Guide to Preventive Cardiology for Women

• AHA Scientific Statements
• prevention
• women
• coronary disease

Coronary heart disease (CHD) is the single leading cause of death and a significant cause of morbidity among American women.¹ Risk factors for CHD in women are well documented.² Compelling data from epidemiological studies and randomized clinical trials show that CHD is largely preventable. Assessment and management of several risk factors for CHD are cost-effective.³ Despite these facts, there are alarming trends in the prevalence and management of risk factors in women.² Smoking rates are declining less for women than for men. The prevalence of obesity is increasing, and ≈25% of women report no regular sustained physical activity.⁴ Approximately 52% of women >45 years old have elevated blood pressure, and ≈40% of women >55 years old have elevated serum cholesterol.⁵ The purpose of this statement is to highlight risk factor management strategies that are appropriate for women with a broad range of CHD risk. A more detailed description, including the scientific basis for these recommendations, is available in the 1997 American Heart Association scientific statement “Cardiovascular Disease in Women.”²

Recently, the Centers for Disease Control and Prevention National Ambulatory Medical Care Survey⁶ showed clinicians are missing opportunities to prevent CHD. In this study of 29 273 routine office visits, women were counseled less often than men about exercise, nutrition, and weight reduction. In the multicenter Heart and Estrogen/progestin Replacement Study (HERS),⁷ only 10% of women enrolled with documented CHD had baseline LDL-cholesterol levels below a National Cholesterol Education Program (NCEP) target of 100 mg/dL. A recent national survey showed that women were significantly less likely than men to enroll in cardiac rehabilitation after an acute myocardial infarction (MI) or bypass surgery.⁸ This finding is especially important because post-MI patients not enrolled in cardiac rehabilitation are less likely to receive aggressive risk factor management.

Recommendations for the primary and secondary prevention of CHD have been published.^{9 10} Although those recommendations apply to women, there are aspects of risk factor management that are unique to women. Pregnancy and the preconception period are optimal times to review a woman’s risk factor status and health behaviors to reduce future cardiovascular disease. Pregnant women should be strongly encouraged to discontinue smoking and not to relapse in the postpartum period. Avoidance of excess weight gain during pregnancy may reduce the risk of developing CHD in the future. An emphasis on prevention of CHD in postmenopausal women is particularly important because the incidence of CHD rises with age. The use of estrogen replacement therapy (ERT) to prevent CHD, osteoporosis, and possibly dementia is a difficult health decision for postmenopausal women. The potential benefits of therapy must be weighed against the possible risks, including breast cancer, gallbladder disease, thromboembolic disease, and endometrial cancer, although the last is reduced by concomitant use of a progestin.

The recent findings from HERS¹¹ have challenged previous observational data regarding the role of hormones in preventing subsequent cardiovascular events. HERS was the first large-scale, randomized, clinical trial in older postmenopausal women with confirmed coronary disease to test the efficacy and safety of hormone replacement therapy on clinical cardiovascular outcome in postmenopausal women. The study population included 2763 women (mean age 66.7 years) with established CHD randomly assigned to 0.625 mg conjugated equine estrogens (CEE) plus 2.5 mg of medroxyprogesterone acetate (MPA) per day or placebo. Participants were monitored for an average of 4.1 years for the main end point of nonfatal MI or CHD death. At study completion, no significant differences existed between groups for any cardiovascular end points.

Surprisingly, after 1 year, HERS showed an increase in cardiovascular events in the treatment arm, but in years 4 and 5, fewer events occurred than in the placebo arm. It has been hypothesized that possible early adverse effects of estrogen in women with CHD may be due to a procoagulant effect that may later be offset by an antiatherogenic benefit. MPA may also have adverse cardiovascular effects and may mitigate some of the beneficial effects of estrogen.² Although these hypotheses deserve further investigation, the overall null result from HERS does not support initiation of CEE combined with MPA in older postmenopausal women with confirmed coronary disease. For women with CHD already on ERT for ≥1 year, it may be reasonable to continue therapy while awaiting the results of a HERS follow-up study and other ongoing trials of ERT with clinical end points. The results of the HERS trial apply to women with preexisting CHD and may not apply to women free of vascular disease. Furthermore, this study does not take into consideration the other potential benefits of this therapeutic protocol, which are beyond the scope of this statement.

Data are lacking for determining the long-term cardiovascular effects of testosterone administered with ERT. Alternatives to traditional hormone replacement therapy are available, including soy phytoestrogens and selective estrogen receptor modulators (SERMs); however, a recommendation regarding their use for prevention of CHD has not been made at this time because of a lack of sufficient data.

Several other aspects of risk factor management are of heightened importance for women. Diabetes is a powerful risk factor in women, increasing CHD risk 3-fold to 7-fold compared with a 2-fold to 3-fold increase in risk in men.¹² This difference may be due to a particularly deleterious effect of diabetes on lipids and blood pressure in women.^{2 12} Therefore, recommendations are provided for management of diabetes with an emphasis on controlling concomitant risk factors.¹³ Low levels of HDL cholesterol are predictive of CHD in women and appear to be a stronger risk factor for women >65 years old than for men >65.¹⁴ Women tend to have higher HDL-cholesterol levels than men, and triglyceride levels may be a significant risk factor in women, especially older women. The current NCEP guidelines are outlined in the Table⇓⇓⇓ with a notation to consider more aggressive targets for HDL cholesterol and triglycerides in women.¹⁵ The NCEP also recommends the use of ERT before cholesterol-lowering drugs to reduce LDL cholesterol in postmenopausal women. In this statement, the recommendation has been modified to consider statins a first-line therapy in postmenopausal women on the basis of recent data that suggest women may have at least as much benefit from LDL-cholesterol reduction with statins as men.¹⁶

Recommendations for aggressive risk factor management are based on the future probability of a cardiovascular event. This strategy allows high-risk patients who have not yet had an event to be considered for more intensive treatment.¹⁷ It also recognizes that CHD is not a categorical event but rather a continuum of a progressive disease process. As the availability and use of noninvasive tools to detect asymptomatic CHD increase, the line between primary and secondary prevention may become less distinct. Substantial data support aggressive risk factor management in the setting of secondary prevention. However, because first cardiovascular events are often fatal in women, careful consideration should be given to individual risk factor management before onset of clinical CHD in women. The current recommendations are developed from previous guidelines and consensus panel statements along with newer gender-specific data when available.^{2 9 10 13 15 18 19 20 21 22 23} The recommendations can serve as a guide to risk factor management but cannot replace clinical judgment. As new knowledge is acquired, revised strategies for the prevention of CHD in women should reflect new science.

• Copyright © 1999 by American Heart Association