by the National Heart, Lung and Blood Institute (NHLBI) to develop stem cell and regenerative medicine therapies. GICD investigators, led by GICD Director Deepak Srivastava, MD, will collaborate with a Stanford team led by Robert Robbins, MD, professor and chair of cardiothoracic surgery, to investigate how to use induced pluripotent stem cells, or iPS cells, to repair damaged heart muscle.

This is an exciting opportunity to work with the most talented investigators in the field to accelerate the application of this promising technology to real patient benefits, said Srivastava. Each research team will receive approximately $10 million dollars over 7 years as part of the larger NHLBI Progenitor Cell Biology Consortium, which will bring together researchers from the heart, lung, blood, and technology research fields.

NHLBI is committed to stimulating stem cell research that will lead to the development of regenerative therapies for the treatment of heart, lung and blood diseases, said NHLBI director Elizabeth Nabel, MD, in a press release. Important gaps remain in our understanding of stem and progenitor cells, and this consortium holds great promise to expand our knowledge and uncover therapeutic applications of great public impact.

iPS cells result from the reprogramming of adult cells into a cell closely resembling an embryonic stem cell. Like stem cells, they can develop into any cell type in the body. This exciting technology was developed by Gladstone investigator Shinya Yamanaka, MD, PhD. the 2009 Lasker Award Recipient for Biomedical Research.

The 17 multidisciplinary teams are organized into nine thematic research hubs. The research will be coordinated and administrated out of the University of Maryland-Baltimore.

While a stem cell can renew itself indefinitely or differentiate into an adult cell, a progenitor cell can only divide a limited number of times and is often more limited than a stem cell in the kinds of cells it can become. Given the potential of these cells for clinical applications, the goals of the consortium are to identify and characterize progenitor cell lines, direct the differentiation of stem and progenitor cells to desired cell fates, and develop new clinical strategies to address the unique challenges presented by the transplantation of these cells.

The joint Gladstone-Stanford project capitalizes on the synergy of Gladstone investigators expertise in guiding cardiac cell fate decisions and iPS technology, with the strengths of Stanford investigators in tissue engineering, use of large animals for pre-clinical trials and high-resolution imaging of cells placed into animal models for regenerative therapies. This consortium brings together the leading scientists in this field in a large-scare coordinated effort that may be a 'Manhattan Project' of stem cell research, Robbins said. The aim is to investigate and evaluate the potential of this for the major diseases of our time.

Women and cardiovascular health conference to highlight need for gender-specific research

Fri, 30 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) The 'Red Alert for Women's Hearts' conference, taking place on 5 November 2009, at the European Heart House, Sophia Antipolis, France, will address the subject of Women and CVD. The conference is jointly organised by the European Society of Cardiology (ESC) and European Heart Network (EHN), as part of Work Package 6 of the EuroHeart project (1).

Heart disease and stroke are the leading causes of death for women worldwide, killing more than 8.6 million, more than the total number who die from cancer, tuberculosis, HIV/AIDS and malaria combined.

However, the risk for women is largely under-estimated, by both the general population and often by the medical profession itself. This is due to the fact that women usually suffer from CVD 10 years later in their life than men: the risk increases after menopause, partly because of ovarian hormone deficiency that favours hypertension, diabetes, hyperlipidemia, central obesity and the metabolic syndrome.

In the report that will be presented at the conference (2), Professor Stramba Badiale, MD, PhD at the Department of Rehabilitation Medicine, IRCCS Istituto Auxologico Italiano, finds that women are underrepresented in cardiovascular research in Europe. In the 62 randomized clinical trials published between 2006 and July 2009, only 33.5% of enrolled participants were women, he says.

This underrepresentation is particularly noticeable in the fields of cholesterol-lowering therapy, ischaemic heart disease and heart failure.

Professor Roberto Ferrari, President of the ESC says: With regard to cardiovascular health, we do lack data for women simply because the majority of clinical trials are conducted on men. It is important to have special clinical trials conducted only on women because their cardiovascular pathology is, at least at some point during their lives, different from that of men and it is incorrect to apply data derived from studies on men to women.

Another finding of the report that supports the conference programme is that only 50% of the clinical trials conducted in the last three years which enrolled both men and women reported the analysis of the results by gender.

Susanne Logstrup, director of the EHN, regrets that, as a result, safety and efficacy of several drugs have been evaluated predominantly in male populations.

Professor Stramba-Badiale is hopeful that the report and the conference will encourage new practice amongst the research community, with a systematic enrolment of women in clinical trials. New data should improve the clinical management of CVD and, in the future, develop possible gender specific diagnostic and therapeutic strategies, he says.

The research is part of the EuroHeart project, which aims at defining areas of policies and public health interventions which can contribute to prevent avoidable deaths and disability across Europe. It is led by the ESC, in partnership with the EHN, and is co-funded by the European Commission Public Health Programme 2003-2008.

The 'Red alert for women's hearts' conference will systematically review the place of women in all aspects of scientific literature, whether clinical trials, guidelines, medical curriculum or regulatory processes.

More than 60 awareness campaigns addressing the particular issue of women and cardiovascular diseases have been organised in the last 20 years in the 19 countries participating in WP 6 of the EuroHeart project. This is evidence that national Heart Foundations and Cardiac Societies have long been aware of the urgent need to promote the issue amongst the female population and health professionals. The results of campaigns showed an increased awareness that cardiovascular diseases are the leading cause of death for women. Despite this, gender-specific training for cardiologists is still lacking in the majority of European countries.

The objective of this conference is to create a series of recommendations for policy makers, research funding agencies and regulatory entities, at both national and EU level.

Red Alert for Women's Hearts is also the opportunity to look at how countries address the lack of information of the population and of health professionals, by giving an overview of past campaigns and their impact, country by country.

Case Western Reserve to lead $14.7M NIH sprint study network in Ohio

Thu, 29 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Case Western Reserve University School of Medicine has received a $14.7 million, nine-year contract from the National Institutes of Health to be one of five institutions to lead a trial to determine if lowering systolic blood pressure in hypertensive patients, without diabetes, to below the currently recommended level can reduce the incidence of cardiovascular and kidney disease and slow cognitive decline. Case Western Reserve will head a Clinical Center Network (CCN) consisting of investigators from its School of Medicine and three other Northeast Ohio clinical centers, as well as The Ohio State University College of Medicine. It will be directed by Jackson T. Wright, Jr., M.D., Ph.D., Professor of Medicine, Case Western Reserve and Director of the Clinical Hypertension Program at University Hospitals Case Medical Center (UHCMC).

The objective of the study is to evaluate whether treating patients to systolic blood pressure of less than 120 mmHg reduces the risk of cardiovascular and kidney disease, or age-related cognitive decline, more than the usually recommended level of less than 140 mmHg, says Dr. Wright. We suspect that treating to the lower level of 120 mmHg will result in fewer cardiovascular and kidney complications. However, this needs to be proven.

The results of this study will grow the small body of evidence supporting this hypothesis. Called SPRINT (Systolic Blood Pressure Intervention Trial), the study findings will be used to reevaluate the optimal blood pressure for patients and have the potential to establish new guidelines for healthcare providers. SPRINT will enroll approximately 7,500 participants, age 55 or older, with systolic blood pressure of 130 mm Hg or higher. All participants will have a history of cardiovascular disease or be at high risk for heart disease by having at least one additional risk factor, except diabetes; between 40- and 50 percent will have chronic kidney disease. Blacks and other minorities will comprise at least 30 percent of the study. The Case Western Reserve CCN will recruit approximately 1,500 patients.

A very important sub-study of SPRINT will evaluate how the higher versus lower blood pressure goals affect cognition function and dementia. Alan Lerner, M.D., Professor of Neurology, and Director of the Memory and Cognition Center at UHCMC will lead the Case Western Reserve University efforts for this cognitive functioning sub-study, called SPRINT-MIND.

The Case Western Reserve CCN is a network consisting of the major academic medical centers in Northeast Ohio and The Ohio State University College of Medicine; the clinical centers and investigators in the CCN include:

Gladstone scientists receive $10 million to identify genetic cause of congenital heart disease

Tue, 27 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Scientists at the Gladstone Institute of Cardiovascular Disease (GICD) will receive $10 million over the next 6 years to find the genetic causes of congenital heart disease. Congenital heart disease affects 1 percent of all children and often leads to death or long-term illness. The team of investigators, led by Benoit Bruneau, PhD, will focus on the gene networks that underlie the disease and the regulatory factors that turn on and off genes related to congenital heart defects (CHDs). GICD was one of four national centers awarded this highly competitive grant to address CHD at a genome-wide level.

We know that specific genes have to be turned on and off during a relatively narrow developmental window to correctly build a human heart, said Dr. Bruneau, who is the William H.Younger, Jr. Investigator at Gladstone. But so far we only understand how a handful of genes change during heart formation. Our study will look at all of the 25,000 genes in the genome to get a full picture of how the entire system is regulated. Understanding the all of the regulatory networks that control heart development will have important implications for preventing and curing congenital heart disease.

According to Bruneau, the research team will use cutting-edge genome-mapping techniques to identify and define the function of transcription factors with known roles cardiac development and human disease, and so-called epigenetic regulators, the factors that open up chromosomes to allow the transcription factors to reach their targets.

Transcription factors are the master regulators of a cell, acting to turn on or off other genes; they function by directly interacting with DNA, but it isn't known how they function in concert with epigenetic regulators.

Dr. Deepak Srivastava, director of GICD and co-investigator, has identified the genetic causes of many CHDs and will use newly developed technology from Dr. Shinya Yamanaka, another co-investigator in GICD, to generate induced pluripotent stem (iPS) cells from patients with transcription factor mutations leading to CHD.

Our studies will yield an important and transformative epigenetic atlas of heart development, which will link for, the first time, transcriptional and epigenetic regulators in a comprehensive network that will illuminate mechanisms underlying CHDs, he said.

Congenital heart defects are the most common and life-threatening problem for newborns in the Unites States, said Elizabeth G. Nabel, MD, director of the National Heart, Lung and Blood Institutes, part of the National Institutes of Health. Our Bench to Bassinet research efforts will offer new insights into how the human cardiovascular system develops and help speed transition of promising laboratory discoveries into treatments that can save young lives.

Other team members include Katherine S, Pollard, PhD and Bruce Conklin, MD (from the Gladstone Institute of Cardiovascular Disease and UCSF), and Laurie Boyer, PhD (Massachusetts Institute of Technology).

Case Western Reserve University receives $20.5 million

Tue, 13 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Case Western Reserve University has received a $20.5 million gift from Donald Goodman, DDS (DEN '45) and Ruth Weber Goodman.

The Donald J. and Ruth Weber Goodman Philanthropic Fund will reside at the University and the Cleveland Foundation. Income will be used to support education and research programs at the schools of medicine and dental medicine. The gift has been used to establish two professorships at the School of Medicine: The Dr. Donald and Ruth Goodman Professorship in Innovative Cancer Therapeutics, which is currently held by Mary J. Laughlin, MD; and The Dr. Donald and Ruth Goodman Professorship in Innovative Cardiovascular Research, which has not yet been appointed.

Don and Ruth Goodman cared deeply about the university, and we are truly thankful to them and their family for their commitment to pre-eminent research and education at our schools of medicine and dental medicine, said Barbara R. Snyder, president of Case Western Reserve University.

Donald Goodman, who died in 2007, was a Cleveland-area dentist who made his fortune through decades of savvy stock market investment. He and his wife, Ruth, who died in 2008, traveled to more than 260 countries and islands, met Mother Theresa and saw the Dalai Lama. Ruth was the daughter of Arthur F. Weber, founder of Cuyahoga Heights, OH-based Triplex Screw Co.. The company was sold to Murray Corp. of America in 1952.

As a couple, Don and Ruth shared the same goal to improve the lives of others. They realized this goal by setting an example with an incredible legacy gift to this community, said Donald Goodman's son, Bruce Goodman.

Donald Goodman's granddaughter Kayleen Goodman-McDowell added, This gift has allowed them to extend their values through a family legacy beyond any of our expectations.

Donald Goodman credited the research at the School of Medicine and Mary Laughlin, MD, of the Ireland Cancer Center with prolonging his life for six years through an experimental treatment for acute myeloid leukemia.

It is always gratifying to see a patient who has directly benefited from the application of cutting-edge medical research and who wishes to recognize the value of this through such a wonderful philanthropic commitment. This gift is truly inspiring, said Pamela B. Davis, dean and vice president for medical affairs at the School of Medicine. In addition to making a substantial investment in our faculty who work at the cutting edge, the endowment income will ensure that the school remains a pace-setter in educating world-class physicians and advancing the cure and treatment of disease.

Donald Goodman was a 1945 graduate of the Case Western Reserve University School of Dental Medicine, which will also benefit from the endowment.

NHLBI to convene symposium on cardiovascular regenerative medicine

Thu, 08 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) With advancements in the field of stem cell research accelerating, the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) will hold its third Symposium on Cardiovascular Regenerative Medicine to review the latest findings in the field and examine future directions. The symposium will include a discussion on ways to move promising findings in the laboratory into clinical trials, in hopes of speeding stem cell-related treatments to patients.

The event will be held Oct. 14 -15 at the Natcher Conference Center on the NIH campus in Bethesda, Md.

This symposium will help us move forward to spur new scientific efforts that will advance the field of cardiovascular stem cell research, said NHLBI Director Elizabeth G. Nabel, M.D., who will deliver the keynote address on the NHLBI Roadmap for stem cell research. With more than 16 million Americans living with damage to heart muscles or blood vessels due to heart attacks, this area of research holds great promise to improve lives.

Nabel noted that the theme of the symposium coincides with the NHLBI's recent funding of stem cell research projects under the American Recovery and Reinvestment Act. The NHLBI has made stem cell research a Signature Project under the Recovery Act and is putting a priority on funding research that could lead to the development of regenerative treatment for heart, lung, and blood diseases, added Nabel.

Some symposium sessions will focus on cardiac development and how epithelial cells transform into mesenchymal cells, a process which is related to organ development and some fibrotic diseases. Another session will review recent advances, and future potential, for embryonic stem cells and induced pluripotent stem (iPS) cells that could be used for cell therapy in the heart. IPS cells are artificially derived stem cells that can give rise to any fetal or adult cell type. The symposium will also feature a series of talks related to the NHLBI's newly launched Progenitor Cell Biology Consortium, whose 18 teams of scientists are developing the field of stem and progenitor cell tools and therapies.

Stem cell experts from the United States, Canada, the Netherlands, Spain, and Sweden are scheduled to speak, and the symposium will also include a number of poster sessions. Among the highlights of the scheduled list of speakers:

George Q. Daley, M.D., Ph.D., Harvard Medical School/Children's Hospital of Boston. Modeling Blood Disease with iPS Cells. Wednesday, Oct. 14, 8:35 a.m. Daley will discuss ways to use induced pluripotent stem cells to model blood disease. This line of research could provide new targets for drug therapy.

Bernhard Kuhn, M.D., Harvard Medical School/Children's Hospital of Boston, Stimulating Myocardial Regeneration with Cardiomyocyte Proliferation Factors. Thursday, Oct. 15, 11 a.m. Kuhn will discuss ways to recruit existing heart tissue into producing new cells, which could help repair heart damage following heart attack or stroke.

Jonas Frisen, M.D., Ph.D., Karolinska Institute, Sweden, Cardiomyocyte Renewal in Humans. Thursday, Oct. 15, 11:20 a.m. Frisen will discuss his work using residual atmospheric radiation remaining from aboveground atomic bomb testing in the 1960s from sites around the world to determine the age of cardiomyocytes, or cardiac muscle cells, in humans. Until now, it has been difficult to determine the age of cells in the heart, so there was little information about whether new tissue was being generated in the heart. Frisen's research suggests that a tiny fraction of tissue cells within the heart are new cardiomyocytes, a finding which could lead to new ways to encourage more such tissue growth.

Women's soccer -- get fit while having fun

Fri, 02 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com )

Over a period of two years, 30 scientist lead by Associate Professor Peter Krustrup, University of Copenhagen, have investigated physiological, sociological and psychological aspects of women's soccer in comparison to running. 100 untrained adult premenopausal women have participated in the study.

The women (65 participated in the physiological study) were randomly divided into three groups: One soccer group, one running group and one control group. The soccer players and runners trained twice a week for one hour. After four and sixteen weeks, all the subjects went through extensive physiological tests. The same 65 subjects + another 35 women playing in soccer clubs were continually observed and interviewed to study the sociological and psychological effects of their training.

Many women find it difficult to fit in sport and exercise in their busy daily lives, and many state family and especially small children as the main reason for not finding the time.

The study reveals that contrary to common assumption, the flexibility of running as exercise form actually makes running harder to stick to for most women than soccer, which requires a fixed time and place.

What is really interesting is that the soccer players differed from the runners in their motivation. The runners were motivated by the idea of getting in shape and improving health. But the soccer players focused on the game itself and were motivated by the social interaction and by having fun with others. As it turns out, the soccer players got in better shape than the runners, and that combined with the social benefits makes soccer a great alternative to running, says Associate Professor Laila Ottesen and continues:

The women who played soccer have continued their soccer training as a group whereas few of the women in the running group continued running after the study. Actually, some of the women from the running group joined teams with the soccer group after the project finished.

When choosing a sport, women tend to favour cardiovascular training to strength training although the build-up of muscles and bone strength are vital to preserve health into old age.

While playing soccer, the women have high heart rates and perform many sprints, turns, kicks and tackles, making soccer an effective integration of both cardio and strength training, says project leader Peter Krustrup.

Our study shows that the 16 weeks of recreational women's soccer causes marked improvement in maximal oxygen uptake, muscle mass and physical performance, including the endurance, intermittent exercise and sprinting ability, explains Peter Krustrup, and continues

This makes soccer a very favourable choice of exercise training for women.

In the recent decade, we have seen a significant rise in women and girls playing soccer. It seems as though women are really beginning to take in soccer and make it a popular sport for women on their own terms. This is a very positive step forward, not only because of the improved physical fitness and health profile but also for the enjoyment of sports, Krustrup concludes.

The present results will be submitted online in the high-level international journal Scandinavian Journal of Medicine and Science in Sports next week (Bangsbo, Nielsen, Mohr, Randers, Krustrup, Brito, Nybo and Krustrup. Performance enhancements and muscular adaptations of a 16-week recreational football intervention for untrained women. Scand J Med Sci Sports, 2009).

In January 2010, the same journal will publish a supplementum describing multiple health effects of recreational football for various subject groups, including men, women, young and elderly. The supplementum includes one review and 13 original scientific papers.

The data will also be presented at the Scandinavian Congress of Medicine and Science in Sports 2010, Copenhagen, Denmark, 4-6 February 2010, and at the 3rd International Football Medicine Conference in Sun City, South Africa, 19-21 February 2010.

The project group currently includes collaborators from Switzerland, Norway and Italy, and major applications are currently being processed to include collaborators from England, Portugal, Belgium, Australia and Kenya.

NIH funds grantees focusing on epigenomics of human health and disease

Wed, 16 Sep 2009 03:59:36 PST

( from http://www.rxpgnews.com ) The National Institutes of Health announced today that it will fund 22 grants on genome-wide studies of how epigenetic changes -- chemical modifications to genes that result from diet, aging, stress, or environmental exposures -- define and contribute to specific human diseases and biological processes.

The awards will build on the important work undertaken as part of the NIH Roadmap for Medical Research's Epigenomics Program. Approximately $62 million will be awarded over the next five years to study the epigenome in a number of diseases and conditions, including tumor development, hardening of the arteries, autism, glaucoma, asthma, aging, and abnormal growth and development.

Epigenomics represents the next phase in our understanding of genetic regulation of health and disease, says NIH Director Francis Collins, M.D., Ph.D. These awards will address the extent to which diet and environmental exposures produce long lasting effects through changes in DNA regulation. The initiative was launched through the NIH Director's Office and, as part of the Roadmap, is expected to profoundly alter the way we understand, diagnose, and treat disease.

This is the largest effort to date to apply epigenetics on a genome-wide scale to specific diseases, said James F. Battey, M.D., Ph.D., director of the National Institute on Deafness and Other Communication Disorders, one of the lead NIH institutes for this Roadmap program.

The Roadmap Epigenomics Program was designed to characterize epigenetic modifications and to correlate the presence or absence of specific modifications with disease status. DNA methylation is a fundamental epigenetic modification that regulates gene expression and chromosome stability. This and other epigenetic modifications control gene activity by changing the three-dimensional structure of chromosomes. (See scientific illustration of epigenetic mechanisms at http://nihroadmap.nih.gov/epigenomics/epigeneticmechanisms.asp.)

The awards announced today are funded by 11 NIH institutes and the NIH Office of the Director and are part of the NIH Roadmap for Medical Research's Epigenomics Program that began in 2007. The NIH contributors include the National Cancer Institute, the National Eye Institute, the National Heart, Lung, and Blood Institute, the National Institute on Aging, the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Drug Abuse, the National Institute of Environmental Health Sciences, the National Institute of Mental Health, and the Office of Behavioral and Social Sciences Research and the Office of Strategic Coordination in the NIH Office of the Director.

The new grantees being announced will join a larger collaborative research effort that is working together to understand epigenetics and how it affects human health and disease, said Nora D. Volkow, M.D., director of the National Institute on Drug Abuse.

This health and disease-focused component of the NIH Roadmap Epigenomics Program builds on the previous four interrelated initiatives, but is the first to tackle questions related to diseases. The other four initiatives include the establishment of four epigenome mapping centers, the funding of an epigenomics data analysis and coordination center. the development of innovative technology in epigenetics, and the discovery of novel epigenetic changes.

These studies will help increase our understanding of how factors such as environmental exposures, alcohol, drug abuse and stress can modify the effect of epigenetics on diseases, said Linda S. Birnbaum, Ph.D., director of the National Institute of Environmental Health Sciences.

The following awards are being made by NIH:

Artificial Neural Network Software Can Diagnose Cardiac Infections

Tue, 15 Sep 2009 11:38:42 PST

( from http://www.rxpgnews.com ) New research suggests that 'teachable software', designed to mimic the human brain, may help diagnose cardiac infections in a non-invasive manner.

Endocarditis -- an infection involving the valves and sometimes chambers of the heart -- can be a problem in patients with implants. It is a serious condition and can be deadly.

The mortality rate can be as high as one in five, even with aggressive treatment and removal of the device. With additional complications, the mortality can shoot up to over 60 percent -- or more than one in two.

Diagnosis usually requires an invasive procedure that also has risks.

The software programme is called an 'artificial neural network' - because it mimics the brain's cognitive function and reacts differently to situations depending on its accumulated knowledge.

That knowledge or training is provided by researchers, similar to how a person would 'train' a computer to play chess, by introducing it to as many situations as possible.

In this case, the ANN underwent three separate 'trainings' to learn how to evaluate the symptoms it would be considering.

'If, through this novel method, we can help determine a percentage of endocarditis diagnoses with a high rate of accuracy, we hope to save a significant number of patients from the discomfort, risk and expense of the standard diagnostic procedure,' says M. Rizwan Sohail, leader of the study and Mayo Clinice, Minnesota, infectious diseases specialist.

The team studied 189 Mayo patients with device-related endocarditis diagnosed between 1991 and 2003.

The ANN was tested retrospectively on the data from these cases. When tested on cases with known diagnosis of endocarditis, the best-trained ANN was correct most of the time -.

These findings were presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy - in San Francisco.

Piece from childhood virus may save soldiers' lives

Sun, 06 Sep 2009 03:58:48 PST

( from http://www.rxpgnews.com ) A harmless shard from the shell of a common childhood virus may halt a biological process that kills a significant percentage of battlefield casualties, heart attack victims and oxygen-deprived newborns, according to research presented Sunday, September 6, 2009, at the 12th European meeting on complement in human disease in Budapest, Hungary.

Introducing the virus's shell in vitro shuts down what's known as the complement response, a primordial part of the immune system that attacks and destroys the organs and vascular lining of people who have been deprived of oxygen for prolonged periods, according to researchers at Children's Hospital of The King's Daughters (CHKD) and Eastern Virginia Medical School (EVMS), in Norfolk, Va.

The complement response kicks in after the victim has been revived, in what is known as a reperfusion injury. It does its work slowly but unrelentingly, killing soldiers, infants or heart attack victims over the course of days.

To find a way to manipulate the complement system pharmacologically has been like a search for the Holy Grail, said one of the lead researchers, Dr. Kenji Cunnion, an infectious disease physician at CHKD and an associate professor of pediatrics at EVMS.

While Cunnion and Neel Krishna, Ph.D., a pediatric virologist at CHKD and assistant professor of microbiology at EVMS, focus on pediatric research, they see clear military applications.

The complement reaction is one of the major causes of death of the battlefield, said Krishna. By the time you get a victim to the hospital, it may be too late.

Dr. L.D. Britt, M.D., MPH, Brickhouse professor and chairman of surgery at EVMS, agrees.

Hemorrhagic shock is the leading cause of death in combat trauma and reperfusion injury plays a significant role both in increased mortality and increased brain damage, said Britt, senior consultant to the military on combat trauma. This research could help save the lives of soldiers, as well as the lives of other trauma victims who have been without oxygen for extended periods.

Britt has joined Cunnion in Krishna in seeking a grant from the Department of Defense to expedite research and development.

The complement system ranks as one of the oldest biological mechanisms in life's evolution and exists in almost identical form in everything from seagulls to starfish.

Essentially, the complement system recognizes and destroys potentially toxic substances that gain entry into an organism's bloodstream. When a starfish loses a limb, for instance, the complement system sends a contingent of killer cells to block and attack anything that tries to work its way inside.

In human evolution, complement provided an essential natural defense.

Up until 100 years ago, the vast majority of humans died from infectious diseases, said Cunnion. Nobody died of old age and almost nobody lived long enough to die of a heart attack.

Thanks to modern medicine, people now live long enough to die from trauma, such as car accidents, or from conditions, such as heart attack and stroke, that can leave cells throughout the body starved for oxygen. Cells deprived of oxygen often undergo biochemical changes, essentially marking themselves for death. When blood flow and oxygen are restored, these changes trigger the complement cascade. The marauding cells unleashed by complement cascade are indiscriminate, killing not only the cell with the biochemical marker but innocent bystander cells as well.

It's like throwing a grenade, said Krishna.

A patient, who has suffered survivable brain damage from oxygen deprivation, might die over several days as swaths of cells are destroyed by this seemingly unstoppable reaction. Animal research has shown that stopping this complement reaction significantly reduces brain damage.

The complement system is so complex that research scientists spend entire careers studying it, publishing in journals that specialize in this primordial defense mechanism.

In the case of Cunnion and Krishna, discovering how to shut down the complement system resulted from happenstance. As they worked in neighboring labs, they noticed a similarity in the structure of molecules Cunnion used in his experiments and the protein shell of the astrovirus Krishna studied. They wondered what would happen if they introduced the astrovirus shell into an assay routinely used in Cunnion's lab to assess complement activation.

It was kind of a shot in the dark, Krishna said. We didn't expect anything to happen.

The complement reaction completely stopped.

Irbesartan reduces heart failure in patients with quivering heart

Tue, 01 Sep 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Barcelona, Spain, 1 September: Most research in atrial fibrillation (AF) has focused on reducing stroke and other embolic events. Yet heart failure occurs more frequently in AF patients, but has not been the focus of intervention research.

In a major international trial, researchers from McMaster University in Canada, found that the hypertension drug irbesartan reduced the risk of heart failure complications and the combination of stroke, other embolic events and transient ischemic events, also known as ministrokes, in patients with atrial fibrillation.

Atrial fibrillation is a common disorder of the heart rhythm that causes the muscles of the atria to quiver instead of beat at regular intervals. The condition affects about one per cent of the population and up to 10 per cent of people over the age of 80. Although strokes are frequent in AF patients (and have been the focus of much research), heart failure is even more common, but no intervention has been shown to reduce this complication.

The findings of the ACTIVE-I (Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events) study will be presented today at the European Society of Cardiology in Barcelona, Spain, by Dr. Salim Yusuf.

Dr. Yusuf is a professor of medicine in the Michael G. DeGroote School of Medicine at McMaster University and director of the Population Health Research Institute at McMaster University and Hamilton Health Sciences.

The approach to the management of AF patients should be multidimensional, said Yusuf, the chair of the ACTIVE-I steering committee. While antithrombotic drugs are important in preventing stroke and other complications, complimentary approaches to reducing these and other complications by lowering blood pressure or controlling heart rhythm are important.

The ACTIVE-I study is part of a larger program of research into atrial fibrillation and involves randomizing over 9,000 patients (enrolled at more than 500 centres in 41 countries) to receive irbesartan or placebo for 4.1 years. The study was completed in June, 2009.

The difference in systolic blood pressure between the groups was approximately 3 mm Hg. The study examined two co-primary outcomes: the composite of cardiovascular death, heart attack or stroke which was unchanged (5.4 per cent/year in each group), but this composite plus heart failure hospitalization tended to be non-significantly lower (7.3 per cent/year irbesartan vs. 7.7 per cent/year placebo). The latter difference was due to a significant reduction in hospitalizations for heart failure (2.7 per cent/year irbesartan vs. 3.2 per cent/year placebo) by 14 per cent. There was also a significant reduction in stroke, non-central-nervous-system embolism, and transient ischemic attacks (2.9 per cent/year irbesartan vs. 3.4 per cent/year placebo) by 13 per cent. There was a significant reduction in hospital admissions and the number of days in hospital for cardiovascular reasons. Irbesartan was similarly tolerated compared to placebo.

The modest BP lowering with irbesartan in the trial likely occurred because patients were already receiving several BP-lowering drugs before entering the trial, and this was intensified to a greater extent in the placebo group during the trial, said Dr. Stuart Connolly, a professor of medicine in the Michael G. DeGroote School of Medicine at McMaster University, a member of the Population Health Research Institute and the principal investigator of the trial.

When one considers that the difference in systolic BP between groups was less than 3 mm Hg, the 13 per cent to 14 per cent relative risk reduction in heart failure and cerebrovascular and other embolic events is clinically important, and suggests that more aggressive BP lowering may have an even larger benefit.

By demonstrating the reduction in cardiovascular hospitalizations, the ACTIVE I study highlights the importance of multiple approaches in tackling the total burden of disease in patients with AF, said Dr. Marc Pfeffer, Dzau Professor of Medicine, Harvard University Medical School at the Brigham and Women's Hospital in Boston. Dr. Pfeffer is the U.S. National Coordinator and a member of the ACTIVE Executive Committee.

Atrial fibrillation: Drugs or ablation?

Tue, 01 Sep 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Barcelona, Spain, 1 September: Atrial fibrillation ablation is one of the fastest growing techniques in cardiology and due to the very high number of patients that might be candidates to this procedure, a significant number of resources will have to be devoted to it to be able to treat them in the following years.

Atrial Fibrillation (AF) is the most frequent cardiac arrhythmia. Its prevalence increases with age affecting more than 5% of the population older than 75 years of age. Overall it is estimated that more than 3.000.000 patients in Europe suffer from atrial fibrillation. Atrial fibrillation doubles the possibility of death mainly due to the higher incidence of thromboembolic events and occurrence of heart failure in patients suffering this arrhythmia.

One treatment objective is directed to avoid the negative consequences of the arrhythmia by trying to maintain normal sinus rhythm. Two strategies exist to obtain this result:

1. Chronic treatment with antiarrhythmic drugs (AAD)

2. Catheter ablation of atrial fibrillation

1. AAD treatment tries to block or modulate the electrical activity of the heart avoiding initiation and perpetuation of the arrhythmia. It is effective in about 60% of patients and requires long-term treatment. Many of the drugs used have side effects, some of them disabling for the patient. Many drugs are available and combination of them might be used in case of failure. Compliance of the treatment is basic for long-term success.

2. Catheter ablation has emerged as an alternative to obtain stable sinus rhythm in this population. It has been demonstrated that a significant number of AFepisodes initiate in the area of the pulmonary veins located in the left atrium. Using one or several catheters inserted through the femoral veins, they are inserted into the heart and brought to the left atrium through a transseptal approach. Once in the left atrium energy (radiofrequency, cold) is delivered in different areas (mainly around the pulmonary veins) to create lesions that block the electrical activity responsible for the arrhythmia. The effectiveness of this technique is around 70% and in about 25% a second procedure is needed to finish the ablation lines. As any invasive procedure some major complications may occur like cardiac tamponade (1%), thromboembolic events (0.5%) or atrio-esophageal fistula (1/1000). In case of success the patient does not requires continuation with AAD and the arrhythmia is cured.

The decision of which treatment to be used will have to be based on a number of considerations: type of patient, willingness of the patient, experience of the centre in ablative techniques, etc.

It is estimated than more than 10.000 atrial fibrillation ablation procedures are performed annually in Europe and the number is increasing exponentially since over the last years availability of more sophisticated techniques and equipment has produced a marked increase in the number of centres performing atrial fibrillation ablation. Three dimensional mapping systems, robotic techniques, new energy sources and new and more reliable catheters are easing the procedure and improving efficacy and safety.

Syncope and implantable loop recorders: Good value for money?

Tue, 01 Sep 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Barcelona, Spain, 1 September 2009: The REVISE Study (Reveal in the Investigation of Syncope and Epilepsy) found that 1 in 8 adult patients in the United Kingdom, previously thought to be suffering from epilepsy or in whom this diagnosis was in doubt, in fact had symptoms as a result of an abnormal pattern of heart beating, commonly found in patients with syncope (fainting).

REVISE is the first study to show that, by means of an implantable ECG recorder, 1 in 8 patients who were previously thought to have epilepsy or in whom this diagnosis was in doubt, have an abnormality in their heart rhythm as a cause of their symptoms. Eighty percent of those who underwent a pacemaker insertion based on the results of the ECG loop recorder were subsequently found to be free of their symptoms.

Four of the 5 patients who underwent a pacemaker as part of this study were subsequently free of symptoms. The average duration of follow-up was 9 months. This study was carried out at the Manchester Heart Centre, Manchester Royal Infirmary, Manchester, UK in collaboration with the Greater Manchester Centre for Neurosciences, Hope Hospital, Salford, UK. A small metallic device * about the size of a memory stick or a packet of gum, was used to record the heart rhythm of patients in this study. This device was inserted underneath the skin, on the left side of the chest in a small, low risk, 20 minute operation. Study patients also underwent a number of other brain and heart tests.

Previous scientific studies, mainly from the United Kingdom, have shown that up to 1 in 4 patients thought to be suffering from epilepsy do not actually have this condition. This conclusion was based on reviewing medical records of patients known to have epilepsy and on the results of the tilt table test, a test in which patients are made to stand at an angle of 60 degrees on a bed with a footboard support in an attempt to induce a blackout. Moreover, the All Party Parliamentary Group on Epilepsy, in their report published in June 2007, found that 74,000 patients in the United Kingdom were taking drugs for epilepsy, which they did not need. Patients with syncope (fainting) as well as epilepsy present with transient loss of consciousness (T-LOC) or 'blackouts'. In some patients syncope (fainting) can mimic epilepsy. A temporary decrease in blood supply to the brain which occurs in syncope (fainting) can result in irritation of brain cells causing abnormal movements, which to a lay person can look very similar to epilepsy. In the general population, syncope (fainting) is much more common than epilepsy, affecting 25% of the population at any given time, more so in the elderly.

The benefits of reperfusion therapy

Tue, 01 Sep 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Barcelona, Spain, 1 September: The wider use of reperfusion therapy in patients with heart attack (AMI) can save millions of lives in Europe. Effective reperfusion therapy in an AMI patient can cut the individual risk of dying by half. AMI is caused by a sudden blockage of a coronary artery, one of the vessels supplying the heart muscle with oxygen and nutrients. Effective reperfusion therapy provides a timely and sustainable reopening of the blockage.

The WHO MONICA* project showed that in European centres in the mid-1990s, in-hospital mortality of AMI patients was 13%; this was a time when only about 40% of the patients had reperfusion therapy. Today, specialist centres can provide effective reperfusion therapy to more than 90% of their AMI patients. In such centres, in-hospital mortality rate is now as low as around 5%.

The first development in reperfusion therapy was the application of fibrinolytic agents to dissolve the blood clots causing the vessel blockage. Analysis of data from earlier studies reveals that, on average, fibrinolytic agents can reduce infarct-related mortality rate by 18% compared with no reperfusion therapy. Fibrinolytic therapy is universally available and is still the mainstay of reperfusion therapy where healthcare resources are limited.

More modern catheter-based reperfusion strategies, however, are more effective. Compared with what can be achieved by clot-buster drugs, catheter-based therapy reduces infarct-related mortality by a further 37%. Using this approach, the coronary artery is re-opened mechanically with a balloon catheter and vessel patency is usually stabilised by placement of a stent. Potent adjunct antithrombotic drug therapy prevents recurrent clot formation. The larger survival benefit from catheter-based reperfusion therapy as compared with fibrinolytic therapy can be attributed to a higher success rate in reopening blocked vessels (90% versus 40-60%) and to better sustainability.

If no reperfusion therapy is initiated and the infarct-related coronary artery continues to be blocked, the heart muscle supplied by this vessel is destined to die. Loss of functional heart muscle can cause death by pump failure or break-down of normal heart rhythm. Moreover, it is a major cause of long-term illness due to heart failure. Effective reperfusion therapy can prevent the death of heart muscle cells and salvages a large proportion of the heart muscle at risk. In this way, reperfusion therapy effectively prevents chronic illness. The percentage of heart-muscle salvage varies to a large extent on reperfusion modality, timing of reperfusion and patient characteristics.

Catheter-based reperfusion usually salvages around 60% of the heart muscle at risk. For the individual patient this often means a normal life, despite having suffered a heart attack.

Pre-hospital organization: The first links in the chain of survival for heart attack patients

Tue, 01 Sep 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Barcelona, Spain, 1 September: Mortality rate following a heart attack has fallen by more than 50% in Europe over the past 25 years. However, because only minor advances in the medical treatment of AMI are expected over the next decade, it is through organisational changes in the pre-hospital phase that mortality rate will continue this decline to below 5%.

We estimate that acute coronary syndromes (ACS) account for 1.5 million hospital admissions throughout Europe each year. Almost half these patients present with ST-elevation myocardial infarction (STEMI), which are major and immediately life-threatening events.

Just 30 years ago, mortality of acute myocardial infarction (AMI, heart attack) in Europe was over 30%. This rate has now dropped dramatically to around 10% within the first month. In clinical trials - where the sickest patients are often excluded - mortality rate is as low as 5%.

This dramatic improvement was initially brought about by the opening of dedicated coronary care units in hospitals. This was followed by 20 years of drug development, and a significant improvement in survival rates. Among the important drugs introduced were those preventing blood from clotting, or even dissolving the clot responsible for blocking the coronary vessel (and so causing the AMI. Other drugs groups include beta-blockers, ACE inhibitors, and statins develeoped to lower cholesterol levels. More recently, the treatment of large heart attacks with balloon angioplasty has been a major advance. Although new and better drugs are being developed and drug combinations being refined, there is less belief in major drug breakthroughs in the next decade.

The pre-hospital phase of AMI treatment has also undergone several changes over the past decade: diagnosis, supported by telemedicine, has improved, and many interventions have been moved from the hospital to the field. It is in this early phase that we must now adopt new collaborations and organisations if mortality rate in this large patient population is to continue its decline. We must adopt new lean principles in the entire organisation of the pre-hospital phase, starting with public awareness of symptoms, and how to raise the alarm. For those patients whose first symptom is cardiac arrest, basic bystander resuscitation should become standard. Despite an abundance of automated external defibrillators (AED) in many regions, their localisation and use are often not well organised. Heart attack victims should call an emergency number, instead of being self or family-transported to the hospital.

There are financial and political disincentives for the transfer of STEMI patients for balloon angioplasty: all of these factors should be addressed:

Primary Hospital

Eating less red meat can prevent cancer, heart attacks and global warming

Mon, 31 Aug 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Barcelona, Spain, 31 August: Raising livestock also accounts for around 18% of greenhouse gases. It is therefore possible to act against climate change and reduce cardiovascular and cancer deaths, by cutting the production and consumption of 'red meat' from these animals. The World Cancer Research Fund and the American Institute for Cancer Research have recommended that an individual should eat no more than 500 grams of red meat per week.

Cardiovascular disease and cancer are two human diseases caused by similar factors influencing climate change. Others are the infectious disease influenza and salmonella, which are also related to animal elevation (zoonoses). Further examples not specifically related to agriculture, are respiratory diseases resulting from the burning of fossil and other fuels for transport and heating.

A different group of diseases cannot be said to share the causes of global warming. Instead they are caused by, or exacerbated by global warming. Examples are thermal stress, accidental and intentional injuries, and malnutrition or famine, all of which are expected to occur more frequently as the planet warms up and the climate becomes less stable. Health care systems all over the world will have to adapt to these changes.

Human disease and global warming are therefore related in several ways, and the World Health Organization (WHO) as well as national medical associations, have adopted policies to take these interrelationships into account. In contrast, professional societies within cardiovascular medicine and research have not yet addressed the relationships of climate change to cardiovascular disease, but they should consider doing so for at least two reasons.

The first is the relationship already described: risk of cardiovascular disease can be reduced by interventions which also reduce the risk of climate change. For example recommendations could be given regarding the consumption of red meat such as those already made by oncology institutions.

The second is advocacy. Physicians and biomedical researchers have the training to understand the physics, chemistry and statistics used in the climatological research that has demonstrated the gravity of the climate problem. Sea levels were for example, at least 15 to 25 meters higher than they are now when the earth's atmosphere last had the same CO2 capacity as now (about 387 parts per million) which was three million years ago. Atmospheric CO2 concentrations are currently rising at 2 ppm / year.

It is difficult for politicians in democratic countries to make the necessary changes in national and international policies for energy, transport, agriculture, urban planning, family planning, etc, without general public understanding of the issues. Physicians and scientists devoted to understanding, preventing and treating cardiovascular disease also have the ability to understand the climate issue. Most importantly, they have the authority to promote this understanding through private and public debate. Not least because they can make statements, backed up by science, demonstrating that reducing the risk of heart attack can also impact upon climate change.

Can we change society?

Mon, 31 Aug 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Barcelona, Spain, 31 August: Cardiovascular diseases (CVD) result from a negative interaction between genes, lifestyle and environment. To prevent CVD, it is necessary to influence the natural history of the disease development in an individual. While we cannot change our genes, we can do a lot to our lifestyles and environments. It is generally agreed that individuals alone should not be blamed for chronic diseases such as CVD, but that society also has its role and responsibilities. Governments, in cooperation with their stakeholders (e.g., industry, nongovernmental organizations, and health professionals), play a central role in creating an environment that empowers and encourages individuals, families, and communities to make positive, life-enhancing behaviour changes in terms of diet and patterns of physical activity. In addition to direct health policy and services, the responsibility of governments includes sectors that have a pivotal influence on health, such as agriculture, education, and transportation. Social determinants of health are also mediated by fiscal policy and employment opportunities. Consequently, it is imperative that the executive of the government, especially the head of the government, and the finance minister be involved in discussions that traditionally have been limited to matters of microeconomic reform inside the health portfolio. Commerce, industry, and labour traditionally have not been invited to the discussion, but should also be involved.

The WHO states that civil society and nongovernmental organizations can help to ensure that consumers ask governments to provide support for healthy lifestyles and ask the food industry to provide healthy products. Civil society is the key platform for mobilizing and actualizing associative behaviours designed to promote awareness, education, and advocacy for health. They advocate for representatives of business and commerce becoming involved in defining the problem, proposing solutions, and implementing those solutions, because a healthy workforce and market are central to these representatives' core business. Recently, it has also been noted that the power of the Internet in promoting what may be called the globalization of associative behaviour is important.

Parents Jury is a case in point. It is an Internet-based initiative that offers parents information and a say in matters that affect their children's physical activity and nutrition (e.g., advertising of junk food during prime time television hours). GLOBALink, another Web site, passes on lessons from one generation of tobacco control advocates to the next, and Patient View, a group that monitors and analyzes developments in health, communicates its findings with health and social campaigners via its electronic publication, HSCNews. The People's Health Movement is another free association that is working to influence social policy. Guided by a vision of a world in which people's voices guide the decisions that shape our lives, The Peoples' Health movement leads the production of Global Health Watch, the first alternative health report. This alternative report, which was started on the basis that civil society needs to produce its own global health report unfettered by political restrictions, challenges the relevance of the WHO World Health Reports.

Although there is a need to invest in building the evidence base around the role of policy, and, in particular, finding the appropriate tools for evaluating a policy's impact, there is clearly a convergence of opinion that it is time to enact policies aimed at creating healthier social and physical environments. This opinion is accompanied by an emerging trend to return to not only the concept but the reality of community: where we live and the types of societies we want. Governments have the classic tools of legislation, regulation, and taxation at their disposal to enact social policies that can serve to turn the tide of CVD, diabetes, obesity, and other chronic conditions. Thanks to the growing and increasingly concerted voices of lobby groups, governments are beginning to take this role more seriously.

The major modifiable risk factors for CVD, smoking, high serum cholesterol, high blood pressure, physical inactivity, obesity and diabetes have shown non-uniform trends; some risk factors have diminished, some increased. Many of those changes are related to changes in society and environment. Smoking is an excellent example, and the food industry and catering has also significantly contributed to the dramatic decrease in CVD mortality in the middle-aged populations in most developed countries. For instance, in Finland CVD mortality has fallen over 70% during the past 40 years in middle-aged men. The epidemiological analysis of the data unequivocally shows that this has mainly happened thanks to improvements in smoking habits, serum cholesterol and blood pressure. These improvements have taken place across the entire population, not only in high risk individuals cared by health sector. Thus, there is no doubt that societal changes have been primarily behind the prevention of premature CVD in this country and many other countries as well. It is important that health sector together with other policies will have a common goal: getting healthier choices in lifestyles and environments easier to adopt and maintain. Increased investments in these areas will bring both health and financial gains in the longer term.

PREDICT score allows personalized antiplatelet therapy

Mon, 31 Aug 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Barcelona, Spain, 31 August: Studies from a growing body of convincing data show that responsiveness to antiplatelet therapy is real. This is a clinically important issue and there is a need to develop individual antiplatelet strategies particularly for patients at risk. Further studies are needed to find out whether a personalized antiplatelet therapy can improve platelet inhibition and net clinical outcome in patients identified by non-genetic and genetic risk analysis.

Prof Gawaz and Geisler, from the Tuebingen University Hospital in Germany have developed the PREDICT-score, that allows the probability of a high RPA to be estimated, as well as the risk of short-term thromboischaemic events.

Results from studies addressing the role of tailored therapy in patients identified as poor responders to conventional therapy by platelet function analysis such as GRAVITAS, TRIGGER-PCI, RESPOND have shown that there is a growing body of evidence that response to clopidogrel is affected by certain genetic variants involving enzymes, which are responsible for absorption (ABCB1-Polymorphism) and bio-activation (CYP2C19 polymorphism) of clopidogrel. In this context, it has been demonstrated that the CYP2C19*2 polymorphism is associated with a higher rate of primary endpoint (death, myocardial infarction and stroke) and of stent thromboses, lower levels of active metabolite and decreased inhibition of platelet aggregation in a subanalysis of the TRITON-TIMI-38 trial. Identification of candidate genotypes in addition to non-genetic risk analysis might also help to improve the individual prediction of poor-responsiveness to clopidogrel. Thus, patients with a high PREDICT-score (e.g. high non-genetic risk) and carriers of CYP2C19*2 were most susceptible to clopidogrel low responsiveness.

Safeguarding of antiplatelet drug efficacy is important for the optimal treatment of patients with symptomatic coronary artery disease, requiring coronary interventions. This represents a challenge to modern cardiology since there has been cumulative evidence that response to common oral antiplatelet therapy is a highly variable phenomenon underlying various mechanisms.

It is known that particular risk groups exhibit high residual platelet aggregability (RPA) despite conventional dual antiplatelet therapy with acetylic salicylic acid and clopidogrel. There is also a relevant association between high RPA and recurrent ischemic events especially stent thrombosis after percutaneous coronary intervention. Individualization of antiplatelet therapy by dose increase or alternative application of novel P2Y12-receptor antagonists (Prasugrel, Ticagrelor, Cangrelor) might therefore lead to improved cardiovascular outcome in defined risk patients. For this reason, measurement of response by point-of-care platelet function tests is reasonable in particular risk patients.

Some clinical conditions are synonymous with increased residual platelet reactivity. Recently, Profs Gawaz and Geisler, developed a score (Residual Platelet Aggregation after Deployment of Intracoronary Stent (PREDICT)-score) to identify the individual risk for poor responsiveness to clopidogrel by non-genetic factors. 1092 PCI-patients were investigated in this study. Clinical and demographic factors were included in univariate analysis and thus possible influencing factors were identified. These factors were then entered into a multivariate model. Thus, increased age (>65 years), acute coronary syndrome, reduced left ventricular function and presence of diabetes mellitus or renal failure could be identified as independent determinants for a high RPA. By weighing these variables according to their statistical influence (for example weighing factor 1 for acute coronary syndrome, age, 2 for diabetes and renal failure, and 3 for reduced left ventricular function) we developed the PREDICT-score, that allows the probability of a high RPA to be estimated, as well as the risk of short-term thromboischaemic events. This can be seen from easily available clinical data.

Aspirin works for primary prevention in moderate and high risk diabetics

Mon, 31 Aug 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Barcelona, Spain, 31 August: The beneficial effects of aspirin in primary prevention of cardiovascular events i.e. stroke, MI and cardiac death are known and generally accepted. In a recent meta-analysis total cardiovascular event rate was shown to be reduced by 12% and the rate of myocardial infarctions by 18% (Lancet 2009; 373, 1849-60). This holds specifically true for individuals with a 10-year risk for cardiac death above 5% or a total cardiovascular event risk above 15%. Several scientific bodies including the ESC do recommend aspirin for primary prevention in this population, including all diabetics.

Recent trial results seem to contradict this general recommendation. Dr Hisao Ogawa et al. published the results of the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) (JAMA 2008; 300, 2134-41) Trial showing no significant effect of aspirin on a combined endpoint of cardiovascular adverse events including fatal or nonfatal ischemic heart disease, fatal or nonfatal stroke and peripheral artery disease. However, the event rate in this trial was much lower than predicted and therefore the trial was largely underpowered to draw a meaningful conclusion. In addition, secondary endpoints focussing on more severe events like death, MI and stroke exerted a significant effect of aspirin in the entire patient cohort, as did the observation of the primary endpoint in diabetics above the age of 65 years.

The key role of antiplatelet therapy (mainly aspirin) for the secondary prevention of myocardial infarction and strokes is firmly established for high-risk patients with established arterial disease, and the proportional reductions in these cardiovascular events appear to be in the range of 20 to 25%, independent if the patients have diabetes or not. However, many young and middle-aged persons with diabetes do not have manifest arterial disease yet - although they are at a significant cardiovascular risk. Therefore, the substantial persons with uncertainty about the role of aspirin for the prevention of myocardial infarctions and strokes among apparently vascular healthy diabetes will remain until results of ongoing trials focussing on diabetics will be published in the years to come.

Until these results are available, the clinical strategy should include aspirin for primary prevention in all diabetics above the age of 65 years, or below 65 years if there is at least one additional cardiovascular risk factor present like obesity, hypertension or dyslipoproteinemia. In the case of a known vascular disease proven by the presence of atherosclerotic plaques in the coronary or carotid circulation, or a reduced ABI for the peripheral circulation, all diabetics should be offered a primary prevention with aspirin.

Childhood obesity: The increasing vascular drama

Mon, 31 Aug 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Barcelona, Spain, 31 August: Obesity is one of the most important health problems in industrialized countries irrespective of socio-economic status, age, sex or ethnicity. The prevalence of childhood obesity in children has reached alarming levels, even in developing countries. It is estimated that about 1 billion people worldwide are overweight, with 22 millions being under the age of 5 years and 300 million people are obese. By 2010 it is estimated that 26 million children in E.U. countries will be overweight, including 6.4 million who will be obese.

The reasons for childhood obesity include environmental factors, lifestyle preferences, and also cultural background. However, in our affluent society an increase in caloric and fat intake is one of the major causes for developing overweight and obesity. On the other hand, there is rising evidence that a marked decline in physical activity also plays a major role in the dramatically increasing rates of obesity all around the world. Consequently, both over-consumption of calories and reduced physical activity are involved in childhood obesity.

Already in early childhood, overweight and obesity are associated with the classical risk factors for the development of cardiovascular diseases like diabetes or pre-diabetes, high blood pressure or high cholesterol levels. These diseases all together contribute to the so called metabolic syndrome. Furthermore, the dramatic increase in weight also results in orthopaedic disorders, like erosions and arthrosis of waist or knee joint, making any physical activity impossible, even if the children were willing to do it.Given the fact that up to 50% of obese children are suffering from metabolic syndrome, it is conceivable that these children are already characterized by vascular damages resulting in developing plaque formation, referred to as atherosclerosis. It is well known that a normal function of vessels depends on a balance between relaxing and contracting factors produced within the internal lining of arterial vessels, the endothelium. The major endothelium-derived relaxing factor is nitric oxide. The availability of nitric oxide is critically influenced by the above mentioned risk factors and diseases leading to a mismatch between relaxation and contraction of the vessels. The occurrence of endothelial dysfunction is considered to be the earliest stage of atherosclerosis and can be present years before an atherosclerotic lesion will be detectable. Moreover, recent studies suggest a prognostic impact of endothelial dysfunction. That means, if endothelial dysfunction is present, the likelihood of developing a cardiovascular disease or to die from it is considerably increased.With our present, still ongoing study, we aim to investigate whether obesity in early childhood is associated with endothelial dysfunction or other damages of the vessels as an early stage of atherosclerosis. Furthermore we are interested in the relationship between markers of metabolic syndrome (high blood glucose, elevated blood pressure or cholesterol) and the degree of vessel injury.

We included 80 obese or overweight children at an average age of 12 years into this study and compared them with 60 age-matched lean control children. We took blood samples to determine cholesterol levels and performed a so called oral glucose tolerance testing, a test investigating the individual blood glucose response to a defined amount of glucose intake. With this standardized test we are able to detect diabetes or pre-diabetic alterations like insulin resistance.

As measures of vessel injury we determined intima-media-thickness of the carotid artery and endothelium-dependent relaxation of the forearm, both well-established markers of early vessel alteration which are easily and non-invasively assessable.

Since we know that vessel integrity is strongly associated with self-healing processes managed by the body's own bone-marrow-derived stem or precursor cells, we measured the number and function of specific stem cells in the blood that are known to contribute to vessel repair und formation of new blood vessels.

In our study, we were able to show that at an average of 12 years obese or overweight children suffer from pre-diabetes as indicated by much higher levels of insulin in oral glucose tolerance testing compared to lean healthy children. The concentration of bad LDL cholesterol was higher and that of good HDL cholesterol much less in obese children. In obese children 24 h-blood pressure monitoring indicates an about 8 to 10 mmHg higher systolic blood pressure over the day. Finally, nearly all components of metabolic syndrome are evident in our population of obese children.

The most result of our trial was that endothelium-dependent relaxation of forearm arteries is already impaired by the same in adults with chronic heart failure, and this in our 12-years old obese children! We found a clear relationship between the degree of obesity and the impairment of endothelial function: those with the highest body weight had the worst vessel function.

Also the extent of intima-media-thickness of carotid artery was increased, and this was again more pronounced in those with severe obesity.

These vascular alterations are accompanied by a significantly impaired release of stem and precursor cells from the bone marrow indicating that self-healing capacity might be diminished.

Considering these disastrous alterations of arterial vessels and also the hampered repair mechanisms in obese children, it is not surprising that this vascular drama obligatory results in atherosclerosis followed by acute myocardial infarctions or strokes even in young adults.

Therefore, primary or secondary prevention strategies starting early in childhood should aim at reversing current increase in childhood obesity. A number of potential strategies can be implemented to target built environment, physical activity, and diet. These strategies can be initiated at home and in preschool institutions, schools or after-school care services as natural setting to influence diet and physical activity in the entire children population. However, further research needs to explore the most effective strategies to prevent and treat obesity.

CABG vs. PCI: Call for multidisciplinary approach to decide in complex CAD cases

Sun, 30 Aug 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Barcelona, Spain, 30 August: Important new evidence about revascularization in patients with severe coronary artery disease can be found in the recently published interim analyses of the SYNTAX Trial of 1,800 patients with left main and/or three vessel coronary artery disease randomised to PCI or CABG. The unique strength of Syntax was not only as an 'all-comer' trial of patients with the most complex coronary artery disease but the maintenance of a parallel registry of patients excluded from randomization (1077 CABG patients whose disease was too complex for PCI and 198 PCI patients considered to be at excessively high surgical risk).

At an interim analysis of one year (with final analyses at five years), 12% of CABG and 18% of PCI patients reached the primary composite end point of death, myocardial infarction, stroke or repeat revascularisation. While the difference was largely driven by repeat revascularization but with no significant difference in mortality, PCI failed to reach the pre-trial specified criteria for non-inferiority, with the authors concluding that 'CABG remains the standard of care for patients with three-vessel or left main coronary artery disease' (and in contrast to the current study did find a greater benefit of CABG with more severe disease). However the one year result may significantly underestimate the survival benefit of CABG which registry data has consistently shown to accrue with time in comparison to PCI and usually reaches statistical difference at 2-3 years.

Furthermore, although all PCI patients received drug eluting stents fewer than 30% of CABG patients benefited from the potential prognostic benefit of bilateral internal mammary artery grafts. Finally, it is uncertain whether the higher incidence of stroke at one year with CABG (2.2% vs 0.6%) was largely procedural or a consequence of substantially inferior secondary prevention (including dual antiplatelet, statin, antihypertensive and ACE inhibitor medication) than in the PCI group.

So what can we conclude from the current evidence and particularly in light of the recently published COURAGE and SYNTAX Trials? For less severe coronary disease (mainly one or two vessel disease and normal left ventricular function) there is little prognostic benefit from any intervention over optimal medical therapy. In such patients who do require intervention, perhaps for symptomatic reasons, there is no obvious survival advantage for either PCI or CABG (at least in non diabetic patients), but there is a significantly higher risk of repeat revascularisation with PCI.

In patients with more severe coronary artery disease, and especially those with diabetes, CABG is superior in terms of survival and freedom from reintervention. However, SYNTAX also underlined that PCI is a good option- at least over the shorter term- in patients who are ineligible for or who refuse CABG and also the importance of rigorous secondary prevention in CABG patients. Finally, in view of the prognostic benefit of surgery, a multi disciplinary team approach should be the standard of care when recommending interventions in more complex coronary artery disease, to ensure transparency, real patient choice and genuine informed consent in the decision making process. For elective patients this will necessitate separation of angiography from the intervention to allow appropriate time to make a truly informed decision.

Failing heart, failing kidney: Double trouble?

Sun, 30 Aug 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Barcelona, Spain, 30 August: Concomitant kidney dysfunction and/or worsening renal function in patients with heart failure is a frequent finding and is associated with a poor prognosis. Current treatment of heart failure has beneficial effects on cardiac function but does not favorably affect renal function. The possibility to improve renal function and/or obtain kidney protection with new drugs or devices is still uncertain.

Heart failure remains the most important cause of hospitalisation for patients aged more than 65 years and this proportion is going to increase because of aging of the general population and improvement in outcomes of most cardiac diseases. Current treatment has improved the clinical course and prognosis of chronic heart failure. However, hospitalisations for heart failure continue to be associated with a poor prognosis with in-hospital mortality rates of 4% to 9%, and post-discharge mortality and re-hospitalisation rates of 9-15% and 30-45%, respectively, in the following 6-12 months.

Comorbidities and, namely, kidney dysfunction play a major role in the poor prognosis of heart failure patients. The development, or coexistence, of kidney dysfunction in patients with heart failure is often defined as cardiorenal syndrome Current treatment has improved cardiac function but seems to have no effect on concomitant kidney dysfunction and this has become a major determinant of outcomes.

A mild to moderate impairment of kidney dysfunction is present in 40-50% of the patients admitted for acute heart failure and 30-40% of the patients develop worsening renal function, generally defined as an increase in serum creatinine >0.3 mg/dl, during their hospitalisations.

The causes of the frequent coexistence of kidney and cardiac dysfunction are multiple. First, these two conditions may share common causes, such as hypertension, diabetes, atherosclerosis, as well as common pathogenetic mechanisms, such neurohormonal and inflammatory activation and endothelial dysfunction. In addition, heart failure causes kidney dysfunction through its hemodynamic abnormalities, namely low cardiac output and increased central venous pressure. Lastly, treatment of heart failure may also favor kidney dysfunction.

Both kidney dysfunction and worsening renal function are associated with a poor prognosis in patients with heart failure. Multiple studies have consistently shown that the prognostic value of simple parameters used to assess renal function, such as BUN, serum creatinine, estimated glomerular filtration rate, is greater than that of parameters traditionally used to evaluate cardiac function, such as the left ventricular ejection fraction. Moreover, the predictive value of renal function is independent from that of other parameters related to the severity of heart failure. This suggests (but not proves!) that renal dysfunction may contribute to the poor outcome of the patients with heart failure.

There are many mechanisms by which kidney dysfunction may contribute to the poor prognosis of the patients with heart failure. First, patients with heart failure and concomitant kidney dysfunction (i.e. the cardio-renal syndrome) have a greater tendency to hydro-saline retention and are less sensitive to diuretics (namely furosemide). The administration of higher diuretic doses in patients with heart failure is also associated with a poor prognosis as it may cause greater kidney dysfunction (thus triggering a positive feedback), electrolyte abnormalities and neurohormonal activation (another deleterious mechanism). Second, patients with renal dysfunction are less likely to tolerate angiotensin converting enzyme inhibitors, angiotensin receptor blockers and aldosterone antagonists, drugs which have a favorable impact on prognosis in heart failure but which may further impair renal function in patients with heart failure. Kidney dysfunction is also associated with anemia, neurohormonal activation, inflammation, oxidative stress and endothelial dysfunction, all conditions that contribute to the progression of heart failure.

Based on the importance of the cardio-renal syndrome, many new agents or tools are currently studied with the aim of improving renal function or at least prevent its deterioration during hospitalisations for acute heart failure. New classes of agents are currently being tested. Vasopressin antagonists have been shown to increase water diuresis and decrease body weight in clinical trials. However, this has not been associated with an improvement in outcomes in a large trial with the vasopressin antagonist tolvaptan.

In the kidney, adenosine causes afferent glomerular arteriole constriction and its release may be triggered by an increase in the sodium load in the distal tubule as after furosemide administration. Therefore, adenosine may be a mediator of the deterioration of renal function occurring in patients with acute heart failure. In addition, it causes an increase in sodium reuptake in the proximal tubule. Adenosine antagonists are therefore currently studied with the aim of preserving renal function during treatment of acute heart failure and to enhance the diuretic and natriuretic effects of furosemide administration in patients with acute heart failure. To date, rolofylline is the first adenosine type 1A receptor antagonists studied in a large trial enrolling more than 2000 patients hospitalized for acute heart failure, the Placebo-controlled Randomized study of the selective A1 adenosine receptor antagonist rolofylline for patients hospitalized with acute HF and volume Overload to assess Treatment Effect on Congestion and renal function Trial (PROTECT). Its results will be presented during this ESC meeting at the Hotline session III.

Other tools currently being tested to improve renal function and treat congestion in heart failure include the administration of lower doses of diuretics, the administration of vasodilators and/or inotropic agents to improve the hemodynamic abnormalities and hence renal function, and the use of new devices, such as ultrafiltration. Their efficacy will need further testing in large randomized trials.

Otamixaban for the treatment of patients with non-ST-elevation acute coronary syndromes

Sun, 30 Aug 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Barcelona, Spain, August 30: Data from a phase II trial of an investigational intravenous drug designed to block the formation of blood clots shows potential to reduce the risk of death, a second heart attack, or other coronary complications compared with the current standard of care in patients presenting with acute coronary syndromes (heart attacks or unstable angina).

Otamixaban inhibits the activity of Factor Xa, a key enzyme involved in the process of blood coagulation. It has already shown promising results when tested in patients undergoing elective angioplasty. In this trial, otamixaban was studied in high-risk patients with acute coronary syndromes (ACS). Otamixaban was compared with heparin, a standard and very commonly used blood thinner for acute coronary syndromes. Heparin, however, has many limitations, including thinning the blood to an unpredictable degree and therefore needing frequent monitoring. There is intense interest in finding a more effective, reliable, and safe replacement for heparin, said study lead Marc S. Sabatine, MD, MPH, an Investigator in the TIMI Study Group and a cardiologist at Brigham and Women's Hospital, who presented the findings today at the European Society of Cardiology meeting in Barcelona.

Sabatine, along with Professor Eugene Braunwald, Chairman of the TIMI Study Group, and colleagues studied the use of otamixaban in 3241 patients from 36 countries around the world who presented with ACS. The study (called SEPIA-ACS1 TIMI 42) was designed to identify the optimal dose of otamixaban. Patients were randomized into one of 5 doses of otamixaban or a comparator of heparin plus the intravenous platelet inhibitor eptifibatide. Researchers tracked the incidence of death, a second heart attack, additional coronary complications, and bleeding through 7 days (the primary endpoint) as well as over the following 6 months.

At the end of the study, Dr. Sabatine and colleagues found that in all of the otamixaban arms except the lowest one, the rate of death, a second heart attack, or additional coronary complications tended to be lower with otamixaban than with heparin plus eptifibatide. Specifically, patients receiving intermediate doses of otamixaban had a significant, 40% lower rate of death or ischemic complications compared with treatment with heparin plus eptifibatide. These benefits persisted through 180 days. The rates of bleeding in intermediate doses of otamixaban were similar to the rate in patients treated with heparin plus eptifibatide.

The data show that intermediate doses of otamixaban may offer a substantial reduction in major coronary complications in patients presenting with an acute coronary syndrome, with bleeding rates comparable to current therapy, says Sabatine. These findings will need to be tested in a large phase III trial to establish the definitive role of otamixaban in the treatment of acute coronary syndromes.

No increased risk with drug eluting stents -- but late stent thrombosis remains a concern

Sun, 30 Aug 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Barcelona, Spain, 30 August: Several large observational data sets have convincingly shown that there is no overall safety issue with drug eluting stents (DES) vs. bare metal stents (BMS). In fact, most registry studies suggest a lower risk of death or myocardial infarction with drug eluting stents. However, late occurring stent thrombosis still remains higher and seems to be uniquely associated with these stents. Late stent thrombosis is a rare but very serious event and all possible efforts should be made to avoid the complication by improving patient selection, optimizing the implantation technique and enhancing anti thrombotic treatment. With highly effective anti thrombotic treatments and novel drug eluting stent designs without potentially toxic polymers a clear reduction of death and myocardial infarction rates is highly probable.

The original SCAAR study published 2007 indicated a higher mortality after the initial six months in patients with drug eluting stents and we concluded that a generalized use of DES should be avoided until large randomized studies with long term follow-up had ruled out any increased risk.

Two years later, a five year follow-up of all patients treated with drug-eluting compared to bare-metal stents in Sweden, shows similar rates of death or myocardial infarction and an important improvement in the rate of restenosis in high risk patients. Among patients at highest risk for restenosis, there was an over 70% relative risk reduction with drug eluting stents compared to bare metal stents. This is a unique presentation of the entire experience of the long-term outcome of treatment with different types of stents in an entire country comprising almost 50.000 patients. Was the original study incorrect?

When the original cohort of patients treated 2003-2004 were followed up to 5 years the increased risk among the patients treated initially in 2003 remained unchanged. With inclusion of new patients treated 2005-2006 there was no increased risk. Also in subgroups of patients at higher risk such as patients with diabetes and ST elevation myocardial infarction the safety of drug eluting stents is now confirmed.

Other large observational studies such as the United States national cardiovascular database that included 260,000 elderly patients from the Medicare program have indicated a lower risk of death or myocardial infarction with drug eluting stents with a surprisingly low reduction in revascularization rates. Similar reassuring safety results were found in a recently published meta analysis of over 30 observational studies.

However, all observational data comparing treatment options should be interpreted with caution because of possible concealed confounders and there is no registry study that can replace any large well performed randomized trial with long term follow-up. The importance of large scale registries has prompted the SCAAR registry to start performing all-comers randomized trials within the registry.

The huge opportunities for transcatheter aortic valve implantation

Sun, 30 Aug 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Barcelona, Spain, 30 August: Today, transcatheter aortic valve implantation (TAVI) represents an effective therapeutic alternative to conventional aortic valve replacement for patients who are at high risk or with contraindications to surgery, and the combination of the transfemoral and transapical approaches further increases the number of patients who can be treated said Prof Dominique HIMBERT from the Bichat Hospital in Paris France, at a press conference at the ESC Congress in Barcelona.

Degenerative aortic stenosis represents a serious and growing public health problem, with regard to the demographic trends expected in the next decades. It should be addressed with appropriate resources to treat a larger number of elderly patients at high-risk or with contraindications to conventional cardiac surgery. These interventions should be less invasive than surgery, less influenced by patients' comorbidities, and allow shorter hospital stays and faster recovery concluded Prof Himbert.

Transcatheter aortic valve implantation (TAVI) is an emerging technique offering the possibility of restoring a normal aortic valve function in patients with severe aortic stenosis, without removing the native valve, on a beating heart, without cardiopulmonary bypass and sternotomy. The prosthesis can be implanted via either a transfemoral approach, like in standard cardiac catheterization, or a transapical approach, using a direct puncture of the left ventricule. Whatever the access used, this technique allows patients who are at very high surgical risk or with contraindications to conventional surgery to benefit from an effective treatment of aortic stenosis. A strategy integrating the transfemoral and the transapical accesses increases the number of patients who can be treated. One-year results are satisfactory in terms of survival and functional improvement, in particular given the patients' risk profile. The most important predictor of late survival is the experience of the medical team, which underlines the necessity of proper training and the restriction of these procedures to high-volume centers.

Degenerative calcified aortic stenosis is the most frequent valve heart disease in Europe and Western countries. Its prevalence increases with age. Mild to severe aortic stenosis is present in 2 to 4% of adults over 65 years. After the onset of symptoms, average survival is 2 to 3 years with a high risk of sudden death. Surgical aortic valve replacement is the reference treatment, leading to 60 000 operations every year in the European Union. However, one third of candidates are denied surgery, particularly in the elderly, because of a perceived high operative risk due to comorbidities, or technical contraindications to surgery. Feasibility and short-term outcomes of TAVI techniques have been demonstrated in these high-risk subsets, but mid- and long-term results need to be evaluated.

The present single-centre study reports the short and mid-term outcomes of 120 patients consecutively treated by TAVI between October 2006 and June 2009. All of them suffered from a very severe and symptomatic aortic stenosis, and multidisciplinary medicosurgical consensus concluded that they had an unacceptably high operative risk or absolute contraindications to surgery.

An anatomical evaluation using echocardiography, angiography and computed tomography was used to define the technical feasibility of TAVI, the approach (transfemoral or transapical) and the type of prosthesis to be used (Edwards SAPIEN THV [balloon expandable] or CoreValve Revalving System [self expandable]). On average, patients were 81 years old, more than half of them had at least 2 severe extracardiac comorbidities, and their estimated operative mortality was comprised between 16% and 27%, according to the predictive risk score used. The risk profile tended to be even more severe in the transapical group than in the transfemoral.

The prosthesis was successfully implanted in 96% of the cases. The most frequent complications were vascular (10%), due to the large diameters of the femoral sheaths, and heart blocks necessitating definitive cardiac pacing (9%). Strokes were rare (3%). Overall, procedural mortality was 3%, and 30-day mortality 9%: 8% in the transfemoral group, and 11% in the transapical group. At one year, overall survival was 79%. There was no statistically significant difference between the transfemoral (83%) and the transapical group (69%). The most important predictor of late mortality was related to the learning curve, involving the patients' selection process, the procedural technique itself, and post-operative care. One-year survival was 60% in the first 25 patients, compared to 85% in the last 95, and this difference was statistically significant in uni- and multivariate analysis. Most important, 87% of the survivors returned to normal life, with no or only mild residual symptoms.

Today, TAVI represents an effective therapeutic alternative to conventional aortic valve replacement for patients who are at high risk or with contraindications to surgery, and the combination of the transfemoral and transapical approaches further increases the number of patients who can be treated. In the future, randomized controlled trials and comprehensive registries with longer follow-up will help to better define the safety and the durability, and subsequently, indications of the technique and the respective places of the transfemoral and transapical approaches.

High caffeine intake can lead to arrhythmias

Sun, 30 Aug 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Barcelona, Spain, 30 August: Coffee is routinely consumed in countries within the Mediterranean basin. Coffee, an infusion of ground, roasted coffee beans, is the most widely consumed behaviourally active substance in the world. It contains several hundred different substances including, antioxidants, carbohydrates, lipids, vitamins, minerals, phenolic compounds and alkaloids. Nevertheless, the effects of coffee on the cardiovascular system have been mainly related to caffeine. Acute and chronic caffeine intake appears to have only minor negative consequence on health. However, high levels of caffeine intake have been related to ventricular arrhythmias.

Epidemiologic studies have already underlined the beneficial role of the Mediterranean dietary pattern on mortality, coronary artery disease, lipid metabolism and on blood pressure. The diet of people living in Mediterranean area, where olive oil is the principal source of dietary fat, encompasses all the beneficial dietary characteristics presented in previous studies. Little information is available on relationship between adherence to Mediterranean Diet and atrial fibrillation (AF).

We aimed to investigate the relationship between diets and atrial fibrillation, one of the most common arrhythmias, and we focused on coffee and caffeine intake explained Prof Mattioli from the University of Modena, Italy.We selected patients presenting with a first detected episode of AF. Nutrition habits were investigated by a self administered food frequency questionnaire that included 116 items, followed by an interviewer-administered 24 h diet recall questionnaire.

The adherence to Mediterranean Diet was assessed using a Mediterranean Score. The Mediterranean Diet is usually represented in the form of a pyramid, the base of which refers to foods which are suggested to be consumed most frequently (non-refined cereals and products, olive oil, vegetables and fruits) and the top of the pyramid to those foods to be consumed rarely (red meat and meat products). The score ranged from 0 to 55. Higher values of score indicate greater adherence to the Mediterranean diet.

Interviewers investigated coffee consumption and other sources of caffeine (i.e. soda drinks, cola, chocolate, tea). Coffee consumption was specifically estimated and we evaluated: type of coffee consumed (filtered or boiled), number of daily cup of espresso coffee, American coffee, decaffeinated and cappuccino.

Coffee intake was divided in 4 categories: low habitual (from 1 cup/day), medium habitual (2-3 cups/day), heavy habitual (more than 3 cups/day) and non-habitual (0 cup/day).

Caffeine intake was estimated adding the caffeine from other sources evaluated as number of chocolate snacks, number of cans of cola soda usually consumed, intake of tea and type of tea.

Findings include:

Get the world on its feet: The role of exercise training

Sun, 30 Aug 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Barcelona, Spain, 30 August: Western societies are struggling to pay for their ever increasing medical budgets. In the US up to 393 billion US-$ were spent in 2005 for cardiovascular diseases alone. Based on epidemiologic studies in primary prevention it is reasonable to estimate that 30% of coronary heart disease and stroke could be prevented by 2.5 hours of brisk walking per week and approximately 284,886 cardiovascular deaths could be prevented per year in the US alone. With regard to metabolic disorders the figures are even more devastating: 91% of cases of diabetes type II may be attributed to high-risk behaviour including BMI>25, low fiber/high fat diet, sedentary lifestyle, and smoking.

In today's obesogenic environment regular physical exercise is more important than ever to reduce cardiovascular events. It does so (1) by modifying classical cardiovascular risk factors and (2) by direct shear stress-mediated effects on the vascular endothelium and on the release of vascular endothelial progenitor cells (EPCs). Data from epidemiologic studies are clear: ad 1) Regular physical exercise improves glycemic control and prevents the development of overt type diabetes in patients with pathologic glucose tolerance. On a molecular basis regular exercise increases the velocity of glucose uptake into the skeletal muscle which reduces glucose levels and improves insulin action. As hyperglycemia may induce endothelial dysfunction, an improved glycemic control is directly associated with improved vasoreactivity. Regular exercise also reduces hypertension and hypercholesterolemia resulting in improved endothelial function. Ad 2) the most immediate effect of exercise on the vascular endothelium is related to the intermittent increase in blood flow, which occurs necessarily during physical activities: Endothelial cells sense even minor increases in shear stress by the deformation of their cytoskeleton and of transmembrane proteins. In recent years our understanding of the biochemical pathways activated by increased shear stress has been greatly enhanced: Today we know that the expression and the activity of the nitric oxide (NO)-producing nitric oxide synthase (NOS) is increased and that detoxification of NO-degrading oxidative radicals is enhanced.

It is never too late to start exercising: Even in the presence of overt cardiovascular diseases (e.g. after acute myocardial infarction) endurance training will significantly increase your survival. As documented by meta-analysis of exercise interventions in stable coronary artery disease (CAD) cardiac mortality is reduced by one third. Among the mechanisms mediating the reduced cardiac event rate are improvement of endothelium-dependent vasodilation, reduced progression of coronary lesions, reduced thrombogenic risk, and improved collateralization.

Traditionally, training interventions were viewed as an adjunct therapy to routine interventional strategies in CAD. While this is certainly true for patients immediately post acute coronary syndromes, the prognostic benefit of percutaneous coronary interventions (PCI) is questionable among patients with stable CAD, in whom more than 50% of all interventions are performed.

Recent clinical trials compared exercise training to an interventional strategy in stable CAD patients. To investigators surprise, the 12 months exercise therapy was associated with a higher event-free survival as compared to conventional percutaneous coronary intervention. This result underscores that by treating the most significant lesion with PCI, the progression of atherosclerosis in other areas of the coronary tree is left unaltered. Exercise, on the other hand, reduces plaque progression, improves endothelial function and collateral formation, and reduces thrombogenic risk in the entire vascular bed.

Before time runs out, we must make physical activity and health education a number one priority of our public health system. Interventions need to start as early as in childhood, when unhealthy eating habits are coined and sedentary lifestyle is copied from adults concluded Prof Hambrecht. The degree to which unhealthy behaviour is regarded a 'private issue' must be publicly discussed. A balance needs to be struck between a reasonable minimum effort of the individual to reduce the healthcare costs and intrusion of an investigative healthcare system into personal lifestyle. The knowledge and the guidelines are there to support regular physical activity, the major issue is implementation.

Why does low Vitamin D raise cardiac risks in diabetics?

Mon, 24 Aug 2009 10:30:35 PST

( from http://www.rxpgnews.com ) Washington, Aug 24 - Researchers have found why low levels of vitamin D are known to nearly double the risk of cardiovascular disease in diabetics.

Researchers at Washington University School of Medicine in St. Louis - have found that diabetics deficient in vitamin D can't process cholesterol normally, so it builds up in their blood vessels, increasing the risk of heart attack and stroke.

The new research has identified a mechanism linking low vitamin D levels to heart disease risk and may lead to ways to fix the problem, simply by increasing levels of vitamin D.

'Vitamin D inhibits the uptake of cholesterol by cells called macrophages,' said principal investigator Carlos Bernal-Mizrachi, Washington University endocrinologist.

'When people are deficient in vitamin D, the macrophage cells eat more cholesterol, and they can't get rid of it. The macrophages get clogged with cholesterol and become what scientists call foam cells, which are one of the earliest markers of atherosclerosis,' Bernal-Mizrachi said.

Macrophages are dispatched by the immune system in response to inflammation and are often activated by diseases such as diabetes.

Bernal-Mizrachi and his colleagues believe that in diabetic patients with inadequate vitamin D, macrophages become loaded with cholesterol and eventually stiffen blood vessels and block blood flow.

These findings will appear in the Tuesday edition of Circulation.

-Indo-Asian News Service

st/sam/jg

Fat in the liver -- not the belly -- is a better marker for disease risk

Mon, 24 Aug 2009 03:59:36 PST

( from http://www.rxpgnews.com ) New findings from nutrition researchers at Washington University School of Medicine in St. Louis suggest that it's not whether body fat is stored in the belly that affects metabolic risk factors for diabetes, high blood triglycerides and cardiovascular disease, but whether it collects in the liver.

Having too much liver fat is known as nonalcoholic fatty liver disease. The researchers report online in the journal PNAS Early Edition that when fat collects in the liver, people experience serious metabolic problems such as insulin resistance, which affects the body's ability to metabolize sugar. They also have increases in production of fat particles in the liver that are secreted into the bloodstream and increase the level of triglycerides.

For years, scientists have noted that where individuals carried body fat influences their metabolic and cardiovascular risk. Increased fat inside the belly, known as visceral fat, is associated with an increased risk of diabetes and heart disease.

Data from a large number of studies shows that visceral fat is associated with metabolic risk, which has led to the belief that visceral fat might even cause metabolic dysfunction, says senior investigator Samuel Klein, M.D. However, visceral fat tracks closely with liver fat. We have found that excess fat in the liver, not visceral fat, is a key marker of metabolic dysfunction. Visceral fat might simply be an innocent bystander that is associated with liver fat.

Klein, the Danforth Professor of Medicine and Nutritional Science, directs the Division of Geriatrics and Nutritional Science and the Center for Applied Research Studies, as well as Washington University's Center for Human Nutrition. He says most of our body fat, called subcutaneous fat, is located under our skin, but about 10 percent is present inside the belly, while much smaller amounts are found inside organs such as the liver and muscle.

This study compared obese people with elevated and normal amounts of liver fat. All subjects were matched by age, sex, body mass index, percent body fat and degree of obesity. Through careful evaluations of obese people with different amounts of visceral fat or liver fat, Klein's team determined that excess fat inside the liver identifies those individuals who are at risk for metabolic problems.

We don't know exactly why some fats, particularly triglycerides, will accumulate inside the liver and muscle in some people but not in others, says first author Elisa Fabbrini, M.D., Ph.D., assistant professor of medicine. But our data suggest that a protein called CD36, which controls the transport of fatty acids from the bloodstream into different tissues, is involved.

Fatty acids are the building blocks for making fats, known as triglycerides. Klein, Fabbrini and their colleagues found that CD36 levels were lower in fat tissue and higher in muscle tissue among people with elevated liver fat.

Fabbrini and Klein say changes in CD36 activity could be responsible for diverting circulating fatty acids away from fat tissue and into liver and muscle tissue, where they are converted to triglyceride. Increased tissue uptake of fatty acids could be responsible for metabolic dysfunction.

Klein says those who are obese but don't have high levels of fat in the liver should be encouraged to lose weight, but those with elevated liver fat are at particularly high risk for heart disease and diabetes. He says they need to be treated aggressively to help them lose weight because dropping pounds can make a big difference.

Fatty liver disease is completely reversible, he says. If you lose a small amount of weight, you can markedly reduce the fat content in your liver. In fact, even two days of calorie restriction can cause a large reduction in liver fat and improvement in liver insulin sensitivity.

Researchers pioneer new technique to eliminate heart surgery

Fri, 14 Aug 2009 13:45:29 PST

( from http://www.rxpgnews.com ) Although open-heart surgery is a frequent treatment for heart disease, it remains extremely dangerous. But an injected protein can potentially regrow blood vessels in the human heart -- doing away with risky surgery altogether.

In heart disease, blood vessels are either clogged or die off, starving the heart of oxygen and leaving it highly susceptible to a cardiac attack.

Britta Hardy and her research partner Alexander Battler, professors at Tel Aviv University's - Sackler School of Medicine, have shown that an injected protein can potentially regrow blood vessels in the human heart -- doing away with risky surgery altogether.

These new vessels in the heart could give millions of people around the world a new lease on life.

'The biotechnology behind our human-based protein therapy is very complicated, but the goal is simple and the solution is straightforward,' said Hardy.

'We intend to inject our drug locally to heal any oxygen-starved tissue. So far in animal models, we've seen no side effects and no inflammation following our injection of the drug into the legs. The growth of new blood vessels happens within a few weeks, showing improved blood circulation.'

The protein solution can also be added as a coating to a stent. Currently, the implantation of a stent is accompanied by a high risk for blood clots, which necessitates the use of blood thinners.

'We could coat a stent with our peptide, attracting endothelial stem cells to form a film on the surface of the stent,' Hardy explains. 'These endothelial cells on the stent would eliminate the need for taking the blood thinners that prevent blood clots from forming.'

These findings were published in Biochemical Pharmacology.

Cardiac arrest resuscitation: Passive oxygen flow better than assisted ventilation

Tue, 11 Aug 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Arizona researchers have added another piece to the mounting body of evidence that suggests during resuscitation efforts to treat patients in cardiac arrest, passive ventilation significantly increases survival rates, compared to the widely practiced assisted ventilation.

The study, published in an online edition of Annals of Emergency Medicine, compared the numbers of patients who had suffered a cardiac arrest outside a hospital setting and were resuscitated in the field by Emergency Medical Services personnel. Rescuers used either bag-valve-mask ventilation, which forces air into the patient's lungs, or facemasks with a continuous flow of oxygen, which work in a similar fashion to those carried on airplanes in case the cabin pressure drops.

Among the 1,019 adult out-of-hospital cardiac arrest patients in the analysis, 459 received passive ventilation and 560 received bag-valve-mask ventilation. Neurologically normal survival after witnessed cardiac arrest with a shockable heart rhythm was higher for the passive oxygen flow method (38.2 percent) than bag-valve-mask ventilation (25.8 percent).

These results are strikingly similar to earlier observations from Wisconsin, where survival rates went up from 15 percent to 38 percent after paramedics abandoned the official guidelines for the modified protocol that we developed, says Gordon A. Ewy, MD, a co-author of the study and director of the Sarver Heart Center at The University of Arizona College of Medicine. The Sarver Heart Center's Resuscitation Research Group developed a modified protocol for treating out-of-hospital cardiac arrest called Cardiocerebral Resuscitation, as opposed to Cardiopulmonary Resuscitation, which should be reserved for respiratory arrest (such as near-drowning or drug overdose).

Under the new concept, first tested in Wisconsin, EMS personnel no longer intubated the patient for ventilation. Instead, they applied a facemask delivering a continuous, low-pressure flow of oxygen.

Our findings provide compelling evidence that positive pressure ventilation is not optimal in the initial management of out-of-hospital cardiac arrest, says lead author Bentley Bobrow, MD, emergency physician at Maricopa Medical Center in Phoenix and associate professor of emergency medicine at the UA College of Medicine. The work from our EMS providers in Arizona further questions the longstanding dogma of tracheal intubation and ventilation for cardiac arrest.

We are most pleased that while we are helping to advance the science of resuscitation, we are saving more victims of cardiac arrest in Arizona than ever before, adds Dr. Bobrow, who also is the medical director for the Arizona Department of Health Services Bureau of Emergency Medical Services.

This study reinforces our belief that survival of out-of-hospital cardiac arrest has more to do with circulating the blood through quality and uninterrupted chest compressions than with ventilation, Dr. Ewy adds.

Transfusions Risky For Cardiac Patients

Sat, 08 Aug 2009 13:45:23 PST

( from http://www.rxpgnews.com ) Blood transfusion to hospitalised cardiac patients doubles the risk of infection and quadruples the risk of death, according to a new study.

The analysis of nearly 25,000 'Medicare' patients in Michigan also showed that transfusion practices after heart surgery varied substantially among hospitals, a red flag that plays into the health care reform debate.

Blood transfusions are extremely common in the US. Some of the typical reasons for transfusions include prevention of anaemia and improving oxygen delivery in heart failure.

Blood transfusion is an area that could be well served with stronger, research-based guidelines, since the current clinical practice is all over the map, said study co-author Neil Blumberg, professor of pathology at the University of Rochester Medical Centre -.

'Doctors are simply doing what they were trained to do, but it turns out that their actions are more harmful than helpful in many cases,' Blumberg said.

'This is an instance in which clinical practice got way ahead of research. And changing the liberal use of transfusions is going to be difficult despite the evidence showing it is usually not essential.'

Blumberg and co-author Mary Rogers analysed patient records in 40 hospitals, from admission to 30 days after discharge.

All had received coronary artery bypass graft surgery from 2003 to 2006. They found that 30 percent of variation in transfusion practices seemed to be due to widely varied practices among hospital sites.

Also, blood use among women patients ranged from 72.5 percent to 100 percent, and blood use among men varied from about 50 percent to 100 percent.

Transfusions with donor blood were associated with infections of the genitourinary system, respiratory tract, bloodstream, digestive tract and skin, the study said.

The study was published in BMC Medicine.

100th heart valve replacement implanted without open-heart surgery at NewYork-Presbyterian/Columbia

Wed, 22 Jul 2009 03:59:36 PST

( from http://www.rxpgnews.com ) NEW YORK (July 22, 2009) -- Over the last four years, heart specialists at NewYork-Presbyterian Hospital/Columbia University Medical Center have implanted an innovative aortic heart valve replacement using a catheter-based approach that does not require open-heart surgery in a total of 100 patients -- the most of any U.S. medical center to date.

Open-heart surgery can require a two- to three-month recovery period, compared to only a few days for the transcatheter approach.

The procedures were conducted as part of multiple clinical research studies of the Edwards SAPIEN transcatheter heart valve. Currently ongoing is the PARTNER (Placement of AoRTic traNscathetER valves) trial, a Phase 3 multicenter study led by national co-principal investigators Dr. Martin Leon and Dr. Craig Smith and focused on the treatment of patients who are at high risk or not suitable for open-heart valve replacement surgery.

The SAPIEN heart valve, made of bovine pericardial tissue leaflets hand-sewn onto a metal frame, is implanted via one of two catheter-based methods -- either navigated to the heart from the femoral artery in the patient's leg, or through a small incision between the ribs and into the left ventricle. It is then positioned inside the patient's existing valve, using a balloon to deploy the frame, which holds the valve replacement in place. Both procedures are performed on a beating heart, without the need for cardiopulmonary bypass and its associated risks.

This breakthrough technology could save the lives of thousands of patients with heart valve disease who have no other therapeutic options, says Dr. Leon, the study's national co-principal investigator, associate director of the Cardiovascular Interventional Therapy (CIVT) Program at NewYork-Presbyterian Hospital and Columbia University Medical Center, and professor of medicine at Columbia University College of Physicians and Surgeons.

Annually, some 200,000 people in the U.S. need a new heart valve, but nearly half of them do not receive a new valve for a variety of reasons.

This study may show that transcatheter valve replacement is a safe and effective alternative to open surgery, which remains the 'gold standard' for most patients, says Dr. Smith, study co-principal investigator, interim surgeon-in-chief and chief of cardiothoracic surgery at NewYork-Presbyterian Hospital/Columbia University Medical Center, and acting Chairman of the Department of Surgery and the Calvin F. Barber Professor of Surgery at Columbia University College of Physicians and Surgeons.

The transcatheter valve procedures take about 90 minutes, compared with four to six hours for open-heart surgery. In open-heart surgery, the surgeon cuts through the breastbone, stops the heart, removes the valve and replaces it.

The PARTNER trial is a prospective randomized study with two separate treatment arms. In the surgical arm, patients are randomized to receive either the Edwards SAPIEN transcatheter heart valve or an Edwards surgical valve via open-heart surgery. In the non-surgical, medical management arm, patients considered to be non-operative are randomized to receive either the Edwards SAPIEN transcatheter heart valve or appropriate medical therapy.

The PARTNER trial is designed for patients with severe aortic stenosis -- a narrowing of the valve that restricts blood flow from the heart -- who are not good candidates for surgery due to age or other concurrent health factors. Interested patients may contact NewYork-Presbyterian/Columbia at (212) 305-6061.

The PARTNER trial is also available at NewYork-Presbyterian Hospital/Weill Cornell Medical Center's Ronald O. Perelman Heart Institute, led by Dr. Karl H. Krieger (vice chairman of cardiovascular surgery at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and the Philip Geier Professor of Cardiothoracic Surgery at Weill Cornell Medical College) and Dr. Shing-Chiu Wong (director of cardiac catheterization laboratories at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and professor of medicine at Weill Cornell Medical College).

Heart stem/progenitor cells improve mouse heart function after a heart attack

Mon, 13 Jul 2009 15:45:29 PST

( from http://www.rxpgnews.com ) One approach being developed as a way to improve heart function following heart attack is the injection of heart stem/progenitor cells directly into the heart. Now, a team of researchers, at Tokyo Women's Medical University, Japan, and Chiba University Graduate School of Medicine, Japan, has found that transplanting sheets of clonally expanded heart cells expressing the protein Sca-1 (cells that are heart stem/progenitor cells and that the authors term CPCs) improves heart function after a heart attack in mice.

The team, led by Katsuhisa Matsuura and Issei Komuro, found that CPCs not only formed heart muscle cells but also secreted a soluble molecule (sVCAM-1) that induced the migration of endothelial cells (which help form new blood vessels) and CPCs and prevented heart muscle cells dying from oxidative stress. In the mouse model of heart attack, preventing sVCAM-1 from binding to the protein VLA-4 inhibited the formation of new blood vessels and blocked CPC migration and survival, leading to a decreased ability of the transplanted CPC sheets to improve heart function. The authors conclude that these data provide new insight into the mechanisms by which heart stem/progenitor cells improve heart function following heart attack.

New research to reduce drug side-effects

Fri, 10 Jul 2009 03:59:36 PST

( from http://www.rxpgnews.com ) They are a group of drugs which millions of people rely on to keep pain at bay but they can have unwanted side-effects which are sometimes more serious than the original health problem. Now scientists at The University of Nottingham are taking part in the largest-ever study on the safety of Non-Steroidal Anti-Inflammatory Drugs (NSAIDS) that has ever been performed.

The project is called SOS (Safety Of non-Steroidal anti-inflammatory drugs) and will study the medical information of 35 million people in Europe to assess the incidence and nature of harmful side-effects on the cardiovascular and gastrointestinal systems of patients. It's hoped the results will lead to better guidance for doctors on how to balance the advantages of prescribing the drugs with the associated risks of heart and digestive problems.

NSAIDS are widely used in medicine for treating pain, inflammation and degenerative diseases like arthritis. The most commonly-used are aspirin and ibuprofen. But their use is associated with an increased risk of minor and serious gastrointestinal complications. It's estimated that there are thousands of these cases in the European Union every year. Prompted by these problems, a new class of NSAIDS called 'Coxibs' have been developed to reduce the risk of this type of side-effect, but the use of these new drugs has since been linked with an increased risk of heart problems such as heart attack and stroke.

Clinicians and scientists now agree that the risk of stomach problems has to be balanced against the risk of cardiovascular interference. Both risks may differ in one person and for the 30 different types of NSAIDS available in the EU. Up to now research studies have been too small to be effective in terms of providing decision models for doctors and drug regulators but it's hoped this new large survey will result in a much more accurate prescription method to minimize drug-related harm.

Over the next two and a half years, published literature on previous clinical trials and observational studies will be scrutinized to identify any methodological inconsistencies and knowledge gaps and this information will be used to design and carry out an EU-wide observational study. This study will be the biggest of its kind ever undertaken in this field. It will include data from more than 35 million Europeans, taken from existing healthcare databases in the UK, the Netherlands, Germany and Italy. The researchers will use the data to create a variety of decision models to help doctors prescribe the most suitable type of NSAID for a particular patient and lower the risk of unwanted gastrointestinal or cardiovascular side-effects.

The University of Nottingham is working with ten other leading European research institutions on the three-year project which is being funded with a 2.8 million Euros grant from the EC's 7th Framework Programme. Fundamental to the project is QResearch, a not-for-profit partnership between The University of Nottingham and leading primary care system supplier EMIS, which uses data collected over the past 17 years.

Professor of Clinical Epidemiology and General Practice, Julia Hippisley-Cox, who founded QResearch, said: The SOS project will help quantify and compare the risks of different NSAIDs based on an individual's profile and should help lead patients and doctors make better decisions regarding treatment options.

New research to reduce drug side-effects

Fri, 10 Jul 2009 03:59:36 PST

EUROPACE raises remote monitoring profile

Sun, 21 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Moving to a more continuous follow-up approach would have the tremendous advantages of enhancing patient safety, decreasing physician and nurse work load, and allowing health staff to focus on medical emergencies, urged Professor Angelo Auricchio, from the European Heart Rhythm Association (EHRA) and official spokesperson of the European Society of Cardiology (ESC), adding that such systems may have the additional advantage of being more cost effective for health care providers.

Currently only around 1 % of patients in Europe with implantable cardiac devices are being monitored with remote devices, the majority are still being followed up by routine face to face clinic visits. Despite wide availability of remote monitoring in many European countries, few countries offer patients such systems. Even in countries that have introduced remote monitoring there are widespread disparities between centres, added Professor Auricchio, who works at the Cardiocentre Ticino (Lugano, Switzerland).

Cardiovascular implantable electronic devices (CIEDs) - which include cardiac pacemakers, implantable cardioverter defibrillators (ICD), cardiac resynchronization therapy (CRT) devices, implantable cardiovascular monitors and implantable loop recorders - have now been developed with numerous programmable features allowing for storage of substantial amounts of diagnostic information.

The European Heart Rhythm Association (EHRA) and Heart Rhythm Society (HRS) expert consensus on monitoring of cardiovascular electronic devices, published last year, estimated that in 2006 approximately 250,000 pacemakers and 50,000 ICDs were implanted in Europe (1). The numbers implanted are estimated to be increasing by 5 to 10 % per year. What has become increasingly apparent, explained Professor Auricchio, is that once the device has been implanted, it needs to be followed up effectively to allow it to work efficiently.

This means that more than two million follow-up encounters with device patients are now needed in Europe each year, which is pushing the health care system to breaking point. Services are so overstretched by routine follow ups that they do not have much spare capacity to deal with emergencies when they come in, said Professor Auricchio.

The solution, suggests Professor Auricchio, is to increase the number of devices that can be interrogated remotely. Technology is available to download data related to device function, arrhythmia frequency, cardiovascular hemodynamic parameters and patient activity, from specific CIEDs and transmit the encrypted data using telephone technology to remote-secure monitoring centres. Here health care staff can both identify errant device behaviour, as well as patient's physiological response to a multitude of programmable therapies.

There are many advantages for remote devices. With the current face to face visit approach, physicians commonly first learn about critical device malfunctions and physiological changes when the patient returns to the clinic for a regular scheduled follow-up and manual device interrogation, which only takes place two to four times per year, depending on the patient status. With remote monitoring, problems can be identified immediately.

Continuous control of the device will permit detection of possible device dysfunction at a very early stage which allows us to take immediate action, thus improving patient safety significantly. said Professor Josep Brugada, President of the EHRA.

The European Heart Rhythm Association (EHRA) and Heart Rhythm Society (HRS) expert consensus document, which set out to determine what was needed to provide appropriate levels of care, concluded: Globalization and new Internet-based technologies for monitoring CIEDs are imposing new rules for patient data management and data-sharing. Competent authorities, national ministries of health, and patient organizations need to find practical and easy solutions for physicians to have rapid and complete access to device relevant data for delivering the most appropriate therapy.

The document adds that payers and regulators need to improve their recognition of the importance of CIED follow-up and develop adequate reimbursement strategies. There is no point investing in the device without comparable investment in the long-term follow-up and therapy! write the authors.

To understand the new models of reimbursement, EHRA in conjunction with Eucomed, now plans to survey the costs involved with in hospital CIED follow-up throughout Europe. In addition to the direct medical costs the survey will also include indirect costs, such as those involved in relatives accompanying patients on hospital visits. We need to have a better idea of the baseline costs so that we can start to understand the cost efficiency of introducing remote monitoring, said Professor Auricchio.

Anemia linked with higher death risk in heart patients

Thu, 18 Jun 2009 15:42:04 PST

( from http://www.rxpgnews.com ) The presence of anaemia in patients with chronic heart failure is linked to a significantly higher risk of death.

Heart failure is a common and serious chronic illness. A large number of patients with heart failure also have anaemia, which is most likely a complication from poor heart function.

The aim of this study was to assess the impact of anaemia on the clinical outcomes of chronic heart failure - by a meta-analysis and systemic review of published literature.

A total of 97,699 patients with CHF were identified from the published studies. From a collective analysis, researchers found that when anaemia occurs, it worsens patient prognosis, making them more likely to be hospitalized or die from heart failure.

'Health professionals may need to improve current practices to better treat anaemia in patients with chronic heart failure,' said Lexin Wang, study co-author and head of the cardiovascular group at Charles Sturt University -, in Australia.

Even with contemporary medical treatment, the mortality rate from CHF is still high, reaching 40 percent in very sick patients, said a CSU release.

Given the clear association between anaemia, mortality rate and hospitalization rate, optimal treatment of anaemia, on top of other heart-failure-specific therapies, may reduce the rate of mortality and further improve patient's prognosis.

These findings will appear in Congestive Heart Failure journal.

Kids with hypertension more likely to fumble in studies

Thu, 18 Jun 2009 13:23:31 PST

( from http://www.rxpgnews.com ) Children with high blood pressure are more likely to have learning disabilities and attention deficit hyperactivity disorder - than other children. If they are both hypertensive and obese, they are also more likely to have anxiety and depression too.

A study by the University of Rochester Medical Centre - shows that children with hypertension are four times as likely to have a learning disability and/or ADHD.

ADHD is a condition characterised by behavioural and learning disorders.

'Physicians should be aware that these conditions commonly occur together,' said Marc Lande, study author and paediatric nephrologist at the URMC.

'More studies investigating the potential association between hypertension and neuro-cognitive deficits are definitely needed,' he added.

Lande had authored a paper earlier that showed children with high blood pressure are not as good at complicated, goal-directed tasks, have more working memory complications and not as adept at planning as their peers without hypertension.

The new study followed 201 children aged 10 to 18 years who were referred to specialists for high blood pressure. Of those, 100 were diagnosed with hypertension while 101 were determined to either not have hypertension or to have white coat high blood pressure -.

Almost 28 percent of children with hypertension had a learning disability and 20 percent had ADHD. Some of those children had both a learning disability and ADHD, so in total, 40 percent of children with hypertension had a learning disability and/or ADHD, said a RUMC release.

Lande pointed out that 'this apparent association between hypertension and learning problems is particularly important in light of the recent increase in hypertension in children in this country that has occurred as a result of the dramatic rise in obesity'.

These findings were presented at the Paediatric Academic Society meeting in Baltimore, US.

Snoring pregnant women at higher risk for gestational diabetes

Thu, 11 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) CHICAGO --- If you are pregnant and your mate complains your frequent snoring is rattling the bedroom windows, you may have bigger problems than an annoyed, sleep-deprived partner.

A new study from researchers at the Northwestern University Feinberg School of Medicine has found that women who reported frequent snoring during their pregnancy were more likely to develop gestational diabetes -- a condition than can cause health problems for the mother and baby. The study also found pregnancy increases the likelihood that a woman will snore.

This is the first study to report a link between snoring and gestational diabetes.

For the study, 189 healthy women completed a sleep survey at the time of enrollment (six to 20 weeks gestation) and in the third trimester.

Pregnant women who were frequent snorers had a 14.3 percent chance of developing gestational diabetes, while women who did not snore had a 3.3 percent chance. Even when researchers controlled for other factors that could contribute to gestational diabetes such as body mass index, age, race and ethnicity, frequent snoring was still associated with the disease.

Principal investigator Francesca Facco, M.D., a fellow at Northwestern's Feinberg School, will present her findings at the SLEEP 2009 23rd Annual Meeting of the Associated Professional Sleep Societies June 11.

Sleep disturbances during pregnancy may negatively affect your cardiovascular system or metabolism, said Facco, who in August will become an assistant professor of obstetrics and gynecology at the Feinberg School and a maternal and fetal medicine physician at Northwestern Memorial Hospital.

Snoring may be a sign of poor air flow and diminished oxygenation during sleep that can cause a cascade of events in your body, Facco said. This may activate your sympathetic nervous system, so your blood pressure rises at night. This can also provoke inflammatory and metabolic changes, increasing the risk of diabetes or poor sugar tolerance.

The study also showed more women became frequent snorers as their pregnancies progressed. Early in pregnancy, 11 percent of women in the study reported frequent snoring; by the third trimester, the number rose to 16.5 percent. Frequent snoring was defined as snoring three or more nights a week.

Facco said snoring during pregnancy may be triggered by weight gain and edema (a buildup of fluid), which can increase airway resistance. Exactly how the snoring is linked to gestational diabetes is not yet known.

About 4 percent of pregnant women develop gestational diabetes, a condition in which women without previously diagnosed diabetes develop high blood sugar levels during pregnancy. Babies born to mothers with gestational diabetes are at increased risk of problems such as being large for gestational age, which may lead to delivery complications. These babies may also have low blood sugar levels and are at increased risk of becoming obese or developing impaired sugar tolerance or metabolic syndrome later in life.

While gestational diabetes usually resolves after pregnancy, women who develop it are at higher risk for type 2 diabetes later in life.

Facco said further studies are needed to understand the association between snoring and gestational diabetes and to develop interventions to treat sleep disorders during pregnancy.

If snoring is bothering a woman who is pregnant, she should seek a consultation with a sleep specialist, Facco said.

In related study, also to be presented at the SLEEP 2009 meeting, Facco found sleep disturbances such as restless legs syndrome and insomnia increase significantly during pregnancy.

Blocking a muscle growth-limiting hormone protects against obesity and atherosclerosis

Thu, 11 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Knockout of myostatin, a growth factor that limits muscle growth, can decrease body fat and promote resistance against developing atherosclerosis, or hardening of the arteries, according to a new study conducted in mice. The results will be presented Thursday at The Endocrine Society's 91st Annual Meeting in Washington, D.C.

Obesity increases the risk of atherosclerosis, which accounts for 75% of all cardiovascular events, such as heart attacks and strokes, said study co-author Shalender Bhasin, MD, professor of medicine at Boston University School of Medicine and chief of the Section of Endocrinology, Diabetes, and Nutrition at Boston Medical Center. Current strategies aimed at preventing heart disease consist primarily of lowering cholesterol levels, but patients reaching the desired cholesterol levels are still at risk for atherosclerosis if they have other risk factors, such as obesity.

Humans and animals with a mutation in the myostatin gene are extremely muscular and have little fat, past research shows. Also, when the gene encoding myostatin is knocked out in mice, their muscle mass increases.

Bhasin and his co-workers wanted to find out if inhibiting myostatin in mice could resist the development of diet-induced obesity and of atherosclerosis, the buildup of lipid deposits called plaque that can narrow and clog coronary arteries.

The researchers took mice that were genetically altered to develop atherosclerosis and then cross-bred them with myostatin knockout mice. Ten generations later, they had mice who were genetically predisposed to both atherosclerosis and inactivation of myostatin. For controls, they studied mice with a genetic predisposition for atherosclerosis but with intact myostatin gene. All mice received a high-fat diet for 12 weeks, to spur the development of atherosclerosis.

Compared with controls, the mice with deleted myostatin gene had much less body fat and 30 percent lower fasting blood sugar and 80% lower fasting insulin levels, showing a reduction in obesity and a strong resistance to developing diabetes, the authors reported. They also had 50 percent lower low-density-lipoprotein (bad) cholesterol and 30 to 60 percent lower levels of total cholesterol and triglycerides (fats in the blood), respectively. These results indicate protection against the development of atherosclerosis, according to Bhasin.

More research is needed to demonstrate the safety and effectiveness of myostatin inhibitors in humans, Bhasin said. However, he said that that this therapeutic strategy already is possible. Experimental drugs called myostatin blockers or inhibitors are being studied as potential treatments of muscle wasting disorders and limb injuries.

Some currently available nutritional supplements are touted as myostatin inhibitors, but Bhasin said he doubts they are effective.

Nicotine induces prediabetes, likely contributes to high prevalence of heart disease in smokers

Thu, 11 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Researchers have discovered a reason why smoking greatly increases the risk of heart disease and stroke. Nicotine promotes insulin resistance, also called prediabetes, which is a risk factor for cardiovascular disease, according to the new study, which was presented at The Endocrine Society's 91st Annual Meeting in Washington, D.C.

Additionally, the study authors were able to partially reverse this harmful effect of nicotine in mice by treating them with the nicotine antagonist mecamylamine, a drug that blunts the action of nicotine.

The study, which the National Institutes of Health funded, was conducted by researchers at Charles Drew University of Medicine and Science in Los Angeles and Western University of Health Sciences in Pomona, Calif.

Their results may explain why cigarette smokers have a high cardiovascular death rate, even though smoking causes weight loss, which should protect against heart disease, said the study's lead author, Theodore Friedman, MD, PhD, chief of the endocrinology division at Charles Drew University.

Prediabetes and diabetes are known risk factors for cardiovascular disease. Past studies show that cigarette smokers tend to be insulin resistant, meaning that their hormone insulin does not work properly. To compensate, their blood glucose (sugar) levels become higher than normal but not yet high enough for diabetes. Smokers also have higher rates of diabetes, but it is not clear whether smoking is the cause, because they could have other risk factors, Friedman explained.

Some studies demonstrate that nicotine and cigarette smoking induce high levels of the stress hormone cortisol. As cortisol excess is known to induce insulin resistance, it has been suggested that glucocorticoids, such as cortisol, are the missing [causative] link between cigarette smoking and insulin resistance, Friedman said.

The new study results suggest this theory is correct, he said. The researchers studied the effects, on 24 adult mice, of twice-daily injections of nicotine for 2 weeks. The mice ate less food than control mice that received injections without nicotine, and they also lost weight and had less fat. Despite this, the mice receiving nicotine developed prediabetes (insulin resistance), which subsequent mecamylamine treatment improved somewhat. These mice also had high cortisol levels in their blood and tissues, and mecamylamine blocked this effect.

Our results suggest that reducing tissue glucocorticoid levels or decreasing insulin resistance may reduce the heart disease seen in smokers, Friedman said. We anticipate that in the future there will be drugs to specifically block the effect of nicotine on glucocorticoids and insulin resistance.

Currently available nicotine antagonists are not specific enough to completely block nicotine's effects or they have bothersome side effects, so better drugs are needed for this purpose, he said.

'Designer molecules' being developed to fight disease

Thu, 11 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Researchers in the Department of Cardiovascular Sciences at the University of Leicester are developing a new way to make protein based drugs with potential applications in stroke, vascular inflammation, blood vessel formation, regenerative medicine and tissue engineering.

The research carried out by Shikha Sharma in Dr Nick Brindle's group in Department of Cardiovascular Sciences aims to allow researchers to rapidly make 'designer proteins' that can bind to disease causing molecules in the body.

Shikha Sharma said There are millions of different proteins that are involved in carrying out numerous functions in the human body. Over time each protein has evolved to optimise its function. Disease could result if any of these fail to perform efficiently.

By generating designer proteins in test tubes, we can produce molecules that have specific actions to control processes in the body. These proteins can be used to make drugs as a treatment for heart disease and cancer.

She said: Whilst most drugs in current use are synthetic, these designer molecules are developed from natural proteins and are likely to have fewer side effects. Proteins perform a well defined but complex set of function in the body and protein therapeutic drugs can perform better when compared to some synthetic small molecule drugs that may have unwanted interactions within the body.

Current methods to generate protein therapeutic are cumbersome and time consuming. At the University of Leicester, we have developed a novel method to revolutionise the way in which we produce these designer protein drugs. In principle this method mimics natural evolution to make new proteins but over a shorter timescale. Instead of taking millions of years, we can create new proteins in just a few weeks.

She said: The fact that this new method utilizes a similar mechanism by which antibodies are generated, suggests the output from this method will be as robust and dynamic as the wide range of antibodies produced in our bodies to fight the rapidly evolving viruses in the environment.

Dr Brindle said: Shikha has made great progress towards this new method, which holds the promise of new better drugs for a wide range of human and animal disease.

In addition to medicine, the method holds promise for a wide range of applications in the chemical, pharmaceutical, and agricultural industries, such as generating protein molecules to prevent uptake of toxins in crops or protein molecules for detection of environmental pollutants.

Shikha Sharma will be presenting her research at the Festival of Postgraduate Research which is taking place on Thursday 25th June in the Belvoir Suite, Charles Wilson Building, University of Leicester between 11.30am and 1pm. This event is open to the public and is FREE to attend.

Middle-aged women experience more stress but have lower blood pressure

Fri, 05 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Both blood pressure and serum lipid levels have improved in Swedish middle-aged women during the past 30 years. Levels of perceived mental stress, however, have increased significantly. These are the of a thesis presented at the Sahlgrenska Academy, University of Gothenburg, Sweden.

The study is part of the Prospective Population Study of Women in Gothenburg, Sweden. This study was initiated at the end of the 1960s, when 1,462 middle-aged women were examined, and interviewed about their lifestyle and other matters. These women have subsequently been followed up into the 21st century, as well as compared with new generations of middle-aged women who have been examined at later dates, as part of the Prospective Population Study.

The level of stress among middle-aged women was stable over a long period, but we can see that the number of women who perceive stress rises significantly after the early years of the 1980s. It is the women themselves who describe that they feel stressed, and other research has shown that it is the perceived stress that is most harmful, says general practitioner Dominique Hange, author of the thesis.

In 1968-1969, 28% of women stated that they suffered from nervousness, and 36% stated that they experienced stress. By 2004-2005, the percentage of women who experienced stress had more than doubled, to 75%.

The women who stated at the end of the 1960s that they suffered from nervousness or perceived stress had a higher frequency of abdominal problems, asthma, headache, and frequent infections. This is true both at the time they were examined and nearly 25 years later. We could also in a longer perspective, see that the women who were mentally stressed had a higher mortality, and a somewhat higher incidence of breast cancer, says Dominique Hange.

The results presented in the thesis show also that the risk factors for cardiovascular disease among women have decreased during the past 30 years. The average body mass index of the women was the same in 2000 as it was in the 1960s, while mean blood pressure and levels of serumlipids were lower.

More women today exercise in their leisure time, and we know that physically active people often have a lower blood pressure. Only 15% of women exercised regularly in the 1960s, while the figure today is around 40%, says Dominique Hange.

The Prospective Population Study of Women in Gothenburg, Sweden The Prospective Population Study of Women in Gothenburg, Sweden, was initiated at the end of the 1960s, when 1,400 middle-aged women took part in a health examination and answered extensive questionnaires about their lifestyles, and other matters. New generations have been invited to take part in the study since then. The follow-up of the women as they become older allows scientists to draw conclusions about various factors that have contributed to poor health and premature death.

ESC Congress 2009: World's biggest cardiology meeting to be held in Barcelona

Wed, 03 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) The European Society of Cardiology Congress 2009, the world's biggest international meeting in Cardiology will be held in Barcelona, Spain, from 29 August to 2 September.

The meeting, which is expected to attract over 30,000 delegates, will provide opportunities for education, hearing about the latest ground breaking research and gaining deeper insights into the most recent developments and innovations in the diagnosis, treatment and prevention of Cardiovascular Disease. Delegates will include clinicians, basic scientists, epidemiologists, nurses, technicians and key opinion leaders in the field.

The latest results will be presented in the Hotline and Clinical trials sessions, with unique opportunities for delegates to have face to face interactions with the investigators. In addition, over 4,000 abstracts, featuring original research, will be show cased at the meeting.

The educational aspects of the congress include the Meet and Read with the Experts sessions and the highly acclaimed FOCUS Sessions with live transmissions and practical take home messages, not to mention reports on the latest ESC guidelines.

Prevention and risk factor identification is the special theme of this year's meeting, giving an opportunity for doctors, scientists, governments and the general public to come together to discuss ways of decreasing the burden of cardiovascular disease on society. Altogether there are 50 separate sessions on prevention in the pre arranged programme, and a special abstract session focusing on prevention research.

Additional highlights of this year's meeting include new joint sessions with sister societies, such as the European Society of Medical Oncology, looking at issues such as the cardiovascular effects of oncology drugs, a full day on Congenital Heart Disease and a new joint session with the European Commission exploring the issues around how the European Commission supports cardiovascular Research. A strong component is dedicated to basic science, including a hotline session looking at the latest development, a translational bench to bedside track and a special abstract session.

For the first time ESC 2009 will offer the opportunity for delegates to gain hands-on image and device education from clinical experts. The sessions, which are being held in purpose-built classrooms, have been organised by our industry partners, will be available free on a first come, first served basis. There will also be over 80 satellite symposia and workshops featuring the latest innovations in pharma and equipment.

All this is set against the truly inspirational city of Barcelona, with is magnificent Gaudi architecture, superb cuisine and world famous football team.

ESC 2009 promises to be a true festival of cardiology. There will be opportunities for hearing about the latest ground breaking trials, continuing education, not to forget the unrivalled opportunity for networking with colleagues from all disciplines of cardiology and finding out about practices in different countries, says Professor Fausto Pinto, Chairperson of the Congress Programme committee.

Aspirin in primary prevention of cadiovascular events of uncertain value

Sat, 30 May 2009 13:21:06 PST

( from http://www.rxpgnews.com ) Low dose aspirin has been shown to be of benefit in the secondary prevention of cardiovascular events in various studies. But a recent meta-analysis published in the Lancet shows no overwhelming benefit of aspirin in primary prevention of cardiovascular events. But as the risk of major bleeding is significant, decisions for aspirin use in this setting need to be decided on individual basis.
Antithrombotic Trialists' (ATT) Collaboration undertook meta-analyses of 6 major clinical trials and 16 secondary prevention trials comparing long-term aspirin versus control. They looked at the occurence of the first event during the treatment period.
Findings
In the primary prevention trials, aspirin use caused a 12% reduction in serious vascular events (0·51% aspirin vs 0·57% control per year, p=0·0001). This was mainly due to a reduction in non fatal myocardial infarction. There was a 0·20% reduction per year in stroke in aspirin users versus a 0·21% reduction per year in the controls which was not significant. There was no significant difference in vascular mortality as well. Major gastrointestinal and extracranial bleeds was significantly higher in those on aspirin versus the control group.(p<0·0001), and the main risk factors for coronary disease were also risk factors for bleeding. In the secondary prevention trials, aspirin use caused a greater reduction in serious vascular events (6·7% vs 8·2% per year, p<0.0001)
The primary prevention of serious cardiovascular events with the use of aspirin is therefore not significant enough to recommend it as a blanket treatment for all, according to the results of this study. There is a need to weight the need for aspirin against the risk of major bleeds which is significantly high.

Better treatment selection and improved therapies -- key to improving prognosis in acute HF

Sat, 30 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Today, acute heart failure represents the most common reason for hospitalisation in the over-65 population. Although hospital care improves symptoms in the first 24 hours after admission in around 50% of these patients, acute heart failure events still remain associated with a more than 50% mortality and rehospitalisation rate at 6-12 months. Indeed, says Professor Marco Metra from the Cardiology Department of the University of Brescia, Italy, it is the very rapid onset of symptoms and the need for urgent therapy which characterise the condition.1,2

Treatments in acute heart failure, he adds, have not undergone any great change in recent decades, despite the demand of heart failure's increasing prevalence and huge personal and public impact. Professor Metra said that treatments are still based on loop diuretics (furosemide), peripheral vasodilators (nitrates) and inotropic agents. Even the more recently approved treatments, he added, such as levosimendan in Europe and nesiritide in the USA, have been associated with uncertain effects on outcomes in randomised trials. So hospitalisations for acute heart failure are still associated with high mortality and rehospitalisation rates, he says. The burden is tremendous because of the large number of patients involved, their poor prognosis and the costs of the treatment.

In a presentation at Heart Failure Congress 2009 Professor Metra defined two major pathways along which this burden might be reduced and treatment improved:

* Better selection of treatments. To date, he said, therapy in acute heart failure has been administered with little attention to the clinical presentation of each patient. Guidelines on heart failure issued by the European Society of Cardiology in 2008 define heart failure as a heterogeneous condition and recommend that different therapies are used on the basis of clinical presentation; for example, patients with fluid overload should undergo fluid removal through diuretics or other means, patients with high blood pressure should receive mainly vasodilators, and patients with low cardiac output should be treated with inotropic agents to improve the force of the heart muscle's contraction.3

* Improved therapies. Many new agents are currently under development, said Professor Metra, which include adenosine type 1 receptors antagonists to enhance the diuretic effects of furosemide and increase renal blood flow, new vasodilators with different mechanisms of action, and new inotropic agents.

Better treatment selection and the development of new agents give us some hope that we will finally be able to improve the symptoms and prognosis of such a large patient population as that suffering from acute heart failure, says Professor Metra. However, he also emphasised that urgent therapy is one of the key recommendations of the latest European guidelines.

Adult bone marrow stem cells injected into skeletal muscle can repair heart tissue

Thu, 28 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) BUFFALO, N.Y. -- University at Buffalo researchers have demonstrated for the first time that injecting adult bone marrow stem cells into skeletal muscle can repair cardiac tissue, reversing heart failure.

Using an animal model, the researchers showed that this non-invasive procedure increased myocytes, or heart cells, by two-fold and reduced cardiac tissue injury by 60 percent.

The therapy also improved function of the left ventricle, the primary pumping chamber of the heart, by 40 percent and reduced fibrosis, the hardening of the heart lining that impairs its ability to contract, by up to 50 percent.

This work demonstrates a novel non-invasive mesenchymal stem cell (MSC) therapeutic regimen for heart failure based on an intramuscular delivery route, said Techung Lee, Ph.D., UB associate professor of biochemistry and senior author on the paper.

Mesenchymal stem cells are found in the bone marrow and can differentiate into a variety of cell types.

Injecting MSCs or factors released by MSCs improved ventricular function, promoted myocardial regeneration, lessened apoptosis (cell death) and fibrotic remodeling, recruited bone marrow progenitor cells and induced myocardial expression of multiple growth factor genes, Lee said.

These findings highlight the critical 'cross-talks' between the injected MSCs and host tissues, culminating in effective cardiac repair for the failing heart.

The paper reporting this development appears online in the Articles-in-Press section of the American Journal of Physiology -- Heart Circulation Physiology at http://ajpheart.physiology.org/cgi/reprint/00186.2009v1

The heart disease death rate has dropped significantly in the last three decades due to better treatments, resulting in large numbers of people living with heart failure. This advance has lead to another health hurdle: The only therapy available to reverse the decline in cardiac function is heart transplantation, and donor hearts are very scarce.

Clinical trials of myocardial stem cell therapy traditionally have relied on surgery -- infusing the stem cells directly into the heart or injecting them into the myocardium, the heart muscle -- invasive methods that can result in harmful scar tissue, arrhythmia, calcification or small vessel blockages.

In our research with a swine model of heart failure, said Lee, we've found that only 1-to-2 percent of MSCs infused into the myocardium grafted into the heart, and there was no evidence that they differentiated into heart muscle cells. In addition, diseased tissue is not a healthy environment for cell growth.

For these reasons, and because patients with heart failure are not good surgical risks, it made sense to explore a non-invasive cell delivery approach, said Lee. An important feature of MSCs is their ability to produce a plethora of tissue healing effects, known as tropic factors, which can be harnessed for stem cell therapy for heart failure.

Lee noted that the multiple trophic factors produced by MSCs have been shown in the literature to be capable of reducing tissue injury, inhibiting fibrosis, promoting angiogenesis, stimulating recruitment and proliferation of tissue stem cells, and reducing inflammatory oxidative stress, a common cause of cardiovascular disease and heart failure.

Since skeletal muscle is the most abundant tissue in the body and can withstand repeated injection of large number of stem cells, we thought it would be a good method to deliver MSCs, Lee said. We hypothesized that MSCs, via secretion of these functionally synergistic trophic factors, would be able to rescue the failing heart even when delivered away from the myocardium.

This study proves our hypothesis, said Lee. We've demonstrated that injecting MSCs, or trophic factors released by MSCs, into skeletal muscle improved ventricular function, promoted regeneration of heart tissue, decreased cell death and improved other factors that cause heart failure.

This non-invasive stem cell administration regimen, if validated clinically, is expected to facilitate future stem cell therapy for heart failure.

Lee said the next step is to use genetic and pharmacological engineering to make the stem cells more active, so good therapeutic effects can be achieved with fewer cells.

That is our goal. It would reduce the cost of stem cell therapy and make it more affordable for patients in the future.

Comprehensive cardiogenetic testing for families of sudden unexplained death victims can save lives

Tue, 26 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Vienna, Austria: Relatives of a young person who dies suddenly should always be referred for cardiological and genetic examination in order to identify if they too are at risk of sudden death, a scientist told the annual conference of the European Society of Human Genetics today (Tuesday 26 May). Dr. Christian van der Werf, a research fellow at the Department of Cardiogenetics, Academic Medical Centre, Amsterdam, The Netherlands said that, although his team's research showed that inherited heart disease was present in over 30% of the families of sudden unexplained death (SUD) victims, the majority of such relatives were currently not being referred for examination.

When an individual aged 1-50 years dies suddenly, autopsy reveals an inheritable heart disease in the majority of the victims. But in approximately 20% autopsy does not reveal the cause of death. We thought that cardiological and genetic examination of surviving first degree relatives of these SUD patients might reveal an inherited heart disease, said Dr. van der Werf.

In the largest such study to date, the team looked at the outcome of first degree relative screening in 127 families who had suffered an SUD and where either there had been no autopsy (53.8%), or the autopsy did not reveal a cause of death. The average age at death of the SUD victims was only 29.8 years old.

The initial examination of the relatives consisted of taking personal and family medical history and a resting ECG. A second cardiac autopsy of the SUD victim was undertaken if tissue had been stored and was available. Additional cardiological examinations of the relatives were performed where necessary. Genetic analysis of the associated candidate gene(s) was performed in material obtained from the deceased person or in those relatives who showed clinical abnormalities.

The researchers found inherited heart disease in 36, or 32% of the families. These results meant that doctors were able to treat affected relatives and try to prevent their succumbing to sudden cardiac death. The scale of heart disease that we found in such families underlines the necessity for general practitioners to refer first degree relatives of SUD victims to a specialised cardiogenetics department as soon as possible, said Dr. van der Werf. Currently we estimate that only 10% of SUD families are being examined for inherited heart conditions.

The study is the second report from the registry of families who attended the Amsterdam centre's cardiogenetics department because of unexplained sudden death of a relative aged 1-50 years. The scientists intend to continue to report the yield of family screening in an increasing number of families.

At present we are conducting a study to stimulate general practitioners and other involved physicians to request autopsy and DNA-storage for SUD patients and to refer relatives to a cardiogenetics department after a case of sudden death at young age. We hope this will lead to identification of more families at risk of sudden cardiac death, in which preventive measures then can be taken said Dr. van der Werf.

Relatives of young sudden death victims are often referred to cardiologists for cardiological examination. We believe relatives should instead be referred to cardiogenetics departments, where clinical geneticists, cardiologists and psychosocial workers cooperate. These professionals specialise in inherited heart diseases and their clinical and psychosocial implications, and can provide a better quality of care. Additionally, cardiologists should receive more education in inherited heart diseases. By taking these measures we can save lives and avoid further distress for families who have already suffered enough, he said.

Scientists find shared genetic link between the dental disease periodontitis and heart attack

Mon, 25 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Vienna, Austria: The relationship between the dental disease periodontitis and coronary heart disease (CHD) has been known for several years. Although a genetic link seemed likely, until now its existence was uncertain. Now, for the first time, scientists have discovered a genetic relationship between the two conditions, a researcher told the annual conference of the European Society of Human Genetics today (Monday 25 May).

Dr. Arne Schaefer, of the Institute for Clinical Molecular Biology, University of Kiel, Germany, said that his team had discovered a genetic variant situated on chromosome 9 which was shared between the two diseases. We studied a genetic locus on chromosome 9p21.3 that had previously been identified to be associated with myocardial infarction, in a group of 151 patients suffering from the most aggressive, early-onset forms of periodontitis, and a group of 1097 CHD patients who had already had a heart attack. The genetic variation associated with the clinical pictures of both diseases was identical, he said. The scientists went on to verify the association in further groups of 1100 CHD patients and 180 periodontitis patients.

We found that the genetic risk variant is located in a genetic region that codes for an antisense DNA called ANRIL, said Dr. Schaefer, and that it is identical for both diseases.

When a gene is ready to produce a protein, the two strands of DNA in the gene unravel. One strand produces messenger RNA, and will express a protein. Antisense RNA is complementary to the mRNA, and is often carried by the reverse strand, the 'anti-sense' strand of the DNA double helix. This strand does not encode for a protein, but can bind specifically to the messenger RNA to form a duplex. Through this binding, the antisense strand inhibits the protein expression of the mRNA .

Coronary heart disease is the leading cause of death worldwide, and periodontitis, which leads to the loss of connective tissue and the bone support of teeth, is the major cause of tooth loss in adults over 40 years. Periodontitis is very common, and around 90% of people aged over 60 suffer from it. Research has already shown a genetic basis for both diseases.

We intend to push ahead with our work to try to understand more about the function of this RNA molecule and the pathway in which it operates in healthy gums and also in periodontitis. In the meantime, because of its association with CHD, we think that periodontitis should be taken very seriously by dentists and diagnosed and treated as early as possible, said Dr. Schaefer.

Need for a revamp of hypertension treatment

Mon, 25 May 2009 02:11:40 PST

( from http://www.rxpgnews.com ) In the British Medical Journal May 23rd 2009 issue, the findings of a meta-analysis by Law and Colleagues has been published. The chief findings are that ß blockers are as effective as other blood pressure medication. Also, they found that regardless of the pre-treatment blood pressure, there was a reduction in cardiovascular risk in patients treated with anti-hypertensive medication who had a reduction in systolic or diastolic blood pressure.
The meta-analysis included 147 trial reports. In the trials that compared ß blockers in individuals with a history of coronary heart disease(CHD), with placebo or untreated control group, CHD was reduced by 29%. This was significantly different from groups on ß blockers without a history of CHD, or even those on other anti-hypertensive medication with or without a history of coronary heart disease, where the reduction was 15%. A 31% risk reduction was observed with the use of ß blockers in patients recruited immediately after a myocardial infarction, with only a 13% risk reduction in CHD when ß blockers were used in other circumstances.
The meta-analysis showed that using any of the five main categories of blood pressure medications (thiazides, ß blockers, Calcium Channel Blockers (CCBs), Angiotensin Converting Enzyme(ACE) inhibitors and Angiotensin Receptor Blockers(ARBs) ) to reduce the systolic blood pressure by 10 mmHg or the diastolic blood pressure by 5 mm Hg , resulted in a 22% reduction in CHD events and a 41% reduction in stroke.
Calcium channel blockers were found to reduce the risk of stoke by 33% compared to the overall reduction of 27% by all groups of anti-hypertensive medication.
The authors have also suggested that using three drugs at half standard dose would produce a greater reduction in risk of CHD and stroke than one drug at standard dose. This is an estimate and would need trials to further validate this.
Their finding that there was a reduction in risk for a specified change in blood pressure, independent of a person’s baseline blood pressure, would now cause us to wonder about blood pressure targets and their validity. “Lower the better” seems the way forward as suggested by the authors. The choice of anti-hypertensive drugs is also less important, except in acute myocardial infarction where ß Blockers have shown to be superior and in stroke where CCBs are preferred. Certain populations have not been specifically looked at in this meta-analysis and one would continue to choose ACE inhibitors and ARBs to treat end stage renal failure patients to protect residual renal function till further studies suggest otherwise. The choice of medication in the general population, therefore, would be determined by the side effects of the medication and that of the lowest blood pressure an individual can tolerate safely. Obviously, this is going to be a point of discussion for sometime to come.

The cardiovascular benefits of daily exercise in school children are evident even after one year

Fri, 08 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) School children as young as 11 can benefit from a daily exercise programme in reducing their levels of several known risk factors for cardiovascular disease. An ongoing study, which began four years ago in the German city of Leipzig, shows already that children assigned to daily exercise lessons reduced their overall prevalence of obesity, improved their exercise capacity, increased their levels of HDL-cholesterol, and reduced their systolic blood pressure.

It's clear that children today have different lifestyles from the past, says investigator Dr Claudia Walther from the Heart Centre of the University of Leipzig. They're less active, and it was our hypothesis that an increase in their exercise activity would result in fewer risks of cardiovascular disease later in life.

The study, whose first-year results are reported at EuroPRevent 2009, randomised 188 school children with a mean age of 11.1 years (from seven classes at three different high schools) to either an active exercise programme in their school routine, or to a conventional curriculum of just two sports lessons a week. The exercise programme comprised daily supervised exercise which included at least 15 minutes of endurance training. So it was well controlled, says Dr Walther, with the teachers making sure that the programme was followed.

The first results presented here in Stockholm already show significant benefits for those in the daily exercise groups: in just one year the proportion of overweight and obese children decreased from 13% to 9%, but increased in the control group from 11% to 13%. These were statistically significant changes. Moreover, exercise capacity (as measured by VO2max) also improved significantly in the exercise groups by 29%. Similarly, levels of HDL-cholesterol and of triglycerides, and systolic blood pressure all improved in the exercise group.

Even from these first-year results we can say that regular physical activity has a significant beneficial effect on body composition, exercise capacity and cardiovascular risk markers in children, says Dr Walther, who adds that follow-up over the next 10-20 years will give some idea of how risk modification at this young age translates into benefit later in life.

The most surprising result, she says, was the effect of daily exercise on body weight, an effect not found so marked or so soon in other studies. These are normal children, explains Dr Walther, so we didn't expect such a significant reduction in the overall prevalence of obesity or excess weight.

Such findings have also raised local interest in Germany, where the investigators hope to extend the study to other neighbouring towns, and eventually to a daily exercise programme incorporated into the basic school curriculum.

It's so easy, says Dr Walther. All it needs is a little more time allocated to exercise lessons. The teachers are there, they supervise, and they all seem enthusiastic. If we can include daily exercise in the school curriculum, I'm sure we'll see an effect.

Penn State professor investigates estrogen, heart disease connection in women

Mon, 04 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) A new study on old rats by a Penn State researcher will shed light on the connection between estrogen deficiency, heart disease and aging in women.

Heart disease is the leading cause of death in women over the age of 75. After menopause, women lose their ability to produce the hormone estrogen and researchers believe that low estrogen levels somehow make women more vulnerable to heart disease and heart attack.

Donna Korzick, associate professor of physiology and kinesiology in Penn State's College of Health and Human Development, has a $1.8 million, five-year project funded by the National Heart, Lung and Blood Institute of the National Institutes of Health to figure out why estrogen deficiency puts women in danger for heart disease.

Korzick will identify proteins in heart cells that might be affected by both aging and low estrogen levels. She will work with Bruce Stanley, director of scientific programs, Penn State Milton S. Hershey Medical Center, to identify these proteins.

Proteins are the work horses of the cells, said Korzick. When they become activated, they can trigger different functions within the cell. Some are even responsible for cell death as we age.

Proteins can become 'activated' in a variety of ways, including by low estrogen levels.

Korzick will analyze the proteins within one segment of heart cells, the mitochondria. These are the gate keepers of cell survival, says Korzick. The mitochondria play a significant role in whether or not a cell lives or dies as we age, especially while experiencing a heart attack.

Cell death is a natural process, explained Korzick But when heart cells die, it means that the remaining cells have to do more work. In this way, cell death is directly linked to how well the heart can withstand a stress like a heart attack.

After identifying the heart cell's proteins, Korzick will determine which proteins respond to low-estrogen environments. She will then use protein-targeting drugs that can activate or inhibit specific proteins in the heart cells to change what is happening inside the cells. Korzick hopes that these experimental results will provide the missing piece to the estrogen deficiency -- heart disease puzzle.

Because of their short life span -- only two years, Korzick will look primarily at rats. According to Korzick, this short life span allows for a true model of aging. Additionally, other researchers have already completed a large body of work involving aged rats so she will have a comprehensive knowledge base with which to work.

At the very least, we'll be learning about heart disease in older females, says Korzick. Right now, most of the estrogen-specific research is based on males, or young rats. Our research focuses on females, both young and old.

With the assistance of Tim Lancaster, who received his master's degree in kinesiology in 2008, Korzick has already identified nearly 600 proteins within the mitochondria of a rat heart cell.

Poor sleep quality leads to poorer prognosis after stroke

Tue, 28 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Stroke victims tend to do worse if they also have diagnosed or undiagnosed obstructive sleep apnea prior to having the stroke, according to a study presented April 28, 2009, at the American Academy of Neurology (AAN) annual meeting in Seattle.

Latha Stead, M.D., professor and chair of the Department of Emergency Medicine at the University of Rochester Medical Center, and professor of Neurosurgery, reported the findings at AAN, along with several other stroke studies measuring the factors that lead to a poor prognosis.

We know that obstructive sleep apnea has been linked to a multitude of cardiovascular problems, yet it is concerning that the vast majority of cases remain undiagnosed, Stead said. In the context of recovering from a stroke, sleep apnea can have a serious impact, and for that reason we encourage people to become more aware of obstructive sleep apnea and to get treatment.

The prospective study included 174 patients who were diagnosed with an acute ischemic stroke in the emergency department at the Mayo Clinic between June 2007 and March 2008. (Stead was the inaugural chair of the Division of Emergency Medicine Research at Mayo before recently joining the URMC.) The stroke-sleep study was conducted in collaboration with Virend Somers, M.D., Ph.D., who is well known for his work in sleep apnea.

Researchers used a standard questionnaire to assess the risk of sleep apnea among all 174 patients, sometimes aided by the patients' sleep partners. They found that 60 percent were at high risk of sleep apnea, seven patients had a previous diagnosis of sleep apnea, and those seven patients had a higher risk of death within the first month following the stroke.

After adjusting for age and stroke severity, researchers also found that high risk of obstructive sleep apnea was a predictor of having a worse outcome. Stroke patients with diagnosed or undiagnosed sleep apnea were also more disabled at the point of discharge from the hospital. Other studies have shown similar results, Stead said, but the latest research included a larger sample size compared to earlier studies.

Strokes are the third leading cause of death and the leading cause of disability in the United States. Since sleep apnea is a breathing disorder associated with the collapse of the pharyngeal airway, it causes potentially dangerous fluctuations in blood pressure.

Researchers do not know the exact mechanisms associated with sleep apnea and poorer outcomes following a stroke. But Stead noted it is more difficult for the brain and related tissue to heal when blood is not properly oxygenated during a disrupted sleep cycle. Furthermore, patients do not respond well to stroke rehabilitation programs when they are repeatedly sleep deprived.

The next step, she said, is to begin routine screening for obstructive sleep apnea as part of the emergency department evaluation of stroke patients.

Stead and research colleagues also presented a study at AAN showing that high blood sugar, or hyperglycemia, is another predictor of early death following a stroke. While other studies have shown that diabetics face poorer outcomes after a stroke, this study focused on non-diabetics or undiagnosed diabetics who had higher-than-normal blood sugar levels in the emergency department.

The important message is that in the Emergency Department setting, it's critical to investigate all of the known risk factors that indicate a poor prognosis following a stroke, Stead said. Other known risk factors include low blood pressure and irregular heart rhythm.

Stead's research is funded by a Mayo Foundation Emergency Medicine Research Career Development Award.

FSU researcher wins $2.2 million grant to study childhood obesity

Mon, 27 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) TALLAHASSEE, Fla. -- In response to a worrisome rise in childhood obesity, Florida school districts have begun to monitor student growth development every year, but there is little research available to determine if the effort is having an effect.

Now, with a $2.2 million grant from the National Institutes of Health and with the cooperation of Leon County Schools, a Florida State University College of Medicine researcher will explore the impact of school-based screening on student fitness and parent behavior.

NIH, the Institute of Medicine, and the Centers for Disease Control really want this question answered. There will be a lot of people interested in this, said Suzanne Johnson, department chair in medical humanities and social sciences at the College of Medicine, who was awarded the four-year grant. It's a very big undertaking, involving the cooperation of 12 elementary schools and a massive amount of data collection.

The stakes are huge. In the past 30 years, according to several studies, childhood obesity has doubled for preschoolers and adolescents and tripled for those ages 6 to 11. High obesity rates are particularly common in ethnic-minority children. An obese child often becomes an obese adult, and obesity opens the door to many health problems.

Among them is type 2 diabetes, previously considered a disease of older overweight adults but now increasingly prevalent among children. At current U.S. rates, a 2003 study indicates, 33 percent of boys and 39 percent of girls born in 2000 are expected to develop it in their lifetime.

Type 2 diabetes is totally preventable, Johnson said. It's just terrible to have kids with type 2 diabetes. It's simply unacceptable.

She and her research team will monitor children at 12 Leon County elementary schools that have a high percentage of ethnic-minority students.

The primary aim is to study the impact of BMI (body mass index) screenings. BMI, calculated from weight and height measurements, is a reliable indicator of whether children are overweight. Each school offers three wellness programs: a free after-school exercise program for children sponsored by Capital Health Plan; expanded health assessments sponsored by the FSU College of Medicine using funds generated by Dance Marathon on the FSU campus; and a wellness Web site that promotes healthy eating and activity. Researchers will track the children to document how much their health changes and how much their parents take advantage of the wellness programs.

Because the study continues over several years, researchers also will get to assess what happens when the children aren't in school.

Data suggest overweight children often show improvement in fitness during the school year if they participate in physical education or other types of physical activity programs. However, they often gain the weight back in the summer, Johnson said. We'll be able to track whether this phenomenon really happens.

Parents are a key part of this project. They play a crucial role in the diet and health habits their children develop.

If you're overweight as a child, you're more likely to be overweight as an adult, Johnson said. If you're an overweight kindergartner and we can get your weight down, you're far less likely to be obese as an adult.

Johnson recently was chosen to receive a Distinguished Research Professor Award from The Florida State University. It honors outstanding research among full professors who have attained national and international visibility. She previously held that distinction at the University of Florida and is the first from the young FSU College of Medicine research program to be selected for the honor.

Dr. Johnson is an outstanding scholar in her field, College of Medicine Dean John P. Fogarty wrote in his nomination letter, and is one of the first behavioral scientists to apply behavioral and psychological science to serious medical problems in children.

Delayed enhancement cardiovascular magnetic resonance to detect non-Q wave heart attacks

Sat, 25 Apr 2009 15:09:44 PST

( from http://www.rxpgnews.com ) In a paper published by PLoS Medicine, Han W. Kim and colleagues from the Duke Cardiovascular Magnetic Resonance Center, United States of America, use a recently developed technique to detect heart damage in patients who don't have symptoms or abnormalities in the electrocardiogram (ECG) that are usually associated with a heart attack ( myocardial infarction ). They show that the prevalence of this type of heart attack which doesn't display ECG abnormalities is more than three times higher than heart damage which does display ECG abnormalities.

Although coronary artery disease is the leading cause of death among adults in developed countries, up to 40 60% of heart attacks are not preceded by typical symptoms and are not immediately identified by patients or physicians, if at all. Therefore, these heart attacks are known as unrecognized myocardial infarctions (UMIs). The diagnosis of UMI is currently based on the appearance of changes in the ECG, leading to so-called Q-waves . However, not all UMIs result in Q-waves. Han Kim and colleagues therefore used a technique known as delayed enhancement cardiovascular magnetic resonance (DE-CMR) to detect heart damage in patients whose Q-waves were absent.

The researchers studied 185 patients with suspected coronary artery disease but with no history of heart attacks. They then followed the patients for 2 years to discover whether a diagnosis of non-Q-wave UMI predicted their likelihood of dying from any cause including from a heart problem. They found that non-Q-wave UMI occurred more than three times as often in patients with suspected coronary artery disease than Q-wave UMI. They also found that patients with this silent heart damage had an 11-fold higher risk of death from any cause and a 17-fold higher risk of death from a heart problem than patients without heart damage.

The clinical implications of the study are discussed in an expert commentary by Clara Kayei Chow from the Population Health Research Institute, McMaster University, Canada, and The George Institute for International Health, University of Sydney, Australia, who was not involved in the study. This important new study has two key clinical implications. First, previous non-Q-wave UMI is potentially being missed in patients with suspected coronary artery disease. Second, non-Q-wave UMI is important because it is significantly associated with increased mortality, she says. She also points out, however, that the results are from a small select group of patients and that further studies need to be done to evaluate the determinants of the increased mortality in patients with non-Q wave UMI. In addition the study will need repeating in other groups of patients. Finally, two of the authors are named on a US patent on the technique used in this study, Delayed Enhancement CMR. The patent itself is owned by Northwestern University.

Embargoed news from Annals of Internal Medicine

Mon, 20 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) EARLY RELEASE ARTICLE: Article available online April 21 (in print June 2)

1. Patient-Tailored Treatment Regimens May Have a More Positive Impact than Strict Glycemic Control in Managing Type 2 Diabetes

Physicians routinely emphasize tight glycemic control for patients with type 2 diabetes. However, tight glycemic control may require highly complex treatment regimens that can result in frustration, non adherence, and financial stress for some patients. Researchers reviewed large trials in which type 2 diabetic patients were randomly assigned to either tight or loose targets for glycemic control. Based on the evidence, the researchers developed practical suggestions for managing these patients. According to the authors, physicians should support healthy lifestyles, preventive care, and cardiovascular risk reduction in patients with type 2 diabetes. Physicians should individualize drug treatment approaches so that patients can aim for a blood glucose level that best balances the burden of medication with the benefit in reducing symptoms and complications of diabetes. The authors advocate for tools and tactics that encourage patient involvement in treatment decisions, as these may lead to treatment programs that are both evidence-based and consistent with patients' lifestyles and informed values.

2. Universal Insurance Coverage May Reduce Race-based Health Care Disparities

Does access to health insurance reduce race-based health care disparities? To find out, researchers studied National Health and Nutrition Examination Survey data collected from 1998 to 2006 on more than 9,000 adults with chronic conditions such as hypertension, diabetes, or coronary heart disease. The authors assessed changes over time in chronic disease control as measured by blood pressure, hemoglobin A1c, and LDL cholesterol. These measures were then compared by race, ethnicity, and education. Finally, the authors compared sociodemographic differences above and below the age of eligibility for Medicare. The researchers found that while control of hypertension, diabetes, and coronary heart disease improved over the years, gaps in disease control between white and nonwhite patients did not change. However, the gaps narrowed after age 65 when Medicare insurance begins. The authors conclude that universal health insurance could reduce disparities in care among patients from different racial or ethnic groups.

3. The USPSTF Reaffirms its Recommendations on Physician Counseling and Interventions to Prevent Tobacco Use

Smoking increases risks for heart disease, lung disease, and cancer. In pregnant women, smoking also increases the risk for miscarriage, low birthweight, and premature delivery. Quitting smoking reduces these risks. Primary care physicians have a unique opportunity to counsel adult patients about preventive healthcare, including quitting smoking. In 2003, the USPSTF concluded that the benefits of smoking cessation interventions by primary care physicians outweighed the risks. Following a review of published research since then, the USPSTF reaffirms its 2003 recommendation on counseling to prevent tobacco use. Clinicians should ask all adults about tobacco use and provide tobacco cessation interventions for those who use tobacco products. For pregnant women, clinicians should ask about tobacco use and provide pregnancy-tailored counseling for those who smoke.

4. Considering Genetic and Other Risk Factors May Help Identify Patients at Highest Risk for Type 2 Diabetes

Telemonitoring changes the working practice of cardiac nurses

Wed, 08 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) The 9th Annual Spring Meeting of the European Society of Cardiology Council on Cardiovascular Nursing and Allied Professions (CCNAP), organised in cooperation with the Irish Nurses Cardiovascular Association (INCA), is being held at the Royal Dublin Society, Dublin, Ireland, on 24-25 April.

The meeting - considered by many to be the premier international event for nurses and allied health professionals - will show case the latest advances in practice, education and research. The 400 plus delegates expected to attend from 26 different countries, will have the opportunity to hear wide ranging sessions covering all aspects of cardiology, including enhancing self care in heart failure populations, managing patients with ventricular assist devices, sudden cardiac death, hypertension, angina, and adult congenital heart disease, and improving primary and secondary prevention.

The theme of this year's meeting is Addressing the Challenges in Cardiovascular Care, with sessions exploring particular challenges of cardiovascular practice in the modern era, including diabetes and metabolic syndrome, behavioural change, and adherence to treatment. Sessions geared towards the practical management of cardiovascular care in daily situations will include how to incorporate guidelines into practice, take a cardiac history, improve assessment of heart sounds and interpret echo cardiograms. One innovative aspect of this year's meeting is the opportunity for health professionals to hear patients' personal perspectives on experiencing an implantable cardioverter defibrillator (ICD) storm, and having a ventricular assist device as a bridge to transplant.

The Spring Meeting is about improving cardiovascular care, and addressing the challenges we face, such as the rapid development of knowledge and technology, and the changing roles of nurses and allied health professionals, says Professor Christi Deaton, Chair person of the ESC Council on Cardiovascular Nursing and Allied Professions (CCNAP).

Mary O'Connor, President of the Irish Nurses Cardiovascular Association, who is co-hosting this year's meeting, adds: The meeting offers an invaluable opportunity for health professionals to network and meet with international colleagues to find out about the different ways of doing things. It allows best practice to be shared and will hopefully give delegates a lot of new ideas that they can introduce into their own clinical practice.

At the meeting more than 100 abstracts will be presented in poster, moderated poster and oral sessions reporting original research and clinical projects by nurses and allied health professionals. One such abstract by Ivonne Lesman (Groningen, The Netherlands) demonstrates that heart failure patients with new onset depression are significantly more likely to be readmitted to hospital (abstract 90082). The study, says Lesman, demonstrates the importance of screening for depressive symptoms in heart failure patients.

We hope that the presentation of high-quality research will encourage more nurses and allied professionals not only to read and review research, but also to conduct more well-designed studies that build evidence for practice, says Professor Deaton.

Scientists switch off nerves to treat high blood pressure

Thu, 02 Apr 2009 11:32:06 PST

( from http://www.rxpgnews.com ) Sydney, April 2 - Medical scientists have pioneered a breakthrough that dramatically deflates high blood pressure, based on a new catheter-based treatment for the life-threatening condition.

The results of this highly anticipated study are expected to revolutionise treatment options for high blood pressure - around the world.

High BP is a major health burden globally, causing many debilitating health problems and even sudden death. Around 30-40 percent of the populace is estimated to suffer from high BP out of which about 15 percent are resistant to traditional therapies.

The trial involved inserting a catheter through the femoral artery - of 50 patients suffering from severe and resistant hypertension - a dangerous form of high BP not responsive to traditional medications.

Conducted under a local anaesthetic, the procedure delivered radio-energy frequency through a catheter to 'silence' sympathetic nerves in the renal artery supplying blood to the kidneys.

It has long been understood that the sympathetic nerve system and nerves in the renal artery are heavily involved in BP regulation in the way they interact with the kidneys - but until now there has not been a safe way to access and 'switch off' these nerves before the damage is done.

This one-off procedure, conducted on both kidneys, has the potential to substantially reduce premature ill health and mortality attributed to high BP.

These findings have been published in The Lancet.

Artificial pump effectively backs up failing hearts

Thu, 02 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Patients with severe heart failure can be bridged to eventual transplant by a new, smaller and lighter implantable heart pump, according to a just-completed study of the device. Results of this third-generation heart assist device were reported at the 58th annual meeting of the American College of Cardiology on March 30.

The device, called a left ventricular assist device (LVAD), is the latest generation of heart assist devices. The LVAD was tested at five main sites: Washington University School of Medicine in St. Louis, the University of Minnesota, Mt. Sinai School of Medicine, Inova Fairfax Hospital and the University of Pittsburgh.

LVADs have allowed us to support patients until they can receive a heart transplant, so they are called a bridge to transplant, says Gregory Ewald, M.D., a Washington University cardiologist at Barnes-Jewish Hospital and medical director of the Heart Failure, Cardiac Transplantation and Total Artificial Heart Program. For patients whose hearts are failing and are awaiting transplantation, these devices can be lifesavers. Washington University is the only medical center in the region where patients can receive these devices at this time.

In addition to Ewald, associate professor of medicine, lead investigators in the trial included Nader Moazami, M.D., associate professor of surgery and surgical director of the Cardiac Transplantation and Total Artificial Heart Program at Washington University, and Andrew Boyle, M.D., associate professor of medicine at the University of Minnesota and medical director of Heart Failure, Cardiac Transplantation and Mechanical Circulatory Support. Boyle presented the findings at the ACC meeting.

An LVAD is implanted inside the chest cavity near the heart and is connected to the heart's left ventricle (pumping chamber). It assists the patient's weakened or damaged ventricle in pumping blood through the body. By restoring a normal blood flow, the device improves patients' health. Because it is powered by portable battery packs, patients usually go home while they wait for a heart transplant.

The LVAD used in this study, the VentrAssist, is termed a third-generation heart assist device. Measuring 2.5-inches across and weighing 10 ounces, the pump is considered an improvement over earlier devices because its size and light weight make it suitable for small adults and children. In addition, its pumping mechanism has no contacting parts for improved durability.

Patients who received the LVAD in the study were approved and listed for cardiac transplantation. The study considered the device successful if a patient survived until heart transplantation or survived at least 180 days after the device was implanted and remained qualified for heart transplantation. Eighty-five percent of patients met this measure of success.

Out of 98 patients who received the device, 60 were transplanted, 19 continued to be supported with the device and 19 died. The median time on LVAD support was 131 days. Adverse events reported during the trial included stroke and bleeding, and the number and type of adverse events was similar to other LVADs but better than that of first-generation VAD devices.

Answering standardized questionnaires for patients with heart failure, they reported a significantly improved quality of life after receiving the device, indicating that their heart failure was less apt to interfere with everyday activities such as housework, hobbies or sleeping or to affect their mood, ability to concentrate or energy level.

Heart failure risk model validated

Mon, 30 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Researchers at Emory University School of Medicine created the Health ABC Heart Failure Model for predicting risk of new onset heart failure in the elderly. Now that model has been strengthened by validating it in a separate library of patient data from an earlier cardiovascular study.

The results suggest the Health ABC risk model can be used to identify high-risk individuals for whom interventions can be targeted cost-effectively to prevent heart failure.

This is a scoring system that could help individuals or their physicians understand their five-year risk for heart failure, using basic risk factors that are easily obtained at relatively low cost, says Javed Butler, MD, MPH, associate professor of medicine and director of heart failure research at Emory University School of Medicine.

Andreas Kalogeropoulos, MD, a post-doctoral research fellow with Butler, presents the findings Monday at the American College of Cardiology conference in Orlando.

Heart failure is the leading cause of hospitalization in people older than 65 and greatly increases the risk of sudden cardiac arrest.

The Health ABC model uses nine clinical measures to estimate the risk of heart failure in patients who haven't necessarily been seen by doctors for coronary heart disease before. The nine measures are: age, history of coronary heart disease, smoking, blood pressure, heart rate, left ventricular hypertrophy measured by electrocardiography, and blood levels of glucose, creatinine and albumin.

Several individual risk factors for heart failure have been identified, but Butler says the model is the first that combines the risk factors into a system for predicting risk for any given individual. The model categorizes individuals into four risk categories ranging from less than 5 (low) to more than 20 percent (very high) 5-year risk, and has been shown to perform well for men, women, Caucasians and African Americans.

Considering the high cost of care and poor outcomes for patients who develop heart failure, any effort to identify these individuals early on and facilitate intervention is likely to be of significant benefit, Butler says.

The Health ABC model grew out of the Health Aging and Body Composition Study, which followed 2,935 elderly people in the Pittsburgh and Memphis areas over seven years starting in 1998. The model was validated by assessing it in 5,335 people without pre-existing heart failure from North Carolina, California, Maryland and Pennsylvania who were participants in the Cardiovascular Health Study beginning in 1989.

Butler and his colleagues also are presenting data from the Health ABC study confirming previous work elsewhere showing that blood glucose can predict heart failure risk even in non-diabetics and evaluating the additional information doctors can glean from different measures of blood pressure.

Reference for the Health ABC heart failure risk model: Circulation Heart Failure 2008,1:125-133

Environment plays role in complex heart defect

Mon, 30 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) A congenital heart disease that often leads to death in newborns is significantly more common during the summer, leading researchers to believe that the environment, and not just genes that affect the heart, may play a role in causing mini-epidemics of this disease.

A cardiac surgeon from Cincinnati Children's Hospital Medical Center presents this research today at the annual American College of Cardiology Meeting in Orlando, FL. The study is a finalist in the ACC's Best Poster Awards Competition.

Hypoplastic Left Heart Syndrome is one of the most complex cardiac defects seen in newborns and remains probably the most challenging to manage of all congenital heart defects. In a child with HLHS, all of the structures on the left side of the heart (the side which receives oxygen-rich blood from the lungs and pumps it out to the body) are severely underdeveloped. This results in the left side of the heart being completely unable to support the circulation needed by the body's organs.

The most common treatment for HLHS is staged reconstruction, in which a series of operations, usually three, are performed to reconfigure the child's cardiovascular system to be as efficient as possible despite the lack of an adequate left ventricle. Current management at major pediatric heart centers has resulted in survival rates of 75 percent or better.

Pirooz Eghtesady, MD, PhD, a cardiothoracic surgeon at Cincinnati Children's, led a study of nearly 1,500 newborns from 38 children's hospitals in the United States who had left-sided congenital heart diseases. Dr. Eghtesady and his colleagues found a seasonal occurrence of HLHS, but not other left-sided diseases, over a 10-year period, 1996 to 2006. Seasonal differences in HLHS occurred each year, with peaks between April and July and low points in January.

Strong seasonality is a clue that environmental factors may play an important role in this disease, as we see, for example, with such common childhood illnesses as asthma and croup, says Dr. Eghtesady. The study augments some prior epidemiologic studies and points the finger at the possibility of additional factors. It also opens the window for genetic studies to consider candidate genes not directly related to cardiac maldevelopment, such as those involved in immune responses, which really have not been considered in the past.

One potential environmental factor being studied by Dr. Eghtesady and colleagues is recurrent maternal exposure to the common agent strep throat, which is also responsible for the devastating condition known as rheumatic heart disease. Numerous studies have indicated that an immune reaction against strep in rheumatic heart disease can lead to injury on the left side of the heart, which is the side also affected in HLHS. Dr. Eghtesady's preliminary study suggests that many mothers whose newborns had left-sided heart injury had a significant history of problems related to strep throat.

Cincinnati Children's is involved in an ongoing clinical trial looking at maternal history of strep exposure compared to mothers with normal hearts and mothers affected by other cardiac defects. Researchers at Cincinnati Children' also are studying whether there are antibodies in the blood of mothers exposed to strep similar to ones found in patients with rheumatic heart disease

Drug-eluting stents safer than metallic ones in preventing cardiac deaths

Sun, 29 Mar 2009 12:22:08 PST

( from http://www.rxpgnews.com ) Washington, March 29 - Drug-eluting stents - were found to be safer and superior than bare metal stents in preventing death and heart attacks among 262,700 patients enrolled in a nationwide registry of cardiovascular disease.

These results have been validated by the largest study of its kind, conducted by the Duke University Medical Centre -, which may end years of controversy over the safety of the devices.

Stents are small tubes that can prop open blocked coronary arteries. The earliest versions were made of bare metal mesh, but later models were designed to release a medication that could suppress the growth of restenosis, new tissue that could clog up the arteries again.

After initially proving more effective than bare metal stents - in preventing restenosis, DES suffered a setback when recent clinical trials found them associated with higher long-term death rates.

'We hope these findings will finally lay to rest any doubt about the safety of drug-eluting stents,' said Pamela Douglas, cardiologist and member of the Heart Centre at DUMC and the study's lead author. 'Our results clearly show that drug-eluting stents are indeed safe.'

Douglas and colleagues followed patients over age 65 enrolled in the National Cardiovascular Data Registry who received stents from 2004 to 2006.

Most of the patients received a DES; only 17 percent were implanted with BMS variety. Investigators matched the patients' data with their Medicare claims and followed them for two-and-a-half years, measuring rates of death, heart attack, stroke, bleeding and the need for additional artery-opening procedures.

They found that over the 30-month period, patients in the DES group had a 25 percent reduction in death and 24 percent reduction in heart attacks, when compared with those who received BMS, but no significant difference in the incidence of stroke, major bleeding or need for additional artery-opening procedures, said a DUMC release.

The findings appear online in the Journal of the American College of Cardiology.

Exercise intensity and duration linked to improved outcomes for heart failure patients

Sun, 29 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) The level of exercise is linked with the reduction of hospitalization and death in patients with chronic heart failure, according to a Henry Ford Hospital study.

Researchers measured the duration and intensity of exercise and found that increasing these parameters improved patients' quality of life and exercise capacity, and lessened their risk for hospitalization and death.

For example, patients who walk at 2 mph for 25 minutes two days a week likely lowers their estimated risk of hospitalization or death by about 10 percent, while patients who walks at 2.5 mph for 25 minutes five days a week likely lowers their estimated risk of hospitalization or death by about 25 percent.

This study shows that while a little exercise is good for health failure patients, a little more looks to be even better, says Steven Keteyian, Ph.D., the study's lead author and program director of Preventive Cardiology at Henry Ford. We believe these outcomes give us a better understanding of how much exercise is needed for patients to lessen their chance of hospitalization or death.

The study will be presented Sunday at the American College of Cardiology's 58th Annual Scientific Session in Orlando. It was funded by the National Heart, Lung and Blood Institute.

The new findings represent a subanalysis of the Heart Failure and A Controlled Trial Investigating Outcomes of exercise traiNing (HF-ACTION) study, which reported in November 2008 that working out on a stationary bicycle or walking on a treadmill just 25 to 30 minutes most days of the week is enough to modestly lower the risk of hospitalization or death for patients with heart failure.

The Henry Ford study looked at the possible link between exercise intensity and exercise duration and clinical events. It focused on 960 patients enrolled in the original study with moderate-to-severe chronic heart failure who were randomly assigned to either guideline-based therapy alone or guideline-based therapy plus supervised and then home-based exercise.

Patients were asked to ride a bicycle or walk on the treadmill for 30-40 minutes, three days a week under supervision, for a goal of 36 sessions. After 18 supervised sessions, patients were provided with a heart rate monitor and a treadmill or stationary bicycle, and were asked to exercise an additional two days per week at home.

When the supervised training phase was completed, patients were asked to exercise five days per week at home for the reminder of their 36 sessions. Exercise intensity was set at 60 percent to 70 percent of heart rate reserve, a moderate-intensity program.

Mayo study shows simple finger device may help predict future heart events, such as heart attack

Thu, 26 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) ORLANDO, Fla. - Results of a Mayo Clinic study show that a simple, noninvasive finger sensor test is highly predictive of a major cardiac event, such as a heart attack or stroke, for people who are considered at low or moderate risk, according to researchers.

The study will be presented Tuesday, March 31, 2009 at 11:30 a.m. EDT at the American College of Cardiology Annual Scientific Session in Orlando (0917-7).

The noninvasive finger test device, called the EndoPAT by Itamar Medical, measures the health of endothelial cells by measuring blood flow. Endothelial cells line the blood vessels and regulate normal blood flow. Research has shown that if the cells don't function properly - a condition called endothelial dysfunction - it can set the stage for atherosclerosis (hardening of the arteries) and lead to major cardiovascular health problems. Previously, there was no simple test for endothelium function, says Amir Lerman, M.D., a cardiologist at Mayo Clinic and the senior author of the study.

Forty-nine percent of patients whose EndoPAT test indicated poor endothelial function had a cardiac event during the seven-year study. Researchers at Mayo Clinic and Tufts-New England Medical Center in Boston used the device to test 270 patients between the ages of 42 and 66 and followed their progress from August 1999 to August 2007. These patients already knew that they had low-to-medium risk of experiencing a major heart event, based on their Framingham Risk Score. The score is the commonly used risk predictor and was developed from the Framingham Heart Study, a longitudinal study of heart disease.

Some of their risk factors included high blood pressure, high cholesterol, obesity and a family history of heart disease, Dr. Lerman says. The results of the study may help identify a discriminating tool beyond the Framingham Risk Score, he says. And the results of these individual tests may help physicians change a patient's medications or recommend other therapies, so they don't have a heart attack or stroke later on.

The test may be used in an individualized medicine model of risk assessment of the patients, Dr. Lerman says.

EndoPAT, which received U.S. Food and Drug Administration approval in 2003, consists of digital recording equipment and two finger probes that look like large thimbles. For the test, which takes 15 minutes, probes are placed on each index finger and hooked up to a small machine to measure blood flow. A standard blood pressure cuff is placed on one arm; the arm without the cuff is the control. A reading of the fingers' blood flow rate begins, and then the blood pressure cuff on one arm is inflated for a few minutes and then deflated, allowing for three timed readings.

The role of the inflated blood pressure cuff is to occlude and then release blood flow to assess reactive hyperemia (RH), the normal blood flow response that occurs when occlusion is released. In the study, 49 percent of the patients who went on to have a cardiac event had a low RH score.

A low RH signal - indicating a lower blood flow response - is consistent with endothelial dysfunction and potentially impaired vascular health that may lead to or serve as a marker for future events, Dr. Lerman says.

Mayo clinic: Retired national football league linemen have high incidence of sleep apnea

Thu, 26 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) ORLANDO, Fla. - Sleep disordered breathing, also known as sleep apnea, is highly prevalent among retired National Football League (NFL) players, and particularly in linemen, according to Mayo Clinic research. This study, involving 167 players, adds to the growing body of research examining the relationship between sleep apnea and heart disease, the investigators say.

The study will be presented Tuesday, March 31, 2009 at 9:30 a.m. EDT at the American College of Cardiology Annual Scientific Session in Orlando (1048-86). The research was conducted in collaboration with the Living Heart Foundation.

The Mayo data showed that 60 percent of linemen, average age of 54, had sleep disordered breathing (SDB), as defined by having at least 10 sleep-related breathing disorder episodes, such as pauses in breathing, per hour. Linemen had an average of 18.1 episodes per hour. The monitoring of breathing at night was conducted while the retired players slept at home. In addition, researchers discovered that age and obesity (measured by the body mass index, which corrects the weight for a person's height) were significantly associated with sleep disordered breathing. Linemen had an average BMI of 34.2; a BMI of 30 or more is considered obese.

Dr. Virend Somers, a Mayo Clinic cardiologist who helped guide the study, noted that the prevalence of sleep apnea and obesity was higher than expected, and serves as a warning that athletes need to monitor their weight and health carefully when they retire, a time when physical activity levels may begin to decline abruptly. While more research is needed to uncover the link between sleep disorders and heart disease, there is evidence that sleep apnea may be a cause of high blood pressure, which is a risk factor for heart disease, he says.

For all other study participants (average age of 53), who played other positions, 46 percent had sleep apnea with an average of 13.4 sleep-related disorder episodes per hour. The average BMI was 30.5.

In addition, 45 percent of the linemen and 32 percent of nonlinemen reported having high blood pressure. High blood pressure is another risk factor for cardiac disease, and may be linked to both obesity and sleep apnea, Dr. Somers says.

Retired football players, and particularly linemen, need to be aware of sleep disordered breathing and its connection to cardiac risk factors, says lead author Felipe Albuquerque, M.D. Many people do not realize that they have a sleep disorder, he says. They may have no symptoms that they are aware of, but perhaps they know they are tired during the day and they're told they snore very loudly. These can be clues to the presence of sleep apnea. Our results show that retired linemen need to realize that they are a very high risk population and may need evaluation and treatment.

Previous research by various institutions and investigators in recent years, much of which has been assisted by the Living Heart Foundation, showed concerning health trends for retired NFL players:

Brain surgery on Monday, home on Tuesday

Wed, 25 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) MAYWOOD, Ill. -- Norma Wooley checked into Loyola University Hospital on a recent Monday morning for brain surgery to repair a life-threatening aneurysm.

She went home on Tuesday, cured of the slurred speech, drooping face and worst headache of her life.

Dr. John Whapham used a less-invasive technique that's becoming increasingly common in brain surgery. The Loyola University Health System neurologist inserted a catheter (thin tube) in an artery in Wooley's leg and guided it up to her brain. The catheter released tiny platinum coils into the bulging aneurysm, effectively sealing it off.

She went home the next morning with a Band Aid on her leg, Whapham said.

Whapham, 36, is part of a new generation of neurologists who are using catheters to repair aneurysms, open clogged arteries, extract blood clots and repair blood vessel malformations in the brain. He also opens blocked carotid arteries in the neck. The catheter technique is much less invasive and risky than traditional brain surgery, which involves cutting a large opening in the skull.

Catheter technology, originally developed for heart surgery, has been modified for narrower and more challenging blood vessels in the brain. There has been a huge evolution in devices over the last five years, Whapham said. Whapham is an assistant professor in the Departments of Neurology and Neurological Surgery, Loyola University Chicago Stritch School of Medicine.

Whapham recently joined Loyola University Health System. He is board certified in neurology and has completed fellowships in endovascular neurosurgery, diagnostic cerebral angiography and stroke/neuro-critical care.

Wooley, 54, of St. Charles, Ill., is one of Whapham's first patients at Loyola. Her successful treatment illustrates the benefits of performing brain surgery with catheters rather than scalpels.

Wooley had a cerebral aneurysm, a weak spot in a blood vessel that balloons out and fills with blood. About six million Americans -- 1 in 50 people -- have brain aneurysms that could rupture. Each year, aneurysms burst in about 25,000 people, and most die or suffer permanent disabilities, according to the Brain Aneurysm Foundation.

Wooley's aneurysm was roughly one-fourth inch across, and shaped like a gumball. It could burst at any time and cause a debilitating or fatal stroke. Her clinical presentation was suspicious for what's called a sentinel hemorrhage, in which an aneurysm on the brink of rupture will often perforate without catastrophic clinical or radiographic findings. One day at work, Wooley began slurring her words, as if she had been drinking. Her mouth and eyelid drooped, and she had a headache that felt like someone was hitting her on the back of her head with a baseball bat. An ambulance took her to a local hospital, and she was transferred to Loyola.

My brain was ready to explode, she said.

Traditional open-brain surgery to repair aneurysms is highly invasive, and recovery can take months. Many patients wind up with cognitive deficits that can, for example, make it impossible to do complex jobs.

Between 80 percent and 90 percent of brain aneurysms can be repaired with less-invasive catheters. Tiny coils of platinum wire are passed through the catheter and released into the bulging aneurysm. The aneurysm fills up with coils, causing the blood to clot. It's like filling a bathtub with concrete, Whapham said.

A landmark clinical trial known as ISAT randomly assigned aneurysm patients to receive either open brain surgery or catheter surgery. The catheter group had significantly lower rates of death and disability. Whapham said catheter surgery techniques and devices have improved dramatically since the study was published in 2002 in the British journal

Stroke survivors improve balance with tai chi

Mon, 23 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Stroke can impair balance, heightening the risk of a debilitating fall. But a University of Illinois at Chicago researcher has found that stroke survivors can improve their balance by practicing the Chinese martial art of tai chi.

Christina Hui-Chan, professor and head of physical therapy at UIC, has studied and used tai chi as a way to improve balance and minimize falls among healthy elderly subjects. Now she and a colleague have seen similar results in a group of stroke survivors.

The study used 136 subjects in Hong Kong who had suffered a stroke more than six months earlier. Participants were randomly assigned to a tai chi group or a control group that practiced breathing, stretching and other exercises that involved sitting, walking, memorizing and reasoning.

Tai chi consists of constant coordinated movement of the head, trunk and limbs requiring tremendous concentration and balance control. Participants learned a simplified form that had been shown to be beneficial to arthritis patients.

Patients were trained in small groups by physical therapists in a weekly class, then practiced at home three days a week for one hour. They received 12 weeks of training but were able to learn the technique in as little as eight. The goal was to make the patients as independent in their treatment as possible, Hui-Chan said.

They were then tested for their ability to maintain balance while shifting weight, leaning in different directions, and standing on moving surfaces to simulate a crowded bus. In these tests the tai chi group out-performed the control exercise group. The two groups performed about the same on another test, which was not focused solely on balance but involved sitting, standing, walking, and returning to sit down.

The tai chi group did particularly better in conditions that required them to use their balance control, Hui-Chan said. In only six weeks, we saw significant improvements. The ability to shift your weight is very important because all reaching tasks require it.

While learning tai chi is not easy, Hui-Chan has found that most people can learn the art if taught by a trained instructor. Many Chinese practice tai chi in morning group exercises, and Hui-Chan thinks the experience can work for Americans and other western nationalities.

It can be taught at community centers, YWCAs or YMCAs, or in parks in the summer, she said.

Hui-Chan said that benefits of tai chi include improved strength and cardio fitness. Group classes also provide a healthy social gathering for isolated seniors at a fraction the cost of physiotherapy or personal training.