African-Americans Have Higher Risk for Blood Clots After Receiving Drug-Coated Stent

/PRNewswire/ -- African-American race is a distinct risk factor for developing life-threatening blood clots after receiving a drug-coated stent, according to research reported in Circulation: Journal of the American Heart Association.

African-American race was the strongest predictor of clotting that occurs more than 30 days after implantation, researchers said.

For the study, researchers examined data on 7,236 patients who had stents, coated with clot-prevention drugs, implanted to prop open narrowing arteries. The drug-coated stents, also called drug-eluting stents, were implanted between mid-2003 and the end of 2008.

Even after considering other known risk factors -- such as diabetes, hypertension and kidney problems -- researchers found that African-Americans still experienced a higher rate of thrombosis or clotting.

The bottom line is this is not just because this population is sicker or less compliant, but there is something else there that needs to be explored," said Ron Waksman, M.D., the study's lead author.

In the study, African-American patients were nearly three times as likely to experience clotting as non-African-American patients. African-Americans' clotting rates compared to non-African Americans were:

-- 1.71 percent vs. 0.59 percent after 30 days;
-- 2.25 percent vs. 0.79 percent at one year;
-- 2.78 percent vs. 1.09 percent at two years; and
-- 3.67 percent vs. 1.25 percent at three years.


The rate of death from all causes at three years was also higher among African-Americans, 24.9 percent vs. 13.1 percent in other races.

"Physicians and patients need to know that African-Americans are at a higher risk of developing stent thrombosis, which is associated with heart attack or death," said Waksman, associate director of the Division of Cardiology at Washington Hospital Center and professor of medicine and cardiology at Georgetown University.

In the study, African-Americans had increased rates of stent thrombosis even though they took post-surgery anti-clotting medication as prescribed at a higher rate than other races.

Further studies are needed to determine what should be done to reduce the blood clotting risks in African-Americans, Waksman said. Possible genetic differences in the way African-Americans' bodies react to the anti-clotting medication clopidogrel may have an impact.

Clopidogrel, a common drug prescribed post-stent implantation, carries a black box warning on its label from the Food and Drug Administration because the drug loses its ability to keep blood clots from forming in some patients whose bodies have trouble converting clopidogrel to its active form.

In some studies, researchers found that this genetic difference occurs more often in African-Americans than in white patients. Blood tests or genetic testing determine if someone is a "poor metabolizer" of clopidogrel.

More African-American participants are needed in key clinical trials to determine if the treatment works before a drug is on the market, Waksman said. "We are committed to further exploring these disparities and how African-Americans can benefit from drug-eluting stents without increasing the risk of stent thrombosis."

Co-authors are Sara D. Collins, M.D.; Rebecca Torguson, M.P.H.; Michael A. Gaglia Jr., M.D., M.Sc.; Gilles Lemesle, M.D.; Asmir I. Syed, M.D.; Itsik Ben-Dor, M.D.; Yanlin Li, M.D.; Gabriel Maluenda, M.D.; Kimberly Kaneshige, B.S.; Zhenyi Xue, M.S.; Kenneth M. Kent, M.D., Ph.D.; Augusto D. Pichard, M.D.; William O. Suddath, M.D.; and Lowell F. Satler, M.D.

Author disclosures and funding information are on the manuscript.


Statements and conclusions of study authors published in American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect the association's policy or position. The association makes no representation or guarantee as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and device corporations are available at www.americanheart.org/corporatefunding.

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Daily Rhythms in Blood Vessels May Explain Morning Peak in Heart Attacks

It’s not just the stress of going to work. Daily rhythms in the activity of cells that line blood vessels may help explain why heart attacks and strokes occur most often in early morning hours, researchers from Emory University School of Medicine have found.

Endothelial cells serve as the interface between the blood and the arteries, controlling arterial tone and helping to prevent clots that lead to strokes and heart attacks, says Ibhar Al Mheid, MD, a postdoctoral cardiology researcher at Emory.

He presented his results in a poster session Monday, Nov. 10 at the American Heart Association Scientific Sessions in New Orleans.

“One of the important ways the lining of our blood vessels is maintained is by progenitor cells that come from the bone marrow,” Al Mheid says. “These are essentially stem cells that help replace endothelial cells at sites of injury and build new vessels at sites deprived of adequate blood supply. The aim of our research was to look at the circadian pattern of both endothelial function -- the ability of blood vessels to relax -- and the abundance of the progenitor cells.”

Working with Arshed Quyyumi, MD, professor of medicine and director of the Emory Cardiovascular Research Group, and colleagues, Al Mheid examined a dozen healthy middle-aged subjects every four hours for 24 hours. They drew blood while the subjects were asleep at 4 a.m. Blood vessel relaxation is assessed by cuff occlusion, a standard technique in measuring blood pressure – and was not measured at 4 a.m.

The researchers measured the ability of subjects’ blood vessels to relax, the abundance of endothelial progenitor cells (EPCs) and their ability to grow in culture. Both the ability of blood vessels to relax and EPCs’ ability to grow peaked (roughly 40 percent more than the middle of the day) at midnight, while cell numbers peaked at 8 p.m.

“The lining of our vessels appears to function better at night than in the day. Endothelial function is particularly depressed in the early morning hours,” Al Mheid says.

He hypothesizes that an innate circadian timer in the brain, which other scientists have shown to be influenced by light and dark and daily activities, drives the cyclical variations in EPCs and endothelial function.

About Emory Heart & Vascular Center Emory Heart & Vascular Center doctors are committed to providing clinically excellent cardiovascular patient care, pioneering innovative clinical research and training the best heart specialists in the world. A component of Emory Healthcare, the Center is consistently recognized by U.S. News & World Report as one of the top heart centers in the country. Emory Healthcare is the clinical arm of Emory University's Woodruff Health Sciences Center and is the largest, most comprehensive health care system in Georgia.

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UGA Study: Even Occasional Smoking can Impair Arteries

Even occasional cigarette smoking can impair the functioning of your arteries, according to a new University of Georgia study that used ultrasound to measure how the arteries of young, healthy adults respond to changes in blood flow.

“Most people know that if they have a cigarette or two over the weekend that it’s not good for their arteries,” said study co-author Kevin McCully, a professor of kinesiology in the UGA College of Education, “but what they may not be aware of—and what our study shows—is that the decrease in function persists into the next week, if not longer.”

Previous studies have shown reductions in the arterial health of people who smoke regularly, McCully said, but what’s surprising about his finding is that the study subjects were occasional smokers (less than a pack a week) who had not smoked for at least two days before their ultrasound. The study, which appears in the early online edition of the journal Ultrasound in Medicine and Biology, found that the arteries of occasional smokers were 36 percent less responsive to changes in blood flow than non-smokers.

McCully explained that the healthier an artery is, the more responsive it is to changes in blood flow. A reduction in responsiveness, known as impaired flow-mediated dilation, is an early sign of arterial damage that often foreshadows cardiovascular disease. The researchers recruited 18 college students for their study, half of whom were non-smokers. The other half smoked less than a pack a week and had not smoked for at least two days before undergoing testing. The researchers measured the responsiveness of the participants’ arteries by inflating a blood pressure cuff around their non-dominant arm to reduce blood flow to the forearm for various durations up to 10 minutes. The researchers then rapidly deflated the cuff and measured how well the main artery in the forearm responded to the sudden increase in blood flow.

“We wanted to determine whether occasional smoking can impair flow-mediated dilation and found that repeated bouts of cigarette smoking—even if classified as occasional—appear to increase the risk for developing cardiovascular disease in otherwise healthy, young people,” said lead author Lee Stoner, a former UGA doctoral student and now a researcher at Christchurch Hospital in New Zealand.

After the occasional smokers underwent their initial test, they smoked two cigarettes and had their arteries re-examined. The researchers found that smoking dropped their arterial responsiveness by another 24 percent compared to before they smoked.

McCully acknowledged that the study used a relatively small sample size and said that further research is needed to determine if the impaired arterial function is a relatively short-term phenomenon or causes long-term damage. But he said that in light of his findings, people shouldn’t assume that smoking occasionally allows them to avoid the harmful effects of tobacco.

“We saw a definite effect of cigarettes on the arteries, even in young people who you would expect to be healthy,” he said.

By Sam Fahmy
University of Georgia

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Arteries Have Unique Immune Functions

Human arteries play distinct roles in the immune system depending on their anatomical location, researchers at Emory University School of Medicine have discovered.

Their findings explain why vascular diseases affect different parts of the arterial network and could help doctors fine-tune the treatment of such diseases as atherosclerosis and vasculitis. Atherosclerosis causes heart attacks and strokes because it occurs preferentially in arteries supplying the heart and the brain.

The results were published online this week by the journal Circulation.

Arteries can play an active role in sensing foreign invasion and bodily injury, because cells embedded in the arterial walls called dendritic cells act like smoke-sensing fire alarms for the immune system, says senior author Cornelia Weyand, MD. PhD, co-director of the Kathleen B. and Mason I. Lowance Center for Human Immunology at Emory University.

"All of our major arteries have this alarm system," she says. "To our surprise, we found that the arteries of the neck, the arms, the abdomen and the legs are triggered by different infectious organisms. Thus, each artery functions in a specialized way."

Some vascular diseases attack arteries only in the abdomen or in the neck and upper extremities, and this selectivity has puzzled doctors for years, Weyand says.

To probe the differences among arteries, Weyand and her co-workers examined the activity of genes that encode Toll-like receptors in blood vessels from human donors.

Toll-like receptors are a cornerstone of the "innate" immune system, which can be activated by common features of infection-causing invaders. The capture of bacterial or viral fragments through Toll-like receptors alerts the immune system early during an infectious attack. Toll-like receptors can respond to whip-like antennas on bacteria called flagellae, parts of bacterial cell walls, or DNA and RNA that leaks from viruses or bacteria.

Each type of artery had a different set of Toll-like receptor genes turned on, the authors found. In contrast to arteries, veins could not be stimulated through Toll-like receptors.

For example, cells in the iliac arteries, located in the vicinity of the gut, respond avidly to flagellae but cells from the subclavian arteries, which transport blood to the upper body, do not.

A possible explanation is that dendritic cells from iliac arteries are better able to sense flagellae because of the abundant bacterial flora that inhabits the gut, Weyand says.

Weyand hypothesizes that the dendritic cells in arteries are mainly performing a protective, calming function. Arteries are in constant contact with blood borne infectious agents, with potentially dangerous consequences of damaging the vessel wall.

"It's when that protective function breaks down that we see inflammation and various vascular diseases," she says.

She says her team is now investigating how the dendritic cells in arteries move and change as they receive various signals.

The first author of the paper is research specialist Olga Pryshchep, with contributions from postdoctoral fellow Wei Ma-Krupa, PhD, Joerg Goronzy, MD, PhD, co-director of the Lowance Center, and Brian Younge, MD, of the Mayo Clinic.

The research team used samples from 37 deceased donors with an average age of 64. Only arterial samples without atherosclerotic lesions were used.

The research was funded by the National Institutes of Health, the Dana Foundation and the McIntyre Family Discovery Fund.

Reference: Vessel-specific Toll-like receptor profiles in human medium and large arteries Circulation, Sep 2008; doi:10.1161/CIRCULATIONAHA.108.789172

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