Gender And Age Differences Found In Clotting Mechanism Of Sudden Cardiac Death

April 27, 1998

DALLAS, April 28 -- Blood clots that can trigger a sudden heart attack often differ between men and premenopausal women -- a finding that may have important implications for preventing sudden cardiac death, which kills 250,000 people each year. This research was reported in a study in today's Circulation: Journal of the American Heart Association.

The study may help explain why sudden cardiac death is four times more common in men than women before age 50, according to the study's senior author, Renu Virmani, M.D. Sudden cardiac death is a heart attack that stops the heart and causes death unless the victim is treated immediately.

"We are finding that atherosclerosis, the underlying cause of sudden cardiac death, is not a single disease. If you look under a microscope, you can see different kinds of plaque in men and premenopausal women," says Virmani, head of the cardiovascular pathology department at the Armed Forces Institute of Pathology, Washington, D.C. Plaque is a collection of cholesterol, fats and calcium inside of the blood vessel.

Previous work by Virmani and other scientists at the Armed Forces Institute of Pathology shows that the blood vessel obstructions that lead to sudden cardiac death can be triggered by two types of clots -- one caused by plaque rupture, which is the most common form in men at any age, and the other by plaque erosion.

The study found that premenopausal women were less prone to plaque rupture and "this may explain why, before menopause, women are less likely to suffer sudden cardiac death than men," says Virmani. However, the study found when premenopausal women suffer cardiac arrest, it is related to a different "mechanism" than men and postmenopausal women. That mechanism is plaque erosion.

In the study researchers examined the coronary arteries, the main blood vessels to the heart, in 51 women who had died of sudden cardiac death. Twenty-one deaths occurred in women 50 years old or younger.

The researchers conducted the study on women to determine if the same factors -- high cholesterol, cigarette smoking and body mass index -- influence the type of blood clots as they do in men. High blood cholesterol is linked to rupture of plaque. The causes of plaque erosion are not known.

The study found that in premenopausal women plaque erosion is the leading cause of sudden cardiac death by clot. It accounts for more than twice the clots than are caused by plaque rupture.

Women with plaque rupture were significantly older than women with eroded plaque, says Virmani. Risk factors such as total blood cholesterol and body mass index, a measure of fatness, were more strongly associated with plaque rupture in older women, while cigarette smoking was more strongly associated with plaque erosion in younger women.

The finding provides additional evidence that tobacco use is associated with heart disease, and that women of any age should be encouraged not to smoke. "The study suggests that quitting smoking may be one important way that younger women can protect against sudden death caused by an erosive plaque," says Virmani. "For older women and men, cholesterol and weight reduction may be more important risk factors to change." Cholesterol may contribute to plaque rupture by increasing the amount of fat under the plaque.

Virmani and her colleagues found that compared to men, younger women who had cardiac arrest had smaller amounts of plaque in the blood vessels where the clots occurred. This finding suggests that younger women had less coronary artery disease than postmenopausal women.

In younger women who died of sudden death, about half of the blood vessel was blocked at the site of the blood clot compared to nearly 80 percent blockage in women older than 50. Other studies by the authors have shown that plaque of young women who have died of sudden cardiac death contains less calcium and that they have fewer narrowings in the blood vessels than men or post-menopausal women.

Allen Burke, M.D, co-author of the study, says that the findings may have important implications for preventing sudden death. Tests that diagnose coronary artery disease narrowing, such as angiography, an X-ray of blood vessels, or ultrafast computed tomography, which detects the plaque by measuring calcium, may not be as useful in young women.

Detected early, coronary artery disease can be treated with drugs, surgery and by making positive changes in lifestyle such as stopping smoking and increasing physical activity.

"Angiography in younger women may underestimate potential lethal coronary artery narrowings. And coronary disease may be less detectable and more likely to be overlooked by ultrafast computed tomography," says Burke, staff pathologist at the Armed Forces Institute of Pathology.

"Even if a young women has chest pain and is a smoker, a physician may not suspect she is at risk for sudden death," he says. "But we had several women who were evaluated and given a clean bill of health and then a few days later they died."

Co-authors are Andrew Farb, M.D.; Gray Malcom, Ph.D.; You-hui Liang, M.D.; and John Smialek, M.D.

American Heart Association

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