Heart Disease and Women

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Heart disease is the number-one killer of American women, though many women underestimate its dangers.

Heart attacks used to be known as “widow-makers,” because of a widespread belief that heart disease was mostly a man’s affliction. In fact, heart disease has long ranked as the number-one killer of women in the United States. Heart attacks claim the lives of more than 250,000 American women annually, 12 times the number of women who die of breast cancer and twice the number of women who die of all forms of cancer combined. More-over, since 1979, mortality rates for women with cardiovascular disease (disease of the heart and blood vessels) have risen, while those for men have fallen.

Over the past 25 years, major studies of heart disease have largely eradicated the widow-maker myth from the medical community. Nevertheless, many women and their doctors still underestimate the dangers women face from cardiovascular disease. For example, a 1999 survey of 200 women ages 41 to 95, one of several surveys with similar results, found that two-thirds of the women aged 65 and older failed to identify heart disease as the leading cause of death among older women. A 1996 survey found that 33 percent of family-care physicians held the same erroneous view.

Until the late 1970’s, cardiovascular studies almost always excluded women, though the results were applied to both men and women. The explanation for this is complex. The widow-maker myth certainly played a role. Unfortunately, that misconception found support in one of the greatest ongoing pieces of observational research ever conducted in the United States: the Framingham Heart Study supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH).

In 1948, researchers began charting the health histories of about 10,000 adult volunteers in Framingham, Massachusetts. By the time the first study results were published in 1954, 98 of the adults had suffered a heart attack—81 of them men. Of the 44 women who had complained to researchers of chest pain, none had experienced a heart attack. However, the study had failed to include older women, for whom heart attack is a leading cause of death, because of concerns that they were too fragile for such studies. Younger women were excluded, too, because of fears of potential harm to fetuses.

Despite these limitations, women have benefited from the breathtaking advances in medicine’s understanding of heart disease. Thanks to the Framingham Study, doctors now recognize certain key risk factors for heart disease in both men and women and the importance of trying to lower or eliminate them. In addition, many treatments developed for men, such as smoking cessation and cholesterol-lowering drugs, have proven successful for women.

That’s the larger picture. Unfortunately, the close-up view is not as rosy. Overall, the standard drugs and treatments for heart disease are not as effective for women as they are for men. In part, this is because of researchers’ past tendency to ignore powerful and important differences in the male and female cardiovascular systems.

By 2000, studies designed specifically to focus on women were yielding valuable information about heart disease in women. One of the most important of these has been the landmark Nurses’ Health Study, a survey of more than 121,000 female nurses by researchers at the Harvard School of Public Health, begun in 1976. The study has revealed useful, though sometimes puzzling, information about how the symptoms, diagnosis, treatment, and survival rates of women with heart attack differ from men’s.

Women’s special risk factors

Numerous studies have clearly established that women face special risk factors for heart disease. The loss of estrogen at menopause may be the single most important of these. Health experts have linked the rising incidence of cardiovascular disease after menopause to declining natural estrogen levels. Before menopause, a woman’s risk of a fatal heart attack is only about one-fifth that of a man of similar age. But by age 54, the risk rises to about one-half that of men. By the time, a woman reaches her mid- to late-60’s, her chances of dying of a heart attack nearly equal those of a man of the same age.

Estrogen appears to offer multiple benefits. It helps keep arteries flexible. It raises levels of artery-clearing high-density lipoprotein (HDL cholesterol) while lowering levels of artery-clogging low-density lipoprotein (LDL cholesterol). As estrogen levels drop, cholesterol is more likely to stick to artery walls, forming plaques that narrow arteries and reduce blood flow. Estrogen also slows spasms (abnormal contractions of the arteries) that can cause blockages, and it appears to keep down blood levels of fibrinogen, a protein that promotes clotting. More than 30 medical studies, including one based on data from the Nurses’ Health Study, have reported that hormone replacement therapy (HRT), a treatment of female sex hormones, cuts the death rate from heart disease among menopausal and postmenopausal women by from one-third to one-half.

Two major studies questioned the heart benefits of HRT for some women, however. In 1998, researchers from the Heart and Estrogen/Progestin Replacement Study (HERS) reported that HRT failed to reduce the risk of heart attack among older women with

established coronary artery disease (CAD), disease of the coronary arteries that nourish the heart itself. The 2,700 women in the four-year study had been diagnosed with atherosclerosis (the buildup of fatty deposits in the coronary arteries), had had a heart attack, or had undergone angioplasty (a procedure to clear clogged arteries) or coronary bypass surgery. During the first year of therapy, researchers found, the women taking HRT actually had a higher rate of heart attack and death than those taking a placebo (inactive substance), though the risk dropped during the study’s final two years.

The second study, the Estrogen Replacement and Atherosclerosis (ERA) Trial, reported in March 2000 that HRT does not appear to slow the progress of atherosclerosis in older women. In a four-year study of 309 women with atherosclerosis, researchers found that while HRT lowered cholesterol levels, it failed to slow the buildup of plaques in the coronary arteries, the major cause of heart attack. By 2000, researchers were still uncertain whether HRT prevents heart disease if taken before menopause or before a woman develops signs of the disease.

Cholesterol: More complicated for women

Numerous international studies have conclusively documented how lowering high blood-cholesterol levels through diet changes maintained for at least five years can dramatically reduce the incidence of CAD in middle-aged people. However, these studies have focused almost exclusively on men. By 2000, studies had shown that determining the danger posed by cholesterol is far more complicated for women than for men.

Both men and women have two main types of cholesterol: HDL-cholesterol and LDL-cholesterol. HDL-cholesterol, commonly known as the “good” cholesterol, actually removes excess cholesterol from artery walls and transports it to the liver for elimination. In contrast, excess levels of LDL-cholesterol, known as “bad” cholesterol, are deposited on artery walls.

The similarities end there. For men, high LDL-cholesterol levels pose the greatest risk. Men can combat LDL-cholesterol simply by bringing down their total cholesterol levels, through diet, exercise, and anticholesterol drugs.

The story is different for women, for whom high cholesterol levels are not necessarily dangerous in themselves, but represent a risk factor only in very specific scenarios. In large part, a woman’s risk level depends on her HDL-cholesterol level. The National Cholesterol Education Program of the NHLBI considers total blood cholesterol levels in the range of 200 to 240 milligrams per deciliter (mg/dl) borderline high.

Most women, however, have an HDL-cholesterol level over 50 mg/dl and many approach 100 mg/dl, amounts that can inflate their total cholesterol levels substantially. As a result, a woman with a

total cholesterol reading of 220 to 230 mg/dl still may have a good cholesterol profile if a high HDL-cholesterol level accounts for part of that total. Conversely, a woman with a normal cholesterol level may still be in danger of heart disease if her HDL-cholesterol level is less than 35 mg/dl.

In addition, blood levels of another fat, triglyceride, may be a more important risk factor for women than men. Triglyceride levels higher than 150 mg/dl appear to increase the likelihood of heart disease in women. In contrast, the risk for men rises only when levels reach 400 mg/dl.

Other risks for women

Diabetes, specifically juvenile-onset, insulin-dependent diabetes (Type 1), equalizes the risk of CAD between men and women. Although women, on average, develop CAD 10 to 15 years later than men, the risk of heart disease for women with diabetes jumps to that of a man with diabetes of the same age. Moreover, diabetes increases the risk of heart attack three to seven times for women (two to three times for men) and doubles women’s risk of a second heart attack (while presenting no added risk for men). And if a diabetic woman has a heart attack, her chances of complications and death are substantially worse than those of a man with the disease.

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The single most preventable risk factor for heart disease for men and women is smoking. Smoking accelerates atherosclerosis and damages blood vessels, causing them to contract or even spasm. In premenopausal women, smoking cancels out the benefits of estrogen. Women who smoke have two to six times the risk of heart attack than nonsmokers and are significantly more likely to die during a heart attack. Smoking is especially dangerous for women taking oral contraceptives.

Like men, women also run a higher risk of heart disease if they have high blood pressure or if a parent or sibling has the disease. After age 55, the percentage of women with high blood pressure exceeds that of men. A sedentary lifestyle may pose a greater risk for women than men, because physically inactive women may be less likely to develop angina (chest pain), an early symptom of heart disease that often occurs during physical activity. Instead, women may feel chest pain at night or when they are emotionally upset, which may lead them and their doctor to look for an alternative cause of the pain.

Differences in diagnosis and treatment

Several studies have found that doctors are less likely to suspect heart disease in women than in men. For instance, men with serious chest pain are more likely to undergo diagnostic procedures than women, according to a February 2000 study from the Mayo Clinic in Rochester, Minnesota. In addition, diagnostic tools and procedures—designed to diagnose heart disease in men—often produce unreliable results in women. For example, women are more likely to have inaccurate electrocardiogram (a test to record the heart’s electrical activity) results than men, according to a 1999 study of 12,000 heart attack victims by researchers at St. Luke’s-Roosevelt Medical Center in New York City. In addition, treadmill stress tests (a procedure that shows whether the heart receives enough oxygen during exercise) generally produce more false-positive results in women.

Success of treatment for heart disease also varies between women and men. Women are twice as likely to die during coronary bypass surgery, though dramatic improvements in protecting the heart during this procedure have reduced the mortality rate to less than 1 to 2 percent for all patients in most hospitals. Some heart experts have suggested that some still unknown “female factor” may account for the difference. More likely, the reasons are that women have smaller hearts and arteries (and are therefore more difficult to operate on) and that they are older and sicker by the time they have surgery.

Heart attack: deadly differences

A heart attack may be a radically different experience for women and men. Women and men often have different symptoms, different previous medical conditions, and different survival rates, a number of studies have found. These differences may reflect underlying differences in the causes of CAD.

Like men, women suffering a heart attack may experience the classic symptoms of pain or heaviness in the chest; pain that spreads to the shoulders, neck, or arms; sweating; and shortness of breath. Frequently, however, women experience a wider variety of symptoms that are more likely to include pain in their upper abdomen, right shoulder, or back; discomfort in the throat or neck; burning pain in the chest; dangerously low blood pressure; or no pain at all. A significant percentage of women also suffer nausea or vomiting, unusual fatigue, dizziness, or unexplained anxiety and weakness.

Unfortunately for women, what they—and their doctors—don’t know can hurt or kill them. A lack of awareness of these varied symptoms often leads women to delay getting treatment, believing they are suffering from flu, indigestion, or another ailment. Some studies suggest that up to 45 percent of heart attacks in women go unnoticed or unreported.

A 1998 study found that women suffering a heart attack wait longer than men before seeking medical help and, on average, arrive at the hospital an hour later after symptoms have begun. Women also are less likely to call for an ambulance when they suspect they may be having a heart attack or don’t take the ambulance to the hospital when it arrives. As a result, time-critical treatments, such as drugs that dissolve blood clots that cause heart attack, may be less effective in women. Studies also show that even when women report having symptoms most commonly associated with heart attack, doctors are more likely to attribute those symptoms to an emotional or psychological problem than they would men.

Gender differences in the death rate from heart attack present another puzzle for researchers. In terms of sheer numbers, more men than women suffer a heart attack at every age. However, until age 75, fewer women survive. This is especially true among women under age 50. A 1999 study of 384,878 heart attack victims by researchers at Yale University in New Haven, Connecticut, found that while 2.9 percent of men under 50 hospitalized for heart attack died, 6.1 percent of women did. Moreover, the death rate among all women during the first month after a heart attack is 70 percent higher than for men and nearly twice as high within the first year after an attack.

Explaining the differences

Researchers have offered a variety of explanations for the disparity in death rates. Women may suffer more serious first attacks than men, a 1998 study found. The St. Luke’s-Roosevelt study attributed about one-third of the difference in death rates to women’s greater likelihood of having weakened heart muscles and dangerously low blood pressure at the time of their attack. Women also are at higher risk of developing complications from heart attack treatment, especially bleeding from blood-thinning drugs.

Significant differences between female and male cardiovascular systems also may help account for women’s higher death rate from heart attack. The St. Luke’s-Roosevelt researchers theorized that women’s tendency to develop CAD years later than men do may be a mixed blessing. As CAD progresses in men, they often develop new blood vessels to take over the work of blocked vessels. Because CAD develops in women more quickly, women’s vessels do not have the time to do this. The researchers also suggested that women may be more likely to experience artery spasms, which can trigger heart attack. Yale researchers theorized that differences in the way blood clots form in women may boost women’s heart attack rate.

In addition, CAD may play a smaller role in heart attack for women than for men. A 1996 study at Massachusetts General Hospital in Boston, for example, found that only 45 percent of women admitted because of a heart attack had CAD, compared with 80 percent of men. Moreover, in cases of sudden cardiac death, nearly two-thirds of women had reported no previous symptoms of heart disease, compared with half the men.

Shifting focus

Research in the late 1900’s produced a wealth of information about heart disease in women. Much more is expected from the NIH’s Women’s Health Initiative. Begun in 1991, this 15-year, $625-million study is the largest clinical research study of women and their health ever undertaken in the United States or elsewhere. The study encompasses 40 clinical research centers and will involve more than 150,000 women. This initiative is the first major study to look in an integrated way at the chronic diseases that threaten women most, including heart disease. It is also one of the first major studies to recognize that cultural, ethnic, racial, and socioeconomic characteristics affect the kinds of illness people develop and the way they respond to treatment.

Unfortunately, because of the widow-maker myth and the knowledge gap, a whole generation of women did not include heart disease prevention in their prescription for better health. Many still don’t. This lack of focus is especially sad because cardiovascular disease can be prevented and even existing CAD can be diminished by adopting a low-fat diet, exercising regularly, and staying away from cigarettes. Indeed, cardiovascular research has provided the strongest evidence yet that, for both women and men, healthy living is the key to a healthy heart.

For additional information: Books

Kra, Siegfried J. What Every Woman Must Know About Heart Disease: A No-Nonsense Approach to Diagnosing, Treating, and Preventing the #1 Killer of Women. Warner Books, 1997.

Legato, Marianne J., and Colman, Carol. The Female Heart: The Truth About Women and Heart Disease. Quill, 2000.

For additional information: Web sites

National Coalition for Women with Heart Disease—www.womenheart.org

National Heart, Lung, and Blood Institute’s Facts About Heart Disease and Women— www.nhlbi.nih.gov/health-topics/heart-disease-women

Office on Women’s Heath—www.womenshealth.gov/heart-disease-and-stroke

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