exercise improves quality of life for heart failure patients

DURHAM, N.C.,14 nov 2008– Heart failure patients who regularly exercise fare better and feel better about their lives than do similar patients who do not work out on a regular basis, say researchers at Duke University Medical Center.

The findings, reported today at the annual meeting of the American Heart Association's Scientific Sessions 2008, go a long way toward addressing concerns about the value of exercise for the nation's five million patients with heart failure. They also raise important policy questions for the country's Medicare program and other insurers.

"Past studies have sent mixed signals about the merit of exercise for patients with heart failure. The HF-ACTION study (A Controlled Trial Investigating Outcomes Exercise TraiNing) shows that exercise is not only safe for patients, but also helps to improve the quality of their lives, overall," says Kathryn Flynn, PhD, a health services researcher at Duke Clinical Research Institute (DCRI) and lead author of the study.

HF-ACTION is the largest clinical trial to date examining the value of exercise in the treatment of heart failure. Investigators enrolled 2331 patients with moderate to severe heart failure at 82 sites throughout the U.S., Canada and France from 2003 to 2008.

Funded by a $37 million grant from the National Heart, Blood, and Lung Institute, researchers randomized participants to receive either standard care or standard care plus an exercise program. The exercise regimen consisted of three months of supervised aerobic training on a bicycle or treadmill, followed by instruction for continued home-based training. Researchers set the exercise goal at five, 40-minute workouts, or 200 minutes of exercise per week. Participants reached about 60 percent of that goal at one year.

Participants had significant heart failure upon entering the study, measured by diminished left ventricular ejection fraction (mean, 25 percent). Ninety-five per cent of the patients were taking medications for heart failure, such as ACE-inhibitors or beta-blockers, and 40 percent were using mechanical devices to boost their hearts' ability to pump or to treat arrythmias. The average age of the patients was 59; 28 percent were women.

Upon enrollment, patients filled out the Kansas City Cardiomyopathy Questionnaire (KCCQ), a 23-item measure shown to be responsive to underlying clinical changes in patients with heart failure. The KCCQ generated an overall measure of quality of life and subscale measures reflecting the patients' physical limitations, symptoms, quality of life and social restrictions. Participants completed the questionnaire at three-month intervals for the first 12 months, and annually thereafter. The average time of follow-up was two and one-half years.

There were no significant differences between the two patient groups at baseline. The average overall KCCQ score among patients in both groups was 66.

At three months, patients in both groups showed improvement, with patients in the usual care group registering a three-point gain on the KCCQ score and those in the exercise group showing a five-point gain (p =.0005). Previous reports had defined a five-point gain as clinically significant.

Researchers also found that a higher percentage of those in the exercise group experienced more robust gains. At three months, 54 percent of those in the exercise group saw a five-point gain in overall KCCQ score, while only 28 percent of those in the usual care group met that goal. (p = .0001).

Exercise group members consistently outscored those in the usual care group on all subscale measures on the KCCQ, as well. "And the best news is that while the gains were modest, they were sustained over time," says Flynn.

During the study period, the incidence of adverse effects was similar between the two groups. There were 41 heart attacks among patients in the exercise arm and 45 heart attacks among those receiving usual care. Arrythmias occurred in about 14 percent of the patients in each group.

Researchers say the findings are important because they demonstrate that a relatively low-cost and readily available intervention can significantly improve the quality of life for heart failure patients, a finding that may be important for the country's Medicare program, which currently does not pay for exercise therapy for patients with heart failure.

"We found that a majority of those who exercised reported a five-point improvement in the KCCQ scale. That means that they experienced significant improvement in many aspects of their day-to-day activities, such as working, walking, being able to dress, bathe, and getting out to visit family and friends," says Ileana Piña, MD, a professor of medicine at Case Western Reserve University and chair of the HF-ACTION Steering Committee. Piña, who is a Quality Scholar at the Cleveland VA, says clinicians should consider using the KCCQ inventory on a regular basis. "It is a quick and easy method to find out valuable information about patients' health status. It only takes about eight minutes to fill out, which is a small burden for patients."

"This study has important implications for the 5 million Americans who have heart failure," noted Elizabeth G. Nabel, MD, NHLBI director. "As the number of people affected by heart failure is expected to rise with the aging U.S. population, it is promising to know that regular aerobic activity can not only help patients extend their lives, but exercise can also positively impact their everyday activities and outlook."

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Additional authors on the study include senior author, Kevin Weinfurt, DCRI, Steven Keteyian, co-chair of the HF-ACTION Steering Committee, Henry Ford Hospital; Kerry Lee, Christopher O'Connor, Kevin Schulman, Li Lin, James Blumenthal, Stephen Ellis, and William Kraus, from DCRI; David Whellan, Jefferson Medical College; Nancy Houston Miller, Stanford University; Jonathan Howlett, Dalhousie University; Dalane Kitzman, Wake Forest University, John Spertus, Mid America Heart Institute; and Lawrence Fine and Lawton Cooper; National Heart, Lung, and Blood Institute.

Over 50 percent of people with high blood pressure unaware they have condition

14 nov 2008--More than half of people diagnosed with high blood pressure do not have it under control and many more go undiagnosed, according to research carried out at the University of Warwick.

Professor Franco Cappuccio from Warwick Medical School at the University of Warwick led the only UK team to participate in a European study examining awareness, treatment and control of high blood pressure, or hypertension. Hypertension is an important cause of serious diseases such as heart attacks and strokes.

The IMMIDIET study, published today in the Journal of Hypertension, examined 1,604 citizens from three geographical areas, south-west London in the UK, Limburg in Belgium and Abruzzo in Italy. All participants underwent a medical examination, including blood pressure measurement, and answered a lifestyle and health questionnaire.

The researchers found 24% of participants had high blood pressure and 56% of these people were not aware of their condition. Of those that were aware, less than half had their high blood pressure under control (less than 140mmHg for systolic pressure and 80 for diastolic pressure).

Looking at the differences between regions, the researchers found the UK participants had lower blood pressure overall and better control than the Italians and Belgians.

Professor Franco Cappuccio said the study was a call for better management of hypertension and the implementation of widespread strategies to prevent the condition in the first place.

He said: "Our results show that high blood pressure is a looming problem for Europe. Although in the UK the management of high blood pressure is better as compared to some other countries, in part due to the incentives that GPs receive to achieve blood pressure targets. We still have too many patients not adequately treated and the incidence of hypertension is rising still."

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The IMMIDIET paper is available in the Journal of Hypertension 2008, 26:1-10. Visit www2.warwick.ac.uk/fac/med/research /csri/cvme/immidiet/ for more details of the research project.

MSU researcher studies ties between cholesterol drugs, muscle problems

Evidence suggests statins can cause muscle weakness, fatigue and deterioration

EAST LANSING, Mich., 13 nov 2008— A Michigan State University researcher is studying whether the most popular class of cholesterol-lowering drugs may cause muscle problems in users.

There is accumulating evidence that the effect statins can have on skeletal muscle – including muscle weakness, fatigue and deterioration – is underestimated, said Jill Slade, assistant professor of radiology and osteopathic manipulative medicine at MSU.

"Statins work by preventing cholesterol from forming," said Slade, whose study is funded by a two-year, $230,000 grant from the National Institutes of Health. "While this is a good thing inside structures such as liver cells, it can be problematic in places such as muscle cells."

About 50 percent of all Americans over the age of 50 are prescribed a statin medication, including Lipitor, Crestor and Torvast, and their use has tripled in the past seven years. Side effects affecting skeletal muscles have been reported in up to 7 percent of users, though Slade thinks that number could be higher.

In August 2001, the Food and Drug Administration pulled the statin Baycol off the market after it appeared to be responsible for 31 deaths through a potentially fatal breakdown of muscle tissue known as rhabdomyolysis. The FDA at the time said the muscle breakdown occurred more frequently in patients taking Baycol than in patients on other statins. The National Lipid Association in 2006 published recommendations on investigating statin-induced muscle problems, and Slade's research will directly address several of those.

As part of her study, Slade will use nuclear magnetic resonance imaging at the MSU Department of Radiology Exercise and Nutrition Lab to measure muscle integrity and function before and during statin treatment. Fifty people – half taking high doses of statins and half taking low doses – will be analyzed over a one- to six-month period.

"While statins have tremendously helped millions of Americans lower their cholesterol and improve their cardiac health, we need to be confident we are not causing other problems in the body," Slade said. "It is important to understand the side effects of using statins and have the tools to identify people who may be more susceptible to them."

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Michigan State University has been advancing knowledge and transforming lives through innovative teaching, research and outreach for more than 150 years.

Exercise is safe, improves outcomes for patients with heart failure

DURHAM, N.C., 13 nov 2008 – Working out on a stationary bicycle or walking on a treadmill just 25 to 30 minutes most days of the week is enough to modestly lower risk of hospitalization or death for patients with heart failure, say researchers from Duke Clinical Research Institute (DCRI).

The findings stem from the HF-ACTION trial (A Controlled Trial Investigating Outcomes Exercise TraiNing), the most comprehensive study to date examining the effects of exercise upon patients with heart failure. The study was reported today as a late-breaking clinical trial at the American Heart Association's Scientific Sessions 2008 by Christopher O'Connor M.D., director of the Duke Heart Center and principal investigator of the trial, and David Whellan, M.D., of Thomas Jefferson University, co-principal investigator.

HF-ACTION enrolled 2331 patients at 82 study sites throughout the U.S., Canada and France. Patients were randomized into a group that received usual care or to a group that received usual care plus an exercise training program that began under supervision but then transitioned to home-based, self-monitored workouts.

Researchers hypothesized that participation in an exercise program would significantly lower the incidence of death and hospitalization among patients with heart failure.

But based on the protocol-specified initial analysis, exercise training produced only a modest, non-significant reduction in the primary endpoint of all-cause hospitalization or all-cause death.

A planned, secondary analysis, however, that took into account the strongest clinical factors predicting hospitalization or death, found exercise to be significantly beneficial.

Researchers hope the findings will finally put to rest long-held fears that exercise may be too risky for some patients. "The most important thing we found from this study is that exercise is safe for patients with heart failure, and when adjustments were made for specific baseline characteristics, it significantly improved clinical outcomes," said O'Connor.

Whellan, who is also director of clinical research at the Jefferson Heart Center, says previous studies sent mixed signals, due, in part, to their small size. Some found exercise beneficial, but others did not, and there was limited safety data. "It took a study of this size and duration to determine that exercise is not only safe, but also effective in lowering risk of hospitalization or death for patients with heart failure."

Clinical guidelines say exercise should be considered for stable patients with heart failure, but the lack of definitive data about its long-term benefits has limited Medicare and other insurers from considering an intervention that should be covered.

Participants in HF-ACTION had a significant degree of heart failure, determined by left ventricular ejection rate (LVEF), a measure of how vigorously the heart pumps blood throughout the body. The patients' mean LVEF was 25; a value less than 35 is considered problematic. And they were already receiving optimal care. Ninety-five percent were taking medications for heart failure, such as ACE-inhibitors or beta-blockers, and 45 percent were using mechanical devices to boost their hearts' ability to pump or to treat arrthymias. The average age of the patients was 59 and almost one-third of them were women.

"These patients were quite sick and were receiving exceptionally good care. That makes the gains they made in the exercise program all the more remarkable," said Whellan.

Patients in the exercise arm started out slowly, with a goal of three, 30-minute workout sessions three times per week. After 18 sessions, they transitioned to workouts at home, with a goal of 40 minutes five days per week on a stationary bicycle or treadmill. Patients kept logs of their exercise times and heart rates.

In contrast, patients in the usual care arm continued their usual medical therapy and were simply encouraged to be active. Members of both groups received education about the value of exercise and supportive phone calls.

Investigators followed the patients for an average of two and half years, tracking various clinical measures of heart failure, quality of life, hospitalization, cardiac events and death rates.

During the study, 796 (68 percent) of patients in the usual care arm died or were hospitalized, compared to 759 (65 percent) in the exercise arm. There were 198 deaths (17 percent) among patients in the usual care arm, compared to 189 (16 percent) in the exercise arm.

In adjusting for clinical characteristics strongly predictive of outcomes, including history of atrial fibrillation, depression, LVEF status, and the patients' initial capacity for exercise, investigators found that exercise led to a significant 11 percent reduction in risk of hospitalization or death for those in the exercise group (p =.03).

They also found that those in the exercise group had a significant, 15 percent lower risk of death from cardiovascular disease and hospitalization due to complications of heart failure (p = .03), a secondary end point of the study.

"We feel these are important findings for patients and physicians alike," said Whellan. "It takes a lot of time and commitment to definitively answer a question that many of us had asked for years: Can exercise provide clinically significant benefit for patients with heart failure? Now we know that the answer is 'yes.' We also know that it is safe: There was no significant difference between the two study groups in the risk of heart attacks, arrhythmias, falls or fractures during the study period."

Investigators say there are some limitations to the study. The benefit of exercise may have been diminished somewhat by the fact that there was a sizable number of patients randomized to the usual care arm who actually decided to exercise on their own.

Researchers say there is important work that still needs to be done. "HF-ACTION was comprehensive and carefully conducted study that answered an important clinical question for all of us," says O'Connor. "But at the same time, it raises new ones: How will physicians incorporate these findings into their practice, and how will these programs be paid for? We are working on a cost/benefit analysis we hope will help answer some of these questions."

"This study has important implications for the 5 million Americans who have heart failure," noted Elizabeth G. Nabel, MD, director of the National Heart, Lung, and Blood Institute of the National Institutes of Health, which funded the $37 million study. "As the number of people affected by heart failure is expected to rise with the aging U.S. population, it is promising to know that patients can benefit from a low-risk method to improve their health."

Preventing anemia is important to kidney disease patients' quality of life

Study indicates that FDA statements may need to be revised

13 nov 2008--Maintaining sufficient red blood cell levels is important to the physical and mental health of patients with chronic kidney disease (CKD), according to a study appearing in the January 2009 issue of the Clinical Journal of the American Society Nephrology (CJASN). The findings indicate that preventing anemia in kidney disease patients should be an integral part of their care.

Erythropoiesis-stimulating agents—medications that elevate red blood cell levels (hemoglobin)—have been a topic of controversy lately, and their use in patients with chronic kidney disease has come into question. Recent studies have shown an increased risk of death, blood clots, strokes, and heart attacks in patients with chronic kidney failure when erythropoiesis-stimulating agents are given at higher than recommended doses. (Current recommendations indicate that treatment should not elevate hemoglobin levels over 12 gm/dl). Other studies have found a link between the recommended doses of these drugs and an increased risk of death in patients with cancer and an increased risk of blood clots in patients following orthopedic surgery. In addition, the US Food and Drug Administration stated that the benefits of erythropoiesis-stimulating agents have not been well documented, particularly as they relate to quality of life. These suggestions are disturbing to nephrologists, who believe that these drugs have significantly helped their CKD patients.

To help clarify the issue, Fredric Finkelstein, MD, of the Hospital of St. Raphael and Yale University in New Haven, CT, and his colleagues studied the relationship between hemoglobin levels and health-related quality of life (which includes both mental and physical components) in patients with CKD.

A total of 1,186 patients with stage three to stage five CKD participated in this study, and they were grouped into categories based on their hemoglobin levels (<11>

The study's findings suggest that maintaining hemoglobin levels is important to the health and well-being of patients with CKD. The authors recommend that additional studies should be done to document the changes in quality of life that occur when erythropoiesis-stimulating agents are used to elevate hemoglobin levels in patients with this disease.

More work also is needed to determine when treatment should be initiated and what the hemoglobin target level should be. "The impact of the answers to these questions for the health-related quality of life of chronic kidney disease patients may well be substantial," the authors wrote.

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The article, entitled "Health-Related Quality of Life and Hemoglobin Levels in Chronic Kidney Disease," is available online at http://cjasn.asnjournals.org and will appear in the January 2009 print issue of CJASN.

3 clinical features identified to avoid misdiagnosis of TIAs

Only 40 percent of emergency room cases are true TIAs

13 nov 2008--For mini-strokes, or transient ischemic attacks (TIAs), both overdiagnosis and underdiagnosis can be perilous. Overdiagnosis neglects the real underlying illness. Underdiagnosis leaves a patient at risk of a full-fledged stroke. Both expose patients to erroneous therapies with potential side effects.

And yet, TIAs are difficult to assess because, by definition, the neurological dysfunction that results is so brief. By the time the patient arrives at a doctor's office or an emergency room, the symptoms are often gone.

Now, researchers at Rush University Medical Center have identified three bedside clinical features that can help more accurately distinguish TIAs from disorders that might mimic their symptoms.

The study has just been published online and will appear in the December issue of Cerebrovascular Diseases.

Two neurologists at Rush University Medical Center, Dr. Shyam Prabhakaran, lead author of the study and head of the stroke service, and Dr. Vivien Lee examined the records of 100 emergency room patients who had an initial diagnosis of TIA and were admitted for further evaluation. Only 40, or 40 percent, of these cases turned out to be true TIAs.

The researchers were able to identify three clinical features that, together, correctly classified 79 percent of the cases.

"Speed of onset, we found, was the strongest indicator of a TIA. I typically ask my patients if their symptoms came on like lightning, within seconds," Prabhakaran said. "With other neurological problems that can mimic a TIA – migraines or seizures, for example – symptoms take more than a minute to manifest themselves."

The researchers found that a TIA was unlikely if a patient reported nonspecific symptoms, such as lightheadedness, tightness in the chest or stomach upset, along with the neurological dysfunction.

A TIA was also unlikely if the patient had a history of similar episodes where a TIA was ruled out.

"It's important not to miss a diagnosis of TIA, as these attacks can be harbingers of stroke and patients need to be treated," Prabhakaran said. "But at the same time, we don't want to overdiagnose TIAs. Overdiagnosis subjects patients to the risks of unnecessary and potentially dangerous medications and tests, and leaves their actual condition untreated or inadequately managed."

Approximately 240,000 TIAs are diagnosed in the United States each year. TIAs carry a particularly high short-term risk of stroke, and about 15 percent of diagnosed strokes are preceded by TIAs. Symptoms vary widely from person to person, depending on the area of the brain affected. The most frequent symptoms include temporary loss of vision, difficulty speaking and weakness, numbness or tingling on one side of the body.

Caring for the caregiver: Redefining the definition of patient

IU study finds 25 percent of family caregivers of AD patients go to ER Or are hospitalized

INDIANAPOLIS, 13 nov 2008 – One quarter of all family caregivers of Alzheimer's disease patients succumb to the stress of providing care to a loved one and become hospital patients themselves, according to an Indiana University study published in the November 2008 issue of the Journal of General Internal Medicine.

Researchers from the Indiana University School of Medicine, the Regenstrief Institute and the Indiana University Center for Aging Research report in a new study that a quarter of family caregivers of Alzheimer's dementia patients had at least one emergency room visit or hospitalization every six months.

While it has long been anecdotally recognized that caring for a family member with Alzheimer's disease is stressful, this work is the first to measure just how stressful providing care is and to examine the impact of this stress on both the physical and mental health of the family caregiver.

The study found that the behavior and functioning of the individual with Alzheimer's dementia, rather than cognitive ability, were the major factors determining whether the caregiver went to the emergency room or was hospitalized.

"Our findings opened our minds to the fact that society needs to expand the definition of patient to include both the person with Alzheimer's dementia and that individual's family caregiver," said Malaz Boustani, M.D., corresponding author. Dr. Boustani is assistant professor of medicine and a Regenstrief Institute research scientist.

The researchers looked at 153 individuals with Alzheimer's disease and their family caregivers, a total of 366 people. Forty-four percent of the caregivers were spouses. Seventy percent of the caregivers resided with their charges.

The average caregiver was 61 years of age. The researchers found that age, education and relationship to the individual with Alzheimer's disease did not impact caregiver use of acute medical services – either emergency room or inpatient facilities.

"While we've long known that Alzheimer's is a devastating disease to the patient, this study offers a look at how it also impacts the caregiver's health. If we don't offer help and support to the caregiver, too, the stress of caring for someone with dementia can be overwhelming, both mentally and physically," said Cathy C. Schubert, M.D., IU School of Medicine assistant professor of clinical medicine.

Approximately four million older adults in the United States have Alzheimer's disease and three million of them live in the community, often cared for by family members. This number is growing rapidly and by 2050 it is estimated that there will be 18.5 million cases of Alzheimer's dementia in the United States.

"For American society to respond to the growing epidemic of Alzheimer's disease, the health-care system needs to rethink the definition of patient. These findings alert health-care delivery planners that they need to restructure the health-care system to accommodate our new inclusive definition of patient," said Dr. Boustani.

Dr. Boustani directs the Healthy Aging Brain Center. Using the findings of this study, the center is leading the nation in expanding the definition of patient to include the individual with Alzheimer's disease and family caregivers and to provide care to both. The Healthy Aging Brain Center is part of the IU Center for Senior Health at Wishard Health Services.

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Dr. Schubert is the medical director of the IU Center for Senior Health at Wishard and Acute Care for Elders at Indiana University Hospital.

'Cognitive Reserve' May Help Fight Alzheimer's

By Ed Edelson

12 nov 2008-- A study using an advanced brain scanning technology supports the growing body of evidence that education levels and some form of intellectual activity decrease the impact of Alzheimer's disease.

People with a greater "cognitive reserve" suffer less damage from the beta-amyloid plaques in the brain that are a leading marker of Alzheimer's disease, according to the study in the November issue of the Archives of Neurology.

Cognitive reserve is the concept that "the way that some people process information, the brain networks they use, allows them to cope better," said study author Catherine M. Roe, a research instructor in neurology at Washington University School of Medicine in St Louis.

The study used education levels as a yardstick of cognitive reserve, a customary practice in Alzheimer's studies, Roe said.

The researchers employed positron emission tomography (PET) scans to study the brains of 37 people with Alzheimer's-type dementia and 161 people with no dementia. All were injected with a radio-carbon-labeled compound that attaches itself to amyloid plaques, allowing the researchers to determine the size of those plaques in the brains of the participants. All the participants also took tests to measure their thinking ability.

"We divided the individuals into two groups, those with high uptake of the compound, indicating more plaques in the brain and those with low uptake, indicating few or no plaques," Roe said. "For people with low uptake, there was no relation to education in their cognitive scores. For high uptake, meaning significant plaques in the brain, we found an association with education. The more education they had, the fewer the symptoms of dementia."

So having a greater cognitive reserve, as measured by educational level, "may help you cope with that [Alzheimer's] pathology without having dementia symptoms," Roe said.

It's hard to say whether people can do anything to increase their cognitive reserve, said Yaakov Stern, professor of clinical neuropsychology at the Taub Institute for Research on Alzheimer's Disease at Columbia University and an originator of the cognitive reserve hypothesis.

Stern has taken part in several studies similar to the one now being reported, measuring blood flow to various parts of the brain as an indicator of Alzheimer's pathology. Those studies also showed that people with greater cognitive reserve "are walking around with more pathology than they exhibit," he said.

Whether people can consciously increase their cognitive reserve "is the big question," Stern said. "I am more and more convinced from studies like this that there are aspects of life experience that allow people to cope with Alzheimer's pathology better."

Any activities in particular? "We really don't know the recipe of what activity and how much would work," Stern said. "We really need controlled studies."

But, as a general rule, he said, "It doesn't hurt to remain active, physically as well as mentally. It's just that there are no studies to show that these activities really make a difference."

Studies: Elderly fare well in open-heart surgery

By MARILYNN MARCHIONE

NEW ORLEANS, 12 nov 2008 – Eighty-year-olds with clogged arteries or leaky heart valves used to be sent home with a pat on the arm from their doctors and pills to try to ease their symptoms. Now more are getting open-heart surgery, with remarkable survival rates rivaling those of much younger people, new studies show.

Years ago, physicians "were told we were pushing the envelope" to operate on a 70-year-old, said Dr. Vincent Bufalino, a cardiologist at Loyola University in Chicago. But today "we have elderly folks who are extremely viable, mentally quite sharp," who want to decide for themselves whether to take the risk, he said.

Even 90-year-olds are having open-heart surgery, said Dr. Harlan Krumholz, a Yale University cardiologist who has researched older heart patients.

"Age itself shouldn't be an automatic exclusion," he said. Not every older person can undergo such a challenging operation, but the great results seen in the new studies show that doctors have gotten good at figuring out who can.

The studies were reported at an American Heart Association conference this week in New Orleans.

People 75 and older are the fastest-growing segment of the population; this group is projected to more than quadruple over the next 50 years. Forty percent have heart disease, and half will die from it.

In recent years, surgical techniques, anesthesia and other medical care advanced, and death rates fell. That led more doctors to operate on older patients for everything from bum knees to cancer to bad backs.

But open-heart surgery is another thing — splitting open an aged chest and putting a patient on a heart-lung machine while doctors repair fragile blood vessels and weak valves.

Treatment guidelines by the heart association and other groups do not have age cutoffs for such operations. It's been up to patients, doctors and insurers to decide whether to risk it.

In Florida, Dr. Paul Kurlansky led a study of 1,062 octogenarians who had heart bypass surgery at Mount Sinai Medical Center in Miami Beach from 1989 through 2001.

"The key issue here is not only, 'Can we operate and are they alive?' but 'How are they doing?'" said Kurlansky, research director at the Florida Heart Research Institute.

The answer: Average survival was roughly six years — almost the same as similarly aged people who do not have heart disease. Overall, 90 percent survived their surgery to leave the hospital. This improved dramatically as the study went on, from 85 percent in the early years to 98 percent by its end.

Even more impressive: 65 percent survived without surgery-related complications and even more without long-term complications — a "very, very remarkable" result, Kurlansky said. Patients also reported a quality of life similar to others their age who did not have bypass surgery.

"What we are really dealing with is chronological age versus physical age," he said. Many elderly patients are hale and hearty, and if they need surgery, "there's no reason to deny them that."

The second study involved 8,796 elderly people in Maine, New Hampshire and Vermont with leaky aortic valves. The condition can kill within two or three years, and "surgery is their best option" for treatment, said Donald Likosky, a researcher at Dartmouth College in New Hampshire.

Six years after valve surgery — which sometimes included a bypass procedure, too — most were still alive. Median survival was seven years — about the same as the general population of that age.

Those 85 and older in the study actually outlived their general-population counterparts.

Earlier research found that people 76 and older recovered more slowly than younger patients after bypass surgery, but a year later most of them reported improvements in pain relief and quality of life similar to those for younger patients.

Bufalino told of a 102-year-old patient at Loyola who had heart surgery 23 years ago, when she was 79. During a recent office visit, she put him in his place about her health.

"I reached up to help her off the examining table and she said, 'I don't need your help, I'm fine,'" he said.

Study: Concerns on mixing Plavix, heartburn drugs

By MATTHEW PERRONE

NEW YORK, 12 nov2008-- Stent patients who take the blood thinner Plavix along with certain heartburn drugs may face a greater risk of heart attack, stroke and other dangerous events, according to a study released Tuesday.

Researchers found that patients who were taking Plavix with popular prescription heartburn drugs, including AstraZeneca PLC's Nexium, were significantly more likely to be hospitalized for a heart attack, stroke, chest pain or a coronary artery bypass operation than those who took Plavix alone.

The study followed more than 14,000 patients from 2005 to 2006 in a database kept by pharmacy benefits manager Medco Health Solutions Inc.

Nexium and other proton pump inhibitors, like Wyeth's Protonix, are used to treat chronic heartburn, in which stomach acids come back up the esophagus, causing pain and inflammation. Doctors frequently prescribe these drugs to patients on Plavix because the blood thinner has been linked to a higher risk of ulcers.

Medco said 40 percent of patients in its study were taking the prescription heartburn medications. The company's chief medical officer, Robert Epstein, said that if over-the-counter medications like AstraZeneca's Prilosec were included, the percentage would likely be even higher.

Epstein said heartburn drugs could interfere with a liver enzyme needed to process Plavix, neutralizing its effects.

He stressed that patients should not stop taking Plavix or heartburn drugs, particularly if they have a history of stomach problems.

"But if you're a person who's otherwise healthy taking Plavix, you might want to consider calling your doctor and asking, 'Do I need really need this' or 'Do I need it every day?' " Epstein said in an interview. "There are ways to look at this question now that we wouldn't have thought about previously."

Bristol-Myers also urged patients to talk with their doctor before taking action and questioned Medco's approach.

"While we are still reviewing the data, in general, retrospective analyses — in contrast to randomized clinical trials — are more subject to confounding factors," said spokesman Ken Dominski.

Academics at the the American Heart Association's annual meeting in New Orleans, where the data was presented, had similar concerns.

Dr. Robert Harrington of Duke University said that without a rigorous study comparing patients with similar health profiles "you cannot assume that the groups are balanced" and the results are real rather than a fluke.

For example, he said, people taking proton pump inhibitors may also have other health problems that skew their risk for heart disease.

"I would not change practice based on these data," said Harrington, who led an American College of Cardiology panel that last month said it was reasonable for doctors to prescribe these two drugs together.

All patients in the Medco study had been implanted with a stent, or a wire-mesh tube used to prop open arteries after they have been cleared of plaque. The study tracked whether they had been hospitalized for the heart and circulatory problems within a year of the stent being implanted.

In patients who had not suffered a previous heart attack, 32.5 percent patients who took Plavix and a heartburn drug experienced one of the severe events within a year of their stent surgery. Those events were seen in just 21.2 percent of patients who took only Plavix.

In patients who had suffered a previous heart attack, 39.8 percent of patients experienced the severe events within a year. In patients who did not take the heartburn drugs, only 26.2 percent did.

Plavix, or clopidogrel, is the second best-selling drug in the world, with global sales of $7.3 billion in 2007. It is marketed by Bristol-Myers Squibb Co. and Sanofi-Aventis SA.

Heartburn drugs were the fourth best-selling class of drugs last year, with sales of $25.6 billion, according to IMS Health.

Keeping a Promise When a Life Is Near Its End

By ELLEN D. FELD, M.D

“If something should happen to me, and I couldn’t help myself, would you be willing to help me?”

12 nov 2008--It is the question so many of us dread hearing. My mother asked it of me around her 75th birthday. Of course I didn’t need to ask what she meant by “something” or “help.” She was a card-carrying member of the Hemlock Society. On her bookshelves were titles like “Final Exit” and “The Peaceful Pill Handbook.”

“Can I think about that?” I said, hoping she might forget to follow up. It was a ridiculous hope: she took as gospel my every medical comment, and she never forgot a single one.

My mother had been ready to die for years. Not that she was suicidal, but she had always been one of those people who found the cloud in every silver lining. For my mother, life’s positives outweighed its negatives, but just barely.

When she lost all but her peripheral vision to macular degeneration and could no longer read, drive or teach, the scales tipped in the opposite direction. Whenever an acquaintance died or received a diagnosis of something swift and painless, her reaction (often to the dismay of those around her) was “Oh, that lucky fellow.”

Her greatest fear was of a stroke or some other catastrophe that would force her to live on for unwanted years, unable to care for herself. Her own mother, after a stroke, had spent the end of her life in a nursing-home wheelchair.

In a phone call two weeks to the day after her initial question, my mother did follow up: “Did you get a chance to think about what I asked?” Of course I had. I had spent large chunks of time obsessing about it. So I gave the only answer I could stand to give, the only kind answer I could think of.

“Yes,” I said. “If you ever need my help, of course I will help you.”

Then I changed the subject, but not before hearing the immense relief and gratitude in her voice. Even though I was quite sure my definition of “help” did not match hers, to answer otherwise would have been cruel. What did it matter, I thought; she couldn’t possibly hold me to it, and with a little luck it will never come up. And in fact, the subject did not come up again for more than a decade.

A couple of months short of her 87th birthday, my mother began to complain repeatedly of being unable to work the remote for her large-screen television. Each time she said this, someone would painstakingly walk her through the steps. But a few days later something would go wrong and she would need help again. A few weeks later, when her shower faucet went on the blink, it finally dawned on me that the fault might lie not in the remote or the faucet but in their user. I persuaded her to see her internist, and I called to let him know my concerns.

The internist called me right after her appointment to tell me she was being admitted to the hospital. She was wheezing, and a chest X-ray showed pneumonia. In addition, the brain M.R.I. showed several lesions — strongly suggestive of a tumor.

Multiple scans and doses of antibiotics later, the pneumonia was reclassified as a lung tumor and the brain lesions as metastases. My mother was put on steroids, and after considering and rejecting brain irradiation, she left her home near Boston and moved into a hospice five minutes from my house in Philadelphia.

She lived three more weeks — three weeks during which the only help she ever asked of me was to bring her chocolate milkshakes (which I did, often several times a day).

The night she died, I sat with her. She was unconscious by then, seemingly comfortable but breathing more and more rapidly, her skin growing more and more mottled. As I held her hand and mopped the bubbles from the corners of her mouth, I remembered a conversation we had had in the hospital in Boston right after her doctor had given me the results of her chest scan. I had told him that I would give the news to my mother.

My mother knew there were “masses” in her brain (she herself was calling them tumors), so I expected the news not to be a great surprise and, more than likely, welcome.

When I finished speaking, she looked concerned and frightened, making me wonder whether all her talk of wishing to die had been just that — talk.

“What if I don’t go quickly?” she asked. “What if this takes forever?”

“It won’t, Ma,” I answered, relieved at such an easy question. “Everything’s going to be O.K.”

“Are you sure?”

“Yes,” I replied, with the certainty I knew she craved and trusted. “All the tests confirm that it won’t be long now.”

Tears filled her eyes. “Do you remember, years ago, you promised you would help me if I ever needed it?”

I nodded.

“Well,” she said, “you just did.”

Speaking Out for a Group Once Unheard-Of: Aging With AIDS

By KAREN BARROW

12 nov 2008--In the early 1990s, a diagnosis of AIDS was both a likely death sentence and a stigma. There were few treatment options, and many Americans were terrified of people infected with H.I.V.

Today, because of antiretroviral therapy and an array of drugs to treat both symptoms and side effects, AIDS has become a chronic condition to be managed, at least in the developed world. No longer is the face of AIDS emaciated and covered with lesions; Americans with the disease are stronger and healthier, their concerns fading from public view.

Myron Gold, 67, is one of them. In 1993, Mr. Gold was walking in Manhattan around Christmastime when he collapsed and was rushed to the emergency room. A social worker later walked in and loudly announced that he had H.I.V.

Mr. Gold remembers the panic on the faces of the other patients. “When you said that in ’93, you emptied the whole emergency room,” he said. “Everyone ran for their lives.”

Still, he was unfazed by his diagnosis. A former fashion designer who became an AIDS and gay-rights activist, he was already familiar with the disease and how it ravaged the body. He was given a prescription for AZT, the most common treatment at the time, and was told he had six months to live.

Fifteen years later, he is alive and relatively well — and that, paradoxically, is the problem.

“This is not an illness about people in their 20s and teens,” he said. “This is an illness about every age spectrum, from young to old.”

In fact, 29 percent of those infected with H.I.V. are over 50. And because the immune system deteriorates with age, the virus is all the more aggressive in older people.

“I’ve been through 28 medications,” Mr. Gold said. His T cells — a component of the immune system, used as a marker of its health — “are low and they’re not working.”

Moreover, conditions that are often part of the aging process, like arthritis and dementia, can also be caused by H.I.V. So sorting through symptoms and effectively treating them — not to mention avoiding dangerous drug interactions — can be daunting.

There is also an alarming rate of infection among older Americans. In 2005, 15 percent of new H.I.V. and AIDS diagnoses were among people over the age of 50, according to the Centers for Disease Control and Prevention. Yet government recommendations call for routine AIDS screening only up to age 64, omitting the elderly population.

“What about people 65 and older?” Mr. Gold asked. “They’re having unprotected sex, they’re using drugs.”

He says that is why he continues his advocacy for people with AIDS and for stronger prevention efforts. He sits on both the New York and national boards of the nonprofit group Association of H.I.V. Over 50, attends City Council meetings and has spoken before Congress and the New York Legislature.

Not long ago, he visited a senior center in the Canarsie section of Brooklyn to discuss safe sex practices. The women who attended, “all over 80 years old,” he said later, rushed toward the table afterward for the free condoms he was distributing. (“They said to me, ‘It’s not for me, it’s for my grandson,’ ” he said.)

Politicians don’t like to talk about the spread of AIDS among the elderly, Mr. Gold says; nobody wants to hear about Grandma’s sex life. But he adds that change cannot happen without open discussion.

Mr. Gold is proud that he has long outlived his initial diagnosis, but AIDS has weakened his body and he now relies on an electric scooter to get to advocacy meetings and speaking events. Still, he keeps going.

“My work is what feeds me now,” he said. “Call me in 10 years, I’ll still be here.”

Risks: First Month After a Heart Attack Is Crucial

By ERIC NAGOURNEY

11 nov 2008--People who survive a heart attack are at much higher risk of sudden cardiac death in the next 30 days, researchers have found.

The findings, which appeared in the Nov. 5 Journal of the American Medical Association, suggest that doctors need to closely supervise patients in the month after a heart attack, and that patients also need to be alert to signs of trouble.

“The first month after a heart attack can be envisioned as a period of healing with heart tissue remodeling, which conceptually is associated with a propensity to experience sudden death,” one of the authors, Dr. Véronique L. Roger of the Mayo Clinic in Rochester, Minn., said in an e-mail message.

The researchers, led by Dr. A. Selcuk Adabag of the Veterans Affairs Medical Center in Minneapolis, followed the health of almost 3,000 people who had a heart attack from 1979 to 2005.

In the first 30 days, they found, the rate of sudden cardiac death was 1.2 percent, about four times the risk that would have been expected in the general population, once age and sex were taken into account.

But the rate improved greatly over the following 11 months, dropping to a level lower than that usually seen in the general population.

In fact, over all, the study found big improvements in the rate of sudden cardiac death for heart attack patients in the past three decades. The decline, the researchers said, was more than 40 percent. They attributed that to improved treatment for people who have just had a heart attack.

Researchers discover new risk factor for cardiovascular disease, and a way to control it

MUHC serves as Canadian centre for international study that could revolutionize treatment options

Montreal, 11 nov 2008- A team of international researchers – including scientists from the McGill University Health Centre (MUHC) and McGill University – have discovered that having high levels of particular protein puts patients at increased risk of developing cardiovascular disease. The results of the study were so conclusive that the clinical trial had to be stopped before its scheduled completion date.

Researchers associated with the international JUPITER Project have demonstrated that high levels of high-sensitivity C-reactive protein (hs-CRP) leads to increased risk of cardiovascular disease. This risk decreases by up to 44% if the patients are treated with statin medications.

Dr. Jacques Genest, of the Research Institute of the MUHC and McGill's Faculty of Medicine led the Canadian component of the JUPITER clinical study, which was initiated by Dr. Paul Ridker of the Harvard University Faculty of Medicine.

"The risk of cardiovascular disease due to increased hs-CRP levels has been greatly underestimated until now," according to Dr Genest. "Our results show that this is an extremely important indicator that doctors will have to consider in the future."

"We hope that this study will prompt a review of current clinical practices, especially in terms of screening and prevention in adults," he added. "However, we still need to do more research to establish specific standards."

The JUPITER study included 17,802 patients from 27 different countries. All had normal levels of cholesterol (LDL-c) and high levels of hs-CRP, and according to current standards, were not considered "at risk" for cardiovascular events, and were therefore not receiving any treatment. During the study, participants received a daily dose of the statin drug rosuvastin, and its consequences were striking: a 44% decrease in the risk of cardiovascular disease and a 21% decrease in mortality.

"These results definitely surpassed our predictions," said Dr. Genest. "We had to stop the study before its scheduled completion, as the benefit of the treatment for the selected patients was so great that we needed to present our findings to the medical community as soon as possible."

Since statins have a cholesterol-lowering effect, they are currently used to prevent cardiovascular disease in patients who are at-risk due to high LDL-c levels. But cardiovascular disease is also caused by vascular inflammation, which is marked by levels of hs-CRP. This study shows that statins indeed act on both cholesterol and inflammation, an effect that has long been suspected but not proven.

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This clinical study was investigators-initiated and funded by Astra Zeneca.

Dr. Jacques Genest is Director of Cardiology at the MUHC and Director of the Cardiovascular Genetics Laboratory at the Research Institute of the MUHC. He also holds the Novartis Chair in Medicine at the Faculty of Medicine of McGill University.

About the Research Institute of the MUHC

The Research Institute of the McGill University Health Centre (RI MUHC) is a world-renowned biomedical and health-care hospital research centre. Located in Montreal, Quebec, the institute is the research arm of the MUHC, the university health center affiliated with the Faculty of Medicine at McGill University. The institute supports over 600 researchers, nearly 1200 graduate and post-doctoral students and operates more than 300 laboratories devoted to a broad spectrum of fundamental and clinical research. The Research Institute operates at the forefront of knowledge, innovation and technology and is inextricably linked to the clinical programs of the MUHC, ensuring that patients benefit directly from the latest research-based knowledge.

Low-dose aspirin does not appear to reduce risk of CV events in patients with diabetes

11 nov 2008--Low-dose aspirin as primary prevention did not appear to significantly reduce the risk of a combined end point of coronary, cerebrovascular and peripheral vascular events in patients with type 2 diabetes, according to a new study in JAMA. However, aspirin did significantly reduce the combination of fatal coronary and fatal cerebrovascular events. The article is being released early online Sunday, November 9 to coincide with its scientific presentation at the American Heart Association meeting. The study will appear in the November 12 print issue of JAMA.

"Diabetes mellitus is a powerful risk factor for cardiovascular events," the authors write. "Individuals with diabetes have a two- to four-fold increased risk of developing cardiovascular events than those without diabetes." The authors note that the "American Diabetes Association recommends use of aspirin as a primary prevention strategy in patients with diabetes who are at increased cardiovascular risk," including those who are older than 40 years or who have additional risk factors, such as family history, hypertension or smoking.

In this study conducted by Hisao Ogawa, M.D., Ph.D., from the Graduate School of Medical Sciences, Kumamoto University, Japan and colleagues from the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) Trial Investigators, the researchers examined whether low-dose aspirin would be beneficial for primary prevention of atherosclerotic (atherosclerosis, which involves narrowing or hardening of the arteries because of plaque build-up) events in patients with type 2 diabetes. From Dec. 2002 through April 2008, 2,539 patients with type 2 diabetes and no history of atherosclerotic disease from 163 institutions from throughout Japan were enrolled in the study. Patients were randomly assigned to the low-dose aspirin group receiving 81 or 100 mg per day (n = 1,262) or the nonaspirin (n = 1,277) group. The average age was 65 and 55 percent of the patients were men. The median (midpoint) follow-up period was 4.37 years. The main outcome measures were atherosclerotic events, including fatal or nonfatal ischemic heart disease, fatal or nonfatal stroke, and peripheral arterial disease.

"A total of 154 atherosclerotic events occurred: 68 in the aspirin group and 86 in the nonaspirin group," the researchers write. "In the 1,363 patients aged 65 years or older (719 in the aspirin group and 644 in the nonaspirin group), the incidence of atherosclerotic events was significantly lower in the aspirin group (45 events, 6.3 percent) than in the nonaspirin group (59 events, 9.2 percent)." In the 1,176 patients younger than 65 the difference among events in the two groups was not significant.

Aspirin was well tolerated: in comparing bleeding events, the researchers reported 13 hemorrhagic strokes, with no statistically significant difference between aspirin takers and non-takers (six such strokes in the aspirin group; seven in the non-aspirin group). There was a comparable number of the combined endpoint of serious hemorrhagic events (hemorrhagic strokes and major gastrointestinal bleeds).

"Myocardial infarction [heart attack] and ischemic stroke are leading causes of mortality and morbidity in patients with type 2 diabetes. Given the rapid increase in the number of patients with type 2 diabetes worldwide and especially in Asia, establishing effective means of primary prevention of coronary and cerebrovascular events is an important public health priority," the authors comment.

While this study did not find that low-dose aspirin significantly reduced the risk of atherosclerotic events in primary prevention therapy in patients with type 2 diabetes, the authors suggest more research is needed. "These findings should be interpreted in context with the low incidence of atherosclerotic disease in Japan and the current management practice for cardiovascular risk factors and suggest the need to conduct additional studies of aspirin for primary prevention of cardiovascular disease in diabetic patients."

(JAMA. 2008;300 [18]: 2134-2141. Available pre-embargo to the media at www.jamamedia.org.)

Editor's Note: This study was supported by the Ministry of Health, Labour and Welfare of Japan. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Aspirin For Primary Prevention – Still an Open Question for Patients with Diabetes

"The use of aspirin for primary prevention of cardiovascular events in individuals with diabetes is widely recommended by existing guidelines, but the evidence supporting its efficacy is surprisingly scarce," writes Antonio Nicolucci, M.D., from Consorzio Mario Negri Sud, Italy, in an accompanying editorial.

"The lack of precision and the low statistical power in the JPAD trial are the consequence of the substantially lower than expected event rate in the trial population." Dr. Nicolucci writes that the study population had a very low baseline risk of cardiovascular events and questions whether the results can be generalized to other populations with substantially higher cardiovascular risks.

"The issue of aspirin therapy for patients with diabetes is an example of how, in the presence of a long-lasting uncertainty, scientific organizations or governmental bodies should provide the foundation for answering this question by promoting pragmatic, large-scale clinical trials. Considering all diabetic patients with no history of cardiovascular disease (except those with documented contraindications or perceived indications) as candidates for randomized clinical trials would represent a major contribution to the credibility of scientific methods in guiding practice."

(JAMA. 2008;300 [18]: 2180 – 2181. Available pre-embargo to the media at www.jamamedia.org.)

Vitamins E and C supplements not effective for prevention of cardiovascular disease in men

11 nov 2008--Neither vitamin E nor vitamin C supplements reduced the risk of major cardiovascular events in a large, long-term study of male physicians, according to a study in the November 12 issue of JAMA. The article is being released early online November 9 to coincide with the scientific presentation of the study findings at the American Heart Association meeting.

Most adults in the United States have taken vitamin supplements in the past year, according to background information provided by the authors. "Basic research studies suggest that vitamin E, vitamin C, and other antioxidants reduce cardiovascular disease by trapping organic free radicals, by deactivating excited oxygen molecules, or both, to prevent tissue damage." Some previous observational studies have supported a role for vitamin E in cardiovascular disease prevention. Some previous observational studies have also shown a role for vitamin C in reducing coronary heart disease risk.

In this study, known as the Physicians' Health Study II, Howard D. Sesso, Sc.D, M.P.H., and colleagues from Brigham and Women's Hospital, Harvard Medical School and School of Public Health and VA Boston Healthcare System, Boston, assessed the effects of vitamin E and vitamin C supplements on the risk of major cardiovascular disease events among 14,641 male physicians. These physicians were 50 years or older and at low risk of cardiovascular disease at the beginning of the study in 1997, and 754 (5.1 percent) had prevalent cardiovascular disease. The study participants were randomized to receive 400 IU of vitamin E every other day or a placebo and 500 mg of vitamin C daily or a placebo.

"During a mean (average) follow-up of 8 years, there were 1,245 confirmed major cardiovascular events," the researchers report. There were 511 total myocardial infarctions (heart attacks), 464 total strokes, and 509 cardiovascular deaths, with some men experiencing multiple events. A total of 1,661 men died during follow-up. Compared with placebo, neither vitamin E nor vitamin C had an effect on the prevention of major cardiovascular events. "Neither vitamin E nor vitamin C had a significant effect on total mortality, but vitamin E was associated with an increased risk of hemorrhagic stroke."

In conclusion the authors write: "In this large, long-term trial of male physicians, neither vitamin E nor vitamin C supplementation reduced the risk of major cardiovascular events. These data provide no support for the use of these supplements for the prevention of cardiovascular disease in middle-aged and older men."

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JAMA. 2008;300[18]:2123-2133. Available pre-embargo to the media at www.jamamedia.org.

Flu shots may cut risk of blood clots forming in veins

11 nov 2008--Flu shots may reduce the risk of blood clots forming in veins by 26 percent, according to research presented at the American Heart Association's Scientific Sessions 2008.

"Our study suggests for the first time that vaccination against influenza may reduce the risk of venous thrombotic embolism (VTE)," said Joseph Emmerich, M.D., Ph.D., lead author of the study and professor of vascular medicine at the University Paris Descartes and head of the INSERM Lab 765, which investigates thrombosis. "This protective effect was more pronounced before the age of 52 years."

VTE is the formation of a blood clot in a vein. The condition is dangerous because the blood clot can break loose and travel through the circulatory system to the right side of the heart. From there it can go to the lungs (a pulmonary embolism), which can be life-threatening or even fatal.

Researchers conducted a case-control study among 1,454 age- and sex-matched patients (average age 52 years) from 11 centers in France (the FARIVE study). They compared 727 patients without personal history of cancer within the last five years who had initial episodes of VTE to a control group of age- and sex-matched patients free of venous and arterial thrombotic disease.

Patients younger than 18 years old — or those who already had VTE, had a diagnosis of active cancer or a history of malignancy less than five years previously, or had a short life expectancy due to other causes — were ineligible to participate in the study.

Potential control subjects with cancer, liver or kidney failure, or a history of venous and/or arterial thrombotic disease were also ineligible.

Researchers interviewed patients using a standardized questionnaire covering age, educational level, medication history, personal and familial history of thrombotic disease, and acquired risk factors for VTE, including pregnancy, use of oral contraceptives or estrogen replacement therapy, trauma or surgery less than three months previously, prolonged immobilization, or travel lasting more than five hours.

Patients were classified as having secondary (provoked) VTE if they had one or more of the above acquired risk factors. All other patients were considered to have had unprovoked episodes of VTE.

Influenza vaccination status during the previous 12 months was also recorded. The outcomes of the cases, documented through half-yearly telephone interviews for five years, include:

• Overall, the adjusted odds risk was 26 percent less for developing VTE after having the flu shot.
• The flu shot's protective effect was more pronounced before rather than after age 52 years, with a 48 percent lower likelihood of VTE in those younger than 52.
• In women under 51 years, getting the flu shot reduced the odds of developing VTE by 50 percent, and by 59 percent for women taking oral contraceptives.
• The protective effect of vaccination was similar for different types of VTE (deep vein thrombosis or pulmonary embolism).

  The mechanism underlying the link between influenza virus infection and the risk of VTE is still unclear, Emmerich said.

"Infections in general increase blood viscosity, and systemic inflammatory reactions to infectious agents can themselves trigger a thrombotic process," he said. "However, influenza vaccination might lower the risk of thrombosis in other ways, as suggested by the even distribution of VTE events across the 12 months of the year in both vaccinated and unvaccinated cases in our study."

Further studies are needed to confirm this relationship between influenza vaccination and VTE, and to explore the underlying mechanisms. It raises the possibility that flu vaccination could be recommended after a first VTE event, Emmerich said.

The American Heart Association recommends heart patients get annual flu shots to protect against this infectious disease. Patients with cardiovascular disease are more likely to die from influenza than patients with any other chronic condition. However, patients with cardiovascular disease should not get the nasal-spray flu vaccine.

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Co-authors are: T. Zhu, M.D., Ph.D.; L. Carcaillon, M.D., Ph.D.; I. Martinez, M.D., Ph.D.; J. Cambou, M.D., Ph.D.; X. Kyndt, M.D., Ph.D.; K. Rivron-Guillot, M.D., Ph.D.; M. Vergnes, M.D., Ph.D.; and P. Scarabin, M.D., Ph.D. Individual author disclosures are available on the abstract.

The University Paris Descartes, INSERM, FRM, Fondation de France and Leducq funded the study.

Editor's note: For more on influenza and cardiovascular disease, visit: americanheart.org.

Wider Benefit Seen From Cholesterol Drugs

By PAM BELLUCK

10 nov 2008--A large new study suggests that millions more people could benefit from taking the cholesterol-lowering drugs known as statins, even if they have low cholesterol, because the drugs can significantly lower their risk of heart attacks, strokes and death.

The study, involving nearly 18,000 people worldwide, tested statin treatment in men 50 and older and in women 60 and older who did not have high cholesterol or histories of heart disease. What they did have was high levels of a protein called high-sensitivity C-reactive protein, or CRP, which indicates inflammation in the body.

The study, presented Sunday at an American Heart Association convention in New Orleans and published online in The New England Journal of Medicine, found that the risk of heart attack was more than cut in half for people who took statins.

Those people were also almost 50 percent less likely to suffer a stroke or need angioplasty or bypass surgery, and they were 20 percent less likely to die. The statin was considered so beneficial that an independent safety monitoring board stopped what was supposed to be a five-year trial last March after less than two years.

Scientists said the research could provide clues on how to address a long-confounding statistic: that half of heart attacks and strokes occur in people without high cholesterol.

“These are findings that are really going to impact the practice of cardiology in the country,” said Dr. Elizabeth G. Nabel, director of the National Heart, Lung and Blood Institute, which was not involved in the research. “It’s at a minimum an extremely important study and has the potential to be a landmark study.”

The study is sparking debate over who should take a blood test to check CRP and under what circumstances someone with high CRP should be given a statin. Because heart disease is a complex illness affected by many risk factors — including smoking, hypertension, being overweight and having a family history of heart disease — most researchers said high CRP alone should not justify prescribing statins to people who have never had heart problems.

Some experts cautioned against testing people for CRP unless they had other indications of being at risk for heart disease, and they said more research was needed to pinpoint the patients for whom the benefit of statins outweighs the risks. Others recommended testing more frequently and using statins for people with low cholesterol if they have high CRP and some other risk factors.

The study, called Jupiter, is also fueling a debate among scientists about CRP’s importance and inflammation’s role in heart disease.

Dr. Nabel said national panels were likely to revise their official guidelines for doctors, which she described as “silent on CRP,” to recommend CRP testing and statin therapy for some people not previously considered candidates.

Current practice, she said, is to treat people with high cholesterol with statins, and to counsel people at low risk for heart disease about diet and exercise.

“What cardiologists have never known what to do about is the intermediate range” of patients, Dr. Nabel said, who may be overweight, smoke or have hypertension, but do not have the most serious red flags of high cholesterol or diabetes. “I think CRP will emerge as a new risk factor added to traditional risk factors.”

The leader of the Jupiter study, Dr. Paul M. Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital in Boston, said his team estimated that expanding statin use to the types of patients he studied could prevent about 250,000 heart attacks, strokes, vascular procedures or cardiac deaths over five years.

Some experts not involved in the Jupiter study said several million more Americans should probably be taking statins. About 16 million to 20 million Americans are estimated to be taking statins.

“The Jupiter trial very convincingly used CRP as a way to identify another group of high-risk individuals who wouldn’t otherwise have been treated, and supports the concept that those people should be treated with a statin,” said Dr. Daniel J. Rader, a heart researcher at the University of Pennsylvania School of Medicine who was not connected to the study.

Several experts said that although the research was significant and would affect clinical practice, the study as published in the journal did not give enough detailed information to indicate exactly which patients should now be tested for CRP or given statins.

In an accompanying editorial, Dr. Mark A. Hlatky, a professor of health research at Stanford University, said among other things that the study, which tested people with CRP levels over two milligrams, did not indicate whether that level or a higher CRP level should be the threshold for treatment. The study also did not answer some questions about risks of giving statins to relatively healthy people, he wrote.

Dr. Sidney Wolfe, director of the health research group for Public Citizen, a nonprofit consumer advocacy organization, said the Jupiter study also did not give enough detail about the effect of statins on participants who had only high CRP, compared with those who also smoked or had a condition called metabolic syndrome. Some experts questioned whether stopping the trial early had limited the possibility of some more meaningful data.

Dr. Ridker said the published study, as well as unpublished data, indicated that all the statin-takers experienced the same benefit, including those considered “very low risk” because they have no risk factors other than high CRP. “We have no evidence at all that stopping early adversely impacted on anything,” he said in an e-mail response, adding, “I think people may simply not have had the time to carefully read the paper yet, and the data so much challenge what they believe to be true that it will take some time to sink in.”

The trial was one of the few to test statins that included many women, Hispanics and blacks, groups that all showed similar benefit from statins.

Like many clinical trials, Jupiter was sponsored by a pharmaceutical company, in this case AstraZeneca. It makes the drug in the trial, rosuvastatin, which is sold as Crestor. The most potent statin on the market, Crestor has been criticized by consumer health advocates who say it is more likely to cause some rare side effects of statins — muscle deterioration and kidney problems.

In 2005, the Food and Drug Administration rejected a petition by Public Citizen to ban Crestor, saying its risks were not substantially different from similar drugs.

In the Jupiter study, in which people either got rosuvastatin or a placebo, there was no increase in muscle or kidney problems for those taking the statin. There was a small increase in diabetes.

Dr. Timothy J. Gardner, president of the American Heart Association, said some recent statin trials “have been either negative or in some ways concerning in terms of complications,” but, he added, “this one is pretty clearly a winner for statin therapy.”

Dr. Ridker, a co-inventor of a CRP test, said he first sought federal financing for the study and was turned down. He and the other scientists interviewed for this article, except for Dr. Nabel, Dr. Gardner and Dr. Wolfe, have consulted for or received research money from companies that make statins.

Although Crestor, which has 9 percent of the American cholesterol-lowering market and costs about $3 a day, was used in this study, several experts said it seemed likely that the effect would be the same for other statins in appropriate doses, including generics, which are much cheaper.

Lisa Nanfra, executive director of commercial operations for AstraZeneca, said the company believed there was a “unique profile of Crestor” and that the drug was “the most effective statin at lowering” bad cholesterol. The company plans to use results from the Jupiter study to seek F.D.A. approval to widens its claim about Crestor’s effectiveness.

The role of CRP and inflammation in heart disease is hotly debated. Dr. Ridker believes inflammation plays an important role, probably by causing plaque in the coronary arteries to rupture.

“Screening for cholesterol alone is like having two passengers in a car but only one air bag,” he said. “If we’re not screening for CRP, we don’t have the opportunity to save that person’s life.”

Others say cholesterol is much more important. Dr. Scott Grundy, a heart expert at the University of Texas Southwestern Medical Center, pointed out that in the Jupiter study, the statin not only lowered CRP but also significantly cut already low cholesterol levels, raising questions about whether the benefit actually came from giving patients superlow cholesterol. And because CRP can rise with short-term infections unrelated to chronic inflammation, some experts said results of a CRP test needed to be weighed against other aspects of the patient’s health.

“CRP is not a standard test that everyone should have,” Dr. Rader said. “It is an additional test that you should do if you’re on the fence.”

Dr. Andrew M. Tonkin, head of cardiovascular research at Monash University in Melbourne, Australia, said though the results for those who took the statin were “strikingly positive,” given that the people in the study were relatively healthy, there needed to be a cost-benefit analysis to decide: “Are there people in whom the potential gains, although significant, are not so great as to warrant taking statins?”

Heart failure hospitalization rates rise among nation's seniors

Heart failure is reaching epidemic levels among seniors in the United States, according to research presented at the American Heart Association's Scientific Sessions 2008.

10 nov 2008--"Both the number of patients hospitalized with a primary diagnosis of heart failure and age-adjusted hospitalization rates for heart failure have increased dramatically over the past 27 years," said Longjian Liu, M.D., Ph.D., M.Sc., author of the study, associate professor of Epidemiology and Biostatistics of the Drexel University School of Public Health in Philadelphia, Pa. "The prevention and treatment of heart failure has become an urgent public health need with national implications."

A chronic disease, heart failure occurs when any part of the heart muscle weakens and the heart can't supply the body's cells with enough oxygen and nutrient-rich blood. Everyday activities can become very difficult due to fatigue and shortness of breath. An estimated 5.3 million Americans live with heart failure, and 660,000 new cases are diagnosed each year, according to the American Heart Association.

Liu's study is the first to examine the disease's hospitalization rates over the last 27 years and is the initial portion of a serial report on heart failure epidemiology in the United States.

This study used data from more than 2.2 million patients (age 65 or older) in the National Hospital Discharge Surveys between 1980 and 2006. This national representative survey provides annual estimates of hospital discharges in the United States. In the study, heart failure was defined as patients with a primary diagnosis of heart failure at hospital discharge. This study broke the data down into three age groups: 65, 75 and 85 or older by gender, and then estimated statistically the hospitalization rates with census population data in terms of gender and time periods.

He found the following:

• The estimated number of patients age 65 and older who were hospitalized for heart failure increased from 348,866 in 1980 to 807,082 in 2006 – a 131 percent increase.
• For men, rates rose from 16.57 hospitalizations per 1,000 members of the population in 1980 to 22.87 in 2006.
• For women, rates rose from 13.95 hospitalizations per 1,000 members of the population to 19.58 in 2006.
• Women had a significantly higher annual percentage increase rate than men (55 percent vs. 20 percent).
• From 2002-2006, the relative risk of being hospitalized due to heart failure was 1.37 times higher than it had been from 1980-84.
• Patients ages 75-84 had twice the risk of being hospitalized for heart failure than those 65-74 those age 85 or older had four times more risk of hospitalization for heart failure than those ages 65-74.

The study also showed that, among the three major forms of cardiovascular disease, coronary heart disease and stroke have shown decreases in hospitalization rates since the mid-1980s. However, heart failure has shown a continuously significant increase in hospitalization rates since 1980.

Directly and indirectly, heart failure is expected to cost $34.8 billion in the United States this year, according to American Heart Association data. The peak of the crisis is still to come, Liu said.

"Over the next decades, the number of U.S. adults age 65 and older will double to a projected 70 million, and more than one in five will be 65 or older by the year 2030," he said. "Because heart failure disproportionately affects the elderly, there is no doubt that the burden of heart failure will increase unless innovative strategies are implemented. The key is to prevent risk factors for the disease."

These risk factors include high blood pressure, coronary heart disease, chronic obstructive pulmonary disease, valvular heart disease, diabetes, stroke, obesity and lifestyle risk factors such as smoking, physical inactivity and fatty food intake. Efforts also should be made to prevent chronic kidney disease and pneumonia as they contribute to heart failure as well, Liu said.

Hispanics less likely to have repeat revascularizations 1 year after angioplasty

10 nov 2008--Hispanic patients were 57 percent less likely than Caucasian patients to undergo coronary artery bypass surgery (CABG) one year after successful angioplasty, a type of percutaneous coronary intervention (PCI) to open blockages in the coronary arteries. Hispanics also had a trend toward lower rates of overall repeat revascularization procedures including stenting and bypass surgery, according to a study presented at the American Heart Association's Scientific Sessions 2008.

The study also found half of Hispanics undergoing PCI had diabetes — increasing their risk for heart attack. They also were more likely to have longer lesions blocking their arteries, with the average length of 15.4 millimeters (mm) compared to 14.1 mm in Caucasians.

"More Hispanics have hypertension and diabetes, especially insulin-treated diabetes," said Shailja V. Parikh, M.D., a fellow in the Department of Internal Medicine, Division of Cardiology, at the University of Texas Southwestern Medical Center in Dallas.

The study — one of the first to examine restenosis rates in Hispanics — included 542 Hispanics and 1,357 Caucasians undergoing PCI from the National Heart, Lung, and Blood Institute (NHLBI) Dynamic Registry Waves from 1999 to 2006. Only clinical centers where 5 percent of patients were of Hispanic ethnicity were included. Despite Hispanic patients being an average three years younger, researchers found more:

• hypertension – 80.4 percent versus 72.3 percent in Caucasians;
• diabetes – 49.2 percent versus 27.8 percent in Caucasians; and
• insulin-treated diabetes – 15 percent versus 7.4 percent in Caucasians.

Hispanic participants had less:

• peripheral vascular disease – 5.6 percent versus 10.3 percent;
• prior heart attack – 25.8 percent versus 30.9 percent; and
• prior PCI – 27.8 percent versus 34.1 percent than Caucasians.

Researchers found that rates of death and heart attack were similar between Hispanics and Caucasians one year after PCI.

"It's interesting that Hispanics were younger and had more risk factors," Parikh said. "With higher rates of insulin treated diabetes, hypertension, and longer lesion lengths, one would expect Hispanic patients to have higher rates of repeat revascularization either though CABG or PCI. However, despite having these risk factors for increased rates of restenosis, Hispanics were found to be revascularized less often after initial PCI than their Caucasian counterparts.

"It is possible that a referral bias exists in which Hispanic patients are not being referred for coronary artery bypass surgery as commonly as Caucasians," Parikh said. "Or, there may be mediating factors intrinsic to the Hispanic patient that could be protective toward restenosis."

Parikh advocates for increased preventive measures and for modification of risk factors among these patients before they reach the cath labs. Better control of the unique set of risk factors in Hispanics could decrease the need for downstream invasive interventions.

Parikh and colleagues are planning to do further research on Hispanics in Dallas, where one-third of all patients undergoing cardiac catheterization at the Parkland Memorial Hospital catheterization laboratories are Hispanic.

According to the American Heart Association, data from the National Health Interview Survey 2005 study of the National Center for Health Statistics showed that among Hispanics/Latinos age 18 and older, 8.3 percent have heart disease, 5.9 percent have coronary heart disease, 20.3 percent have hypertension, and 2.2 percent have had a stroke.

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Co-authors are: Jonathan R. Enriquez, M.D.; Faith Selzer, Ph.D.; James N. Slater, M.D.; Warren K. Laskey, M.D.; Robert L. Wilensky, M.D.; Oscar C. Marroquin, M.D.; and Elizabeth Holper, M.D., Ph.D. Individual author disclosures are available on the abstract. The Dynamic Registry is funded by the National Heart, Lung and Blood Institute and data coordination is performed at the University of Pittsburgh.