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Heart disease: women at risk.

Five years ago, at the bedside of a patient in a cardiac intensive care unit, a senior cardiologist remarked to me that he hoped I never had to be on a balloon pump. Intra aortic balloon pumps are ingenious sausage-shaped devices that sit deep in the aorta and temporarily assist the failing hearts of patients awaiting open-heart surgery. Ingenious though they may be, the cardiologist explained, they are one-size-fits-all-the size appropriate for an average man, which means that for smaller women, the pumps either can't be used at all or can lead to complications. Somehow the comment lingered, and several years later I found myself cross-referencing "women" and "heart disease" in a computer journal-search system to see what was known about the relationship between the two. My efforts turned up a single, unsatisfying result: a paper on the finding that a man's risk of cardiac arrest rises with his wife's level of education. Until very recently, the medical community thought of coronary artery disease as a masculine affliction. Consequently, men were almost exclusively the subjects of research and prevention efforts. But because of the aging of the American population, it has become clear that in later years women become equally vulnerable. This finding has sent scientists scrambling to learn more about women's hearts and has left public-health advocates with the task of spreading the word that women, too, are at risk.

"There's a longstanding myth that women don't get coronary artery disease. They do. They just get it a little later," says Dr. William Castelli, director of the Framingham Heart Study, which since 1948 has painstakingly monitored the habits and health of more than 5,000 men and women, providing invaluable information about the genesis of heart disease.

"Heart disease in men is very different from heart disease in women," says Pamela Douglas, an assistant professor of cardiology at the University of Pennsylvania and the editor of the medical textbook Heart Disease in Women. "And that's not even really common knowledge among cardiologists yet. I treat my female patients based mostly on male studies and tell them, We just don't know a lot.' "

More than 500,000 American women die of cardiovascular diseases each year. Heart disease is the leading killer of women over 40, and an equal number of women and men will die of atherosclerosis, or hardening of the arteries. Yet statistics show that a man is three times more likely than a woman to be referred for cardiac catheterization and four times more likely to be treated with bypass surgery. These are worrying numbers, for the death rate from heart disease has decreased 7 percent each year over the last decade for white men in the United States, but only slightly for all women and for black men.

o one knows precisely why, but it is extremely rare for a woman to have a heart attack before age 50, and women typically lag ten years behind men in developing heart disease. (Only 6 of the 1,600 premenopausal women in the Framingham Heart Study developed heart disease.) After menopause, however, the rate of cardiac problems in women increases dramatically, nearly catching up with the male rate by the time women enter their 70s.

"When I ask women what health issue concerns them most, they inevitably say, Breast cancer,' " says Trudy Bush, an epidemiologist at the Johns Hopkins School of Hygiene and Public Health. "It's very frustrating. Out of 2,000 postmenopausal women in one year, 20 will get heart disease and 12 will die of it, 6 will develop breast cancer and 2 will die of it, 3 will develop cancer of the uterus, and one will die of it."

The gender bias in the medical understanding of heart disease has deep roots. Until the present decade, hardening of the arteries was felt to be a normal part of the aging process, and therefore large studies concentrated on "premature" coronary artery disease-which really is a man's disease. Almost all the classic cardiology studies included only men as research subjects: the Multiple Risk Factor Intervention Trials (known as the "Mr. F.I.T." trials), the Lipid Research Clinics Coronary Primary Prevention Trial, and the Veterans Administration Cooperative Study. Others, like the huge Coronary Artery Surgery Study (C.A.S.S.), included too few women to draw many conclusions. Only the Framingham Study enrolled nearly equal numbers of men and women.

These investigations have uncovered several risk factors for heart disease, notably smoking, a family history of cardiac disease, high blood pressure, high cholesterol, and diabetes. But subsequent studies have shown that not all of them apply with equal force to men and women. And certain risks, such as oral contraceptive use, are unique to women.

For both women and men, smoking is the leading cause of heart disease an individual can control. For women, the strong relationship between the two has been substantiated by the huge Boston-based Nurses' Health Study, in which 120,000 female nurses have filled out questionnaires every other year since 1976 about their habits and illnesses. The study has shown that cigarette smoking is "far and away the most important factor, accounting for 50 percent of heart disease," says Walter Willett, a co-director of the study.

The Nurses' Health Study has also shown a high risk of suffering premature cardiac death for women now using birth-control pills. That finding lies behind the current medical wisdom that women over 35 (and women over 30 who smoke) should use other means of contraception. Almost all contraceptive pills now on the market have much lower doses of hormone, however, and they are thought to be much less dangerous. (The Nurses' Health Study will enroll 100,000 younger nurses this fall in an attempt to find out whether this is so.)

Some of the conventional risk factors for heart disease affect men and women differently. High blood pressure may be less of a problem for women, and diabetes takes a much greater toll on female than on male hearts. The Framingham data base shows that if a woman develops diabetes, she loses her natural ten-year grace period and acquires the same chance of developing heart disease as a man has.

Although the government has recently recommended that all adults with cholesterol levels above 200 seek treatment, studies done over the past several years have shown that blood cholesterol content in women is probably not as strongly linked to heart disease as it is in men, except at extremely high levels. The Framingham study found that a woman with a cholesterol count of 295 is still less than half as likely to have a heart attack as a man with a cholesterol count of less than 204.

One key to this discrepancy seems to be a particular subtype of cholesterol called high-density lipoproteins (HDL). In the past five years it has become clear that not all cholesterol is alike: there is "bad" low-density lipoprotein (LDL) cholesterol, which in men has been clearly associated with heart attacks, and "good" HDL cholesterol, which actually prevents the development of cardiac disease. Although little is known about how HDL cholesterol works, HDL cholesterol levels of women before menopause average 25 percent higher than those of men, and many researchers believe it is this substance that protects their hearts' arteries.

In men, either LDLs or low HDLs can hasten heart problems. But this does not appear to be the case with women, who seem affected less by fluctuations in LDL but extraordinarily more by HDL shifts. One Israeli study showed that women could enjoy perfect health with any level of cholesterol and LDL, as long as HDL made up more than 23 percent of the total. In fact, the Lipid Research Clinics Follow-Up Study found that except for the subject's age, the level of HDL cholesterol was the single most accurate predictor of cardiac death in women. Weight reduction, exercise, and perhaps modest alcohol consumption (up to two drinks a day) lead to higher HDL levels.

The lack of information about women and heart disease has been a cause of confusion for physicians and scientists interested in preventive health.

It is unclear whether women should take an aspirin every other day to help prevent heart attacks. A highly publicized study using 22,000 healthy men has shown that doing so decreases the heart attack rate. But cardiologists are uncertain about dispensing this advice to women, We tell our female patients to take aspirin, but we're not entirely comfortable with that," says Dr. Richard C. Becker, a cardiologist at the University of Massachusetts Medical Center, who organized a consciousness raising" symposium on heart disease in women last year. Several small studies provide evidence that regular aspirin use may lead to a higher risk of undesirable side effects, notably stroke.

Several new studies aim to develop preventive measures specifically for the female population, especially post menopausal women. Theorizing that the cardiac advantage enjoyed by younger women is related to estrogen production, which slows after menopause, the studies see whether the advantage can be sustained in older women administered hormone supplements. This approach looks promising. Women in the Nurses' Health Study who took hormones to control postmenopausal symptoms turned out to be only one-third as likely to develop hear' disease as those who didn't.

This month, after five years of preparation, the National Institutes of Health will open the Post-Menopausal Estrogen Progestin Intervention P.E.P,I.) Trial, its first large-scale clinical trial directed at evaluating risk factors for heart disease in women. Inna Mebain, the director of the study, says 850 female volunteers between 45 and 64 will receive hormone therapy and researchers will assess its effect on women's cardiac risk factors, including HDL cholesterol.

Researchers are also at work improving the diagnosis of heart disease in women. For now, diagnosis is notoriously difficult because the standard early warning signs of heart disease-a squeezing chest pain during exercise, for example-have proved far less reliable as indicators of blocked arteries in women than in men. And the time honored "exercise tolerance test" of heart function, in which a patient walks on a treadmill while attached to a cardiogram machine, tends to set off false alarms for women.

In one typical study conducted at Baylor College of Medicine, only 40 percent of women with chest pains and poor" exercise tolerance tests proved to have heart disease when dye was injected into their coronary arteries; the comparable figure for men is about 88 percent. Cardiologists are refining exercise tolerance tests to make their results for women more helpful. They are also turning to the more expensive, and more accurate, "nuclear" stress tests, in which the patient receives an injection of an isotope taken up by the heart. The physician observes the heart's motion on a gamma camera as the patient exercises.

Some doctors worry that "false positive rates" among women-reports by the patient and ominous test results that prove to be nothing at all-make their peers less thorough in evaluating female patients. Indeed, recent studies have shown that women with chest pains and positive nuclear stress tests are referred ten times less often for further testing and treatment than equivalent men. "We've all been sensitized by these false positives," Dr. Richard Becker says. "Is there a bias? Probably. In women with risks, we need to be more aggressive."

Physicians are also influenced, says Dr. Becker, by studies which suggest that women subjected to invasive or surgical therapy do worse than men. Women run four times the risk (4 percent versus one percent) of dying during or immediately after open-heart coronary-artery surgery, in which narrowed stretches of the arteries are "bypassed" using vessels borrowed from the leg. And after surgery, women often have continued chest pain, which suggests that blood flow to the heart muscle remains poor after the operation. Surgeons explain that women's tinier coronary arteries are more difficult to manipulate in the operating room.

Most women who undergo bypass operations do extremely well, however. Of the more than 95 percent of women who leave the hospital after bypass, more than 90 percent will be alive five years later, and about 70 percent ten years later-the same statistics as for men. The challenge now is to determine which women benefit most from the operation. Says Dr. Becker, "We're going to have to repeat a lot of the old clinical trials-but this time with women."

That is a big prescription to fill. To produce statistically significant results, such studies often require huge numbers of subjects observed over decades. The C.A.S.S. investigators, for example, have followed more than 7,000 subjects 6,000 men, 1,000 women) after bypass operations for almost 15 years. The Mr. F.I.T. trial enrolled 15,000 men. When P.E.P.I. researchers tried to structure the trial to follow volunteers until a significant number of heart attacks occurred, they discovered that they would probably have to follow "30,000 women for 15 years to draw adequate conclusions about whether steroids affect mortality," Irma Mebain says. Instead, they recorded the short-term effects of hormones on known cardiac risks.

So it may be some time before there is a full-blown Ms. F.I.T. trial. But smaller trials are under way. It may be a sign of the times that the New England Journal of Medicine recently ran as its lead article a study that examined the effects of low-tar cigarettes on the incidence of heart attacks-in women. "People are beginning to include gender when they do large clinical trials," Dr. Pamela Douglas says. "And remember, we've got these huge data bases accumulating around the country. Now someone just has to press the male-female' button."

New Study Needs Volunteers

More than 800 postmenopausal women, 45 to 64, are being recruited for a major national heart study sponsored by the National Heart, Lung, and Blood Institute. The project will test the effects of various estrogenprogestin combinations on cholesterol, blood sugar, insulin, fibrinogen, and other clotting factors that can affect a woman's risk of developing head disease and osteoporosis.

Each volunteer will visit a designated clinic 14 times within the three year study period. She will undergo physical examinations, blood tests, electrocardiograms, bone-density studies, biopsies of uterine tissue, mammography. She will be given medication' (All monitoring and medications for die study are provided free.)

Prospective volunteers can call the project information line at 1-800-8827374 or (in Washington, D.C.) 202676-5214. Volunteers must have experienced a natural or surgical menopause, and they must be able to visit one of the clinic locations in San Diego; Baltimore; Los Angeles; Washington, D.C.; San Antonio, Texas; Iowa City; or Palo Alto, California.
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Author:Rosenthal, Elisabeth
Publication:Saturday Evening Post
Date:Jan 1, 1990
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