RxPG News : CAD

Nanoparticles - possible alternative to drug eluting stents

Mon, 18 Jan 2010 14:00:58 PST

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Mon, 13 Jul 2009 15:45:29 PST

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

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

Delayed enhancement cardiovascular magnetic resonance to detect non-Q wave heart attacks

Sat, 25 Apr 2009 15:09:44 PST

( from http://www.rxpgnews.com ) In a paper published by PLoS Medicine, Han W. Kim and colleagues from the Duke Cardiovascular Magnetic Resonance Center, United States of America, use a recently developed technique to detect heart damage in patients who don't have symptoms or abnormalities in the electrocardiogram (ECG) that are usually associated with a heart attack ( myocardial infarction ). They show that the prevalence of this type of heart attack which doesn't display ECG abnormalities is more than three times higher than heart damage which does display ECG abnormalities.

Although coronary artery disease is the leading cause of death among adults in developed countries, up to 40 60% of heart attacks are not preceded by typical symptoms and are not immediately identified by patients or physicians, if at all. Therefore, these heart attacks are known as unrecognized myocardial infarctions (UMIs). The diagnosis of UMI is currently based on the appearance of changes in the ECG, leading to so-called Q-waves . However, not all UMIs result in Q-waves. Han Kim and colleagues therefore used a technique known as delayed enhancement cardiovascular magnetic resonance (DE-CMR) to detect heart damage in patients whose Q-waves were absent.

The researchers studied 185 patients with suspected coronary artery disease but with no history of heart attacks. They then followed the patients for 2 years to discover whether a diagnosis of non-Q-wave UMI predicted their likelihood of dying from any cause including from a heart problem. They found that non-Q-wave UMI occurred more than three times as often in patients with suspected coronary artery disease than Q-wave UMI. They also found that patients with this silent heart damage had an 11-fold higher risk of death from any cause and a 17-fold higher risk of death from a heart problem than patients without heart damage.

The clinical implications of the study are discussed in an expert commentary by Clara Kayei Chow from the Population Health Research Institute, McMaster University, Canada, and The George Institute for International Health, University of Sydney, Australia, who was not involved in the study. This important new study has two key clinical implications. First, previous non-Q-wave UMI is potentially being missed in patients with suspected coronary artery disease. Second, non-Q-wave UMI is important because it is significantly associated with increased mortality, she says. She also points out, however, that the results are from a small select group of patients and that further studies need to be done to evaluate the determinants of the increased mortality in patients with non-Q wave UMI. In addition the study will need repeating in other groups of patients. Finally, two of the authors are named on a US patent on the technique used in this study, Delayed Enhancement CMR. The patent itself is owned by Northwestern University.

Post-arrest survival better in high volume hospitals

Sat, 10 Jan 2009 09:37:19 PST

( from http://www.rxpgnews.com ) Efforts to fight the toll of cardiac arrest have typically focused on pre-hospital factors -- bystander CPR education and improvement, public defibrillation programs, and quicker EMS response. But new research from the University of Pennsylvania School of Medicine reveals that the hospital where patients are cared for after being resuscitated plays a key role in their chances of survival following these incidents, which takes the lives of more than 300,000 Americans each year.

Patients in large, urban, and teaching hospitals are more likely to survive compared to those in small, often rural, non-academic hospitals, according to a study published recently in the journal Intensive Care Medicine. A second study, published in Resuscitation, suggests that patients who are cared for in the highest volume intensive care units after cardiac arrest are also most apt to survive. The findings points to a need to explore the development of specialized, regional post-cardiac arrest care centers modeled after those that treat serious trauma patients, says lead author Brendan Carr, MD, an assistant professor of Emergency Medicine and Epidemiology, and associate director of the Division of Emergency Care Policy & Research.

Carr's findings also underscore the importance of the recent move by New York City to require ambulances to take cardiac arrest patients to hospitals that provide therapeutic hypothermia -- the so-called "cooling" therapy that protects against damage to the brain and other organs in the crucial hours after the heart is restored to its normal rhythm -- even if those facilities are further away.

"We are describing the variability that exists in cardiac arrest outcomes – not at the level of the patient but at the level of the hospital. Hospitals with more resources and hospitals with higher volumes have better outcomes," Carr says. "There are two possible implications: Either we need to get everyone up to speed on how to optimize survival, or we need to selectively transfer patients to hospitals that have expertise in the post-arrest period."

The two studies, which examined a combined 115,000 cases in two different national datasets, also point to an overall improvement in cardiac arrest care. Over the course of the five years studied, the authors found a small reduction in mortality that translates to about 11,000 additional lives saved per year -- a significant decrease for a condition that is typically fatal. Better survival odds are multifactorial, but likely related to advances in critical care, the recognition of the role of hypothermia, and the creation of national guidelines for post-cardiac arrest care.

"There has been a fundamental shift such that we now recognize the condition patients experience after cardiac arrest as a treatable disease," says senior author Robert Neumar, MD, PhD, associate professor of Emergency Medicine and associate director of Penn's Center for Resuscitation Science, and Chair of the Advanced Cardiac Life Support Subcommittee for the American Heart Association. "Among the patients that regain a pulse after cardiac arrest, only one out of three survive to hospital discharge, and there appears to be significant variability among hospitals. Further research is needed to determine if this variability in outcome is caused by the quality of post-cardiac arrest care. If it is, we need to identify best practices and develop mechanisms to deliver optimal care for all patients."

Carr and his colleagues say further study of post-cardiac arrest care among these large, urban, and teaching hospitals will be crucial in mapping strategies that maximize a patient's chances to be discharged without the neurological deficits that often plague cardiac arrest survivors. And he emphasizes that practitioners can learn lessons from the connections between the way hospitals care for patients with cardiac arrest and other emergent conditions.

"For me, cardiac arrest is the tip of the iceberg with respect to disparities in care for time-sensitive conditions," Carr says. "Whether you've had a cardiac arrest, a stroke, or a heart attack, it is our job to build a system that promises you the best possible care no matter where you are, who you are, or what time of day it is."

New European guidelines on the management of ST segment elevation myocardial infarction

Sun, 16 Nov 2008 09:03:37 PST

( from http://www.rxpgnews.com ) New European guidelines on the management of heart attack emphasise speed of action and the importance of "reperfusion" therapy to restore blood flow to the heart and improve survival rates. "A well-functioning regional system of care... and fast transport to the most appropriate facility is key to the success of the treatment," state the guidelines, which have been developed by a Task Force of the European Society of Cardiology (ESC).

Professor Frans Van de Werf (Leuven, Belgium), chairman of the Task Force, describes the guidelines as "important" and says their broad uptake and adoption would make a "huge difference" to heart attack survival rates.

The new guidelines cover management of a common type of classical heart attack known as STEMI (ST-segment elevation acute myocardial infarction), a reference to its appearance on an ECG. Around one-third of all acute coronary events are diagnosed as STEMI.

Although precise numbers are missing, it is likely that 30-50 per cent of victims of heart attack die before reaching the hospital, most of them in the first hours after the onset of symptoms. While this fatality rate has remained fairly constant in recent years, survival rates in hospital have markedly improved – from a rate of 75 per cent in the 1960s to around 95 per cent today. The introduction of coronary care units, new techniques of coronary intervention and treatments to dissolve blood clots (thrombolysis) have all improved in-hospital care.

The principal features of the new guidelines – and the major changes since the previous edition of 2003 – relate to emergency systems and a speedy emphasis on reperfusion therapy, performed either by "percutaneous coronary interventions" (PCI, with balloon angioplasty and stent) or thrombolysis treatment (with clot-dissolving drugs).

Key to management, say the guidelines, is early diagnosis and risk assessment after "first medical contact" (FMC).

Primary PCI is the "preferred treatment" if available within two hours of FMC.
If PCI is not possible within two hours, pre- or in-hospital thrombolysis should be performed as soon as possible after FMC (and within 30 minutes at the latest).

The guidelines state: "Primary PCI is deﬁned as angioplasty and/or stenting without prior or concomitant thrombolytic therapy, and is the preferred therapeutic option when it can be performed expeditiously by an experienced team." The shorter the delay, the better the outcome – and FMC-to-balloon should be within two hours "in all cases". However, the guidelines add that only hospitals with an established interventional cardiology programme – 24/7 - should use primary PCI.

The guidelines also recommend that most patients following successful thrombolysis should be routinely referred for angiography, a technique whereby the condition of the coronary arteries and heart muscle can be assessed and long-term risks and treatments determined.

Professor Van de Werf concedes that not all hospitals nor all regions have the emergency networks or PCI facilities recommended in the guidelines. Indeed, current registry data suggest that around 20-30 per cent of all STEMI patients in Europe still receive no reperfusion therapy. However, adherence to the guidelines, he suggests, could "dramatically" improve STEMI patient survival.

The ambulance is also crucial to improving survival rates – for speedy transfer, defibrillation if needed, diagnosis by ECG, early thrombolysis therapy if needed, and early alert to the hospital. The guidelines recommend that an ambulance should be available within 15 minutes of a call and all should be equipped with 12-lead ECG. Also recommended is that the techniques of basic life support should be part of the school curriculum.

Bivalirudin during primary angioplasty better than heparin and glycoprotein IIb/IIIa inhibitors (GPI).

Sat, 24 May 2008 11:38:05 PST

( from http://www.rxpgnews.com ) A study led by Gregg W. Stone, M.D., professor of medicine at Columbia University Medical Center/NewYork-Presbyterian and chairman of the Cardiovascular Research Foundation, has shown that heart attack patients who were administered the direct thrombin inhibitor bivalirudin during primary angioplasty had a reduced rate of adverse clinical events, a lower rate of major bleeding, and a lower mortality rate than those who were treated with a regimen of heparin and glycoprotein IIb/IIIa inhibitors (GPI).

In the landmark global trial, bivalirudin was compared to heparin plus GPI in more than 3,600 patients with ST-segment (a specific electrocardiogram wave) elevation myocardial infarction (STEMI), the most severe form of heart attack. The findings from the trial are presented in the May 22, 2008 issue of the New England Journal of Medicine.

The HORIZONS-AMI trial is a prospective, single-blind, randomized, multicenter study conducted in 11 countries. A total of 3,602 patients undergoing angioplasty were randomly assigned to receive either bivalirudin with provisional use of GPI or heparin plus GPI. The two primary endpoints of the trial were major bleeding and net adverse clinical events, a composite of major adverse cardiovascular events (death, reinfarction, stroke or ischemic target vessel revascularization) or major bleeding at 30 days. The secondary endpoint was major adverse cardiovascular events at 30 days. Those patients receiving bivalirudin within 30 days had significantly reduced net clinical adverse events by 24 percent, as well as reduced the risk of overall mortality by 33 percent and cardiac mortality by 38 percent, when compared to a regimen of heparin and GPI.

“The HORIZONS-AMI data show that using bivalirudin instead of heparin with a GPI during angioplasty increases survival in heart attack patients who are at high risk for death or disability,” Dr. Stone said. “As the first multicenter randomized primary angioplasty trial since the introduction of balloon angioplasty to show improved survival, we expect HORIZONS-AMI to have an immediate impact on which drug therapy cardiologists choose for their patients with heart attack.”

HORIZONS-AMI is the largest study ever to focus on the appropriate use of anticoagulant medications in patients experiencing STEMI and undergoing primary percutaneous coronary intervention (PCI). Only 7.2 percent of patients in the bivalirudin group received provisional GPI. The study also found that bivalirudin significantly reduced rates of major bleeding by 40 percent and demonstrated comparable rates of major cardiovascular adverse events. Bivalirudin has previously been shown to result in less bleeding and similar rates of composite ischemia compared to heparin plus GPI in patients undergoing angioplasty for stable angina, unstable angina and non-ST-elevation myocardial infarction (NSTEMI).

Dr. Stone emphasized the importance of reducing the risk of bleeding. “In multiple previous trials, major bleeding has been shown to be a strong predictor of short and long-term mortality in patients undergoing angioplasty and in those with acute coronary syndromes,” he said.

Intermittent hypoxic treatment for reduced myocardial infarction and lethal arrhythmias

Sat, 24 May 2008 11:27:23 PST

( from http://www.rxpgnews.com ) Researchers at the University of North Texas Health Science Center, Fort Worth, Texas have demonstrated that, contrary to prevailing dogma, hypoxia can be remarkably beneficial to the heart. These discoveries, to be reported in the June 2008 issue of Experimental Biology and Medicine, may lead to a new paradigm to protect hearts of patients at risk of coronary disease. Hypoxia is generally considered harmful to the heart, since a steady supply of oxygen is required to maintain cardiac function. However, this research has demonstrated that a 20 day program of brief, repetitive, moderate reductions in the amount of oxygen in the arterial blood induce adaptations which increase the heart’s resistance to the more severe insult of a heart attack. In particular, intermittent hypoxic treatment of dogs remarkably reduced myocardial infarction and lethal arrhythmias following coronary artery occlusion and reperfusion.

The research team, led by Robert T. Mallet, Associate Professor of Integrative Physiology, H. Fred Downey, Regents Professor of Integrative Physiology, and doctoral student Myoung-Gwi Ryou explored mechanisms that may be responsible for this remarkable cardioprotection. Specifically, the investigators tested the hypothesis that intermittent hypoxia treatment suppressed harmful over-production of nitric oxide, the precursor of a host of toxic compounds, by heart tissue upon coronary artery reperfusion. One day after completing 20 days of intermittent hypoxia treatment, dogs were anesthetized and a coronary artery was surgically obstructed for 60 minutes, and then the obstruction was removed and artery was reperfused. An explosive burst of cardiac nitric oxide production occurred during the first few minutes of reperfusion in untreated dogs, but this harmful burst was considerably dampened in hypoxia-treated dogs, without compromising recovery of coronary blood flow. Hypoxia treatment also suppressed cardiac activity of nitric oxide synthase (NOS), the enzyme that produces nitric oxide, as well as the heart’s content of the principal NOS isoform, endothelial NOS.

According to Dr. Mallet, “reduced NOS activity may contribute to the cardiac benefits of hypoxia treatment by decreasing formation of a free radical, superoxide, as well as nitric oxide. Both of these compounds are produced by NOS. When these two compounds are produced simultaneously, they combine to form peroxynitrite, an extremely aggressive chemical by-product that injures the heart by damaging the molecular components of cells. By decreasing NOS activity in the heart, hypoxia treatment could minimize formation of peroxynitrite and other harmful products of nitric oxide and superoxide.”

“Intermittent hypoxia treatment may be a powerful adjunctive therapy for patients at risk of heart disease” says Dr. Downey. “The brief periods of moderate hypoxia are easily tolerated by most people, require neither surgery nor expensive medications, and can be administered by the patient at home or work using available devices. Indeed, intermittent hypoxia has been used for several decades in Eastern Europe to treat heart and neurological diseases and high blood pressure.” Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine stated “This study by Robert Mallet and colleagues may suggest a simple treatment to minimize the impact of a heart attack and should stimulate further study of this phenomena”.

MDCT accurate in detecting stenosis in calcified coronary artery plaque

Fri, 11 Apr 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Multidetector CT angiography can accurately predict the presence of obstructive disease (stenosis) in small and moderate-sized calcified coronary artery plaque (CAP), and is even fairly accurate in diagnosing large and heavily calcified CAP, according to a recent study conducted by researchers at Thomas Jefferson University Hospital in Philadelphia, PA.

The study evaluated 31 patients who had one or more calcified CAP, comparing the results from CCTA to cardiac catheterization. “It is commonly believed that when coronary artery plaque is calcified, (particularly when it is heavily calcified), MDCT is unreliable in determining the degree of stenosis,” said David C. Levin, MD, lead author of the study. However, in this study CCTA and cardiac catheterization were concordant in 58 of 61 small calcified CAPs (95%), 20 of 22 moderate-sized (91%) and 29 of 43 large calcified CAPs (67%). The study showed that overestimation of stenosis occurred in 2 of the small lesions, 2 of the moderate-sized lesions and 14 of the large lesions.

“The results indicate that even when heavily calcified plaque is present, MDCT is pretty accurate in determining how much vessel narrowing it has caused. However, we have to recognize that when large and heavily calcified plaques are seen on MDCT, we tend to overestimate the degree of stenosis that results. This overestimation seems to be unavoidable in many cases,” said Dr. Levin.

Clopidogrel does not increase postoperative bleeding risk in patients with Acute Coronary Syndrome

Wed, 05 Sep 2007 08:39:22 PST

( from http://www.rxpgnews.com ) Aspirin combined with clopidogrel is the treatment of choice for acute coronary syndromes. Although the maintenance of aspirin until surgery does not affect postoperative bleeding after coronary artery bypass graft (CABG) surgery, the latter may be dramatically increased when clopidogrel is continued over a period of 5 days preoperatively.

This prospective observational study included 217 consecutive patients scheduled for first-time CABG. Postoperative bleeding and blood transfusion requirements were compared (equivalence) between patients pretreated during a period of 5 days prior surgery by either aspirin alone (n = 157) or combined with clopidogrel (n = 60).

Aprotinin was systematically used in all these patients considered as high risk for bleeding.

The authors found no significant difference between both groups concerning the preoperative characteristics except for unstable angina (33 vs. 19%, P = 0.02) and left main coronary artery stenosis (27 vs. 13%, P = 0.02), which were more frequent in patients receiving clopidogrel.

The median chest tube output was similar in both groups 24 h postoperatively at 350 mL (95% CI 150–850) vs. 375 mL (95% CI 175–875), and the difference between groups (7%, 95% CI –9 to 22) did not encompass the predetermined margins of equivalence (25%). No significant difference was found on blood transfusion use (38 vs. 38%, P = 0.99). After adjustment by a propensity score, it was found that clopidogrel was not associated with an increased risk of excessive bleeding.

The sudy concluded that in patients undergoing first-time CABG and treated prophylactically with aprotinin, aspirin and clopidogrel may be continued until surgery without increasing postoperative bleeding or transfusion requirements.

British Cardiovascular Society's Report comments on the future of Coronary Angiography

Wed, 05 Sep 2007 06:39:26 PST

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

A report from the British Cardiovascular Society Working Group throws light on the future of coronary angiography - a technique which is at present, the most popular test among the physicians in the diagnosis and management of the ischemic heart disease.

Coronary angiography has been the gold standard for determining the severity, extent and prognosis of coronary atheromatous disease for the past 15–20 years. However, established non-invasive testing (such as myocardial perfusion scintigraphy and stress echocardiography) and newer imaging modalities (multi-detector x ray computed tomography and cardiovascular magnetic resonance) now need to be considered increasingly as a challenge to coronary angiography in contemporary practice. An important consideration is the degree to which appropriate use of such techniques impacts on the need for coronary angiography over the next 10–15 years.

This review aims to determine the role of the various investigation techniques in the management of coronary artery disease and their resource implications, and should help determine future service provision, accepting that we are in a period of significant technological change.

ACC/AHA Release Revised Guidelines for the Management of Unstable Angina and NSTEMI

Fri, 31 Aug 2007 17:34:56 PST

( from http://www.rxpgnews.com ) The American College of Cardiology and the American Heart Association have jointly released revised Guidelines for the Management of Patients with Unstable Angina (UA)/Non-ST- Elevation Myocardial Infarction (NSTEMI).

Major changes to the guidelines include: suggesting an initial non-invasive set of preliminary tests, such as a stress test, echocardiogram or radionuclide angiogram; recommending the use of anti-platelet therapy clopidogrel for at least 1 year after receiving a drug-eluting stent; highlighting the importance of more intense lipid and blood pressure control; and advising cessation of non-steroidal anti-inflammatory drugs (NSAIDS) use for all UA/NSTEMI patients during hospitalization.

Coronary artery disease (CAD) is the leading cause of death in the United States, and UA and NSTEMI are acute manifestations of this condition. In 2004, the National Center for Health Statistics reported 669,000 hospitalizations for UA and 896,000 for myocardial infarction (MI).

Unstable angina, which causes chest pain and discomfort, occurs when a coronary artery is partially blocked. Myocardial infarction, or heart attack, occurs when a coronary artery is completely blocked, cutting off blood flow to the heart resulting in death of heart muscle.

The ability to detect and treat these conditions earlier has greatly improved over the last several years.

"New evidence from pivotal trials over the past five years has been gathered together in these guidelines to give physicians up-to-date and detailed information on which treatment options will provide the best possible outcomes for their patients," said Nanette K. Wenger, MD, FACC, FAHA, a member of the guidelines writing committee and professor of medicine in the Division of Cardiology at Emory University School of Medicine in Atlanta. "This is a major educational document for health professionals, and I trust it will become part of the core teaching for medical students, residents and graduate physicians."

The guidelines, which were last published in 2002, have been developed for cardiovascular specialists, emergency room physicians and healthcare professionals who evaluate and treat patients with acute coronary syndrome. They focus on the diagnosis, treatment and management of patients with UA and the closely related condition of NSTEMI.

The 2002 guidelines recommended an early invasive strategy -- diagnostic angiography and revascularization – as the way to treat UA/NSTEMI patients. The revised guidelines differentiate more extensively between high- and low-risk UA/NSTEMI groups, and recommend an early invasive strategy for unstable and high-risk patients, with an initial conservative (non-invasive) strategy -- stress test, echocardiogram or radionuclide study -- as a possible treatment option in stabilized UA/NSTEMI patients and low-risk patients. Risk status is determined by risk scores.

For clinical practitioners, the revised guidelines emphasize secondary prevention, recommendations that should be continued after the UA/NSTEMI patient is discharged from the hospital to reduce risk of a recurrent heart attack.

"We are emphasizing the use of ACE inhibitors -- drugs that protect the muscle – and prescribing aldosterone receptor blockade, a new drug category that wasn't available previously for people with heart failure," Wenger said. "High-dose antioxidant vitamin supplements such as beta carotene, vitamins E and C and folic acid for secondary prevention are no longer recommended because results from clinical trials have shown no benefit and possible harm." There is also a greater emphasis on smoking cessation.

Also new in the guidelines is the call for more intense lipid and blood pressure control. More stringent LDL cholesterol-lowering therapy and blood pressure management is recommended for UA/NSTEMI patients. LDL should be lower than 100 mg/dL and ideally reduced to 70 mg/dL. Blood pressure should be lower than 140/90 and for those with diabetes or chronic kidney disease, a reading lower than 130/80 is recommended.

Because platelets are thought to play a key role in recurrent heart attack, the anti-platelet therapy clopidogrel is now recommended for at least one year after placement of a drug-eluting stent and shorter term for bare metal stent and with medical therapy. "In addition, we are emphasizing the value of intensive, long-term platelet therapy," Wenger said.

Additional updates to the guidelines include recommendations to discontinue the use of hormone replacement therapy in postmenopausal women; add troponin biomarkers as markers of cardiac damage and B-type natriuretic peptide (BNP) markers as potentially useful for cardiac risk assessment; and stop the usage of non-steroidal anti-inflammatory drugs (NSAIDS) for all UA/NSTEMI patients during hospitalization.

"Lite" cigarettes impair blood flow through the heart as severely as regular cigarettes

Mon, 14 May 2007 20:11:47 PST

( from http://www.rxpgnews.com ) Low tar "lite" cigarettes impair blood flow through the heart as severely as regular cigarettes, reveals a small study published ahead of print in the journal Heart.

The findings are based on 62 people in their mid 20s, with no evidence of coronary artery disease.

Twenty had smoked low tar, low nicotine cigarettes (8 mg tar, 0.6 mg nicotine, and 9 mg carbon monoxide) for at least three years.

Twenty others had smoked regular cigarettes for the same period (12 mg tar, 0.9 mg nicotine, and 12 mg carbon monoxide), and the remainder were non-smokers.

Cigarette smoking is responsible for a fifth of all deaths from cardiovascular disease and triples the risk of heart failure in later life.

All participants were assessed for cardiovascular fitness, and in the case of the smokers, these tests were carried out two days before and 30 minutes after smoking two of their usual cigarettes within the space of 15 minutes.

The researchers focused on coronary flow velocity reserve (CFVR), which is a measure of how readily coronary arteries can dilate in response to increased blood flow.

The two groups of smokers were similar in terms of their general health and the number of cigarettes they regularly smoked.

The test results showed that blood pressure and heart rate both climbed after smoking, irrespective of cigarette type.

Similarly, CFVR, which was already lower in both groups of smokers than it was in the non-smokers, fell further still after smoking. This was irrespective of cigarette type.

CFVR fell sharply from 2.68 to 2.05 in the low tar smokers, and from 2.65 to 2.18 in the regular tar smokers. The CFVR was 3.11 in the non-smokers.

The authors say their results show that both light cigarettes and regular cigarettes impair blood flow through the coronary arteries to a similar degree. They add that many smokers switch to low tar, low nicotine cigarettes in the mistaken belief that they will reduce some of the hazardous effects of smoking.

Aspirin less effective for women than men

Sat, 28 Apr 2007 12:10:35 PST

( from http://www.rxpgnews.com ) A new study shows that aspirin therapy for coronary artery disease is four times more likely to be ineffective in women compared to men with the same medical history.

Historically, studies have shown that aspirin therapy is less effective in women than in men, but it has remained unclear how much less effective and whether this affects patient outcomes, said Michael Dorsch, clinical pharmacist and adjunct clinical instructor at the University of Michigan College of Pharmacy.

Dorsch is the lead author of the paper, "Aspirin Resistance in Patients with Stable Coronary Artery Disease," which appears online today in the Annals of Pharmacotherapy.

Originally, Dorsch and his team set out to determine if patients with a history of heart attacks were more apt to be aspirin resistant than those with coronary artery disease but no history of heart attack. They found that gender and not medical history was a predictor for aspirin resistance, Dorsch said. The results surprised him.

"I was surprised by how big of a difference it was for females," said Dorsch, who has appointments at the U-M Health System and the U-M College of Pharmacy, and started the study as a resident at the University of North Carolina. "This is another piece of information that affirms we need more studies in women."

Aspirin therapy is a cornerstone in managing heart disease because it inhibits blood clotting. Aspirin therapy can reduce the risk of a nonfatal heart attack or stroke by about 23 percent, and an estimated 20 million men and women take a low dose of aspirin (81-325 mg daily) to control heart disease. But despite its effectiveness, there is evidence that aspirin is less effective in some patients, and researchers don't really know why. This can be frightening because most doctors do not check for aspirin resistance before prescribing aspirin therapy and therefore presume it's working in the patient when it may not be, he said.

There isn't enough evidence to show if people who are aspirin resistant can simply take larger doses, but Dorsch warns that people taking aspirin on the advice of a doctor shouldn't stop therapy on account of these results.

Not only did the study quantify how much more effective aspirin therapy is for men than for women, it is also the first study that Dorsch knows of to measure aspirin resistance in men and women with stable coronary artery disease. Previous studies have looked at the impact of aspirin therapy on people who have had a heart attack.

For the study, researchers randomly selected 100 patients who were visiting their cardiologist for a regularly scheduled appointment. All had coronary artery disease but only half had a history of heart attack. Researchers used a device called VerifyNow Aspirin Assay to test the percentage of platelet reactivity after blood samples were exposed to a chemical that causes clotting.

Aspirin works by causing platelet inhibition in the blood, which means that platelets cannot stick together and this slows the formation of blood clots that cause a heart attack or stroke.

"This does happen in women, but it doesn't happen in as many women and it's not as effective," Dorsch said. The testing device uses an optical sensor to "see" what percentage of the platelets in the blood sample clump together. Anything less than 40 percent platelet inhibition is considered aspirin resistant.

"We really don't know the mechanism," Dorsch said. "It could be that women have a more active platelet system in the body so it's less likely that platelet action would be inhibited."

In the future, researchers hope to look at aspirin therapy outcomes in women only and see if those outcomes can be changed. The majority of testing for aspirin therapy has been on men, so not much is known about how women respond.

"Heart disease is the number one killer of women in the United States. Future research should be aimed at finding out the cause of this increase in aspirin resistance and the effect on outcomes in women with heart disease." Dorsch said.

New genetic biomarkers could predict coronary heart disease

Sun, 01 Apr 2007 11:58:51 PST

( from http://www.rxpgnews.com ) New genetic markers may be able to predict whether a person is likely to have coronary heart disease (CAD) in the future. Research carried out by Dr. M. Balasubramanyam and Dr.V.Mohan at the Madras Diabetes Research Foundation (India) shows that people who are pre-diabetic or who have Type 2 diabetes have much shorter telomeres1 and, since these people are prone to CAD, an early test could indicate their susceptibility and help them to alter their lifestyle to avoid or delay the onset of the disease. This work will be presented by Dr Adaikala Koteswari at the Society for Experimental Biologyâs Annual Main Meeting on Sunday 1st April 2007.

Tests have been carried out on pre-diabetics and Type 2 diabetics which have shown that telomere shortening is greater as a person progresses from being pre-diabetic through to being type-2 diabetic. Diabetics are more susceptible to oxidation and inflammation which could be the one of the reasons for telomere shortening and so an early indication of their telomeres starting to shorten could indicate the onset of diabetes and ultimately be a predictor for CAD. In other words, telomere shortening in prediabetics could predict those predisposed subjects who are at the cross-road of developing type 2 diabetes and cardiovascular disease.

1 Telomeres have been compared with the plastic tips on shoelaces because they prevent chromosome ends from fraying and sticking to each other, which would otherwise result in genomic instability. Telomeres are also thought to be the "clock" that regulates how many times an individual cell can divide. Telomeric sequences shorten each time the DNA replicates. When the telomeres reach a critically short length, the cell stops dividing and ages (senesces) which may cause or contribute to age-related diseases. Telomeres are essential regulators of the cellular lifespan and chromosome integrity, however it has recently been shown that telomeres may also play a role in complex genetic disorders such as hypertension and diabetes.

Genetic Regulator for Coronary Artery Smooth Muscle Cells Identified

Mon, 31 Jul 2006 11:39:37 PST

( from http://www.rxpgnews.com ) Through studying pigeons with genetic heart disease, researchers at Wake Forest University School of Medicine have discovered a clue about why some patients' heart vessels are prone to close back up after angioplasty.

"We identified a regulator of genes that controls the growth of artery smooth muscle cells," said William Wagner, Ph.D., senior researcher. "Learning to modulate the uncontrolled growth of these cells could potentially solve the problem of vessels re-closing after angioplasty."

Angioplasty uses a balloon-like device to crush the material blocking an artery. But, within three to six months, even if a stent is placed in the artery to keep it open, the vessel becomes re-blocked in about 25 percent to 30 percent of patients. This process, known as restenosis, has been described as "over exuberant" tissue healing and involves the smooth muscle cells. It is not known why this happens in some people and not in others, but many scientists believe that genes are to blame, Wagner said.

The researchers sought to find the answer in two breeds of pigeons one that is genetically susceptible to heart attacks and heart vessel disease (white carneau) and one (show racer) that is resistant. A major difference between the two breeds is that smooth muscle cells from the heart vessels of white carneau pigeons are prone to uncontrolled growth.

"Understanding the factors that play a role in this increased cell growth may provide an opportunity to target its role in both the initial development of artery blockages and in the restenosis following angioplasty," said Wagner, a professor of pathology and fellow of the American Heart Association.

Genes "express," or produce, proteins that are used in building tissue. The process begins with "transcription," or the copying of a gene's DNA sequence.

It is not known which genes might control the pigeons' heart vessel tissue-building process, so Wagner's group focused on "transcription factors," which regulate whether a gene is expressed and at what rate. The group's aim was to see if certain transcription factors might be found in altered amounts in the smooth muscle cells of pigeons that are prone to atherosclerosis.

They screened 54 different transcription factors and found that one, known as STAT4, was 10 times higher in the white carneau pigeons with genetic heart disease. Further testing showed that stimulating STAT4 in smooth muscle cells in the laboratory resulted in a threefold increase in cell growth.

"We were very surprised," said Wagner. "This is one of the first reports of this factor being found in smooth muscle cells."

Wagner said the finding has potential for helping scientists solve the problem of restenosis.

"Interfering with these factors and the signaling pathways involving STAT4 may be potentially important in atherosclerosis therapy," he said. "We may identify ways to reduce or block its effect and slow or stop the unwanted growth of cells."

He said that by finding the transcription factor, researchers can concentrate on modifying its pathway, and won't need to know which or how many genes it affects.

New Risk Factors Do Not Improve Assessment Of Coronary Heart Disease Risk

Wed, 12 Jul 2006 05:29:37 PST

( from http://www.rxpgnews.com ) Screening for levels of C-reactive protein and other compounds recently found to be associated with coronary heart disease may not help physicians predict risk for the condition with any more accuracy than traditional major risk factors, according to a report in the July 10 issue of the Archives of Internal Medicine, one of the JAMA/Archives journals.

Major risk factors for coronary heart disease (CHD), which include age, race, sex, blood pressure, diabetes, total and HDL (good) cholesterol levels, smoking status and the use of medications to control blood pressure, predict an individual's probability of developing the condition with reasonable accuracy. Most are also modifiable, so physicians can advise patients on how to change their lifestyle to reduce their risk, according to background information in the article. In recent years, researchers have identified additional risk factors and chemical markers associated with CHD, such as C-reactive protein, a compound in the blood that signifies inflammation caused by injury or infection.

Aaron R. Folsom, M.D., M.P.H., University of Minnesota, Minneapolis, and colleagues with the Atherosclerosis Risk in Communities (ARIC) Study assessed the benefits of screening patients' levels of 19 novel chemical markers, including C-reactive protein, antibodies against infectious diseases, B vitamins and compounds involved in the functioning of blood vessel lining. The ARIC Study enrolled a total of 15,792 adults between the ages of 45 and 74 years in 1987-1989. The participants underwent a physical examination, including assessment of major risk factors, at the beginning of the study and every three years afterward. At four times during the follow-up period, researchers collected blood and DNA samples for analysis. Patients continue to be tracked for the development of CHD.

Several of the compounds tested, including C-reactive protein and vitamin B6, were significantly associated with CHD. The researchers looked at each marker and assessed the probability that a participant who developed CHD within a five-year period had a higher risk score than a participant who did not develop CHD. Using this method, they determined that most of the novel markers did not significantly increase the ability of physicians to predict CHD.

"Although the significant and independent association of a novel risk factor with CHD often does not equate to improved prediction of CHD beyond that of basic risk factors, this does not imply that the novel risk factor is pathophysiologically unimportant or unsuitable as a target for intervention," the authors write. "Based on the totality of evidence, however, C-reactive protein level does not emerge as a clinically useful addition to basic risk factor assessment for identifying patients at risk of a first CHD event."

Routine screening is not warranted for any of the other 18 novel risk factors tested either, the authors conclude. "On the other hand, our findings reinforce the utility of major, modifiable risk factor assessment to identify individuals at risk for CHD for preventive action," they write.

Angioplasty: door-to-balloon time matters regardless of time to presentation

Sat, 03 Jun 2006 09:14:37 PST

( from http://www.rxpgnews.com ) Slicing minutes off the time it takes hospitals to deliver emergency angioplasty (the "door-to-balloon" time) improves the survival of appropriate heart attack patients, even when patients have been feeling symptoms for a few hours, according to a new study in the June 6, 2006, issue of the Journal of the American College of Cardiology.

"There is a belief among some clinicians that patients presenting late will not benefit from faster door-to-balloon time (a "cow is already out of the barn" philosophy). We were able to show that door-to-balloon time matters for all patients regardless of time to presentation. Furthermore, we were able to show that door-to-balloon time mattered for both low and high risk patients. In summary, all patients can benefit from shorter door-to-balloon times," said Robert L. McNamara, M.D., M.H.S. from the Yale University School of Medicine in New Haven, Connecticut.

Dr. McNamara noted that it is already well-documented and widely accepted that patients benefit from reducing the overall time between the onset of heart attack symptoms and effective treatment to restore blood flow in coronary arteries. As a result, most hospitals have taken steps to reduce the amount of time it takes to diagnose patients arriving through their emergency departments, activate treatment teams, and begin angioplasty procedures.

However, when patients have been feeling symptoms for a few hours before reaching the hospital, it has not been as clear whether zipping them from the emergency department into a catheterization lab still improves survival.

The researchers used data from a national registry in which hospitals voluntarily enter information about heart attack patients they have treated. The National Registry of Myocardial Infarction (NRMI) is sponsored by Genentech Inc. of South San Francisco, California. In particular, they looked at data on 29,222 heart attack patients treated with angioplasty (percutaneous coronary intervention (PCI)) from 1999 to 2002 at 395 hospitals within 6 hours of alerting health care providers to their symptoms.

Overall, when patients underwent angioplasty (in which a tiny balloon is threaded into a narrowed coronary artery and inflated to reopen blood flow) within 90 minutes of arriving at a hospital, 3 percent died in the hospital. That in-hospital mortality rate rose to 7.4 percent for patients who were in the hospital for more than three hours before being treated.

When the researchers analyzed subgroups of patients who had arrived at a hospital within an hour of reporting symptoms, between one and two hours, or longer than two hours, they still saw the same pattern: within each subgroup, faster action in the hospital meant lower death rates. The same benefits of swift hospital response were seen regardless of whether patients had high-risk factors or not.

The results of this study indicate that while getting to the hospital as quickly as possible is vital, rapid action by the hospital makes just as much of a difference for patients who come in late as it does for those who arrive right away.

"I think the most surprising finding is that mortality decreases with shorter door-to-balloon time to a similar degree for each group, regardless of time to presentation. Many clinicians think that time matters much more for early presenters than for late ones," Dr. McNamara said.

Co-author Harlan M. Krumholz, M.D., S.M., said the nature of heart attacks and how patients perceive symptoms may help explain why quick work in the hospital is important for all patients.

"From my perspective, the reason that time of onset to hospital presentation is not so important is because many patients may not completely occlude their arteries at the time they first recognize symptoms -- and so the actual time of artery occlusion may not be easily predicted from the time it takes them to present to the hospital. Also, some people have waxing and waning symptoms and only present when the symptoms become worse, complicating the determination of the time the heart has been deprived of blood," Dr. Krumholz said.

"The key thing about this study is that it reinforces the value of the increasing national focus on reducing door-to-balloon times and suggests that improving our speed will likely result in many lives being saved," he emphasized.

Dr. McNamara noted that this study looked only at whether patients left the hospital alive. He said it is likely the same benefit would be seen with longer-term survival, but other studies will be needed to document the long-term effects.

Jeffrey J. Cavendish, M.D., F.A.C.C. from the Naval Medical Center in San Diego, California, who was not connected with this study, said the results emphasize the importance of streamlining hospital procedures.

"The main message that this study re-enforces is, not only the concept of "time is muscle," but that "time is life." The sooner we can get patients into the cardiac catheterization lab and unclog the blocked artery causing the heart attack, the lower the likelihood that that patient will die from the heart attack. The National Registry of Myocardial Infarction provides us with an enormous amount of real world data. Dr. McNamara and his colleagues are commended for their vigorous work educating us about where we can and need to do better in treating patients with myocardial infarctions," Dr. Cavendish said.

"Emergency Medical Services and hospitals throughout this country must do better to create a more seamless system to get patients into the catheterization lab in the shortest amount of time. We need a collaborative effort with EMS, Emergency Departments, Nursing, Cardiac Catheterization lab staff and Cardiologists all working together in order to shorten door to balloon times to less than 90 minutes for all patients 24 hours a day, seven days a week," he added.

David A. Halon, M.B., Ch.B., F.A.C.C. from the Lady Davis Carmel Medical Center in Haifa, Israel, who also was not connected with this study, said the results "should spur individual hospitals to examine how each can reduce door-to-balloon time in their own institutional setting."

Dr. Halon noted that patients with at least one risk factor for an adverse outcome of their heart attack appeared to gain the most absolute benefit from rapid angioplasty (PCI) once they reached the hospital. He also noted that each hospital will need to determine how to speed treatment for these patients.

"As pointed out by the authors in the limitations section of the manuscript, although every effort should be made to shorten door-to-balloon time, a registry study does not necessarily point to cause and effect relationships. There are many important factors, both procedural and related to subsequent hospital care, influencing the outcome of primary PCI for acute heart attack. A shorter door-to-balloon time might imply better overall hospital care and benefit correlating with shorter door-to-balloon times may relate to better overall care in those hospitals more efficient at bringing their heart attack patients to rapid PCI," Dr. Halon said.

Earlier studies by this group of researchers found that less than half the hospitals in the United States meet the goal of providing angioplasty within 90 minutes after the arrival of an appropriate heart attack patient. The researchers also outlined the common features of hospitals that successfully reduced door-to-balloon times, including good coordination with ambulance crews to make preliminary diagnoses and a willingness to scramble angioplasty teams early.

ESC Updated Guidelines for Stable Angina Pectoris Management

Thu, 01 Jun 2006 13:20:37 PST

( from http://www.rxpgnews.com ) The European Society of Cardiology released new Guidelines for the Management of Stable Angina Pectoris. The updated Guidelines include information on new developments in cardiovascular care, advances that have been made in improving the prognosis of coronary artery disease including the use of statins and ACE inhibitors, as well as strategies to alleviate symptoms.

The Guidelines also provide updated information in the area of risk stratification and define which patients should go on for invasive investigation and treatment.

"Stable angina pectoris is responsible for considerable morbidity and mortality throughout the world," said Professor Kim Fox, chairperson of the ESC Guidelines on the Management of Stable Angina Pectoris. "Improvements in the investigation, management and treatment of this condition has been one of the most remarkable success stories in the last decade. The last European guidelines were published in 1997 and therefore these guidelines provide a new landmark in our mission to reduce the burden of cardiovascular disease in Europe."

Guidelines are critical to appropriate clinical practice, comprising specific recommendations on treatment methods, collated by senior European experts and opinion leaders in the field. For maximal relevance, Guidelines must be well presented, practical and relevant to the clinician on both a national and local level. The formulations and continual update of such Guidelines is one of the primary activities of the ESC. The ESC aims to produce Guidelines that both encompass and allow for national variations across Europe and works with its National Cardiac Society members to facilitate national adaptations and translations of each Guideline issued.

Antioxidant Selenium Offers No Heart-Disease Protection

Wed, 26 Apr 2006 15:07:37 PST

( from http://www.rxpgnews.com ) Selenium does not protect against cardiovascular disease, despite its documented antioxidant and chemopreventive properties, analysis of a randomized placebo-controlled clinical trial covering 13 years has shown.

The selenium-CVD association was a secondary endpoint in the Nutritional Prevention of Cancer Trial, which was designed primarily to determine if selenium supplementation could prevent the recurrence of non-melanoma skin cancer.

Results of the trial, the only large randomized clinical trial to date to examine selenium supplementation alone in the prevention of CVD, appear in the April 15 issue of the American Journal of Epidemiology. Saverio Stranges, M.D., Ph.D., assistant professor of social and preventive medicine in the School of Public Health and Health Professions, University at Buffalo, is first author.

"Our results extend previous research based on smaller intervention trials focusing on cardiovascular risk factors," said Stranges. "Our findings are consistent with those from previous studies that have shown no beneficial effect of selenium supplementation in combination with other antioxidants on the primary prevention of cardiovascular disease."

Several antioxidants, vitamins C and E in particular, that were thought to play a role in preventing heart disease based on observational studies have turned out not to be protective in randomized clinical trials, and selenium now has joined this group.

The main findings of this report focus on the 1,004 participants in the study, conducted from 1983-96, who were free of cardiovascular disease when they were recruited. Participants came from seven dermatology clinics in low selenium areas of the eastern United States: Augusta and Macon, Ga.; Columbia, S.C.; Miami, Fla.; Wilson and Greenville, N. C.; and Newington, Conn.

Enrollees were assigned randomly to take a tablet containing 200 micrograms of selenium daily or a placebo. Information on sociodemographics, health habits, education and body mass index also was collected.

Participants provided blood samples at their respective clinics twice a year and reported any new illnesses or medications. Individuals were followed for an average of 7.6 years.

Results showed no association between selenium supplementation on any of the endpoints studied: coronary heart disease, stroke or deaths from cardiovascular disease, Stranges said. There also was no difference in the endpoints based on the level of selenium at baseline. In addition, the lack of significant association with CVD endpoints was confirmed even in the 246 participants who had CVD at baseline. (This data does not appear in the published manuscript.)

"These results must be interpreted cautiously," said Stranges, "because they result from exploratory analyses, although from the largest randomized clinical trial available that has selenium only as the intervention. However, this report adds important information to our knowledge on the role of selenium in cardiovascular-disease prevention, indicating no overall benefit of supplementation by selenium alone in prevention of cardiovascular disease."

Coffee not linked with coronary heart disease

Tue, 25 Apr 2006 20:51:37 PST

( from http://www.rxpgnews.com ) Good news for caffeine addicts - coffee, in any quantity, does not raise the risk of coronary heart disease and could actually reduce the chances, says a study.

Researchers led by Esther Lopez-Garcia of the School of Medicine at the Universidad Autonoma de Madrid in Spain studied 44,005 men and 84,488 women and found that people who drink six or more cups of coffee a day could have less risk than those who consumed a cup or less a day.

The relative risk (RR) of coronary heart disease among men was 1.0 for men who drank less than a cup of coffee a month and 1.04 for men who drank one cup a month to four cups a week.

For those who drank about a cup a day the RR was 1.02 and for those who said they drank two to three cups a day the risk was 0.97, it said.

For those who drank four to five cups daily the risk was 1.07 while for those who drank six or more cups every day the RR dropped to 0.72, it said.

Among women, RR for those who drank less than a cup a month was 1.0 and for those who consumed one cup a month to four a week it was 0.97. For women drinking a cup a day the RR was 1.02 and for those drinking two to three cups a day it was 0.84.

Women who drank four to five cups a day had an RR of 0.84 and for those who said that had at least six cups a day it was 0.87.

Although the study found no evidence to suggest an increased risk of coronary heart disease based on total caffeine consumption, researchers cautioned that in "certain genotypes" caffeine may increase the risk of coronary heart disease but said that remains to be proven.

The researchers said their findings apply to standard percolator or drip coffee, not to high intakes of unfiltered coffee such as the increasingly popular "French press" coffee, which produces a dark, strong cup.

Adding abciximab to the antithrombotic regimen significantly reduces post-stent complications

Sun, 19 Mar 2006 03:01:37 PST

( from http://www.rxpgnews.com ) Patients admitted to the hospital with an acute coronary syndrome (ACS) are often treated with a catheter-based procedure known as percutaneous coronary intervention, or PCI. But doctors are unclear about the optimal antithrombotic therapy to prescribe after procedure to prevent clotting, and new research suggests a possible alternative, according to a study presented today at the American College of Cardiology's 55th Annual Scientific Session. ACC.06 is the premier cardiovascular medical meeting, bringing together more than 30,000 cardiologists to further breakthroughs in cardiovascular medicine.

Previous research has shown that adding the antithrombotic drug abciximab, (a glycoprotein IIb/IIIa receptor inhibitor) to therapy with ticlopidine plus aspirin significantly reduces post-stent implantation complications, including death, repeat heart attack or reintervention. The drug ticlopidine has been replaced by clopidogrel in recent research, which is safe and acts more rapidly in a 600 mg dosage level, offering better platelet inhibition within two hours of administration.

In a previous trial of low-to-moderate risk patients, the use of clopidogrel was associated with such a low frequency of early complications that the use of abciximab offered no clinical benefit. However, higher risk patients with ACS may benefit from a more potent antithrombotic regimen. The ISAR-REACT 2 trial evaluated for the first time the value of abciximab in patients with ACS undergoing PCI after pretreatment with 600 mg of clopidogrel.

"No specifically designed randomized studies have previously been conducted on the value of abciximab plus a high-dose of clopidogrel during PCI in ACS patients," said Adnan Kastrati, M.D., of the Deutscshes Herzzentrum Munich, Germany and lead author of the study. "Together with other current trials, this will help to define the current optimal adjunct antithrombotic therapy in patients with ACS managed with PCI."

The randomized, multi-center, double-blind, placebo controlled study of 2,022 patients undergoing PCI after pretreatment with clopidogrel were randomized to receive abciximab or placebo. The researchers measured for 30-day combined incidence of death, heart attack or urgent revascularization, as well as bleeding complications. The trial results show the role of the combination - intensive clopidogrel pretreatment plus abciximab - during PCI for ACS. They will enable us to know whether patients with ACS or any subset of them can benefit from this combination.

Dr. Kastrati will present the results of the "Prospective, Double Blind, Placebo-Controlled Trial of Glycoprotein IIb/IIIa Inhibition with Abciximab in Patients with Acute Coronary Syndromes Undergoing Stenting After Pretreatment with a High Loading Dose of Clopidogrel" (ISAR-REACT 2) study on Monday, March 13, at 2:40 p.m.

Stenting just the left main stem gives equivalent results

Sun, 19 Mar 2006 02:48:37 PST

( from http://www.rxpgnews.com ) Cardiologists increasingly use non-invasive methods to treat patients with diseased arteries that previously required open-heart surgery. A late-breaking clinical trial presented today during the American College of Cardiology's inaugural Innovation in Intervention: the i2 Summit 2006. Innovation in Intervention: i2 Summit is an annual meeting for practicing cardiovascular interventionalists sponsored by the American College of Cardiology in partnership with the Society for Cardiovascular Angiography and Interventions.

When both a main artery in the heart and a smaller branch connected to it are narrowed by coronary artery disease, repairing the damage with the use of multiple stents (small, lattice-shaped, metal tubes inserted permanently into an artery) is technically challenging. Further, this type of coronary artery disease called a "bifurcation lesion" is prone to re-narrowing or blocking again after treatment. The use of drug-eluting stents coated with medicine to keep the artery from re-narrowing has improved the outcome of this kind of procedure, but the optimal method to treat bifurcation lesions has not been established.

This study examined two ways of treating severe diseased arteries: by placing stents in both the main artery and the side branch or by stenting the main artery alone with the option of stenting the side branch. Researchers looked at major adverse coronary events (MACE if some of the patients died, suffered from a heart attack, needed re-treatment or had a clogging of the artery) to determine which strategy would provide the best outcome.

A total of 413 patients with extensive cardiac artery disease were randomized in a multi-center study conducted by the Nordic PCI Study Group. The patients were randomized in two groups: one treated with drug-eluting stent in both the main vessel and the side branch (206 patients), the other group treated with drug-eluting stent only in the main vessel (207 patients). The treatment was successful in nearly 100 percent of patients. Only 4.3 percent of patients in the group originally scheduled for stenting in only the main branch ultimately received stents in both branches. This is a very low rate of crossover, according to presenting author Terje K. Steigen, M.D., Ph.D., contributing to more reliable findings.

At six months, clinical results show that patients in both groups had similar positive outcomes and very low rates of complications less than 5 percent in both groups experienced MACE. The patients who were stented in both the main artery and the side branch the more complex procedure of the two experienced a longer time in the cardiac catheterization lab with more exposure to X-rays and contrast medium necessary to complete the procedure. These patients showed increased rates in procedure-related biochemical marker release, a blood test that indicates injury to the heart muscle. While eight percent of patients who underwent the simpler procedure showed significant biochemical marker release, 18 percent of those in the more complex procedure group showed significant biochemical marker release.

"Since the clinical results are equally good in both groups, you have to look at the advantages of one technique over the other," said Dr. Steigen, of University Hospital of Northern Norway, Tromsoe. "Due to the elevated markers, the prolonged procedure time and the increased volume of contrast used, it is probably wise to use the simpler strategy. It's not prohibitive to take the complex approach however, because both procedures had the same, excellent clinical outcome."

Serotonin may play role in hardening of the arteries

Sat, 04 Mar 2006 16:00:37 PST

( from http://www.rxpgnews.com ) A less active brain serotonin system is associated with early hardening of the arteries, according to a study presented today by University of Pittsburgh researchers at the 64th Annual Scientific Conference of the American Psychosomatic Society in Denver. These findings, which are the first to establish a link between serotonin messages in the brain and atherosclerosis, could lead to an entirely new strategy for preventing heart disease and stroke, say the researchers.

"Many of the known risk factors for heart disease and stroke high blood pressure and cholesterol, obesity, diabetes, smoking and lack of exercise can, to some extent, be controlled by our lifestyle choices," said Matthew F. Muldoon, M.D., M.P.H., associate professor of medicine, University of Pittsburgh School of Medicine. "Until now, no one had studied the possibility that brain abnormalities could explain why some people make these poor lifestyle choices and have multiple risk factors for heart disease."

In the study being presented today, which included 244 adult volunteers between the ages of 30 and 55 years, researchers measured serotonergic activity using a pharmacological approach and carotid artery thickness using ultrasonography. At the time of testing, participants were free of clinically evident vascular disease. Yet, those with low levels of serotonergic function were more likely to have thickening of the carotid artery than those with higher levels.

"If, through further studies, we can establish that risk factors for heart disease and stroke are, in part, controlled by the serotonin systems in the brain, it could open a whole new avenue for preventing heart disease and stroke," said Dr. Muldoon.

Serotonin is a type of neurotransmitter, a chemical that sends messages between neurons in the brain. It is thought to play an important role in the regulation of mood, appetite and blood pressure. Previous studies by Dr. Muldoon and colleagues have found that people who get little exercise, are overweight, have high blood pressure, blood sugar and cholesterol have low levels of serotonergic function. A number of research studies have established a link between serotonin and mood. However, until now, the relationship between the serotonin system and atherosclerosis had remained unstudied.

Severe Heart Disease, Poor Prognosis Linked To Erectile Dysfunction

Wed, 25 Jan 2006 00:13:37 PST

( from http://www.rxpgnews.com ) In a study, researchers report that men with ED may have more severe cases of coronary heart disease and more risk factors for adverse outcomes than those without ED.

James K. Min, M.D., and colleagues at the University of Chicago Hospitals evaluated 221 men with an average age of 58.6 years who were referred for nuclear stress testing, a noninvasive diagnostic test for evolution of heart disease. The researchers screened the men for ED and then compared their results on the tests.

Of the 221 men, 121 (54.8 percent) reported ED. Patients with ED were older than men without ED and more likely to have heart disease, diabetes and hypertension and have undergone previous procedures to restore blood flow to the heart. They also were more likely to have results on the stress test that indicated they were at high cardiovascular risk, and more of them had already developed severe heart disease.

In patients referred for stress testing, "the presence of ED is common and is a strong predictor of clinically significant coronary heart disease and established markers of an adverse cardiovascular prognosis" as indicated by the tests, the authors write. "Erectile dysfunction is a stronger predictor than traditional coronary heart disease risk factors in this population," they conclude. "Sexual function questioning may be useful to stratify risk in patients suspected to have coronary heart disease. Further studies are needed to establish whether patients with ED but no cardiac symptoms should be screened for overt coronary heart disease."

Framingham score underestimates the risk of developing coronary heart disease in women

Tue, 20 Dec 2005 00:23:38 PST

( from http://www.rxpgnews.com ) Traditional risk-factor scoring fails to identify approximately one-third of women likely to develop coronary heart disease (CHD), the leading cause of death of women in the United States, according to a pair of reports from cardiologists at Johns Hopkins.

"Our best means of preventing coronary heart disease is to identify those most likely to develop the condition, and intervene with lifestyle changes and drug treatment before symptoms start to appear," says the senior author of both studies, cardiologist Roger Blumenthal, M.D., an associate professor and director of the Ciccarone Preventive Cardiology Center at The Johns Hopkins University School of Medicine and its Heart Institute. "The goal is to strongly consider therapies, such as aspirin, cholesterol-lowering medications and, possibly, blood pressure medications for individuals at higher risk, so that heart attacks will be less likely to occur in the future."

The Hopkins findings, the latest of which appear in the American Heart Journal online Dec. 16, is believed to be one of the first critical assessments of the Framingham Risk Estimate (FRE) as the principal test for early detection of heart disease. The researchers wanted to determine why many of these women at risk for heart disease are not identified earlier.

The FRE is a total estimate of how likely a person is to suffer a fatal or nonfatal heart attack within 10 years, and it is based on a summary estimate of major risk factors for coronary heart disease, such as age, blood pressure, blood cholesterol levels and smoking.

However, Blumenthal says, many women with cardiovascular problems go undetected despite use of the Framingham score. While the death rate for men from cardiovascular disease has steadily declined over the last 20 years, the rate has remained relatively the same for women, he says.

In their latest report, the Hopkins researchers examined the risk of premature CHD in women whose average age was 50 and who were participating in the Sibling and Family Heart Study, a long-term study of how heart disease develops among family members. Study subjects had no symptoms of heart disease, but had a sibling who had been hospitalized for a coronary event, such as a heart attack before age 60.

The researchers calculated each woman's Framingham score and found that 98 percent were gauged to be at very low risk for future CHD, with an FRE of less than 6 percent, while only 2 percent of participants were judged to be at intermediate risk for future CHD, with an FRE between 10 percent and 20 percent.

When the results were contrasted with evidence gleaned from CT-scan measurements of calcium build-up in the arteries, the researchers found that one-third of women originally classified as very low risk actually had coronary atherosclerosis, a hardening and narrowing of the arteries that can lead to heart attacks if not controlled with drug therapy along with diet, exercise and other lifestyle changes. Indeed, 12 percent of women in the study had advanced stages of atherosclerosis, while another 6 percent had severe calcium build-up.

"We wanted to verify if the Framingham score truly captured who was most at risk, but it turns out to have underestimated a large number of those who should be considered for preventive therapies," says Blumenthal.

According to the researchers, performing cardiac CT scans on everyone with a low Framingham score is not a practical option for improving upon traditional risk-factor screening. To better determine who should get scanned, even if they have a low risk assessment, the Hopkins team began to search for additional predictors of who was most at risk. They found that people with two or more risk factors, such as obesity, smoking or metabolic syndrome, plus a family history for heart disease were those most likely to have a high calcium score. It is this group, the researchers say, who should be considered for a fast cardiac CT scan regardless of low Framingham scores and if the physician or patient is unsure about the need to go on long-term preventive therapies.

In a related, second investigation, published online in the May edition of the journal Atherosclerosis, the Hopkins team analyzed the Framingham scores of 2,447 women age 45 to 65, all of whom were participating in another long-term study in Ohio of adults referred by a physician for a cardiac risk assessment.

Again, when the FRE results were compared to calcium scores, 84 percent (408 of 489) of those classified as low risk by FRE actually had some coronary atherosclerosis. Twenty percent of those who were classified at intermediate risk by FRE had signs of advanced atherosclerosis.

"Our results show that if a CT scan had not been performed in addition to traditional risk-factor scoring, a large number of women would have missed the chance to begin preventive therapies," says cardiologist Erin Michos, M.D., a clinical research fellow at Hopkins and its Heart Institute. Michos led both Hopkins studies.

"For some women, especially those with a family history of heart disease and multiple risk factors for it, additional screening using CT scan and calcium scoring may be warranted," she adds.

Octagenarians have higher mortality risk after CABG

Tue, 22 Nov 2005 15:52:38 PST

( from http://www.rxpgnews.com ) Patients aged 80 and older have a higher risk of death and disease than younger patients after undergoing coronary artery bypass graft (CABG) surgery or valve surgery, and age alone influences these outcomes, according to a study in the November issue of Archives of Surgery, one of the JAMA/Archives journals.

There were 4.2 million Americans aged 85 or older in 2000, and this number is projected to increase to 8.9 million by 2030, according to background information in the article. Approximately 40 percent of all octogenarians have symptomatic cardiovascular disease. Previous observational studies have shown that octogenarians undergoing open heart surgery for CABG or valve replacement are at higher risk for postoperative death. But until recently, no large studies have determined whether age is an independent risk factor for disease and death in octogenarians undergoing open heart surgery.

W. Michael Johnson, M.D., of Good Samaritan Hospital, Cincinnati, and colleagues conducted an eight-year hospitalization cohort study to determine whether being an octogenarian is an independent risk factor for mortality, as well as for nine other measured outcomes. Data were collected on a consecutive sample of 7,726 patients undergoing coronary artery bypass grafting or valve surgery between October 1, 1993, and February 28, 2001. There were 522 octogenarians in the study sample. The researchers controlled for 16 potential confounding variables to isolate outcome differences according to age.

"...octogenarians were found to have a higher risk for death (72 percent higher), longer length of hospitalization (3 percent higher), and a higher risk for neurologic complications (51 percent higher); they were also more likely to undergo re-operation to treat bleeding (49 percent more likely)," the authors report.

There were no significant differences between octogenarians and patients under the age of 80 in regard to kidney, lung, or gastrointestinal tract complications, returns to intensive care, or intraoperative complications-such as heart attack, hemorrhage, and irregular heartbeat.

"Like other investigators, we found that octogenarians were at higher risk for postoperative death," the authors write. "However, our results show that after controlling for differences between octogenarians and non-octogenarians, age is an independent risk factor for morbidity and mortality."

The authors point to projections that an estimated 12 million Americans will swell the ranks of octogenarians by the year 2010, as the younger population ages and life expectancy rises. "An increasing number of octogenarians undergoing coronary revascularization or valve surgery are certain to strain an already burdened health care system," they assert.

"It is, therefore, incumbent on researchers to develop more refined algorithms to predict postoperative outcomes," the authors conclude. "As this study indicates, age should be considered a component of any such algorithm."

Diabetic black men have less atherosclerosis

Wed, 02 Nov 2005 13:31:38 PST

( from http://www.rxpgnews.com ) In a surprising outcome, investigators at Wake Forest University Baptist Medical Center found that diabetic black men have dramatically lower amounts of atherosclerosis, or hardening of the arteries, than diabetic white men.

Barry I. Freedman, M.D., and colleagues report in the December issue (Volume 48, No. 12) of Diabetologia that African-American men had significantly lower levels of calcified atherosclerotic plaque in the coronary (heart) arteries and the carotid arteries in the neck that supply blood to the brain. The report was published on line today (Nov. 1, 2005.)

"This striking result was observed despite black subjects having higher levels of conventional risk factors for heart disease," said Freedman. "These risk factors would normally be expected to promote coronary artery disease in the black participants."

This result was also observed in the face of increased thickness of carotid artery walls in black diabetic subjects. Increased wall thickness is widely accepted including by the U.S. Food and Drug Administration as a marker for atherosclerosis and a predictor of coronary heart disease, so the result was surprising.

Freedman said that in women, "ethnic differences in calcified carotid artery plaque, but not coronary artery plaque, were observed."

The amount of plaque was measured using high-speed computed tomography (CT) scans.

The results came from the Diabetes Heart Study, made up of North Carolina families in which at least two siblings have type 2 or non-insulin-dependent diabetes. The investigators all from Wake Forest recruited 1,000 white participants from 369 families and 180 blacks from 74 families for this study.

Freedman said the black subjects had higher blood pressures, higher levels of low-density lipoprotein (LDL ) cholesterol (the bad cholesterol), higher overall cholesterol, elevated blood sugars and a host of other measures that are considered risk factors for atherosclerosis.

Freedman, the John H. Felts III, M.D., Professor of Internal Medicine and head of the Section on Nephrology, said the study was the first to compare blacks and whites who had type 2 diabetes for differences in atherosclerosis.

"Hardening of the arteries appears to be a different disease in blacks and whites. We have demonstrated this in diabetic subjects; other groups have shown it in people with hypertension," said Freedman. "We should be studying what causes these biologic differences. Perhaps inherited or genetic influences may contribute to these differences."

He said that these differences are in line with the results from two large clinical studies. These studies revealed that the risk of heart attack in blacks was half that in whites, when access to care was equal.

"No one would disagree that in the general population, blacks have higher death rates from heart attack and stroke. This may relate to the fact that blacks don't always have equal access to quality healthcare," Freedman said. "But once you have equal care, there are differences in outcome that suggest that biologic differences exist in atherosclerosis."

Freedman said 14.9 percent of all blacks have diabetes some undiagnosed and an additional 6.3 percent have impaired glucose tolerance, which means that the body is processing carbohydrates much more slowly. "On average, an African-American individual is twice as likely to have diabetes as his or her white peer. The prevalence of diabetes among African-Americans aged 40 to 74 doubled from 8.9 percent in 1976-1989 to 18.2 percent in 1988-1994."

Fair Treatment at Workplace Reduces Risk of Coronary Heart Disease

Tue, 25 Oct 2005 05:17:38 PST

( from http://www.rxpgnews.com ) A sense of fair treatment in the workplace was associated with a reduced risk of coronary heart disease in a large long-term study of British office workers published in the October 24 issue of the Archives of Internal Medicine, one of the JAMA/Archives journals.

People feel a sense of justice at work when they believe their supervisor considers their viewpoint, shares information concerning decision-making and treats individuals fairly and in a truthful manner, according to background information in the article. An earlier study had shown that employees had lower blood pressure on days spent working with a supervisor they perceived as fair. The authors suggest that it is plausible to connect a high level of justice with a reduction in chronic stress and its attendant association with coronary heart disease (CHD).

Mika Kivimäki, Ph.D., of the Finnish Institute of Occupational Health, Helsinki, Finland, and colleagues analyzed data from 6,442 male office staff in 20 civil service departments in London, England. Justice at work was measured at phase one (1985-1988) and two (1989-1990). Each participant was given a score based on a self-reported justice scale. They were divided into three groups based on their average score. Participants were followed for incidence of coronary heart disease from 1990 to 1999. Conventional risk factors for coronary heart disease were measured at phase one.

"These data enable us to determine whether the addition of justice would add to risk estimates based on other risk factors," the researchers write. "In the present study, we examined whether justice at work predicted incidence of new CHD among employees and whether this association was independent of coronary risk factors, including cholesterol concentration, hypertension, body mass index (BMI), smoking, alcohol consumption, physical inactivity, and other psychosocial characteristics of the work environment."

"In men who perceived a high level of justice, the risk of incident CHD was 30 percent lower than among those who perceived a low or an intermediate level of justice," the researchers report. "This finding was not accounted for by baseline factors such as age, ethnicity, marital status, educational attainment, socio-economic position, cholesterol level, obesity, hypertension, smoking, alcohol consumption, and physical activity. The association between the level of justice and CHD was also independent of other psychosocial factors at work, as indicated by the two leading stress models, job strain and effort-reward imbalance."

"Most people care deeply about just treatment by authorities," the authors conclude. "Just treatment may communicate status and value, whereas lack of justice may be a source of oppression, deprivation, and stress. Justice, equity, and altruism have been the drivers of benign developments in human societies according to a wide range of studies across a broad spectrum of disciplines. Our findings on CHD, the leading cause of death in all Western societies, suggest that organizational justice is also a topic worthy of consideration in health research."

EUROASPIRE II2 - One in five heart patients continue to smoke after first coronary event

Thu, 06 Oct 2005 22:58:38 PST

( from http://www.rxpgnews.com ) An international survey published today (Thursday 6 October) in Europe's leading cardiology journal, European Heart Journal1, reveals that fewer than half of the heart patients in the study who smoked quit after suffering their first coronary event, with one out of five continuing to smoke despite advice to stop.

Epidemiologist and lead author of the study, Dr Wilma Scholte op Reimer, said it was "unbelievable" that so many carried on smoking after a life-threatening event for which smoking is a major risk factor. "It makes me wonder if they are truly aware of the risk that they are taking," she said.

The survey EUROASPIRE II2 undertaken during 1999 and 2000, involved 5,551 coronary patients aged up to 70 in 47 hospitals in 15 European countries. They were interviewed around 16 months after the event or condition for which they entered hospital coronary artery bypass, balloon angioplasty, heart attack or unstable angina. The patients were asked if they had ever smoked, whether they had smoked in the month prior to hospital admission and whether they currently smoked, with smokers who denied currently smoking being tested for carbon monoxide in their breath. The survey was a follow-up to EUROASPIRE I five years earlier and found similar results.

Of the 5,551 patients, 21% were still persistent smokers 39% of those under 50, 26% of those aged 50-60 and 14% of those aged around 60. Men and women had similar prevalence. Nearly all (99%) of the 2,244 pre-heart event smokers had been advised by a health professional to stop, and 48% had done so.

"We found that younger patients were less likely to quit only 41% of under 50s and that those with angina were less likely to quit than those who had suffered a heart attack (38% as against 52%)," said Dr Scholte op Reimer who works at the Erasmus University Medical Centre in Rotterdam, The Netherlands.

The worrying finding that those with angina were less likely to stop than heart attack patients may be due to a lack of awareness of their risk, according to Dr Scholte op Reimer. A heart attack was often the first manifestation of coronary disease. Doctors were keen on achieving good risk management in these cases and the patients themselves were motivated because they probably realised the seriousness of their diseases.

However, for angina patients, the risk may have been under-estimated. "In fact, their long term mortality is no better than that of patients who have had a heart attack," she said. "Perhaps this needs to be spelled out to them. The need to stop is highest in patients with established coronary heart disease (CHD) as within two to three years the risk of subsequent events falls to that of CHD patients who have never smoked. In people with no symptoms it takes up to ten years for risks to fall to the level of non-smokers. This shows how much a patient can gain from quitting often much more than most of the medication they take. I think professionals should confront their patients with these facts more often."

Another surprising finding was that only one fifth of those who had stopped reported having received written advice compared with 30% of those who continued smoking. "We can't tell from our study why this is," said Dr Scholte op Reimer. "Perhaps most patients who stopped had already made the decision when the written advice was given to them and therefore didn't register it, or maybe the advice was offered or put out for them to take away, but having decided to stop smoking, not accepted because they felt no need to take it."

The survey showed there was still a need for the development of more intensive, effective smoking cessation programmes, particularly focused on younger patients, those with lower levels of education (who the survey found were less likely to stop than those with university education) and those whose disease had first manifested as angina.

Dr Scholte op Reimer said that, in line with current guidelines on cardiovascular disease (CVD) prevention, a doctor's firm advice at the time of diagnosis was the most important factor in starting the quitting process. Many patients succeeded without special programmes, but for those who needed support, there should be a specific plan that is followed through. Nicotine replacement and certain anti-depressants should also be available if necessary.

There may also be a difference, she said, between patients having the general knowledge that smoking is a bad habit, and learning their precise risk as an individual. Individual risk could now be worked out via HeartScore a computer program launched recently by the European Society of Cardiology, aimed at preventing CVD (primary prevention). The program can also calculate how much a person can change his or her risk of fatal CVD within 10 years by stopping smoking.

Another survey EUROASPIRE III is planned to see whether the situation improves. "It was disappointing that there was hardly any change in the five years between the first two surveys. However, we believe that the European guidelines on CVD prevention, tools such as HeartScore and interventions by governments might mean that attitudes will have improved by the time we carry out the next survey," Dr Scholte op Reimer concluded.

Medication-Releasing Stent Reduces Risk Of Artery Re-Narrowing

Fri, 16 Sep 2005 18:03:38 PST

( from http://www.rxpgnews.com ) Compared to bare metal stents, placement of stents that release the medication paclitaxel reduces the risk of the artery re-narrowing nine months following angioplasty for patients with complex coronary artery lesions, according to an article in the September 14 issue of JAMA.

Drug-eluting stents have revolutionized the treatment of atherosclerotic coronary artery disease, according to background information in the article. These stents (which release medications, such as sirolimus and paclitaxel) have been shown to safely reduce clinical and angiographic restenosis (narrowing again of the artery after treatment) compared with bare metal stents. Enrollment in the trials for these stents, however, was restricted to relatively simple stenoses (vessel diameter of 2.5-3.75 mm with lesion length 30 mm or less). More than 55 percent of lesions currently treated with these bioactive devices may fall outside this range. The efficacy of drug-eluting stents has not been established for small vessels (in which the utility of stents as a class is still uncertain), large vessels (in which outcomes with bare metal stents are favorable), or in long lesions requiring multiple stents.

Gregg W. Stone, M.D., of Columbia University Medical Center and Cardiovascular Research Foundation, New York, and colleagues conducted a study (the TAXUS V trial) to investigate the safety and efficacy of a paclitaxel-eluting stent in a patient population with more complex coronary lesions than previously studied. The trial, conducted from February 2003 to March 2004 at 66 academic and community-based institutions, included 1,156 patients who underwent stent implantation in a single coronary artery stenosis (vessel diameter, 2.25-4.0 mm; lesion length, 10-46 mm), including 664 patients (57.4 percent) with complex or previously unstudied lesions (requiring 2.25-mm, 4.0-mm, and/or multiple stents) and had 9-month clinical and angiographic follow-up. Patients were randomly assigned to receive 1 or more bare metal stents (n = 579) or identical-appearing paclitaxel-eluting stents (n = 577).

The average reference vessel diameter was 2.69 mm, the reference lesion length was 17.2 mm. An average of 1.38 stents (total average length, 28.4 mm) were implanted per lesion. Stents of 2.25 mm and 4.0 mm in diameter were used in 18 percent and 17 percent of lesions, respectively; multiple stents were used in 33 percent of lesions.

"Compared with bare metal stents, implantation of paclitaxel-eluting stents reduced the 9-month rate of target lesion revascularization from 15.7 percent to 8.6 percent and target vessel revascularization from 17.3 percent to 12.1 percent. Among patients receiving the paclitaxel-eluting stent compared with a bare metal stent, the rate of in-stent restenosis was reduced with from 31.9 percent to 13.7 percent and analysis segment angiographic restenosis was reduced from 33.9 percent to 18.9 percent," the authors write.

"By multivariate analysis, randomization to the paclitaxel-eluting stent was an independent predictor of freedom from 9-month target lesion revascularization [2.2 times more likely], target vessel revascularization [1.7 times more likely], and restenosis [2.9 times more likely]. These benefits were achieved with comparable safety in both groups, with similar rates of cardiac death, myocardial infarction, and stent thrombosis at 1 and 9 months."

Angiographic restenosis was also reduced among patients receiving 2.25-mm stents (49.4 percent vs. 31.2 percent), 4.0-mm stents (14.4 percent vs. 3.5 percent), and multiple stents (57.8 percent vs. 27.2 percent).

"In conclusion, the TAXUS V trial investigated the use of paclitaxel-eluting stents in a patient population with more complex lesions than had been previously studied. Angiographic restenosis and target vessel revascularization were significantly reduced in the entire cohort, as well as in those patients with complex disease," the authors write.

Clopidogrel Before Angioplasty Cuts in Half Risk of Death - PCI-CLARITY study

Wed, 14 Sep 2005 02:16:38 PST

( from http://www.rxpgnews.com ) A new study from Brigham and Womens Hospital (BWH) finds that early use of clopidogrel, an oral antiplatelet medication, started prior to rather than at the time of angioplasty, reduces the odds of death, heart attack or stroke following the angioplasty by more than 45 percent. Results of the PCI-CLARITY study were presented by Marc S. Sabatine, MD, MPH, an associate physician in the Cardiovascular Division at BWH and an instructor in Medicine at Harvard Medical School (HMS) at the European Society of Cardiology (ESC) Congress 2005 in Stockholm, Sweden on September 3 7, 2005.

Earlier this year, Sabatine and colleagues at BWH published the results of CLARITY-TIMI 28 (Clopidogrel as Adjunctive Reperfusion Therapy Thrombolysis in Myocardial Infarction) in the New England Journal of Medicine, demonstrating that clopidogrel helped open blocked arteries and decreased the odds of a second heart attack by 31 percent. Now, this group of researchers has found that the administration of clopidogrel before angioplasty offers profound protection against major complications.

Angioplasty, also known as percutaneous coronary intervention (PCI), is a procedure performed by cardiologists to relieve coronary narrowing. More than two million PCIs are performed each year worldwide, the majority of which involve insertion of a coronary stent to help keep the artery open. Patients undergoing PCI are routinely given clopidogrel after the procedure to help prevent complications, noted Sabatine. We found that starting treatment with clopidogrel before the procedure led to a significant reduction in the risk of cardiovascular death and ischemic complications following the angioplasty.

The PCI-CLARITY trial analyzed 1,863 patients with a recent heart attack that went on to undergo PCI. Within this group 933 had been randomized to receive clopidogrel (300 mg loading dose, then 75 mg once daily) and 930 had been randomized to receive placebo when they first presented to the hospital. Primary outcomes were death, recurrent heart attack or stroke from PCI to 30 days after randomization. After analyzing results, researchers found that clopidogrel pretreatment reduced the odds of death, recurrent heart attack or stroke by 46 percent. Pretreatment also reduced the odds of a recurrent heart attack or stroke while awaiting PCI by 38 percent. The researchers found that pretreatment was beneficial regardless of the patients age or sex or delay until the procedure. According to Christopher P. Cannon, MD the Principal Investigator of CLARITY-TIMI 28, an associate physician in the Cardiovascular Division at BWH and an associate professor of Medicine at HMS, For every 23 patients we treated with clopidogrel before PCI, we prevented one major cardiovascular event. That is an amazingly big benefit that results from one to three extra doses of clopidogrel.

The rich data from CLARITY-TIMI 28 has shown us that clopidogrel is important in the treatment of heart attacks. Now we have direct evidence that it also helps reduce odds of death associated with angioplasty and stenting procedures, said senior author BWHs Eugene Braunwald, MD, HMS Distinguished Hersey Professor of Medicine and chairman of the TIMI Study Group. I am proud that BWH continues to define the standard of care for heart attack patients around the world. I believe these results are an important contribution to how we treat patients with coronary artery disease.

Genetic risk of acute coronary event (GRACE) study presented today

Mon, 05 Sep 2005 23:37:38 PST

( from http://www.rxpgnews.com ) An unusual British Heart Foundation (BHF) 'DNA database' from brothers and sisters across the UK has enabled researchers to pinpoint six genetic 'hotspots' that can double the risk of developing early heart disease.

By providing DNA samples, 2871 siblings from 930 families have taken part in the important genetic risk of acute coronary event (GRACE) study, aiming to find culprit genes that make some people more vulnerable to heart problems in middle age.

Researchers at University of Leeds analysed the samples for genetic differences between brothers or sisters with heart disease and those that are unaffected. They found that certain variations lead to more than a doubling of risk for some family members.
The results are being presented today to heart specialists at the European society of cardiology congress in Stockholm, Sweden.

The Congress will hear that the analysis of the GRACE collection has unearthed variations in three genes important in our natural defense to infections that seem to confer protection to heart disease, while another three also part of our immune responses seem to contribute to causing disease.

Whereas many studies compare disease sufferers to the general population, who will naturally have lots of genetic differences, the GRACE study was able to focus in on the important, hard-to-find, disease-causing variations because they were comparing siblings, who have very similar genetic make-up.

The research team led by Professor Alistair Hall found that although variations in individual genes increased the chance of heart disease, the cumulative effect of carrying lots of the 'bad' genes and fewer of the 'good' genes could double the risk.

Dr Ben Brown, who is presenting the study, said, "This is a really exciting finding. We are one of the first studies to examine such a large number of families affected by heart disease giving us real confidence in the results.

"We are starting to see how examining what we inherit from our parents and share with our brothers and sisters may put us at an increased risk.

"Importantly, we probably already have the medicines available to reduce the risk from these genes but sadly not all who need them are taking them. This greater understanding will eventually allow us to identify those most at risk, reducing the numbers dying each year by preventing the problem in the first place."

Professor Peter Weissberg said, "The GRACE collection is special because it allows us to cut down the background genetic 'noise' and focus on those genes that are important in our fight against heart disease.

"The next step will be to see if the results are consistent in different populations and then test how the genetic variations are causing increased risk. The future should see us being able to accurately predict which family members need to be most diligent in reducing their heart disease risk through a healthy lifestyle and careful health monitoring."

Coronary Heart Disease Is Under-Diagnosed And Under-Treated In Women

Fri, 02 Sep 2005 18:39:38 PST

( from http://www.rxpgnews.com ) Coronary heart disease is under-diagnosed, under-treated, and under-researched in women, says a senior doctor in this weeks BMJ.

Cardiovascular disease remains the leading cause of death in men and women worldwide, exceeding the number of deaths from all cancers combined. In Europe, cardiovascular disease kills a higher percentage of women (55%) than men (43%). Yet it is still considered a disease of men.

Many women are unaware that coronary heart disease is their main killer; their biggest fear is breast cancer, writes cardiologist Ghada Mikhail. Even more worrying is the apparent lack of awareness of cardiovascular disease in women among healthcare professionals.

Women and men with heart disease tend to differ in their presenting symptoms, their access to investigations and treatment, and their overall prognosis. For example, women may have less common symptoms, are less likely to seek medical help, and tend to present late in the process of their disease.

They are also less likely to have appropriate investigations, which can delay the start of effective treatment.

Women also continue to be under-represented in research on heart disease, making it difficult to draw conclusive evidence on managing cardiovascular disease. To remedy this, the author suggests that participants sex must be considered in the design and analysis of cardiology studies.

Better awareness and education, earlier and more aggressive control of risk factors, and appropriate access to diagnosis and treatment are desperately needed to tackle this potentially fatal disease, she concludes.

C-reactive protein can be an early indicator of stiffened arteries

Tue, 23 Aug 2005 20:48:38 PST

( from http://www.rxpgnews.com ) The Mayo Clinic research report appears online and in the August issue of the American Journal of Hypertension, http://www.sciencedirect.com/science/journal/08957061. The Mayo Clinic collaborative study with researchers from the University of Michigan looked at 214 men and women with an average age of 59, who had no history of heart attack or stroke. Results suggest that low grade inflammation is associated with arterial stiffness (hardening). This inflammation may be a potential mechanism through which C-reactive protein is related to heart attack and stroke, and why testing for C-reactive protein in a blood test may be an effective early warning test for asymptomatic, or presymptomatic heart disease.

Significance of Mayo Clinic Research

Researchers around the world agree that C-reactive protein is associated with increased risk of heart attack and stroke. But it remains controversial whether C-reactive protein is a risk factor that affects the function of blood vessels, or if it is simply a marker signifying the presence of disease.

In addition to taking into account the traditional risk factors for heart disease--such as male sex, presence of diabetes, high blood pressure, high cholesterol and smoking--the research team also measured C-reactive protein levels as well as three indicators of arterial stiffness. Stiffening of arteries indicates a loss of their elastic properties and predisposes to heart attack, stroke and congestive heart failure.

Says lead Mayo Clinic researcher Iftikhar Kullo, M.D., "The current inability to accurately predict cardiovascular events such as heart attack is a problem, and anything we can do to improve risk assessment is a public health priority. Our study provides a new insight into how low grade inflammation could be related to heart and stroke by its association with arterial stiffness. Thus suppression of inflammation may be a target of drug therapy to improve arterial health."

Prognosticating chest pain now easier and more accurate

Tue, 28 Jun 2005 00:59:38 PST

( from http://www.rxpgnews.com ) A new, more precise test is available to improve the accuracy of detecting coronary artery disease and risk of heart attack, and can be done right at the bedside.

Physicians in emergency departments are challenged in diagnosing the cause and risk factors of chest pain in their patients. Now, using real-time myocardial contrast echocardiography (RTMCE), a type of ultrasound, physicians are able to rapidly and accurately detect coronary artery disease - a risk factor that leads to heart attacks.

This study, from the University of Nebraska Medical Center and supported by a local grant (Hubbard Foundation), performed dobutamine stress echoes in 158 patients presenting with chest pain and possible acute coronary syndrome using the RTMCE test method. They found that perfusion imaging was better than wall motion analysis during dobutamine stress echo for detecting coronary artery disease and predicting patient outcome.

This study suggests that by using this non-invasive method of determining the prognosis for patients with unexplained chest pain, patients can be set on the proper course for long-term survival.

A change of heart for MEF2A in coronary artery disease

Sun, 03 Apr 2005 13:10:38 PST

( from http://www.rxpgnews.com ) Coronary artery disease (CAD) is one of the major killers in Western societies. Recently, mutations in a gene called MEF2A on chromosome 15 were reported to be causative of premature CAD. The authors of the report failed to find the mutation in a large number of control individuals and thus concluded that the MEF2A mutation was the cause of the CAD. Only a single family was observed to carry the putative mutation, however.

A new study appearing in the April 1 print issue of The Journal of Clinical Investigation overturns these findings. Len Pennacchio and colleagues from Lawrence Berkeley National Laboratory have sequenced the MEF2A gene in about 300 patients with premature coronary heart disease and fail to find any causative mutations.

The researchers do find the precise mutation (a 21 base pair deletion) that was previously reported to be causative of CAD, but in this new JCI study, this mutation was found in three control subjects who did not have CAD or any other coronary heart disease. Thus, the studies demonstrate that MEF2A mutations are not common cause of heart disease and suggest that another one of 93 genes in that area of chromosome 15 was responsible for heart disease in the original family. These data question the role of MEF2A in CAD. In an accompanying commentary, David Altshuler and Joel Hirschhorn write, "the genetic evidence available to date does not demonstrate that these mutations play a causal role in CAD in humans.These [new] studies remind us that replication and multiplicity in human genetic research are critically important."