Statement by Claude Lenfant, M.D., Director,
National Heart, Lung, and Blood Institute (NHLBI)
Postmenopausal hormone therapy is not beneficial in the short term to either prevent the progression of or induce the regression of atherosclerosis in coronary arteries in women with established coronary heart disease (CHD). This is the key finding reported in "Effects of Estrogen Replacement on the Progression of Coronary-Artery Atherosclerosis," (ERA) by David M. Herrington, M.D., and colleagues in the August 24, 2000 issue of The New England Journal of Medicine (NEJM). The results extend the debate on the role of hormone-replacement therapy (HRT) in preventing CHD.
In the study, 309 women with diagnosed coronary disease were randomly assigned to receive either placebo, 0.625 mg of conjugated estrogen alone, or 0.625 mg of estrogen in combination with 2.5 mg medroxyprogesterone acetate (MPA). The researchers found that both the single and combined hormone therapies had an important impact on atherosclerosis risk factors. However, neither estrogen alone nor estrogen plus MPA affected the progression of coronary atherosclerosis in women with established coronary heart disease.
The ERA trial has some important limitations. The study lasted only 3 years, while HRT's benefits for heart disease may not be evident for several years following initiation of therapy. Also, it is possible that HRT has beneficial effects on the coronary arteries that are not seen on the angiogram. More studies of women with pre-existing heart disease may provide a more definitive answer on HRT's benefits in this population.
Furthermore, the results of the ERA study cannot be generalized to all postmenopausal women. Women in the ERA study were approximately 65 years old, and therapy was initiated an average of 23 years after menopause. It remains to be seen whether the study results apply to women of all ages, and to HRT started soon after the beginning of menopause. Again, more studies of postmenopausal women with pre-existing heart disease are needed.
We also need information from trials studying HRT's effects on women without heart disease. Such a study is NHLBI's ongoing Women's Health Initiative (WHI), one of the largest prevention studies ever conducted in the United States. WHI is examining the effect of HRT in preventing heart disease in more than 27,000 postmenopausal women aged 50-79.
In the same NEJM issue, Frank B. Hu, M.D., Ph.D., and colleagues report on the benefits of lifestyle modification for the prevention of CHD in women with no existing coronary heart disease. The authors evaluated the effects of risk factors on the incidence of CHD in nearly 85,000 women aged 34-59 who were participating in the Nurses' Health Study. The scientists
found that over 14 years of follow-up between 1980 and 1994 positive lifestyle patterns
resulted in significant declines in the incidence of coronary disease in women who had no previously diagnosed cardiovascular disease (CVD).
During the 14 years, the incidence of coronary heart disease declined by 31 percent, after adjustment for age. Smoking declined by 41 percent, the rate of HRT use among postmenopausal women increased by 175 percent, and diet improved considerably. Taken together, the changes in these variables explained a decline of 21 percent in the incidence of
CHD. Read individually, the reduction in smoking explained a 13 percent decline in the incidence of CHD, improvement in diet explained a 16 percent decline, and an increase in postmenopausal hormone use accounted for a 9 percent decline.
Conversely, during the same follow-up period, the proportion of women in the study who were overweight (defined as a body mass index, BMI, of at least 25) increased by 38 percent. BMI measures weight relative to a person's height and is a key indicator of overweight and obesity major risk factors for CHD. An increase in BMI in the Nurses' Health Study cohort explained an 8 percent rise in the incidence of coronary disease.
These two studies highlight critical research and public health education needs. We must aggressively pursue clinical trials to determine how best to prevent coronary heart disease. In addition, as noted by NHLBI's Scientific Director of Clinical Research, Dr. Elizabeth Nabel, in an editorial in the same NEJM issue, we must exert greater efforts to educate the public about the importance of lifestyle behaviors in the prevention of coronary disease.