HARVARD GAZETTE ARCHIVES

Women Advised About Preventing Heart Disease

By William J. Cromie

Gazette Staff

About 500,000 women in this country will die from heart disease this year. Advice on how to avoid becoming one of them fills bookstore racks, television spots, and advice columns.

"Scientific studies" urge women to swallow aspirin and vitamin E pills, take estrogen, or lower their cholesterol with drugs. How conclusive are these studies and how much of this is good advice? Do preventive strategies that work in men work as well in women?

"We have good evidence that lifestyle changes can significantly reduce the risk of heart disease in both women and men," JoAnn Manson, associate professor of medicine, told a meeting of the American Heart Association in Chicago last month. "However, not enough reliable information exists about other highly publicized strategies, such as vitamin E and beta carotene supplements, cholesterol-lowering drugs, and estrogen replacement treatment to recommend them to all women (or men)."

Manson is co-director of women's health at Brigham and Women's Hospital, and principal investigator at the Medical School for the $625 million Women's Health Initiative, the largest research study of women ever sponsored by the federal government.

Vitamin E Pills Not Recommended

Popular articles on heart disease tout "evidence" that vitamins E and C and beta carotene decrease the risk of heart disease. All three reportedly inhibit reactions between oxygen and cholesterol which lead to fatty deposits in blood vessels. From this connection, it's easy to jump to the conclusion that taking such antioxidants in pill form will provide extra protection.

Manson won't jump to that conclusion. Most antioxidant studies to date have been what are known as "observational." People are asked how much vitamin E or C they take in food or pill form, then researchers compare these amounts with the incidence of heart disease. But people who take part in such studies do other things besides consume vitamin E. They have different lifestyles and diets that can skew the result of studies based on vitamins alone.

"Women and men eating a diet rich in antioxidant vitamins will also have high intake of fruits and vegetables, and thus may be protected by other nutrients in these foods," Manson says. "Additionally, such people might engage in other healthy behaviors that contribute to a lower rate of heart disease, such as exercising and not smoking."

The gold standard among scientists is the so-called "randomized clinical trial." These trials involve randomly assigning people to a group that takes the vitamin under investigation, or one that does not, following both for years, then determining who comes up with less heart disease.

Such studies are now under way. The Women's Health Study, based at Harvard, tests the value of vitamin E and aspirin in preventing heart disease. The Women's Antioxidant Cardiovascular Study (WACS) looks at the role of vitamins E and C and beta carotene in helping those who already have heart or blood vessel disease.

Folate, or folic acid, B6 and B12 also have been acknowledged as lowering the risk of heart disease, but these vitamins have not yet been adequately tested. (Folic acid, however, is recommended for pregnant women to protect their embryos against spine and brain defects.)

"Until randomized trials provide evidence for benefits, it's premature to recommend regular use of any antioxidant supplements," Manson declares. "Rather than support the wishful thinking that popping a pill is the answer, we recommend a diet rich in fruits and vegetables, no smoking, and moderate exercise for reduction for heart disease prevention. No one knows yet what effects the long term use of vitamin supplements will have."

A randomized study published recently in The New England Journal of Medicine concluded that large doses of vitamin E (2,000 international units a day) show promise for delaying the deleterious effects of Alzheimer's disease. The vitamin reportedly delayed entry into nursing homes for those with moderately severe Alzheimer's and reduced the loss of daily activities, including dressing, bathing, and handling money.

Manson, however, does not recommend giving Alzheimer's sufferers large doses of E until further studies show a long-term benefit without serious side-effects.

Lowering Bad Cholesterol

Another study published last month in The Journal of the American Medical Association found that most women with heart disease have dangerously high cholesterol levels. Sixty percent of the women, whose average age was 66.7 years, had levels of LDL, or bad cholesterol, high enough to promote build up of fatty deposits in their arteries. Federal guidelines recommend LDL levels of 100 or lower in those with heart disease. Less than 10 percent of the women met that standard.

Several different studies have concluded that proper use of cholesterol-lowering drugs can save the lives of many women who already have heart disease. Although Manson agrees with their use among these high-risk women, she cautions women with no history of heart disease against taking these drugs. "There is not enough evidence to recommend cholesterol-lowering drugs to prevent a first heart attack in women at low risk for heart disease and only mildly elevated cholesterol," she says.

Aspirin For Heartache

Aspirin is another drug that extends the lives of those with heart disease, but its role in the prevention of first heart attack has not been conclusively determined.

"However, there is strong evidence that aspirin benefits both men and women with a history of heart attack, stroke, and other cardiovascular events," Manson adds.

The Harvard Physicians' Health Study concluded that regular use of aspirin cuts risk of a first heart attack almost in half (44 percent). That finding, together with other evidence, led to federal recommendations that men 40 years and older should consider aspirin if they are at an increased risk of heart disease. In other words, an aspirin every other day, or a baby aspirin a day, reduces the risk of a first heart attack among older men who smoke, are overweight, or have high blood pressure or high cholesterol.

Another Harvard effort, the Nurses' Health Study, found that women who took from one to six aspirins a week reduced their risk of a first heart attack by 25 percent. For women 50 years and older, the risk reduction increased to 32 percent.

Yet Manson stops short of recommending that all women take aspirin regularly. The Nurses' Health Study is an observational investigation conducted mainly by questionnaire. She prefers to wait for results of the Women's Health Study, a tightly controlled randomized trial. But those results won't be available for three years.

In the meantime, she says that women at high risk for heart disease should talk to their doctors about taking aspirin. Regular use of aspirin, even baby aspirin, can cause stomach upsets and bleeding.

Estrogen Dilemma

Manson also is skeptical about the benefits of every woman taking estrogen after menopause. The protection against heart disease that this hormone gives to younger women is lost following menopause. A large number of studies have suggested that replacing the lost estrogen reduces risk of heart disease, stroke, and bone- weakening osteoporosis. However, that apparent protection may come at the high price of increased risk of breast cancer.

In the latest analysis of such studies, researchers at New England Medical Center in Boston concluded that fewer than one in 100 healthy women "would fail to benefit from estrogen replacement therapy."

Manson and others point out that this conclusion comes from mathematical analysis of observational studies. "You can do endless mathematical modeling, but if the data come from observational studies you cannot eliminate the possibility of confounding factors and biases," she says.

The Women's Health Initiative is now enrolling 160,000 women nationwide, ages 50-79 years, to do a conclusive randomized trial. Women who receive hormone treatment will be matched with those who take inactive pills to conclusively determine the risks and benefits. But results will not be available for seven to eight years.

Until then, to take or not take estrogen treatment remains a tough personal choice.

"Women who are not at high risk for heart disease, and are doing everything they can to minimize that risk, may not want to increase their chances of getting breast cancer by 30 to 40 percent," Manson says. "That's especially true if there is a family history of breast cancer. Also, for some women, it's more important not to have breast cancer than to avoid heart disease no matter what the numbers are."

Those numbers are scary. Breast cancer kills about 43,600 women a year in this country alone, compared to about 236,000 who die from heart attacks. Another 65,000 die as a result of hip fractures.

"When all these factors are considered, most women will be good candidates for hormone replacement therapy," Manson admits. "But it's important for them to know that there are uncertainties about the risks and benefits."

Exercise and Diet

Manson is most enthusiastic about the value of exercise and a plant-based diet for every woman and man.

"The most important thing anyone can do for their health after quitting smoking is to exercise regularly," she says. "Exercise favorably impacts every other risk factor. It lowers blood pressure, cholesterol, and stress. It also lowers risk of adult-onset diabetes by improving glucose tolerance, and it reduces risk of osteoporosis."

A recently completed study of more than 40,000 postmenopausal women concluded that older women can reduce their chance of premature death by as much as 30 percent with regular, moderate exercise.

"Earlier guidelines called for vigorous endurance exercise, the kind where you break a sweat and significantly boost your heart rate," Manson notes. "Now there's increasing evidence that moderate exercise lowers risk of heart disease, stroke, high blood pressure, and diabetes. There are also studies linking exercise to decreased risk of colorectal, breast, uterine and other cancers.

A study of 25,624 females in Norway, published last week, concluded that the risk of breast cancer is lowest in lean women who exercise at least four hours a week.

The latest guidelines in this country suggest 30 minutes a day of moderate intensity exercise, such as brisk walking. The Nurses' Health Study found that such activity cuts the risk of heart disease and stroke in women 40 to 60 years old.

The premature-death study mentioned above concluded that even doing moderate exercises as little as once a week was associated with a decrease in death from all sources. Of course, more frequent activity results in larger reductions of risk.

These findings agree with earlier studies done on men. Despite such an easy recipe for longer, healthier life, however, "60 percent of the U.S. population does not exercise regularly," Manson point out.

And a majority of Americans don't eat right, either. Manson gives the following widely accepted advice: Eat at least five servings of fruits and vegetables a day. Eat more fiber, including bread and cereals made with whole grains rather than white bread and baked goods containing lots of sugar and butter. Don't eat saturated fat, burgers, marbled red meat, butter, and hard margarine. Do eat fish, monounsaturated fat, olive oil, and canola oil.

The results of a national study, published this month, show that such a diet dramatically reduces high blood pressure, a leading cause of heart disease. If everyone ate 8 to 10 servings of fruits and vegetables a day, 2 to 3 portions of low-fat dairy foods, and avoided fatty red meat, there would be 225,000 fewer hearts attacks and 100,000 fewer strokes every year, according to Thomas Moore, associate clinical professor of medicine at Brigham and Women's Hospital.

What's more, the diet works without restriction on salt. And drinking one (women) or two (men) glasses of red wine a day may further protect you against heart disease.