RxPG News : Hypertension

Osmoreceptors in liver help increase blood pressure

Thu, 27 Jan 2011 06:17:04 PST

( from http://www.rxpgnews.com ) For 60 years, scientists have puzzled over the possibility of a hepatic osmoreceptor that influences blood pressure regulation. Now, researchers of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, the Experimental and Clinical Research Center (ECRC) of the MDC and Charité and the Hannover Medical School (MHH) appear to have made a breakthrough discovery. Dr. Stefan Lechner and Professor Gary R. Lewin (both of MDC), Professor Friedrich C. Luft (ECRC) and Professor Jens Jordan (ECRC; now MHH) have discovered a new group of sensory neurons in the mouse liver which mediates the regulation of blood pressure and metabolism. This peripheral control center outside of the brain is triggered simply by drinking water and leads to an elevation of blood pressure in sick and elderly people. (Neuron, No. 69 (2) pp. 332-344)

More than ten years ago Professor Jens Jordan, MD, then a research fellow at Vanderbilt University in Nashville, Tennessee, observed a phenomenon together with his colleagues, more or less by accident. Later, at the former Franz Volhard Clinic of the Charité in Berlin-Buch, Jens Jordan again observed that in patients with a damaged nervous system, blood pressure readings rose by as much as 50 mm Hg if the patients drank a half liter of water all at once. "In young people whose sympathetic nervous system was stimulated by drugs, water intake also caused blood pressure levels to rise," said Professor Friedrich C. Luft of the ECRC. "Even in healthy older people, water drinking triggers a regulator for blood pressure." The two clinicians invited neuroscientists at MDC to collaborate with them and started a joint research project.

For 60 years researchers have suspected that there must also be a control center for the body's self-regulation located outside of the brain. Motivated by findings of recent studies, the researchers in Berlin-Buch therefore looked for sensory neurons specifically in organs peripheral to the central nervous system that would detect body changes caused by water intake and would thus be able to activate a regulator which in old and sick people causes blood pressure to rise and which stimulates metabolism in healthy young people.

"In this entire process, osmolality plays a key role," explained Dr. Stefan Lechner, a member of Professor Lewin's research group. "It is the measure of the body's water balance. And it indicates how many molecules are dissolved in a liter of fluid. Each species has a characteristic set point for osmolality, which depends to a great extent on the immediate living conditions. We wanted to know how deviations of osmolality are able to activate a regulator."

The researchers observed in the mouse model that specific neurons in the liver react actively to water intake. The water the mice drink is absorbed in the small intestine and reaches the blood system via the liver. Due to the sudden water intake, the osmolality in the blood vessels of the liver falls under its set-point value. This deviation is registered by sensory neurons in the liver, the so-called osmoreceptors, as the researchers could now demonstrate. They found that the osmoreceptors transform the information into an electrical signal, which in turn triggers a reflex and stimulates the hepatic blood vessels to raise blood pressure.

Ion Currents Help to Elucidate the Mechanisms

To study the activation of the osmoreceptors under realistic physiological conditions, the researchers stained this newly discovered group of osmoreceptors in the liver with a dye. In their experiments they could thus show that after drinking water, even the slightest shifts of osmolality in the blood flowing through the liver activate nerve fibers in the liver and cause ion currents to flow. The ion currents were similar to those that can be measured in an ion channel located both in the central nervous system and in the internal organs (heart, liver, kidney, testicles, pancreas). This ion channel, abbreviated TRPV4, reacts very sensitively to changes and functions quasi as an osmoreceptor.

"The TRPV4 ion channel opens in just a few hundred milliseconds like the lens of a camera, letting the electrical signal through and thus activating a regulator," explained Dr. Stefan Lechner. "We were now interested in whether the TRPV4 ion channel is acting alone or whether it needs subunits to aid it, and we wanted to know how the whole thing works mechanically."

In further experiments, to elucidate the role and function of TRPV4 in this regulation process, the researchers studied mice in which the gene for the TRPV4 ion channel had been inactivated. After giving these knockout mice water to drink, they did not observe any activation of the osmoreceptors in the liver. No ion currents flowed and as a consequence, no reflex was triggered. The researchers concluded that the elevation of the blood pressure due to water intake must be associated with the presence of the TRPV4 ion channel.

Consequences for therapy

"We are now able to describe the characteristics of a completely new group of hepatic osmoreceptors on the molecular level, which in humans are possibly an extension of a very important regulating reflex," said Professor Lewin. "The research findings not only improve our understanding of the physiological role of osmoreceptors in mediating blood pressure, metabolism and osmolalic self-regulation, over the long term they could also lead to new strategies in the treatment of diseases caused by the absence of the gene encoding the TRPV4 channel protein."

"The effect of drinking water on blood pressure regulation is already leading to therapeutic consequences in the daily routine of the hospital," Professor Jordan added. "We tell patients to drink water who, due to blood pressure regulation disorders, suffer from fainting attacks when standing. This alleviates the symptoms and at the same time we are able to reduce the amount of medication. Healthy people can also suffer fainting attacks when they stand for a long time or are otherwise under strain, e.g. when they donate blood. In many cases these can be avoided by drinking water. Our decade-long persistence in investigating osmolalic self-regulation has really paid off!"

Renal sympathetic nerve ablation may cure high blood pressure

Mon, 28 Dec 2009 16:20:14 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.

Kids with hypertension more likely to fumble in studies

Thu, 18 Jun 2009 13:23:55 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.

Need for a revamp of hypertension treatment

Mon, 25 May 2009 02:12:04 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.

Scientists switch off nerves to treat high blood pressure

Thu, 02 Apr 2009 11:32:30 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.

Low potassium levels likely to trigger high blood pressure

Mon, 10 Nov 2008 23:58:06 PST

( from http://www.rxpgnews.com ) Washington, Nov 10 - Low potassium levels are likely to trigger high blood pressure, thanks to a specific gene, says a new study.

'There has been a lot of publicity about lowering salt or sodium in the diet, but not enough on increasing dietary potassium,' said the study's co-author Susan Hedayati, of the University of Texas - Southwestern Medical Centre in Dallas, Texas.

Researchers analysed data on approximately 3,300 subjects from the Dallas Heart Study, half of whom were African American. The results showed that the amount of potassium in urine samples was strongly related to blood pressure -.

'The lower the potassium in the urine, hence the lower the potassium in the diet, the higher the blood pressure,' said Hedayati. 'This effect was even stronger than the effect of sodium on blood pressure.'

The link between low potassium and high BP remained significant even when age, race, and other cardiovascular risk factors - including high cholesterol, diabetes, and smoking - were taken into account, said an U-T release.

Research by Chou-Long Huang, co-author of this study, found evidence that a specific gene, called WNK1, may be responsible for potassium's effects on BP.

'We are currently doing more research to test how low potassium in the diet affects blood pressure through the activity of this gene,' added Hedayati.

Co-authors include Abu Minhajuddin, Orson W. Moe and Chou-Long Huang.

These findings were presented at the American Society of Nephrology 41st annual meting in Philadelphia.

BP response to stress can point to better treatment

Sat, 16 Aug 2008 14:44:30 PST

( from http://www.rxpgnews.com ) Washington, Aug 15 - Two-thirds of patients' high blood pressure remains beyond control inspite of the best efforts of doctors, according to a medical expert.

'We are trying to identify the mechanisms through which blood pressure is regulated under normal everyday conditions - which is what stress is - and take that information back to the clinic to better determine what sort of therapy is going to be most effective at treating your blood pressure,' said Gregory Harshfield, a director at Georgia Medical College -.

More than a dozen researchers have teamed up to do parallel studies in animal models and young adults to learn more about what factors like genes, stress and obesity contribute to BP and ways to control this.

'This research will give us information that allows us to identify what treatment is going to be effective in what individual by genotype, by obesity and other factors. What kind of treatment is going to be effective at keeping an individual's blood pressure down or maybe preventing it from ever getting high,' said Harshfield, principal investigator of the project funded by National Institutes of Health's National Heart, Lung and Blood Institute.

Some 72 million Americans are hypertensive, according to the institute.

Studies will explore fundamentals such as why about 30 percent of young healthy blacks and 15 percent of whites can't effectively excrete sodium, a problem that raises blood pressure by increasing the body's fluid volume.

'We think there is a defect in their kidneys, in the normal mechanisms that allow them to excrete salt,' said David Pollock, renal physiologist at GMC. 'When blood pressure goes up due to stress, their kidneys ought to get rid of more salt so their blood pressure will come down, and they don't.'

Statins may help lower blood pressure

Mon, 14 Apr 2008 13:57:25 PST

( from http://www.rxpgnews.com ) The medications known as statins, typically prescribed to lower blood cholesterol levels, may also modestly reduce blood pressure, according to a report in the April 14 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Several previous studies have suggested that statins may have an effect on blood pressure, particularly in patients with hypertension (high blood pressure), according to background information in the article. Statins may activate compounds that widen blood vessels and improve their function.

Beatrice A. Golomb, M.D., Ph.D., and colleagues at the University of California, San Diego, La Jolla, conducted a randomized, double-blind trial comparing statins to placebo in 973 individuals who did not have diabetes or cardiovascular disease. For six months between 2000 and 2004, 322 participants were assigned to take 20 milligrams of simvastatin, 323 to take 40 milligrams of pravastatin (doses frequently prescribed for cholesterol-lowering purposes) and 328 to take placebo. Participants’ blood pressure was measured at the beginning of the study, at one and six months during treatment, and again two months after ending treatment (eight months after the beginning of the study).

Among individuals assigned to take statins, systolic [top number] blood pressure decreased by an average of 2.2 millimeters of mercury and diastolic [bottom number] blood pressure decreased by an average of 2.4 millimeters of mercury. “Blood pressure reductions ranged from 2.4 to 2.8 millimeters of mercury for both systolic blood pressure and diastolic blood pressure with both simvastatin and pravastatin, in those subjects with full follow-up and without potential for influence by blood pressure medications (i.e., neither receiving nor meriting blood pressure medications),” the authors write.

The effect of statins on blood pressure was not evident at one month of treatment, was significant at six months of treatment and dissipated two months after treatment ended.

“This study adds to our understanding of the effects of statins, currently the best-selling prescription drugs in the world,” the authors write. “The reduction in blood pressure seen with statins may contribute—among other identified factors—to some of the ‘rapid’ cardiovascular benefits of statins, arising too swiftly to be explained by effects of statins on plaque accumulation.”

Now a new way to regulate blood pressure

Sat, 25 Aug 2007 12:36:37 PST

( from http://www.rxpgnews.com ) London, Aug 25 - British scientists claim to have found a new way to regulate blood pressure, offering hopes of new drugs to treat those suffering from high or low blood pressure.

Blood pressure is the pressure that circulating blood places on the walls of the arteries, the veins and chambers of the heart. High blood pressure is known as hypertension and low blood pressure is known as hypotension. Both can both cause cardiovascular problems.

The pathway found in a study by King's College London involves a process called oxidation -. Until now, oxidation has largely been linked with harm rather than good.

Free radicals - and oxidants, such as hydrogen peroxide, can cause cell damage. But they also play crucial roles in normal cell function.

The scientists discovered that oxidants such as hydrogen peroxide cause a bond to form between two amino acids -, which, in turn, activates PKG, an important protein in all tissues, and lowers blood pressure, reported the online edition of BBC News.

In the cardiovascular system, PKG plays a fundamental role in blood pressure regulation, say scientists.

Every fourth adult has high blood pressure. Although powerful drugs are already available, few manage to achieve target blood pressure levels.

Philip Eaton, who led the King's College team, said: 'The research could lead to the development of drugs which activate this new pathway.'

The researchers now plan to explore the role of this new pathway in the events leading to a heart attack.

Posture linked to blood pressure

Mon, 13 Aug 2007 12:18:34 PST

( from http://www.rxpgnews.com ) London, Aug 13 - Scientists in Britain have said that the position in which you hold your body plays a role in maintaining blood pressure.

Scientists who conducted studies on mice suggest that good posture could help keep blood pressure level normal while bad posture could increase it, reported the online edition of the New Scientist

Posture is the position in which body is held upright against gravity while standing, sitting or lying down.

Good posture involves training body to stand, walk, sit and lie in positions where the least strain is placed on supporting muscles and spine during movement or weight-bearing activities.

Scientists had earlier suspected a link between the muscles in the neck, blood pressure and heart rate.

Now, researchers at the University of Leeds in Britain have found a direct connection between these neck muscles and a part of the brainstem, which plays a crucial role in regulating heart rate and blood pressure.

Brainstem is the lower part of the brain where it connects to the spinal cord.

Researchers said their finding could explain why blood pressure and heart rate sometimes change when the neck muscles are injured. Similarly, it is possible that hours spent hunched over a computer may raise blood pressure.

Cocoa Found to Reduce Blood Pressure

Sat, 14 Apr 2007 15:17:09 PST

( from http://www.rxpgnews.com ) Foods rich in cocoa appear to reduce blood pressure but drinking tea may not, according to an analysis of previously published research in the April 9 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Current guidelines advise individuals with hypertension (high blood pressure) to eat more fruits and vegetables, according to background information in the article. Compounds known as polyphenols or flavonoids in fruits and vegetables are thought to contribute to their beneficial effects on blood pressure and cardiovascular risk. âTea and cocoa products account for the major proportion of total polyphenol intake in Western countries,â the authors write. âHowever, cocoa and tea are currently not implemented in cardioprotective or anti-hypertensive dietary advice, although both have been associated with lower incidences of cardiovascular events.â

Dirk Taubert, M.D., Ph.D., and colleagues at the University Hospital of Cologne, Germany, conducted a meta-analysis of 10 previously published trials, five of cocoaâs effects on blood pressure and five involving tea. All results were published between 1966 and 2006, involved at least 10 adults and lasted a minimum of seven days. The studies were either randomized trials, in which some participants were randomly assigned to cocoa or tea groups and some to control groups, or used a crossover design, in which participantsâ blood pressure was assessed before and after consuming cocoa products or tea.

The five cocoa studies involved 173 participants, including 87 assigned to consume cocoa and 86 controls, 34 percent of whom had hypertension (high blood pressure). They were followed for a median (middle) duration of two weeks. Four of the five trials reported a reduction in both systolic (the top number, when the heart contracts) and diastolic (the bottom number, when the heart relaxes) blood pressure. Compared with those who were not consuming cocoa, systolic blood pressure was an average of 4.7 millimeters of mercury lower and diastolic blood pressure was an average of 2.8 millimeters of mercury lower.

The effects are comparable to those achieved with blood pressureâlowering medications, the authors note. âAt the population level, a reduction of 4 to 5 millimeters of mercury in systolic blood pressure and 2 to 3 millimeters of mercury in diastolic blood pressure would be expected to substantially reduce the risk of stroke (by about 20 percent), coronary heart disease (by 10 percent) and all-cause mortality (by 8 percent),â they write.

Of the 343 individuals in the five tea studies, 171 drank tea and 172 served as controls, for a median duration of four weeks. Drinking tea was not associated with a reduction in blood pressure in any of the trials.

Tea and cocoa are both rich in polyphenols, but while black and green tea contain more compounds known as flavan-3-ols, cocoa contains more of another type of polyphenol, procyanids. âThis suggests that the different plant phenols must be differentiated with respect to their blood pressureâlowering potential and thus cardiovascular disease prevention, supposing that the tea phenols are less active than cocoa phenols,â the authors write.

The findings do not indicate a widespread recommendation for higher cocoa intake to decrease blood pressure, but it appears reasonable to substitute phenol-rich cocoa products such as dark chocolate for other high-calorie or high-fat desserts or dairy products, they continue. âWe believe that any dietary advice must account for the high sugar, fat and calorie intake with most cocoa products,â the authors conclude. âRationally applied, cocoa products might be considered part of dietary approaches to lower hypertension risk.â

Statins also have an anti-hypertensive effect

Thu, 08 Mar 2007 14:10:12 PST

( from http://www.rxpgnews.com ) A new study led by researchers at Warwick Medical School at the University of Warwick reveals that patients using cholesterol busting statins get a bonus benefit from such drugs as the Warwick researchers have now found that statins also have a positive effect on blood pressure levels.

The research, led by Professor Francesco Cappuccio at Warwick Medical School, examined 20 studies on the effects of statins that covered 828 patients. Of those 20 studies 291 patients were given statins, 272 were given a placebo and 265 were on crossover trials. Some of the studies looked specifically at hypertensive patients, the others considered a full range of conditions.

The researchers found that the use of statins did produce a drop in blood pressure. The overall effect of the use of statins was a 1.9 mmHg reduction in systolic blood pressure and 0.9 mmHg in diastolic blood pressure. The effect was even more pronounced in patients with high blood pressure (systolic over 130 mmHg) who showed an average drop of 4.0 mmHg if treated with statins.

This research clearly shows that treatment with statins produces a small but significant reduction in blood pressure. The effect is lower than the average effect of regular antihypertensive drugs. However this is an added bonus for patients already using statins to reduce cholesterol and the use of statins may reduce the dose and number of drugs a patient would require to keep their blood pressure at a satisfactory level.

CRP as a cause of hypertension?

Sun, 18 Feb 2007 23:40:36 PST

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

Drs. Wanpen Vongpatanasin and Philip Shaul have discovered in mice that CRP is not merely a marker of the risk of hypertension, but plays a direct role in the onset of the condition.

C-Reactive Protein, widely regarded as a risk factor for hypertension and other forms of cardiovascular disease, plays a direct role in the onset of hypertension, researchers at UT Southwestern Medical Center have found.

"We have discovered that C-Reactive Protein (CRP) is not merely a marker of the risk of hypertension, it actually induces hypertension," said Dr. Wanpen Vongpatanasin, associate professor of internal medicine and lead author of the study appearing in the February issue of Circulation.

UT Southwestern researchers studied mice with an engineered gene for CRP that was under the regulation of a second gene responsive to changes in dietary carbohydrate intake. The levels of circulating CRP, which is produced by the liver, were directly manipulated by altering the mice's diets, and the effect on blood pressure was determined. In this manner the actions of CRP were segregated from the actions of other mediators of inflammation.

"We found that when we switched on the gene that causes increases in CRP, the blood pressure went up, and when we turned off the gene and CRP levels went down, the blood pressure fell. Diet changes in the control mice had no effect, indicating that the blood pressure responses were due to CRP," said Dr. Vongpatanasin. "The cause of elevated blood pressure induced by CRP was also determined."

Clinical studies over the past decade have suggested that chronically elevated levels of CRP indicate inflammation that puts an individual at risk for hypertension and other cardiovascular ailments such as hardening of the arteries.

The mice in the latest study were supersensitive to angiotensin II, which is a major circulating factor regulating blood pressure via arterial constriction. This was due to alterations in key proteins in the vascular wall that are involved with angiotensin II.

Also, the researchers discovered that the initiating mechanism is a lack of the key signaling molecule nitric oxide in the artery wall, which has multiple beneficial roles in the cardiovascular system, as well as made a connection between nitric oxide and the proteins responsible for angiotensin II activity.

"Whether these same processes are operative in humans is yet to be determined," said Dr. Vongpatanasin. "We are also pursuing follow-up studies to further understand better how CRP causes the high blood pressure in the mice."

The ultimate goal of the research is to discover how CRP interacts with molecules in the artery wall, leading to a better understanding of hypertension and pointing to new ways to treat it, Dr. Vongpatanasin said.

"We have uncovered a series of mechanisms that link a circulating factor that rises with chronic inflammation, obesity and aging to the regulation of blood pressure," said Dr. Philip Shaul, professor of pediatrics at UT Southwestern and the study's senior author. "Doing so provides a new perspective on how these conditions have a negative impact on cardiovascular health."

Nitrates in Vegetables Lower Blood Pressure

Thu, 28 Dec 2006 12:41:44 PST

( from http://www.rxpgnews.com ) London, Dec 28 - Nitrates, a chemical found in vegetables like spinach and lettuce, may be responsible for keeping blood vessels healthy, says a new study.

Past studies have shown that a diet rich in fruits and vegetables can reduce blood pressure.

But it has been difficult to determine exactly which nutrients in fruits and vegetables are responsible for these blood-pressure-lowering effects.

Scientists at the Swedish School of Sport and Health Sciences examined the effects of short-term nitrate supplementation in a group of 17 healthy, non-smoking young adults.

Each participant rotated between taking a daily dose of nitrate supplement equivalent to the amount normally found in 150 to 250 gm of a nitrate-rich vegetable -- such as spinach, lettuce, or beetroot -- for three days, and taking a placebo for a different three days.

The results showed that average diastolic blood pressure was lower after three days of nitrate supplementation than it was after taking the placebo for three days.

The researchers claimed to have found nitrates in vegetables like spinach and lettuce, which they say may be Mother Nature's way of keeping blood pressure in check.

Since it was a small study the researchers say the chemical's blood-pressure-lowering effects merit further study.

The report has not mentioned the names of the researchers involved in the study.

Uric acid levels closely related to hypertension in Blacks

Thu, 02 Nov 2006 21:21:00 PST

( from http://www.rxpgnews.com ) New research shows that higher levels of uric acid are strongly associated with high blood pressure in blacks, suggesting that a simple blood test could predict risk and that treatments to lower uric acid may be a novel way to reduce hypertension-related complications in this population.

"The novel angle of our study is that the association between uric acid and hypertension is much stronger in blacks, a group that disproportionately suffers from kidney disease, stroke and other complications of hypertension," said Philip B. Mellen, M.D., M.S., assistant professor internal medicine, and lead investigator.

The results are reported online in Hypertension, a journal of the American Heart Association.

Uric acid levels are influenced by dietary factors, such as high levels of protein, and by the breakdown of the body's cells. Most uric acid is eliminated in urine. However, if excess uric acid is being produced or if the kidneys cannot remove enough of it, levels build up in the blood.

Very high levels of uric acid cause gout, but recent animal and human studies suggest that modest elevations of uric acid are one cause of hypertension. Currently, studies are under way to evaluate whether lowering uric acid prevents hypertension.

"If these studies show that lowering uric acid is an effective treatment, our research suggests that it may be especially appropriate for blacks," said Mellen.

Uric acid can be lowered by medications such as allopurinol and newer agents under development.

Previous studies have linked high levels of uric acid and hypertension, but they did not include a large number of blacks. For the current study, researchers evaluated data from the Atherosclerosis Risk in Communities study.

The 9,104 participants were free of hypertension when the study began. They were evaluated for hypertension at three-year intervals over four examinations. At the start, participants were between 45 and 64 with a mean age of 53 years.

A statistical analysis revealed that overall, uric acid levels in the highest quartile increased the risk of hypertension by about 15 percent. These results held true even after adjusting for other variables that could have affected results, such as age, baseline blood pressure, body mass index, kidney function, diabetes and smoking.

The link between uric acid and hypertension was particularly strong among black men. Black men in the highest quartile had a two-fold risk of developing hypertension, compared to black men in the lowest quartile. In black women in the highest quartile, the increase in risk was 30 percent, compared to black women in the lowest quartile.

"Uric acid in the blood was positively associated with hypertension over nine years of follow-up, and this relationship was stronger in blacks than in whites," said Mellen. "More research is warranted concerning the clinical consequences of high uric acid, especially in blacks."

Is TROPHY misleading?

Fri, 27 Oct 2006 16:39:00 PST

( from http://www.rxpgnews.com ) There may be as many as 70 million Americans with prehypertension. If these people can be treated pharmacologically to avoid or delay progression to clinical hypertension, there would be significant benefits to them and the overall health of the population. The recent TROPHY study seems to lead to that conclusion. However, two editorials published in the November issue of the American Journal of Hypertension emphatically argue that the study is flawed and the conclusions reached are misleading.

Persons with prehypertension, generally defined as having a systolic blood pressure in the range of 120-139 mm Hg or a diastolic blood pressure of 80-89, will usually develop hypertension at the rate of about 10% per year. The recent Trial of Preventing Hypertension (TROPHY) examined whether treating patients with candesartan for two years resulted in a sustained reduction in the incidence of high blood pressure after the drug was discontinued. The TROPHY study concluded that the treatment significantly reduced the risk of incident hypertension over the four year study.

According to Stephen Persell, MD, MPH, TROPHY results are likely invalid. He and co-author David W. Baker, MD, MPH, both of the Feinberg School of Medicine at Northwestern University, argue that the study used an unusual definition of incident hypertension which could not accurately discriminate whether the drug had a sustained effect. They demonstrate that because blood pressure readings taken during active treatment were combined with readings taken after treatment had ended, a difference between treatment and placebo could appear even if blood pressures were identical after the treatment had ended. They also analyze how the results could be misleading due to the methods used to calculate the mean blood pressures.

In the second editorial, Jay I. Meltzer MD, Clinical Specialist in Hypertension in the Nephrology Division of the Columbia College of Physicians and Surgeons, also zeros in on the study endpoint. He argues that clinical practitioners would require a more realistic, classical definition of incident hypertension than was used in TROPHY.

Dr. Meltzer also identifies two other issues in the study. He explains, "Further straining the question of applicability is the confusion between what the authors said they would do and what they actually did. They renamed TROPHY a 'feasibility' study, without specifically defining the term. It usually means a pilot study, but TROPHY was not designed as a pilotClinicians rightly suspect bias when the trial language is changed post hoc to allow more accommodation to the data." Finally, he argues that the major conclusion that the drug did prevent the development of hypertension was compromised by the choice of an arbitrary endpoint.

Persell and Baker caution that "the consequences of drawing erroneous conclusions from studies of treatments to prevent progression from pre-hypertension to hypertension are enormous. An expert panel of statisticians and trial methodologists without ties to pharmaceutical companies should be convened to provide consensus recommendations for how future studies addressing the prevention of hypertension should be conducted and reported. Computer models should also be used to confirm that the study methodology would not make it appear that a treatment for prehypertension had sustained benefits when, in fact, none existed."

Dr. Meltzer is equally direct. "What conclusions might actually be appropriate? TROPHY proved that two years of candesartan treatment of patients with 'high normal' or 'prehypertension' did not prevent or delay the development of hypertension, but instead caused a 'slow unmasking.' Reasonable acceptance of the author's own predetermined guidelines for the interpretation of 'slow unmasking' would have necessitated publishing a negative study, which, paradoxically, could have been a great benefit to the hypertension literature. Instead, TROPHY was presented in a way that enables those who want to believe in the original idea despite the evidence against it, still can and still do. Even as the authors trumpet candesartan's success in the paper's conclusions and in public presentations, the conclusion section of TROPHY paradoxically states that they do not advocate treating the 25 million people with prehypertension, but don't explain why."

High blood pressure induces low fat metabolism in heart muscle

Mon, 07 Aug 2006 13:42:00 PST

( from http://www.rxpgnews.com ) "The heart is the single most energy-consuming organ per weight in the body," says Lisa de las Fuentes, M.D.

Under some conditions this energy-hungry organ is prone to defects in its energy metabolism that contribute to heart disease, according to research published in a recent issue of the Journal of Nuclear Cardiology by de las Fuentes and colleagues at Washington University School of Medicine in St. Louis.

Earlier research led by de las Fuentes' colleague Robert J. Gropler, M.D., showed that heart muscle in people with diabetes is overly dependent on fat for energy. Even though fat is an efficient fuel, burning it for energy creates an unusually high demand for oxygen, making the diabetic heart more sensitive to the drops in oxygen levels that occur with coronary artery blockage.

Gropler is director of the Cardiovascular Imaging Laboratory at the Mallinckrodt Institute of Radiology at the School of Medicine and professor of radiology, medicine and biomedical engineering.

Now this group of Washington University researchers has shown that hearts of non-diabetics with muscle thickening due to high blood pressure have an energy metabolism skewed in the opposite direction -- away from the use of fat for energy.

"Whereas Dr. Gropler found that a high level of fatty acid metabolism could be detrimental, we show that a low level may also be harmful," says de las Fuentes, co-director of the Cardiovascular Imaging and Clinical Research Core Laboratory and assistant professor of medicine. "These findings aren't contradictory. The heart has to be able to choose the energy source, either fats or glucose, most appropriate for its current energy needs and the availability of fuel."

De las Fuentes explains that hearts with muscle thickening, or hypertrophy, get less energy because of their reduced fat metabolism, which leads them to rely more heavily on carbohydrates.

"Carbohydrates produce less energy per molecule than fatty acids," she says. "With hypertrophy, the heart has a higher energy demand because there's more muscle to feed. With less fat metabolism, a greater reliance on carbohydrates may represent a shift to a less-efficient fuel."

The metabolic abnormality can eventually lead to impaired contraction of the heart and to heart failure.

Animal studies by collaborators at Washington University have shown that in mice with thickened heart muscle, genes associated with transporting and breaking down fatty acids are less active than normal -- in other words, the heart's fat-burning machinery is malfunctioning.

In this human study, the researchers studied patients who had high blood pressure that resulted in hypertrophy of the muscle of the left ventricle, the chamber of the heart that pumps blood to the body. The study showed that the greater the muscle mass of the hypertrophic heart, the lower the ability to burn fat. Magnetic resonance scans suggested that hypertrophic heart muscle had subtle abnormalities in contractile function at rest and was less energy efficient.

Normally heart muscle will alter between using fats and carbohydrates as fuel depending on availability. But at times of the day when blood glucose is low -- such as when a person hasn't eaten in a while -- hypertrophic hearts can't switch to burning fatty acids as normal hearts would, possibly leaving them energy deficient, de las Fuentes explains.

"This is the first time these data have been shown in humans," says senior author Victor G. Dávila-Román, M.D., director of the Cardiovascular Imaging and Clinical Research Core Laboratory and professor of medicine, anesthesiology and radiology. "That is particularly significant because hypertension (high blood pressure) is a huge public health problem in the United States. Of the 65 million people with hypertension, between 25 and 50 percent of them have some evidence that their heart has been affected by high blood pressure."

Not everyone who has high blood pressure will develop hypertrophy, and not everyone with hypertrophy has long-term problems, according to de las Fuentes. Some people appear to be protected while others appear to be at increased risk, likely due to genetic factors.

"Because we have this evidence that shows that fatty acid metabolism may play a role in this process, we are looking for variations in the metabolism genes in an ongoing clinical study," de las Fuentes says.

Dávila-Román adds that by looking at the genetics of hypertension and hypertensive heart disease, they hope to identify genes that predispose people to both good and bad traits associated with these disorders. Such information promises opportunities for both prevention and treatment of cardiac disease.

Beta Blockers No More First Choice for Hypertension

Thu, 29 Jun 2006 01:18:00 PST

( from http://www.rxpgnews.com ) The National Institute for Health and Clinical Excellence (NICE), UK and the National Collaborating Centre for Chronic Conditions, in conjunction with the British Hypertension Society (BHS) on Wednesday 28 June launched the keenly awaited updated clinical guideline on the management of hypertension. The guideline updates the recommendations for the pharmacological management of hypertension contained in the original NICE guideline published in August 2004. Based on a thorough review of recently published data, the guideline sets the gold standard for the optimum pharmacological management of hypertension and in so doing seeks to decrease morbidity and mortality resulting from cardiovascular diseases such as stroke, chronic renal failure and coronary heart disease for which hypertension is a significant risk factor.

It is estimated that some 40 per cent of adults in England and Wales have hypertension and this proportion increases with age. In 2001, the NHS funded 90 million prescriptions for drugs that lower blood pressure, accounting for nearly 15 per cent of the total annual cost of all primary care drugs. Nonetheless, hypertension is often inadequately treated.

In formulating the recommendations, the Guideline Development Group (GDG) considered not only data from the new studies, but also adverse events data and a detailed health economic analysis comparing the cost-effectiveness of the main drug classes. The GDG also considered the cause, development, and effects of hypertension and the mechanism of action of the different classes of blood pressure lowering drugs allowing for age and ethnicity.

Courtesy: Blood Pressure Association (BPA)

The updated recommendations in the guideline include the following:
In hypertensive patients aged 55 and over, or Black patients* of any age, first choice of initial therapy should be either a calcium channel blocker or a thiazide-type diuretic.
*Black patients are those of African or Caribbean descent, and not mixed race, Asian or Chinese patients.

In hypertensive patients younger than 55, first choice initial therapy should be an ACE inhibitor (or an Angiotensin receptor blocker if an ACE inhibitor is not tolerated).

If initial therapy was with a calcium channel blocker or thiazide-type diuretic and a second drug is required, add an ACE inhibitor (or an Angiotensin receptor blocker if an ACE inhibitor is not tolerated). If initial therapy was with an ACE inhibitor, add a calcium channel blocker or a thiazide-type diuretic.

If treatment with three drugs is required, the combination of ACE inhibitor (or an Angiotensin receptor blocker if an ACE inhibitor is not tolerated), calcium channel blocker and thiazide-type diuretic should be used.

The decision not to recommend Beta-blockers for first line therapy is based on evidence that suggests that they perform less well than other drugs, particularly in the elderly, and the increasing evidence that the most frequently used Beta-blockers at usual doses carries an unacceptable risk of provoking type 2 diabetes. The guideline also makes recommendations beyond a 3-drug combination, where, although the evidence is less certain, the GDG took into account existing guidelines and constructed recommendations most compatible with current good practice.

Job stress does not raise blood pressure

Sun, 07 May 2006 18:28:00 PST

( from http://www.rxpgnews.com ) Hassles at work do not shoot up blood pressure, say scientists, dismissing notions that job stress lead to high blood pressure and hypertension.

Samuel J. Mann, professor of clinical medicine at Weill Medical College of Cornell University, reviewed dozens of studies on the subject and found that the evidence that workplace stress has a lasting effect on blood pressure is very weak and very inconsistent, reported Newswise wire.

"When you realise that doctors may be advising patients to quit or change jobs to help them avoid hypertension, it's clear that this misconception can have life-altering effects," Mann points out.

In his review, Mann analysed data from 48 studies on job stress and blood pressure, all published in English-language journals from 1982 to 2004.

Overall, more than 100,000 people were included in the trials.

Mann found that most studies actually found no relationship between job stress and blood pressure, and that findings were very weak in most of the studies that did report a relationship.

Blood Pressure Readings Lower when Patients Slow Down

Sat, 22 Apr 2006 18:01:00 PST

( from http://www.rxpgnews.com ) According to a new study from a team of nurses headed by Melly Turner, R.N., systolic blood pressure can be an average of 14 points higher when taken immediately after arriving in the exam room and sitting on an examination table rather than sitting in a chair with your back supported and feet flat on the floor. In fact, all study participants had lower systolic and diastolic blood pressure measurements when seated in a chair versus the exam table.

With a desirable blood pressure reading around 120/80, and the American Heart Associations definition of hypertension as 140/90 or greater on two consecutive tests, a 14-point difference can mean the difference between a clean bill of health and an inaccurate diagnosis.

Currently, most patients get called back for their appointment, sit on the table, and immediately get their blood pressure measured, Turner said. Our study reaffirmed the American Heart Associations technique that patients should sit in a calm environment with feet flat on the floor, resting their back against the chair for at least five minutes before taking a blood pressure measurement on a bare arm at heart level. All too often, this doesnt happen.

In the first study of its kind conducted by nurses, the group found that taking a blood pressure reading in a chair after at least five minutes of waiting provided more accurate results than the traditional approach. Turners team even factored in anxiety when seeing a doctor, or the white coat syndrome into their research. White coats did not result in any statistically significant differences as compared with health care personnel wearing scrubs or street clothes.

Patients should know what their blood pressure is. If they have a diagnosis of high blood pressure, they need to know what the goal of their blood pressure should be, and how to get it there. This requires making necessary lifestyle changes, such as eating a balanced diet, lowering fat intake, lowering salt and sodium intake, in addition to incorporating at least 30 minutes of physical activity into their schedule most days of the week, Turner said.

The American Heart Association estimates that nearly one-third of Americans have high blood pressure, which can lead to stroke, stiffness of the heart over time, and an enlarged heart if untreated.

Promising evidence of new drug therapies in Pulmonary arterial hypertension (PAH)

Mon, 10 Apr 2006 16:07:00 PST

( from http://www.rxpgnews.com ) Several promising new treatments may prolong lives as well as improve the quality of life for people living with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH), high blood pressure in the pulmonary arteries in the lungs, is a life-threatening disease. Therapeutic options have, until recently, been limited and many patients with PAH faced lung transplantation. In recent years, research has identified a number of novel drug therapies that have shown to improve both quality and quantity of life in patients with this very serious illness.

During the ISHLT Meeting, researchers will discuss the results of new trial evidence of drugs including the endothelin antagonists Sitaxentan and Bosentan, prostenoids including Trepostenil and Prostacyclin, and Viagraâ (sildenafil citrate), marketed as RevatioTM for PAH, used as single agents and in combination.

PAH is caused when the smaller blood vessels in the lungs become more resistant to blood flow forcing the right ventricle of the heart to work harder to pump enough blood through the lungs. For example, Revatio (Viagra) helps patients by causing the pulmonary arteries to dilate which lessens the lungs resistance to blood flow and reduces the workload of the heart.

"It is an extremely exciting time for physicians involved in the care of patients with pulmonary arterial hypertension because of the explosion of novel drugs within the last few years," commented Paul A. Corris, Professor of Thoracic Medicine at the University of Newcastle upon Tyne, UK and Director, North of England Pulmonary Vascular Service. "Although these drugs cannot yet be considered a cure for pulmonary arterial hypertension, results of medical therapy are extremely encouraging for patients who have this serious disease and there is good evidence to show that patients who otherwise would have required urgent listing for lung transplantation may be treated satisfactorily in the interim with these drugs."

Fewer hours of sleep could lead to hypertension

Wed, 05 Apr 2006 14:11:00 PST

( from http://www.rxpgnews.com ) Fewer hours of sleep at night could raise your blood pressure, particularly if you are middle aged, says a new study.

Sleep deprivation has been shown previously to increase appetite and compromise insulin sensitivity.

Now researchers led by James E. Gangwisch of Columbia University's Mailman School of Public Health and the College of Physicians and Surgeons have found that middle aged people who sleep for five hours or less at night could face the risk of developing high blood pressure, reported science portal EurekAlert.

The researchers studied data from 4,810 people aged 32-86 who did not have high blood pressure at baseline. The 1982-84 follow-up survey asked participants how many hours they slept at night.

During eight to 10 years of follow-up, 647 of the 4,810 participants were diagnosed with hypertension.

Compared to people who slept seven or eight hours a night, people who slept five or fewer hours a night also exercised less and were more likely to have a higher body mass index.

They were also more likely to have diabetes and depression and to report daytime sleepiness.

Short sleep duration was linked to a new diagnosis of high blood pressure among middle-aged participants, but the association was not observed among people age 60 or older, he said.

The differences between the younger and older subjects might be explained by the fact that advanced age is associated with difficulties in falling and staying asleep.

Since the study is based on observational data, Gangwisch said more research was needed to confirm the association between short sleep duration and high blood pressure.

Loneliness linked to high blood pressure in aging adults

Tue, 28 Mar 2006 20:37:00 PST

( from http://www.rxpgnews.com ) Loneliness is a major risk factor in increasing blood pressure in older Americans, and could increase the risk of death from stroke and heart disease, new research at the University of Chicago shows.

Scholars found that lonely people have blood pressure readings that are as much as 30 points higher than in non-lonely people, even when other factors such as depressive symptoms or perceived stress are taken into account, said Louise Hawkley, Senior Research Scientist with the Center for Cognitive and Social Neuroscience at the University of Chicago, and John Cacioppo, the Tiffany & Margaret Blake Distinguished Service Professor in Psychology. This is equivalent to the difference between a normal blood pressure of 120 and a level of 150 which signifies Stage 1 hypertension. Blood pressure differences between lonely and non-lonely people were smallest at age 50 and greatest among the oldest adults tested, those at retirement age.

Hawkley and Cacioppo are authors of the paper, "Loneliness is a Unique Predictor of Age-Related Differences in Systolic Blood Pressure," published in the journal Psychology and Aging. Other co-authors were Christopher Masi, Assistant Professor of Medicine at the University of Chicago, and Jarett Berry of the Department of Preventive Medicine, Northwestern.

The increase in blood pressure associated with loneliness is about the same magnitude as reductions attained through weight loss and regular physical activity in people suffering from hypertension. "By these standards, improvements in a sense of social connectedness may have clinical benefits comparable to lifestyle modifications," the authors wrote.

The team based their research on a study of 229 people aged 50 to 68. The randomly chosen group includes whites, African Americans and Latinos who are part of a long-term study on aging. Members of the group were asked a series of questions to determine if they perceived themselves as lonely.

They were asked to rate their connections with others through a series of topics, such as "I have a lot in common with the people around me," "My social relationships are supeficial," and "I can find companionship when I want it."

The research team also examined data on weight, alcohol consumption, smoking, blood pressure medications, and demographic characteristics and found that people who rated high on being lonely had a significantly higher blood pressure than non-lonely people with similar profiles on the other measures.

The research also showed that the normal increases in blood pressure associated with aging are augmented by loneliness.

The paper builds on Cacioppo's earlier research that demonstrated that the loneliness is related to increased peripheral vascular resistance among young people. Although both lonely and non-lonely people in that study experienced stress, subjects in both studies reacted to stress differently.

"Lonely people differ from non-lonely individuals in their tendency to perceive stressful circumstances as threatening rather than challenging, and to passively cope with stress by failing to solicit instrumental and emotional support and by withdrawing from stress rather than by actively coping and attempting to problem solve," Cacioppo said.

The study on young people showed that stress caused an increase in resistance to blood flow brought on by their response to stress. Greater resistance to blood flow in lonley people compared to non-lonely idnvidiauls could increase blood pressure over the lifetime of lonely people, Cacioppo said.

Longitudinal studies are underway to look at how loneliness, now associated with an increase in blood pressure, may play a causal role in the increase, he said.

"I'm surprised by the magnitude of the relationship between loneliness and hypertension in this well-controlled cross-sectional study," said Richard Suzman, Ph.D., director of the Behavioral and Social Research Program at the National Institute on Aging (NIA), a funder of the research "Older people's relationships are often disrupted by death, illness and geographic mobility. One of NIA's goals is to help determine what can be done to improve the quality of relationships and social connectedness as a way to ease loneliness and reduce blood pressure."

Grape seed extract may be effective in reducing blood pressure

Mon, 27 Mar 2006 04:04:00 PST

( from http://www.rxpgnews.com ) Grape seed extract lowered the blood pressure of patients who participated in a UC Davis study of the benefits of the supplement on people with high blood pressure.

Conducted by UC Davis cardiovascular researchers, the study was the first human clinical trial to assess the effect of grape seed extract on people with metabolic syndrome, a combination of risk factors that increase the risk for heart disease, including high blood pressure, excess abdominal body weight, high blood cholesterol fats and high blood sugar. The researchers will present the results at the American Chemical Society Meeting and Exposition on March 26 in Atlanta, and at the Federation of American Societies for Experimental Biology's 2006 meeting in San Francisco April 2.

It is estimated that 40 percent of American adults, or 50 million people, have metabolic syndrome.

The one-month study involved 24 male and female patients diagnosed with metabolic syndrome. The patients were divided into three groups of eight. The first group received a placebo, while the second and third groups received 150 milligrams and 300 milligrams, respectively, of a new grape seed extract. All participants' blood pressure was automatically measured and recorded for 12 hours after ingestion.

"Participants in the two groups receiving grape seed extract experienced an equal degree of reduced blood pressure. The average drop in systolic pressure was 12 millimeters. The average drop in diastolic pressure was 8 millimeters," said the study's lead researcher, C. Tissa Kappagoda, professor of cardiovascular medicine and director of the Preventive Cardiology Program at UC Davis.

Kappagoda adds that the group taking 300 milligrams of grape seed extract also had reduced serum oxidized LDL cholesterol levels.

"Generally, the higher their initial oxidized LDL level was, the greater the drop by the end of the study," he said. The extract has received the GRAS (generally recognized as safe) certification from the FDA and has no known side effects.

TROPHY Trial: Incidence of hypertension reduced with early intervention

Wed, 22 Mar 2006 07:05:00 PST

( from http://www.rxpgnews.com ) Treating pre-hypertension with medication and lifestyle modifications reduces the risk of patients progressing to hypertension, a new study involving researchers at UT Southwestern Medical Center has concluded.

The findings, appearing in an upcoming issue of The New England Journal of Medicine, are the result of a four-year study of more than 800 patients who had a condition known as pre-hypertension. A blood pressure between 120 and 139 mm Hg systolic and 80 to 89 mm Hg diastolic indicates pre-hypertension.

"The recommended guidelines currently list lifestyle modifications for treatment of pre-hypertension," said Dr. Shawna Nesbitt, associate professor of internal medicine at UT Southwestern and an author on the study. "But the long-term maintenance of a lifestyle change is dismal. Patients typically don't stick to it."

Present guidelines recommend that pre-hypertension be managed with changes in the patient's lifestyle through weight loss, salt restriction, exercise and dietary modification. Despite intense efforts to keep patients from developing hypertension, an increasing number of people are diagnosed each year. Hypertension is one of the leading causes of other cardiovascular ailments, including heart disease and stroke.

Dr. Nesbitt collaborated with researchers at several institutions to find out if treatment with angiotensin-receptor blockers, or ARBs, could prevent the development of hypertension. This is the first human study involving treatment of prehypertension with an ARB.

"We chose to administer a low dose of the ARB medication candesartan cilexetil because it has qualities that suggest it changes characteristics of the blood vessel an effect that may be maintained beyond the period of treatment," Dr. Nesbitt said. "As hypertension develops, the walls of the blood vessels actually get thicker, setting the stage for high blood pressure to propagate. This medication and others like it seem to decrease that thickness and improve the function of the blood vessels."

In the study, patients between the ages of 30 and 65 with blood pressures between 130 and 139 mm Hg systolic and 85 to 89 mm Hg diastolic were treated over a four-year period with either a placebo or with ARB medications.
"In a prior study, it was shown that over four years, if left untreated, 40 percent of people with prehypertension become hypertensive," Dr. Nesbitt said.

Half of the participants were given candesartan cilexetil for two years and then were removed from the medication for two years; the other half of the group was untreated for the four years. Even up to two years after treatment was stopped, the candesartan-treated pre-hypertensive patients had a 15.8 percent lower risk of developing hypertension compared with untreated pre-hypertensive patients. Both groups were advised to modify their diet and exercise habits.

"I think this is the tip of the iceberg in the further study of new treatment protocols for pre-hypertension" Dr. Nesbitt said. "We've typically waited until people have hypertension before we treated them, and it's really hard to stave off the disease's progression when you treat it later in its development. This is an opportunity for us to investigate early treatments and to see if we can prevent patients from having to be on life-long therapy for hypertension."

Gene at heart of poor prognosis in hypertension

Sun, 20 Nov 2005 22:08:00 PST

( from http://www.rxpgnews.com ) Having high blood pressure and a particular genetic alteration dramatically increases the risk of heart attack, stroke or death, and may explain why some hypertensive patients fare worse than others - even if they take the same medication, University of Florida researchers announced this week.

The discovery, reported at the annual Scientific Sessions of the American Heart Association, brings scientists a step closer toward determining how certain genes influence the development of hypertension and the bad outcomes associated with the condition. Just as discriminating shoppers buy made-to-order suits to flatter their figure, this type of research may someday enable patients to seek out medicine tailored to fit, based not on their size and shape but on their genetic makeup.

UF researchers studied about 5,700 patients ages 50 and older who were participating in a National Institutes of Health-funded substudy of the International Verapamil SR-Trandolapril study, or INVEST-GENES. Other scientists had previously found that hypertensive patients with a certain version of the alpha-adducin gene were less likely to suffer a heart attack or stroke if they were taking a diuretic.

"Specifically, their data suggested that one genotype group benefited from the diuretic and had a reduction in heart attack and stroke, while the other genotype group did not," said Julie Johnson, Pharm.D., director of the UF Center for Pharmacogenomics and chairwoman of the department of pharmacy practice at UF's College of Pharmacy. "We felt we had an ideal population for trying to replicate this finding, which if true could have important clinical implications.

"In our study, carriers of the genetic variation had an approximately 43 percent higher risk of death, heart attack or stroke," she said. "Thus, this helps us piece together the puzzle of the various genes that lead to some people having worse outcomes than others when they have hypertension."

Genes likely determine nearly half one's risk of developing hypertension, and factors such as diet, age, health status and the environment determine the rest. Similarly, certain genes are associated with the risk of the adverse consequences of hypertension, such as heart attack, stroke and kidney failure, said Johnson, a member of the UF Genetics Institute.

"One of the goals of our research is to identify the genes that are related to patient-to-patient differences in response to medications," Johnson said. "Personalizing drugs based on genetic makeup instead of taking a trial-and-error approach could lead to safer, more effective treatments for individual patients."

About 65 million Americans have high blood pressure, and another 25 million are at high risk of developing hypertension in the next decade, Johnson said. Elevated blood pressure is associated with kidney disease and up to half of all cases of coronary artery disease, the No. 1 killer of men and women in the United States. Many patients fail to achieve targeted blood pressure goals.

In the INVEST substudy, nearly a third of the participants were carriers of the tryptophan version of the alpha-adducin gene, a protein associated with the movement of ions, especially sodium, across cells. In these individuals, the amino acid glycine has been swapped with the amino acid tryptophan. Up to 40 percent of the population carries at least one copy of the tryptophan form of the gene.

In the UF study, those with this version had a 43 percent higher risk of heart attack, stroke or death than those with the glycine form in the 2 ½ years after the study began; 258 patients, about 5 percent, experienced a heart attack or stroke, or died. But unlike previous research, the UF study did not show that patients with the glycine form benefited more from diuretics, which help lower blood pressure by ridding the body of excess salt and water.

"We were not able to show any relationship between the genetic variations and benefits associated with diuretic therapy," Johnson said. "Thus, our data suggest that we would not use this genetic information to help determine who should get a diuretic. However, it does provide us clues into at least one gene that likely places people at risk for death, heart attack and stroke, and so perhaps in the future this information can be used to be more aggressive in the preventive therapies for these individuals."

As researchers learn more, they hope to better understand the complex interplay between genes, disease development and the treatments that work best depending on one's DNA. For now, identifying patients at risk remains a challenge, and treatment is often inadequate, Johnson said.

"There are five first-line drug classes, with probably an average of seven to eight drugs in each class, then an additional half-dozen or so other drug classes that aren't considered first-line," Johnson said. "This means there are many choices for drug therapy in hypertension - a good thing - but also adds to the trial-and-error element of finding the right drug for the right person, as any specific drug has only about a 50 percent chance of being effective in a specific patient."

Identifying genetic risk factors is only the first step, said epidemiologist Sharon Kardia, Ph.D., director of the Public Health Genetics Program at the University of Michigan School of Public Health.

"Large research studies need to be undertaken to prove that genetic risk can be reduced through medical or public health interventions. Second, this whole new realm of genomic medicine greatly expands the responsibilities of doctors, nurses and pharmacist to assure the proper use of genetic information in prescribing, dispensing and administering drug therapies," Kardia said. "Lastly, we have to tread lightly until we have assurances that people's genetic information will be properly protected so that identifying someone as more expensive or difficult to treat won't result in insurance or perhaps job discrimination. As Dr. Johnson's research illustrates, we now have good evidence that we should be investing in genetics education, regulation and social engagement so that we can move these results to the next level - namely, decreasing health-care costs and saving lives."

Coffee not associated with hypertension

Wed, 09 Nov 2005 20:34:00 PST

( from http://www.rxpgnews.com ) Habitual coffee drinking is not associated with an increased risk of hypertension in women, although an association was found with the consumption of sugared or diet colas, according to a study in the November 9 issue of JAMA.

Approximately 50 million people in the United States have hypertension, and the prevalence is increasing, according to background information in the article. Hypertension is a major risk factor for coronary heart disease, stroke, and congestive heart failure. Therefore, even small reductions in the prevalence of hypertension could have a potentially large public health and financial impact. Several previous studies have indicated a possible association between caffeine intake and the risk of hypertension. Short-term studies have demonstrated that caffeine intake acutely increases blood pressure, but over time, weakening of this effect does occur. A long-term effect of caffeine intake on the risk of developing hypertension would be of substantial public health importance given the widespread consumption of beverages containing caffeine, but currently, studies of this association are scarce.

Wolfgang C. Winkelmayer, M.D., Sc.D., of Brigham and Womens Hospital and the Harvard School of Public Health, Boston, and colleagues conducted a study to determine whether caffeine intake or consumption of certain caffeine-containing beverages is associated with an increased risk of incident hypertension in women. The researchers analyzed data from the Nurses Health Studies (NHSs) I and II of 155,594 U.S. women free from physician-diagnosed hypertension, who were followed-up over 12 years (1990-1991 to 2002-2003). Caffeine intake and possible confounders were ascertained from regularly administered questionnaires.

Over the 12 years, 19,541 incident cases of physician-diagnosed hypertension were reported in NHS I and 13,536 in NHS II. In both cohorts, no linear association between caffeine consumption and risk of incident hypertension was observed after multivariate adjustment. When studying individual classes of caffeinated beverages, habitual coffee consumption was not associated with increased risk of hypertension. By contrast, consumption of cola beverages was associated with an increased risk of hypertension, independent of whether it was sugared or diet cola.

"In this study with more than 1.4 million person-years of follow-up [the number of women in the study times the number of years of follow-up per woman], the relevant exposures and outcomes have been found valid and accurate, and coffee intake was updated to reflect changes in individual behavior. We found strong evidence to refute speculation that coffee consumption is associated with an increased risk of hypertension in women," the authors write.

Concerning the link found between colas and hypertension, the researchers write: " we speculate that it is not caffeine but perhaps some other compound contained in soda-type soft drinks that may be responsible for the increased risk in hypertension. If these associations are causal, they may have considerable impact on public health."

Deep brain stimulation can reduce blood pressure

Sun, 23 Oct 2005 18:11:00 PST

( from http://www.rxpgnews.com ) The possibility of a patient lowering their blood pressure at the flick of a switch has been raised by research led by Oxford University, which shows that stimulating parts of the brain with electrodes can change a patients blood pressure.

In a paper published today by Neuroreport, researchers at Oxford University and Imperial College London report that they have found the exact area of the brain that controls blood pressure and how to make use of it.

A team of neurosurgeons and physiologists have found that they can make patients blood pressure increase or decrease by stimulating with electrodes very specific regions of the brain.

Deep brain stimulation placing very thin electrodes onto exact locations in the brain is already used to relieve pain or to help Parkinsons sufferers to move better. Fifteen patients having the operation to implant electrodes for pain control agreed to take part in a study to see whether stimulating another location in the brain could alter blood pressure.

It was found that blood pressure could indeed be changed, and that it could be raised or lowered very precisely by stimulating different, very specific parts of the brain. This potentially offers a cure to sufferers of high blood pressure that does not depend on taking drugs long-term.

As the electrodes can be switched on and off, another condition that could potentially be treated using this method is postural hypotension, a condition where a patients blood pressure falls uncontrollably upon standing up.

Mr Alexander Green from Oxfords Department of Neurosurgery, lead author of the paper, said: Obviously, as this is brain surgery, we have to proceed with great caution: it would initially only be warranted in those patients for whom drug treatments just arent working. However, other research groups are working on less invasive methods of stimulating exact locations in the brain, for example using nanotechnology, and if this becomes available then the treatment would be attractive to a much larger number of people.

GRK5 have an important role behind essential hypertension

Sat, 08 Oct 2005 05:31:00 PST

( from http://www.rxpgnews.com ) Researchers at Jefferson Medical College have implicated a protein called GRK5 as having an important role behind essential hypertension, which affects more than 65 million Americans.

When Andrea Eckhart, Ph.D., associate professor of medicine at Jefferson Medical College of Thomas Jefferson University in Philadelphia, and her co-workers turned up the volume on GRK5, overexpressing a mouse gene that makes the protein, the researchers saw extreme rises in blood pressure even when the animals were resting.

Not only that, they found that high blood pressure segregated with gender. That is, female mice with an overexpressed GRK5-making gene had a lesser spike in blood pressure than males, which Dr. Eckhart says, has intriguing implications.

This difference suggests it could be a great model for human hypertension, especially for premenopausal women, says Dr. Eckhart, who is director of the Eugene Feiner Laboratory in the Center for Translational Medicine in the Department of Medicine at Jefferson Medical College. Is the difference due to a protective effect of estrogen, or because males with testosterone make it worse? Were now looking at the effects of these androgens in conferring differences.

Dr. Eckhart thinks it could be a powerful hypertensive model to look at different new hypertensive therapies that different drug companies come up with to look at the effects of estrogen.

To Dr. Eckhart and her group, which reported their results August 23, 2005 in Circulation, a journal of the American Heart Association, the finding is another step in the laboratorys goal of uncovering the molecular roots of hypertension. More than 90 percent of cases cant be pinned to a particular molecular cause.

GRK5, short for G-coupled protein receptor kinase, was known to rise in animal models with high blood pressure. According to Dr. Eckhart, this kinase acts as a switch that essentially turns off receptors. Such receptors bind catecholamines, which are sympathetic system neurotransmitters like epinephrine and norepineprhine. They also bind peptide hormones such as angiotensin, which is implicated in high blood pressure.

Dr. Eckhart and her co-workers dont think that GRK5 is necessarily the sole cause of hypertension. But because it is correlated with some types, they wanted to look at the molecular mechanisms and try to get a better idea of its role. They created mice that overexpressed GRK5 in the vascular smooth muscle, hoping to begin seeing what receptors and signaling pathways might be involved in hypertension with elevated GRK5 levels. What they found surprised them.

There are not too many molecules shown in mice to raise basal blood pressure straight up, she says. The effect is quite profound. There are a lot of checks and balances that keep the pressure down. We were surprised there was such an increase at resting. We might have thought this would happen if we stressed the animal, but we saw it at baseline. Obviously it is affecting receptors important in the resting state.

When they looked more closely, they found that increases in blood pressure differed according to sex.

Ultimately, wed like to see if GRK5 is a biomarker, a predictor for a multifactorial disease like high blood pressure, she says. Developing a good therapeutic profile for such patients might helps us prescribe the correct drugs more quickly. We hope the work might lead to better, more specific ways to treat high blood pressure than currently used diuretics and specific receptor blockers.

She notes that even though these mice have hypertension, their blood vessels are not enlarged, which is typical of progressive heart failure and kidney disease and are associated with high blood pressure. These mice didnt have these associated cardiovascular risks, she says. Maybe the GRK5 is somehow protective of other organs, despite its role in causing hypertension.

Dr. Eckharts group, in collaboration with Bonita Falkner, M.D., professor of medicine at Jefferson Medical College and Kumar Sharma, M.D., director of the Center for Diabetic Kidney Disease at Thomas Jefferson University and professor of medicine at Jefferson Medical College, currently is studying children with hypertension to examine white blood cell levels of GRK5.

Mechanisms behind portal hypertension uncovered

Thu, 29 Sep 2005 20:46:00 PST

( from http://www.rxpgnews.com ) A physician-scientist at UT Southwestern Medical Center and his research team have identified mechanisms causing a potentially deadly type of hypertension that results from liver damage - findings that could lead to its prevention.

This particular type of hypertension, called portal hypertension, affects the blood flow into the portal vein, which feeds blood to the liver.

Dr. Don Rockey, chief of the division of digestive and liver diseases at UT Southwestern, has reported new findings on a potentially deadly form of hypertension that results from liver damage.
Dr. Don Rockey, the new chief of the digestive and liver diseases at UT Southwestern, identified the cellular activity that results in portal hypertension. He and his colleagues then took the research a step further, showing that if the process can be interrupted, the hypertension subsides.

The National Institutes of Health-funded research - available online and scheduled to appear in a future issue of the journal Nature Medicine - was conducted by Dr. Rockey while he was at Duke University Medical Center.

"Portal hypertension is a deadly disease that complicates many forms of chronic liver injury," Dr. Rockey said. "When this occurs, in its most severe form, the prognosis definitely becomes guarded," often leading to the need for a liver transplant.

The short-term mortality for patients with portal hypertension is about 30 percent. The latest research opens new ground scientifically and has implications for possible clinical approaches, said Dr. Rockey.

"The end result of portal hypertension is bleeding and development of ascites [fluid in the abdomen]; so if you could treat it early, you could prevent bleeding and/or the formation of ascites," he said.

Portal hypertension is similar to the widely known essential hypertension, which impairs blood flow to the heart systems. But portal hypertension affects blood flow to the liver-related systems.

The liver is an essential organ that washes the body's blood of wastes and poisons. Cirrhosis of the liver occurs when the cells are damaged. Scarring often results, reducing blood flow into the liver and raising pressure on veins not designed to handle that much blood flow. The high pressure can cause veins to burst, resulting in internal bleeding and potentially death.

Previous studies have shown that, at the cellular level, portal hypertension results from reduced production of needed nitric oxide, which regulates expansion of the blood vessels.

Dr. Rockey's research identified how the nitric oxide production breaks down due to the effects of the protein GRK2. The protein attaches to another protein called AKT, interrupting the creation of nitric oxide.

"We've shown that the endothelial cells that line the blood vessels in the liver don't work quite right. Specifically, they don't produce nitric oxide," Dr. Rockey said. "The problem is that there are a number of signaling pathways that are disrupted and that results in the reduced production of nitric oxide."

In addition to identifying how the system breaks down, Dr. Rockey's study showed that reducing the GRK2 production restored AKT production, allowing nitric oxide levels to stabilize and blood pressure to return to normal.

Further research will be needed, Dr. Rockey said, to determine how to control GRK2 proteins that interfere with AKT or ways to bolster AKT protein production to maintain nitric oxide production.

Chromosome 2 region linked to ACE inhibitors & beta blockers non-responders

Sat, 24 Sep 2005 15:39:00 PST

( from http://www.rxpgnews.com ) For the first time, researchers have mapped a genetic location that explains why certain blood pressure-lowering drugs aren't effective for some people.

"The findings bring us a step closer to developing targeted therapies for patients with high blood pressure who might otherwise be started on medications that won't help," said lead author Sandosh Padmanabhan, Ph.D., specialist registrar at the British Heart Foundation Glasgow Cardiovascular Research Centre at the University of Glasgow in Scotland.

Goal blood pressure is less than 140/90 mm Hg, or less than 130/80 mm Hg for those with diabetes or kidney disease.

Uncontrolled high blood pressure can lead to stroke, heart attack, heart failure and/or kidney failure. The World Health Organization estimates that suboptimal blood pressure is responsible for 62 percent of cerebrovascular disease and 49 percent of ischemic heart disease.

The cause of 90 percent to 95 percent of the cases of high blood pressure isn't known, but is likely to be due to multiple genes and environmental factors.

Researchers have been trying to identify genes responsible for high blood pressure. But most studies have been inconclusive, "probably because so many genes are working together," Padmanabhan said.

The research team from the United Kingdom studied a large group of severely hypertensive Caucasian families to try to identify the location of some of these genes. The investigation (MRC Bright Study) included 2,142 Caucasian families with severe hypertension. The researchers noted what drugs the study participants were taking to control their hypertension and measured their blood pressure after treatment.

The researchers identified 89 sibling pairs who did not respond to ACE inhibitors and beta blockers and 76 sibling pairs who did not respond to calcium channel blockers and diuretics. For purposes of the study, lack of response was defined as a failure to reach target blood pressure levels of 140/90 mm Hg or a reduction in blood pressure of less than 20 points.

Using genome-wide linkage analysis, they located a region on chromosome 2 that appears to be involved in causing high blood pressure in people who do not respond to ACE inhibitors and beta blockers.

African Americans, not Caucasians, typically have salt-sensitive high blood pressure that does not respond to ACE inhibitors and beta blockers, he said. And coincidentally, a recent American study showed that high blood pressure in African Americans maps to this exact same chromosome region.

Taken together, "the studies show that there is a strong likelihood that this region on the short arm of chromosome 2 may contain the gene or genes responsible for a salt-sensitive form of hypertension that is unresponsive to ACE inhibitors and beta blockers," Padmanabhan said.

The next step, he said is to pinpoint the exact mutant gene or genes responsible for this drug response.

Analgesics Not Linked to Increased Risk of Hypertension in Men

Wed, 14 Sep 2005 02:03:00 PST

( from http://www.rxpgnews.com ) Brigham and Women's Hospital (BWH) is a leading source of research on the public health benefits and potential side effects of over-the-counter pain medications. Previous research has suggested a link between pain reliever use and increased risk of hypertension in women. As the data in women has grown, another BWH team set out to further define the association in men. Now, BWH epidemiologists studying the medication and health habits of participants in the landmark Physicians Health Study report that frequent use of analgesics and specific use of acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), and aspirin does not appear to substantially increase a mans risk of developing hypertension. The findings are published in the September 12, 2005 issue of the journal, Archives of Internal Medicine.

Over-the-counter pain relievers are one of the most commonly used classes of medications.

"The incidence of hypertension, one of the leading causes of stroke and heart attack, has increased over the last decades and obesity seems to be a major contributing factor, but there may be other factors driving this trend such as changes in medication use," said lead author Tobias Kurth, MD, ScD, a researcher in BWHs Divisions of Aging and Preventive Medicine. "Given the data linking analgesics and hypertension in women and widespread use of over-the-counter analgesics in general, we were interested in looking at the potential hypertensive side effects of commonly used pain relievers in men. Contrary to what has been reported in women, we did not observe a significant trend toward increased risk of hypertension among men who frequently consumed over-the-counter pain medications. However, with all observational studies small to moderate effects cannot be ruled out."

The data was based on more than 8,200 healthy male physicians between the ages of 53 and 97 enrolled in the Physicians Health Study. The men filled out questionnaires about their cumulative analgesic use and reported diagnosis of hypertension over a six-year period. After controlling for a variety of factors including body mass index, smoking status and physical activity levels, the researchers found no apparent association between men who consumed high levels of pain relievers and increased incidence of hypertension.

ASCOT Trial - Amlodipine Reduces Cardiovascular Mortality

Thu, 08 Sep 2005 01:05:00 PST

( from http://www.rxpgnews.com ) Results of the landmark Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) showed that patients with high blood pressure and additional cardiovascular risk factors who received a treatment regimen based on Pfizer's calcium channel blocker Norvasc (amlodipine besylate) experienced significant reductions in cardiovascular death, all-cause mortality and total cardiovascular events and procedures, including heart attacks and strokes, compared to patients who received a standard beta-blocker based regimen.

Patients receiving the Norvasc-based regimen experienced a reduction in the primary endpoint (fatal coronary heart disease and non-fatal heart attack) which did not reach statistical significance. The final results of ASCOT confirmed the Data Safety and Monitoring Board decision to stop the trial early.

The results were presented this week at the annual meeting of the European Society of Cardiology in Stockholm, and September 4 online issue of The Lancet.

"The results of ASCOT clearly demonstrate that a Norvasc-based antihypertensive regimen can reduce the risk of cardiovascular death and a broad range of cardiovascular events in patients with hypertension who have additional risk factors," said Professor Peter Sever, ASCOT principle investigator, clinical pharmacology and therapeutics, International Centre for Circulatory Health at London's Imperial College.

The five-year ASCOT Study, which was one of the largest hypertension trials ever conducted, involved over 19,000 patients in Europe who had high blood pressure. The trial compared the cardiovascular effects of a Norvasc-based regimen versus a standard beta-blocker based regimen in reducing cardiac events in patients with hypertension and multiple cardiovascular risk factors. In the Norvasc-based regimen, patients received the ACE-inhibitor perindopril and the alpha-blocker Cardura XL (doxazosin GITS) as add-on therapy if additional blood pressure control was needed. Patients receiving the beta-blocker based regimen of atenolol, received a diuretic (thiazide) and Cardura XL (doxazosin GITS), if needed.

The final ASCOT results showed an 11 percent reduction in total mortality shown in patients taking the Norvasc-based regimen compared to patients taking the beta-blocker based regimen. Norvasc patients also experienced a 23 percent reduction in fatal and non-fatal strokes and a 24 percent reduction in cardiovascular death, compared to patients taking the beta-blocker-based regimen. In addition, patients taking the Norvasc based regimen experienced a 10 percent reduction in the primary endpoint of fatal coronary heart disease and non-fatal heart attack, which did not reach statistical significance.

"We have shown that an effective treatment strategy can provide the optimal benefits for patients and even save lives if physicians focus on early intervention that begins with targeting hypertension along with other cardiovascular risk factors such as lowering cholesterol with Lipitor," said Professor Sever.

In addition to treatment for high blood pressure, 10,000 patients in ASCOT who had normal to mildly elevated cholesterol levelsnot typical candidates for lipid-lowering treatmentreceived Lipitor 10mg (atorvastatin calcium) or placebo to evaluate the cardiovascular benefits of lipid-lowering therapy. In October 2002, the lipid-lowering arm of ASCOT was stopped earlier than expected due to a significant benefit in the reduction of heart attacks in Lipitor-treated patients.

The results of the lipid lowering arm of ASCOT provided critical information in the development of national guidelines including the National Cholesterol Education Program and the Joint European Guidelines which now call for more aggressive lipid lowering in patients who have elevated cardiovascular risk, including patients with high blood pressure.

"The ASCOT results, including results of the Lipitor arm, play an essential role in effectively reducing cardiovascular events and death in hypertensive patients with additional risk factors," said Dr. Michael Berelowitz, Pfizer's senior vice president of Worldwide Medical and Outcomes Research. "These results imply that physicians may want to consider a more comprehensive approach to managing overall cardiovascular risk which may involve other available therapies such as Caduet, which offers the benefits of Norvasc and Lipitor in a single tablet."

Hypertension is one of the most prevalent risk factors for cardiovascular disease, affecting as many as 800 million people worldwide. It is estimated that at least 80 percent of people with high blood pressure may also have other uncontrolled cardiovascular risk factors with elevated cholesterol being the most common.

Funded by Pfizer, ASCOT was an investigator-led trial coordinated by an independent steering committee. The study began in 1998 and enrolled patients in the United Kingdom, Ireland, Sweden, Norway, Denmark, Finland and Iceland. In December 2004, the ASCOT steering committee endorsed the recommendation of the Data and Safety Monitoring Board to stop the trial early due to favorable benefits, including mortality, demonstrated in patients who received the Norvasc-based regimen.

Caduet is a prescription drug that combines 2 medicines, Norvasc® (amlodipine besylate) and Lipitor® (atorvastatin calcium). It is used to treat both high blood pressure (hypertension) or angina (chest pain) and high cholesterol, or to lower the risk of heart attack in patients with multiple risk factors for heart diseasesuch as family history of heart disease, high blood pressure, older than 55, low HDL-C, or smokingalong with diet and exercise.

Caduet is not for everyone. It is not for those with liver problems. And it is not for women who are nursing, are pregnant, or may get pregnant. Patients should tell their doctor if they feel any new muscle pain or weakness. This could be a sign of serious side effects. Patients should also tell their doctor about other medicines they are taking. This may help avoid serious drug interactions. The doctor may do blood tests to check liver function before and during treatment. If a patient has any heart problems, they should tell their doctor before taking Caduet. The most common side effects are edema, headache, and dizziness. They tend to be mild and often go away.

Norvasc (amlodipine besylate) is indicated for high blood pressure and angina. In clinical trials, the most common side effects for Norvasc versus placebo were edema (8.3% vs 2.4%), headache (7.3% vs 7.8%), fatigue (4.5% vs 2.8%), and dizziness (3.2% vs 3.4%).

The most common side effects are swelling, headache and dizziness. They tend to be mild and often go away. Patients should talk to their doctor about all medicines they are taking to help avoid serious drug interactions. Doctors may do blood tests to check liver function before and during treatment. Patients treated with Caduet should tell their doctor if they feel any new muscle pain or weakness which could be a sign of serious side effects.

BHF comments on ASCOT trial results

Tue, 06 Sep 2005 01:22:00 PST

( from http://www.rxpgnews.com ) The British Heart Foundation has commented on the results of the ASCOT trials, which have been presented at the European Society of Cardiology Congress 2005 in Stockholm.

The trials have revealed that new classes of blood pressure-lowering drugs could save lives by preventing strokes and heart attacks even more effectively.

Professor Peter Weissberg, Medical Director of the British Heart Foundation, said:

"This is an important study because it provides evidence on the efficacy of the newer blood pressure lowering agents at reducing the risk of a heart attack or stroke.

"We have known for some time that they are effective at lowering blood pressure but this new study shows that they are even better at preventing heart attacks and strokes than the blood pressure lowering drugs we have been using for many years.

"In addition, when these drugs are combined with atorvastatin, a commonly prescribed lipid lowering drug, they are even more effective.

"The guidelines for treatment of high blood pressure are constantly being revised in the light of results of new clinical trials like this one. We expect that this study will have a major influence on future guidelines published by organisations such as NICE and consequently on future prescribing of antihypertensive drugs.

"However, people taking the older types of drug should however, be reassured that they are on effective treatment and there may be good medical reasons why they should continue on these drugs, rather than swap to the newer ones.

"The results of this trial serve to re-emphasise just how important it is to reducing blood pressure and cholesterol in patients at risk of a heart attack or stroke."

ASCOT-BPLA : An Overview of Largest European Hypertension Trial Results

Mon, 05 Sep 2005 16:53:00 PST

( from http://www.rxpgnews.com ) Combination of effective, modern antihypertensives with cholesterol lowering drugs can abolish most strokes and heart attacks in people with high blood pressure by reducing the risk of strokes by about 25%, coronaries by 15%, and cardiovascular deaths by 25% and new cases of diabetes by 30% compared with the standard treatment. The success of this treatment strategy has been shown for the first time in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) - which was presented at the congress of the European Society of Cardiology on 4 September 2005 and is published online in The Lancet. ASCOT is the largest study of high blood pressure treatment ever conducted in Europe. Also, it is the only major European study to-date to combine these two treatment strategies.

What is already known on this topic?
Previous studies have suggested that newer agents would confer advantages over diuretics and Beta-blockers. However, no individual trial using standard diuretic or Beta-blocker therapy, or both has shown a significant reduction in coronary heart disease.

Results
The final results of the Blood Pressure Lowering Arm (BPLA) of Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), a large randomised controlled trial with sample size of 19000 and prospective randomised open blinded end point design (PROBE), which was conducted in the UK, Ireland and the Nordic countries, showed that the combination of newer blood pressure lowering drugs reduced the risk of strokes by about 25%, coronaries by 15%, and cardiovascular deaths by 25% and new cases of diabetes by 30% compared with the standard treatment. The addition of the cholesterol lowering drug, atorvastatin, still further reduced the remaining risk irrespective of the patient's original cholesterol level. Indeed, the ASCOT patients only had average or below average levels of cholesterol at the outset of the study.

As a result of the reductions in heart attacks and strokes in patients receiving the cholesterol lowering drug and those treated with the modern blood pressure lowering drugs, both parts of ASCOT were terminated early by the independent Data Safety Monitoring Board.

Methodology
The investigators recruited 19257 patients aged between 4079 years with high blood pressure who had a least three other risk factors for cardiovascular events (moderate risk) such as smoking, non-insulin dependent diabetes, history of a cerebral vascular or a peripheral vascular disease and microalbuminuria.

Therapeutic targets of the study are a blood pressure of less than 140/90 in non-diabetics and less than 130/80 in diabetics with no fixed target for the lipid-lowering limb. Half of the patients were assigned the atenolol based regimen (traditional combination: a beta-blocker, atenolol and a diuretic) and half the amlodipine-based regimen (newer drugs: a calcium antagonist, amlodipine and the ACE inhibitor, perindopril ). After 5 years the investigators found those allocated the amlodipine-based regimen had lower blood pressure values than those on the atenolol -based regimen.

Comments
"The patients treated in ASCOT were those generally seen in everyday practice. They had high blood pressure plus three additional risk factors, e.g. aged over 55, male gender, smoker. They were seen as being at moderate risk. Said Professor Peter Sever, Professor of Clinical Pharmacology and Therapeutics, Imperial College London, International Centre for Circulatory Health, London, UK, Co-Chairman of the ASCOT Steering Committee. He continued Compared with patients receiving standard blood pressure lowering therapy of a beta-blocker and diuretic, the combination of the contemporary blood pressure lowering drugs, amlodipine and perindopril, plus effective lowering of cholesterol abolished about half the risk of strokes and heart attacks - the most important causes of death in millions of men and women with high blood pressure."

"High blood pressure is a major public health problem. Despite the availability of effective blood pressure lowering drugs, many people who are being treated still suffer strokes, heart attacks and other related diseases, such as diabetes. Now, the evidence from ASCOT offers us a simple and effective combination of treatments which both control the blood pressure and lower cholesterol to more effectively reduce this risk. This is very important news for patients and their physicians." said Professor Bjorn Dahlof, Associate Professor in the Department of Medicine at Sahlgrenska University Hospital/Ostra, University of Gothenburg, Sweden and Co-Chairman of the study.

On balance, the ASCOT results endorse the European guidelines for the treatment of hypertension, which leave the responsibility to choose the drug class to initiate antihypertensive to the doctor. ASCOT also supports the use of newer drugs, especially in patients with complicated hypertension, associated risk factors and/or metabolic disturbances . . . Governments and health care insurers will have to accept that the use of antihypertensive drugs cannot be rationed. - Jan Staessen (University of Leuven, Belgium)

The investigators believe that international recommendations for managing high blood pressure may need to be reviewed after the publication of these results. Additionally, they suggest that most patients with hypertension should also be considered for a cholesterol lowering drug.

Professors Sever and Dahlof concluded: "Diuretics and beta-blockers are an effective and proven combination for lowering blood pressure and its associated risks. What ASCOT has shown is that for many patients the combination of newer drugs may be an even better option. Patients should discuss the implications of ASCOT with their physicians before any modification of treatment is considered."

The Lancet in January 2005 reported that more than 330 million adults in Europe and North America suffer from high blood pressure which also affects a further 639 million men and women in the rest of the world. According to World Health Organization about 80% of people with high blood pressure have additional uncontrolled cardiovascular risks.

Explanations for the benefits seen from this study are reviewed in a separate paper also published in The Lancet online with the title 'Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) In this paper Neil Poulter (Imperial College London, UK) and colleagues looked at differences in blood pressure and other variables in patients assigned the newer drugs versus those allocated the standard drugs. They found that a reduction in blood pressure was the single biggest contributor to the effect on stroke events, but other factors, such as differences in cholesterol, were more important for coronary events.

Background of ASCOT Trial
ASCOT (The Anglo-Scandinavian Cardiac Outcomes Trial) commenced patient recruitment in 1998. It was designed as a randomised controlled trial of the prevention of coronary heart disease (CHD) and other vascular events by blood pressure lowering, and uses a factorial design to assess the same endpoints by cholesterol lowering. The impetus for ASCOT was the lack of outcome data on newer types of blood pressure lowering agents, the absence of data on the evaluation of specific combination treatment regimens in hypertension, and the shortfall of CHD prevention using standard therapies based on diuretics and β-blockers. It was also felt that there was a need to evaluate multiple risk factor intervention in the prevention of CHD, as there were few data on the benefits of lipid lowering among hypertensive patients. Pre-study discussions focused on two major issues. Firstly, previous trials investigated the efficacy of diuretic and/or β-blocker-based treatment (together with older drugs, such as methyldopa and hydralazine) in reducing cardiovascular events in hypertensive patients. However, no outcome data was available with two classes of drugs that were being readily accepted into common clinical practice, namely calcium channel blockers and ACE inhibitors.

The second issue focused on the observation from individual studies and subsequent meta-analysis that there was a shortfall in protection against CHD events in hypertensives treated primarily with β-blockers and diuretics. This was in contrast to the impressive evidence for protection against stroke. It quickly became apparent that new trials were needed to compare two or more active treatments. These would require a very large number of patients to address whether CHD outcome depends on the type of drugs used to lower blood pressure. Discussions centred around the comparison of individual drugs as first line treatments, with other drugs added to control blood pressure, or comparing specific treatment regimens using combination therapies. Similar discussions in the USA led to ALLHAT, a study which compares individual drugs with a uniform add-on drug for the treatment of inadequate blood pressure control. The other obvious need was for a trial to compare the standard treatment regimen of diuretic + beta-blocker with a combination of newer agents. So, following on from earlier discussions, the possibility of a factorial design trial was considered, in which additional hypotheses could be tested, such as the benefits of lipid lowering and anti-platelet agents in the hypertensive population. These initial plans did not progress any further until 1991 when a British Hypertension Society Working Party was set up to re-visit the question of such a trial and to seek financial support for the study. The Working Party readdressed the issues discussed previously and proposed a trial design to the annual meeting of the British Hypertension Society in September 1993. This was broadly similar to the earlier proposal for a comparison of individual drugs with a common add-on antihypertensive agent for those patients who failed to achieve adequate blood pressure control with first line therapies. They also ratified the earlier proposal for a factorial design study. At the same time on-going discussions were being held in Scandinavia along the same lines.

In 1995, following discussions between Peter Sever and Neil Poulter (London), and Bjorn Dahlöf and Hans Wedel (Gothenburg), a joint proposal for an outcome study was submitted to Pfizer, who agreed to support a study which later became known as ASCOT. The study outline was announced in 1996 and a Steering Committee was formed. After several meetings a working protocol was agreed and formed the basis of the study which began in early 1998. The primary objective of ASCOT is to assess and compare the long-term effects on non-fatal myocardial infarction and fatal coronary heart disease of a standard anti-hypertensive regimen of a beta-blocker ± a diuretic with a more contemporary regimen of a calcium channel blocker ± an ACE inhibitor. The study also aims to compare the effects of a statin vs placebo among patients with a total cholesterol of 6.5mmol/l on non-fatal myocardial infarction and fatal coronary heart disease. For those with higher cholesterol levels it was felt that contemporary clinical practice dictated the recommendation of lipid lowering therapy, and it would be considered unethical to randomise such patients to placebo, even though in fact they were not receiving active lipid-lowering therapy. The study was designed with large number of secondary and tertiary objectives including, in both the BP and lipid lowering limbs of the trial, an evaluation of the effects of the different treatment regimens on stroke, all cause mortality, heart failure, cardiovascular events and procedures.

It also studied the development of diabetes and renal impairment and focus on major study endpoints in ethnic minority groups and other important subgroups. ASCOT has a prospective randomised open blinded end point design (PROBE). A total of about 19,000 patients have been recruited into a 2X2 factorial trial of an antihypertensive first line regimen of atenolol vs amlodipine to which a thiazide diuretic or the ACE inhibitor perindopril respectively may be added, with cholesterol lowering using atorvastatin vs placebo. It was predicted that 1,150 primary events will occur over a five year follow up period (an annual total CHD event rate of approximately 2%). In the hypertensive limb the study has >80% power at a significance level of 5%, to demonstrate a relative 20% additional benefit of the "new" drug regimen over the older treatment. In the lipid lowering limb there is >90% power with a significance level of 1%, to detect a 30% relative risk reduction on coronary end points of statin vs placebo.

In order to achieve the desired event rate in the trial, hypertensive patients had three additional risk factors for cardiovascular disease, such as smoking, non-insulin dependent diabetes, history of a cerebral vascular or a peripheral vascular disease and microalbuminuria. Therapeutic targets of the study were a blood pressure of less than 140/90 in non-diabetics and less than 130/80 in diabetics with no fixed target for the lipid-lowering limb.

ASCOT Investigators
Peter Sever MB, BChir (Cambridge), MA (Cambridge), MRCP (UK), Ph.D (London), FRCP (London) , FESC 1990, is Professor of Clinical Pharmacology and Therapeutics at Imperial College London, Honorary Consultant Physician at St Marys Hospital, London, and Director of the International Centre for Circulatory Health. After graduating from Cambridge, Professor Sever completed his training at St Marys Hospital Medical School. Following a succession of appointments in general medicine, cardiology and chest diseases, followed by lectureships in medicine and pharmacology, he became an Honorary Consultant Physician and Senior Lecturer in Medicine in the Medical Unit at St Marys Hospital in 1976. In 1980 he was appointed Professor of Clinical Pharmacology and Therapeutics at St Marys Hospital Medical School, which was subsequently incorporated into the Imperial College School of Medicine. During the past decade he established a major research programme in the pathogenesis and treatment of cardiovascular disease. He is Joint Editor in Chief of the Journal of the Renin-Angiotensin-Aldosterone System. He has been a member of the editorial boards of several journals, including the Journal of Hypertension, Journal of Human Hypertension and Clinical Science. Professor Sever is a past-president of the British Hypertension Society and the European Council for Blood Pressure and Cardiovascular Research. He is also a Fellow of the European Society of Cardiology and Chairman of the Fellowships Committee of the British Heart Foundation. His current research interests include all aspects of cardiovascular disease, including the pathophysiology of vascular disease, the evaluation of anti-hypertensive drug therapy and multiple risk factor intervention in hypertensive populations. He is also interested in the epidemiology of hypertension with particular reference to environmental influences on blood pressure, and ethnic differences.

Bjorn Dahlof MD, PhD, FACC, is presently Associate Professor of Medicine at Sahlgrenska University Hospital/Östra in Göteborg, Sweden. Also holds a position as Vice President of the University based clinical trials company Scandinavian CRI AB. Married with 1 child. Studied medicine at University of Göteborg and became MD 1978. Member of the Hypertension Research Group at Sahlgrenska University Hospital/Östra, Göteborg, since 1982. Naval certificate for practising hyperbaric medicine. Research experience mostly in the field of CV medicine in particular hypertension with a special interest in CV disease prevention. A thesis on Pathogenesis and Regression of Structural Cardiovascular Changes in Hypertension, in particular LVH, was defended 1992, became PhD 1994 and FACC 1995. Have published around 200 peer reviewed scientific papers. Previous and present involvement in large mortality-morbidity studies: coordinator of the the two STOP-Hypertension studies, secretary SC of the CAPPP and HOT studies and participated as a SC member of the NORDIL study. Currently chairman of LIFE, co-chairman of ASCOT and SC member in the JIKEI Heart study, ACCOMPLISH study and PRoFESS.

Neil Poulter MBBS MSc FRCP, Professor of Preventive Cardiovascular Medicinis a Director of the International Centre for Circulatory Health, Imperial College London and President of the British Hypertension Society. He co-authored the 1998 and 2005 Joint British Recommendations on Prevention of CHD; 2003 WHO-ISH Statement on Management of Hypertension; 2003 ESH-ESC guidelines for the management of arterial hypertension; 2004 BHS guidelines for management of hypertension. Research interests include the optimal investigation and management of essential hypertension and dyslipidaemia, the association between birth weight and hypertension, the cardiovascular effects of exogenous oestrogen and progesterone, and ethnic differences in cardiovascular disease.

Hans Wedel is Professor of Epidemiology and Biostatistics at the Nordic School of Public Health since the early 1980ies. His special research area is cardiovascular epidemiology and clinical trials. He was the responsible statistician for several large cohort studies in Goteborg during the1970ies. He has been a member of the Steering Committee for 4S, MERIT, CONSENSUS-2, HOT, DIGAMI 1+2, CORONA and ASCOT. He was a member of the Data Safety and Monitoring Committee for STOP I+II, IDEAL, ALERT and EXPRESS.

References

1. 'Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial' Bjorn Dahlof, Peter S Sever, Neil R Poulter, Hans Wedel, D Gareth Beevers, Mark Caulfield, Rory Collins, Sverre E Kjeldsen, Arni Kristinsson, Gordon T McInnes, Jesper Mehlsen, Markku Nieminen, Eoin O'Brien, Jan Ostergren, for the ASCOT investigators. Lancet 2005, Volume 366, DOI:10.1016/S0140-6736(05) - 67185-1

2. 'Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA)' Neil R Poulter, Hans Wedel, Bjorn Dahlof, Peter S Sever, D Gareth Beevers, Mark Caulfield, Sverre E Kjeldsen, Arni Kristinsson, Gordon T McInnes, Jesper Mehlsen, Markku Nieminen, Eoin O'Brien, Jan Ostergren, Stuart Pocock, for the ASCOT investigators Lancet 2005, Volume 366, DOI:10.1016/S0140-6736(05) - 67186-3

3. 'ASCOT background: An International Perspective', by Professor Peter Sever & Professor Björn Dahlöf

4. the ASCOT website: www.ascotstudy.org

Non-aspirin painkillers linked to Hypertension in Nurses' Health Study

Thu, 18 Aug 2005 02:10:00 PST

( from http://www.rxpgnews.com ) Women who consume higher doses of non-aspirin painkillers are much more likely to develop high blood pressure than women who do not use them, according to research reported in Hypertension: Journal of the American Heart Association.

"We sought to investigate whether higher doses of analgesic drugs, specifically acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), and aspirin, increase a woman's risk of developing new-onset high blood pressure," said lead author John Phillip Forman, M.D., instructor in medicine, Harvard Medical School, and associate physician, renal division, Brigham and Women's Hospital, Boston, Mass. "Because high blood pressure is among the most important causes of death and disease in the United States, and analgesics are the most frequently used medications, a relationship between the two would be important from a public health standpoint."

Researchers studied 1,903 women ages 51-77 who participated in the first Nurses' Health Study, and 3,220 women ages 34-53 from the second Nurses' Health Study. The women did not have high blood pressure when the studies began.

Researchers gathered information about whether the women used analgesic drugs, which type, how much, and why they used them, then tracked whether they subsequently developed high blood pressure. The NSAIDs taken were mostly ibuprofen and naproxen.

"In our study, women who took 500 milligrams (mg) or more of acetaminophen per day, on average, were about twice as likely to develop high blood pressure as women who did not use acetaminophen," Forman said.

"In addition, older women (ages 51-77) who used an average of 400 mg or more per day of ibuprofen were about 80 percent more likely to develop high blood pressure compared to older women who did not use this drug. Younger women (ages 34-53) who used more than 400 mg/day of ibuprofen had a 60 percent higher chance of developing high blood pressure," he said.

"We did not find that aspirin increased women's chances of developing high blood pressure," he added.

According to the researchers, doctors are generally aware that NSAIDs have the potential to increase women's blood pressure. However, acetaminophen is perceived as a safe drug without significant effects on blood pressure.

The researchers suggest that these results call for greater caution among women using acetaminophen, ibuprofen and naproxen and more research to investigate the blood pressure effects of acetaminophen.

"More research is needed to confirm our findings," Forman said. "It is important to emphasize that our study is not proof that these drugs will raise blood pressure in all women. Rather, women and their doctors should use caution when using these drugs."

Risk of high blood pressure in salt workers working near salt milling plants

Mon, 25 Jul 2005 17:35:00 PST

( from http://www.rxpgnews.com ) Workers in salt factories, who inhale large amounts of salt particles, are at risk of high blood pressure due to the increased salt intake. A study published today in the Open Access journal Environmental Health shows for the first time that breathing in large quantities of salt particles has just the same effect on blood pressure as eating a salty diet. Wearing face masks and plastic eyeglasses is enough to protect workers who are highly exposed to salt from salt-related high blood pressure.

A high consumption of salt has been shown to be directly linked to high blood pressure and the development of cardiovascular and kidney diseases, which are major causes of mortality worldwide. The European Food Safety Authority recently issued an opinion stating that current salt intakes in Europe far exceed nutritional requirements and may cause adverse health effects.

The present study, conducted by Kripa Haldiya and colleagues from the Desert Medicine Research Centre in Jodhpur, India, provides new data suggesting that inhaling large amounts of salt particles has the same effect as consuming a salty diet and increases blood pressure considerably, thus putting workers in salt factories around the world at risk of high blood pressure. This study represents the first demonstration of an occupational hazard linked to table salt.

Haldiya et al. measured the blood pressure of workers in two salt milling factories in Rajasthan, India. They divided the workers in two groups: one group worked close to the salt milling plant and was directly involved in crushing, grinding, milling and packing salt; the other group worked far away from the salt milling plant and was much less exposed to salt particles. The results of the study show that the first group of workers had a mean systolic blood pressure of 122.1 mmHg, which is significantly higher than the mean systolic blood pressure of 118.8 mmHg measured in the second group. In addition, workers from the first group had an incidence of hypertension of 12.2%, compared with an incidence of 7.0% in the second group. Wearing face masks and plastic spectacles for four days caused the mean systolic blood pressure of workers from the first group to drop significantly from 127.8 mmHg on the first day to 117.5 mmHg on the fourth day.

"This is a new observation, though it is in line with the hypothesis that, after being inhaled, salt may be absorbed from respiratory tract or [] the gastrointestinal tract. Consequent increases in plasma sodium may be responsible for increases in the blood pressure", explain the authors.

Their findings also suggest that workers in factories such as the ones studied could easily protect themselves from the negative effects of exposure to salt particles by wearing face masks and plastic glasses.

Gene therapy to reverse pulmonary arterial hypertension

Sat, 04 Jun 2005 02:02:00 PST

( from http://www.rxpgnews.com ) A University of Alberta research team has discovered important new information they hope will lead to more effective treatments for pulmonary arterial hypertension (PAH)--a deadly form of high blood pressure in the pulmonary arteries caused by uncontrolled cell growth. Therapies are currently limited for a disease that can lead to heart failure and death within a few years.

The researchers have shown that Survivin, a protein almost exclusively expressed in cancer, is also heavily expressed in both human and animal lung arteries with PAH. Survivin is an inhibitor of apoptosis--or programmed cell death--which promotes cancer by suppressing the body's ability to limit excessive cell growth.

Armed with this new information and using animal models, the researchers developed a nebulized and inhaled gene therapy to deliver an inactive Survivin-mutant via a virus--known in science as a "dominant negative construct"--effectively inhibiting endogenous Survivin. The therapy reversed PAH in rats and improved their heart function and their survival, thus holding out some promising avenues of treatment for human PAH. The team members believe that as in cancer, Survivin drives excessive cell growth in the PAH lung blood vessels.

"The most intriguing aspect," explains principal researcher Evangelos Michelakis, "is we've shown for the first time that this cancer protein is also expressed within the blood vessels of the lung in patients suffering with PAH, but not in normal human blood vessels, making survivin a very attractive target for selective intervention.

"This makes the proliferation of lung blood vessels in this disease a 'form of cancer' or a form of neoplasia to be more precise, first proposed by Drs. Voelkel and Tuder from the University of Colorado. We've demonstrated for the first time that, like cancer, apoptosis is suppressed in the lung blood vessel wall in this disease."

"Our biggest challenge in treating PAH is the fact we don't know what makes the cells in the lung blood vessel wall grow excessively," says the University of Alberta cardiology professor and Canada Research Chair holder. "And therapies also have to target the lung blood vessels and spare the normal cells in the rest of the body."

The paper is entitled Gene therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertension. It's published in the June issue of The Journal of Clinical Investigation. In an accompanying editorial entitled Lessons learned from cancer may help in the treatment of pulmonary hypertension, written by French researcher Serge Adnot, the journal stated: "These findings raise important issues regarding the role of survivin in the pathogenesis of PAH, its value as a prognostic indicator, and its use as a target for new therapeutic strategies."

Other authors include: Sean McMurtry, Pulmonary Hypertension Program; Stephen Archer, Canada Research Chair in Translational Cardiovascular Research; Dario Altieri, Department of Cancer Biology and the Cancer Center, University of Massachusetts Medical School; Sebastien Bonnet, Alois Haromy, Gwyneth Harry and Sandra Bonnet, the Vascular Biology Group and Pulmonary Hypertension Program; and Lakshmi Puttagunta, Department of Laboratory Medicine and Pathology, U of A.

The latest research builds on previous work by the group, published a few months ago in Circulation Research, showing that an orally available drug, Dichloroacetate, selectively enhances apoptosis in PAH and thus reverses PAH, prolonging the survival of rats. Because this oral therapy has already been tried in humans with congenital mitochondrial diseases, the team is initiating a clinical trial in human PAH. Similarly, newer drugs that inhibit Survivin, currently in trials in oncology, might also be directly applicable to PAH patients, Dr. Michelakis explains.

ALLHAT findings are 'color blind'

Wed, 06 Apr 2005 13:05:00 PST

( from http://www.rxpgnews.com ) The analysis by race of the "Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial" (ALLHAT), confirms earlier findings that diuretics rather than newer, more expensive drugs such as ACE inhibitors, calcium channel blockers, or beta blockers should be preferred as a first therapy for most patients.

The multi-center ALLHAT study is conducted under a National Institutes of Health contract with The University of Texas Health Science Center at Houston. Barry R. Davis, M.D., Ph.D., professor of biostatistics in the UT School of Public Health is the Principal Investigator and a co-author of the JAMA article.

"There was question whether the diuretics' success with hypertension applied by race because black patients have less success than non-black patients with the ACE inhibitors," said Davis, who also is director of the Coordinating Center for Clinical Trials at the UT School of Public Health. "However the results showed diuretics were as good or better than the newer drugs regardless of race."

The study concludes that diuretics are similar to or superior to newer drugs in lowering blood pressure, in tolerability and in preventing the major complications from high blood pressure. Across both racial subgroups, there was substantially higher risk of heart failure--37 percent--among participants taking calcium channel blockers compared with those on diuretics. When compared to ACE inhibitors, diuretics were more effective in preventing cardiovascular disease, especially heart failure, for all participants and significantly more effective in reducing high blood pressure and preventing stroke in blacks.

"These findings confirm ALLHAT's original conclusion that diuretics should be the preferred initial therapy for high blood pressure," Davis said.

The kidney is only part of the blood pressure problem

Sun, 03 Apr 2005 13:11:00 PST

( from http://www.rxpgnews.com ) Abnormal blood pressure is a widespread problem thought to be triggered by changes in the kidney. More recent studies have shown that vascular function can also affect blood pressure.

In a paper appearing in the April 1 issue of The Journal of Clinical Investigation, Thomas Coffman and colleagues at the Durham VA Medical Center explore the relationship between the kidney and non-kidney tissues in mice with low blood pressure.

The mice lack a receptor (AT1) to a protein called angiotensin, which regulates blood pressure. The authors provide direct evidence that actions of AT1 receptors both inside and outside the kidney each contribute to determining the level of blood pressure.

In an accompanying commentary, Michael Mendelsohn states that the findings have "important implications for the ways we diagnose and treat blood pressure disease in humans."

Implanted medical device Rheos System aims to lower blood pressure

Sun, 03 Apr 2005 11:41:00 PST

( from http://www.rxpgnews.com ) Doctors at the University of Rochester Medical Center are the first in the nation to implant an investigational medical device that lowers blood pressure by activating the body's natural blood pressure regulation systems.

"The Rheos System works by electrically activating the baroreflex system based in the carotid arteries in the neck, regulating blood pressure in a manner similar to a pacemaker regulating heart rhythm," Illig says. "Low-level electrical stimulation to this area sends signals to the brain, 'telling' it to take action to lower blood pressure through a variety of mechanisms, including blood vessel dilatation, heart rate reduction, and promotion of fluid excretion by the kidneys. In this way, the Rheos System provides a physiologic approach to reducing high blood pressure by allowing the brain to direct the body's own control mechanisms."

"This device, if found effective, would offer a way to lower blood pressure in patients who have not been able to control their blood pressure with medications, and could conceivably reduce the need for pressure-lowering medications in patients with lesser degrees of hypertension," Illig says.

The Rheos system consists of a battery-powered implantable generator, which is inserted under the skin near the collarbone, and two carotid sinus leads, which run from the generator to the left and right carotid sinus in the neck. While implantation is slightly more involved, the general principle is quite similar to the implantation of cardiac pacemakers.

Following the Phase II trial, if results continue to be good, a larger, nationwide trial will begin.

Trial patients receive the device as part of a minimally invasive surgical procedure, followed typically by a one- or two-night stay in the hospital. The device initially will be tested for effect in the operating room and then turned off for one month, to ensure there are no health problems associated with the implant. At one month, a graduated scale of stimulation will be applied until the best possible blood pressure response is achieved. Patients will be evaluated on a regular schedule until the device receives FDA approval, and generally will be followed for life.

"Findings from this study could have a significant impact on how we are able to treat hypertensive patients in the future," Illig says. "We are honored that the University of Rochester can be at the forefront of this technology."

Two-part blood pressure control suggests new approach

Sun, 03 Apr 2005 11:39:00 PST

( from http://www.rxpgnews.com ) The kidneys have long been known to play a major role in many cases of high blood pressure, but a new study by researchers at Duke University Medical Center reveals that the body's control of blood pressure depends as much on other organs in the body. The researchers said the findings about a "two-part system" may lead to improved methods for treating high blood pressure, which affects nearly one in three American adults.

The findings further suggest how the underlying causes of high blood pressure may vary among patients, with some cases resulting from kidney abnormalities and others from abnormalities in other areas, such as the blood vessels, researchers said. Such differences might lead to variability in the response of patients to particular treatment regimens. For example, it might explain why reductions in dietary salt effectively lower blood pressure for some people, but not others, they said.

Through a series of kidney transplantation experiments involving both normal mice and mice in which a critical molecular component of blood pressure regulation had been rendered nonfunctional, the researchers found clear evidence that the kidneys and other systemic tissues have distinct and equally important roles in controlling blood pressure. The researchers report their findings in the April 1, 2005, issue of the Journal of Clinical Investigation.

The findings provide new insights into how the kidney interacts with other organs to control blood pressure, said the researchers. These insights may augment scientists' understanding of how common blood pressure medications work and lead to improved treatments for hypertension and its complications, including stroke and organ failure, they added.

"Our study provides the first direct evidence that the job of blood pressure regulation is split into two parts that controlled by the kidneys and that controlled by other systems throughout the body," said Thomas Coffman, M.D., chief of nephrology at Duke University Medical Center and the Durham VA Medical Center and lead author of the study.

"Many people with high blood pressure take multiple medications -- each with its own side effects -- to control blood pressure," Coffman added. "As we understand more precisely the molecular basis for blood pressure control, we might identify novel therapies for hypertension that better prevent organ failure."

Scientists have long thought that blood pressure abnormalities are tied closely to changes in the kidneys that affect salt excretion.

"The prevailing view holds that the kidneys play a dominant role in the maintenance of blood pressure," Coffman said. "While abnormalities in other elements, such as the blood vessels, might perturb the system, it's been thought that the kidneys could adjust accordingly to normalize blood pressure."

Within the kidney, evidence has shown that proteins called type 1 angiotensin (AT1) receptors are integral to salt excretion and blood pressure control, Coffman said. Mice lacking the receptors exhibit low blood pressure and profound salt sensitivity, he said. Furthermore, drugs that block the function of AT1 receptors and their binding protein angiotensin II so-called angiotensin receptor blockers and ACE inhibitors effectively treat patients with hypertension.

However, the presence of AT1 receptors in tissues throughout the body, including the heart, blood vessels and brain, has made it difficult to pinpoint the proteins' roles in individual tissues, Coffman said.

To clarify the function of AT1 receptors, the researchers transplanted the kidneys of normal mice into mice in which the AT1 receptor had been rendered nonfunctional, and vice versa. Mice with AT1 receptor defects only in the kidneys exhibited low blood pressure, they found.

However, mice with the opposite condition having the AT1 receptor defect everywhere but the kidneys exhibited a nearly identical drop in blood pressure, the team reported.

Further study indicated that the receptors in the kidneys versus other parts of the body carry out distinct, though equally, important roles. For example, when fed a high salt diet, mice without AT1 receptors in their kidneys exhibited a significant increase in blood pressure. However, mice with normal kidneys that lacked the receptors in other tissues tolerated dietary increases in salt and maintained blood pressures comparable to mice fed a normal diet.

"These findings indicate that angiotensin receptors in the kidney have unique and non-redundant actions in blood pressure control," Coffman said. "However, receptors outside the kidney also make a unique contribution to blood pressure homeostasis that is virtually equivalent to and independent of their actions within the kidneys."

The results illustrate the complexity of blood pressure regulation and suggest that maximal efficacy of hypertension drugs, including ACE inhibitors and angiotensin receptor blockers, requires complete blockade of receptors in both the kidney and outside of the kidney.

The findings further suggest that the degree of salt sensitivity exhibited by patients with high blood pressure might be explained by the level of involvement of the kidneys compared to other organs, Coffman said.

While the findings confirm an important role for both the kidneys and other tissues in maintaining normal blood pressure, further research is required to examine their relative roles in mice with high blood pressure, the researchers said.

Garlic protects against Pulmonary Hypertension

Sun, 03 Apr 2005 10:33:00 PST

( from http://www.rxpgnews.com ) Small daily doses of allicin, the active metabolic in garlic, proved effective in preventing a severe form of pulmonary hypertension in rats, according to a study reported Saturday, April 2 by University of Alabama at Birmingham researchers at the Experimental Biology 2005 meeting in San Diego. The human form of the disease primary pulmonary hypertension often leads to cardiovascular complications such as right heart hypertrophy and failure and is frequently lethal.

Dr. David D. Ku says the findings confirm an earlier study by the team that garlic protects against a less lethal form of acute pulmonary hypertension in rats. The new study by Ku, graduate student Hsien Chin Wu and research assistant Xiaowei Sun, not only looks at a chronic form of the disease but also goes a big step further by pinpointing the effective ingredient in garlic and demonstrating that it achieves its protective effects through vasorelaxation.

The presentation at Experimental Biology 2005 was part of the scientific sessions of the American Society for Pharmacology and Experimental Therapeutics.

In the UAB study, rats were given a single dose of monocrotaline, a well-established mechanism for inducing vasoconstriction of the pulmonary arteries. Within three weeks, half the rats had developed chronic pulmonary hypertension, with markedly increased pulmonary arterial pressure, just as expected. But the other half experienced no such increase. These rats had received the hypertension-causing drug but their diets also had been supplemented daily for three weeks with small doses of allicin. And it was the allicin, not the garlic itself that protected the supplemented rats from developing the disease, emphasizes Dr. Ku. Animals that consumed garlic from which the active metabolite had been removed or inactivated with heat experienced no benefit.

In a separate but related study also presented at Experimental Biology 2005, in the scientific sessions of the American Society for Pharmacology and Experimental Therapeutics, Dr. Ku's team found that garlic treatment also could protect coronary vascular function and lessen the severity of right heart hypertrophy, two of the serious byproducts of chronic pulmonary hypertension.

Garlic has long been thought to have medicinal properties, and reports have suggested that garlic supplementation in humans could help lower blood pressure, decrease ischemic injury, reduce serum cholesterol, inhibit platelet function and enhance thrombolysis. Garlic also has been suggested to improve arterial oxygenation associated with pulmonary dysfunction in patients with hepatopulmonary syndrome. However, obtaining concrete scientific data to substantiate many of these claims has remained elusive, notes Dr. Ku, in part because it has been difficult to accurate detect and quantify the active garlic metabolite.

Recently the UAB team developed a new highly effective method for doing just that, for quantifying the actual amount of metabolite included in treatments. In what the researchers describe as a "very simple" analytical method, reversed-phased high performance liquid chromatograph method is coupled to mass spectrometry with multiple ions reaction monitoring. Using this method, the team has been able to demonstrate that varying concentrations of garlic active metabolite from either pure allicin, freshly crushed garlic, or commercial freeze-dried garlic preparations, directly correlate to the extent of their vasorelaxation/vasodepressor responses in isolated pulmonary arteries and in living animals.

What does this mean for human diets? Dr. Ku says studies are needed to prove similar beneficial effects from the allicin in garlic will occur in humans his new method should make such studies a little easier but in view of the low toxicity associated with eating garlic, including garlic in one's daily food intake seems a reasonable approach, especially for people with respiratory and pulmonary ailments. The amount of garlic that delivered the protective effects to the rats in his study was the equivalent, for humans, of two cloves of garlic a day.