Coronary Heart Disease in Women -- An Ounce of Prevention

Cardiovascular disease, including stroke, is the leading killer of women in the United States and in most developed
countries. In 1997, cardiovascular disease accounted for 43 percent of all deaths in women in the United States.
For the nearly 50 million American women who will be more than 50 years of age in the year 2000, there is no
greater health-related issue than the prevention of cardiovascular disease and cancer. Epidemiologic studies and
randomized clinical trials provide compelling evidence that coronary heart disease (CHD) is largely preventable.
The extent to which changes in lifestyle reduce the incidence of CHD and its complications in women
has not been well documented. Furthermore, the role of hormone-replacement therapy in the primary and
secondary prevention of CHD in women has not been firmly established.
The Nurses' Health Study was established in 1976, when 121,700 female nurses, then 30 to 55 years of age,
agreed to participate in a long-term study of their medical history and lifestyle. Questionnaires have been sent
every two years to update information on risk factors and newly identified diseases. After the return of the 1980
questionnaire, women with known cardiovascular disease or cancer were excluded from further analyses of risk
factors for CHD; the remaining 85,941 women were followed for the next 14 years. Hu et al. measured the
effects of risk factors on the incidence of CHD, including nonfatal myocardial infarction and deaths due to
coronary disease from 1980 to 1994. (4) The large sample, the high rate of follow-up, and the detailed
information collected on diet and lifestyle factors make the results of this study extremely powerful.
During the 14 years of follow-up, the incidence of CHD declined by 31 percent, after adjustment for the effects of
age. Smoking declined by 41 percent, the rate of use of hormone-replacement therapy among postmenopausal
women increased by 175 percent, and diet improved considerably. Taken together, the changes in these variables
explained a decline of 21 percent, or two thirds of the 31 percent overall decline, in the incidence of CHD. During
the same period, the proportion of women who were overweight (defined, as having a body-mass index [the
weight in kilograms divided by the square of the height in meters] of 25 or more) increased by 38 percent. The
increase in weight among women from 1980 to 1994 -- despite other improvements in lifestyle variables-is
disappointing and undoubtedly mirrors trends among men and children as well.
These findings complement another recent report from the Nurses' Health Study. (6) In that study, which involved
84,129 of the same women, investigators examined the combined effect of lifestyle-related risk factors-
specifically, smoking, overweight, lack of exercise, and poor diet-on the risk of coronary disease. The women
who had none of the risk factors (3 percent of the study population) had an 83 percent lower risk of coronary
events than the rest of the women. Eighty-two percent of coronary events in the study population could be
attributed to a lack of adherence to a low-risk lifestyle as defined in the study. The data in both studies
overwhelmingly support the modification of risk factors and improvement in lifestyle as a means to prevent the
onset of CHD in women.
For example, the Heart and Estrogen/Progestin Replacement Study (HERS) (7) found that 4.1
years of treatment with conjugated estrogen plus medroxyprogesterone acetate had no overall effect on the rate of
nonfatal myocardial infarction or death among women with established coronary artery disease. However, an
increased risk of cardiovascular events was associated with the study regimen in the first year, (7) although an
analysis of trends over time showed that the regimen had benefit in later years. The selective estrogen-receptor
modulators (SERMs), a new type of nonhormonal therapy, bind estrogen receptors and function as tissue-specific
estrogen antagonists or agonists. Raloxifene and Nolvadex, SERMs that decreases bone loss but do not affect the
endometrium and may protect against breast cancer, recently became available for the treatment of osteoporosis.
(8) Its role in the secondary prevention of CHD in postmenopausal women is unknown and is being evaluated in a
large, randomized, prospective trial.
The Women's Health Initiative, funded by the National Institutes of Health, will definitively evaluate the efficacy of
current hormone-replacement therapy for the primary prevention of CHD, (12) whereas the RUTH trial will
determine the magnitude of cardioprotection afforded by one SERM in secondary prevention. Until data from
these studies are available, findings from large, prospective studies, like the Nurses' Health Study, provide
meaningful data to support guidelines for the prevention of CHD in women. The message from the two studies
described in this issue of the Journal is clear. Adherence to a healthful lifestyle and use of hormone-replacement
therapy, when prescribed for current indications, reduce the risk of primary CHD in women. The role of
postmenopausal hormonal therapy, including the SERMs, in secondary prevention awaits a definitive answer from
ongoing clinical trials.
Do the encouraging findings about the reduction in the incidence of CHD among women and the positive effect of
lifestyle modification allow us to reduce our efforts to understand further the pathophysiology of CHD or to
reduce educational efforts? Absolutely not. The next step in prevention must be to design and test programs to
help women modify their behavior and achieve a more healthful lifestyle. We must not relax our efforts; rather, we
must move forward aggressively to educate the public, with the goal of reducing the incidence and preventing the
complications of the most common disease among both women and men in our country.