Heart disease remains the leading cause of death for women in the United States (Table 32.1); coronary heart disease (CHD) alone accounts for 241,622 deaths annually (1). Despite public education efforts, only 46% of women identified heart disease as the leading cause of death in 2003, although this was improved from 30% in 1997 (2). CHD risk factors are similar in men and women, although the magnitude of risk associated with some risk factors differs between genders. For example, diabetes mellitus confers greater risk (3) and high-density lipoprotein-cholesterol greater protection in women (4). Once women develop CHD, they are less prompt in seeking medical attention for acute coronary symptoms than men (5) and have poorer outcomes following myocardial infarction (6).

The prevalence of modifiable risk factors generally increases with age (Table 32.2). Cigarette smoking is an exception. In 2002, 25%, 22%, 24%, 21%, and 9%, respectively, of women aged 18 to 24, 25 to 34, 35 to 44, 45 to 64, and 65 years or older smoked, slightly lower than rates for men (7).

Mean age at menopause in the United States is 51 years. Consequently, the postmenopausal years constitute a significant proportion of a woman’s lifespan. A relatively hypoestrogenic state is attained at menopause, unfavorably affecting several CHD risk factors. Thus, although interventions directed at CHD prevention should be undertaken at all ages, the need for effective prevention measures is particularly acute during and after menopause.

In a longitudinal study of premenopausal women undergoing natural menopause, total plasma cholesterol rose by 6%, triglycerides by 11%, and low-density lipoprotein cholesterol (LDL-C) by 10%, all significantly higher than premenopausal levels (9). High-density lipoprotein cholesterol (HDL-C) began to fall 2 years prior to the last menses and declined gradually, but significantly, with menopause. Other unfavorable lipid changes with menopause include smaller LDL-C particle size (10) and an increase in plasma lipoprotein (a) levels (11).

Weight gain is common during midlife among women, but appears to be independent of menopausal status (12). Menopause is associated with a steeper increase in diastolic blood pressure, independent of age (13). Studies of glucose and insulin levels during menopause have provided mixed results.

Primordial, primary, and secondary prevention measures can reduce CHD risk across a woman’s lifespan. The goal of primordial prevention is to deter development of coronary risk factors, usually through healthy lifestyle practices. Women are unlikely to receive lifestyle counseling; fewer than 5% of physicians advise women to engage in physical activity at least 6 days per week as recommended by national guidelines (14).

In 2004, the American Heart Association and American College of Cardiology (AHA/ACC) jointly endorsed cardiovascular prevention guidelines for women (15). Lifestyle interventions, generally appropriate for primordial, primary, and secondary prevention purposes, and which were categorized as class I recommendations, that is, useful and effective for cardiovascular disease prevention in women, included (a) not smoking, (b) obtaining at least 30 minutes of moderate-intensity physical activity on most days, (c) maintaining a healthy body
weight, and (d) consumption of a heart-healthy diet, which includes a variety of fruits, vegetables, grains, low-fat or nonfat dairy products, fish, legumes, and sources of protein low in saturated fat.

Adherence to a prudent lifestyle reduces coronary risk. During 14-year follow-up of the Nurses’ Health Study cohort (16), the incidence of CHD was 80% lower among women who did not smoke cigarettes, were not overweight, maintained a prudent diet, engaged in moderate to vigorous physical activity for 30 minutes daily, and consumed alcohol in moderation, compared to women not adhering to these lifestyle practices.

The hypothesis that reducing saturated fat and cholesterol consumption, preventing weight gain, and increasing physical activity would prevent a rise in LDL-C during menopause was tested in a randomized trial of 535 women (12). LDL-C was 10 mg/dL lower at 6 months among women randomized to cognitive–behavioral intervention, and 5.4 mg/dL lower at 54 months (p = .009). The intervention group lost 1 pound, whereas the comparison group gained 5.2 pounds (p < .001).

Among the 2,191 women with prediabetes randomized in the Diabetes Prevention Program, physical activity of moderate intensity for 150 minutes/week in conjunction with 7% weight loss reduced progression to diabetes by 54% (95% confidence interval [CI] 40%–64%) (17).

Exercise alone has not been shown to prevent hypertension, although a multicomponent lifestyle intervention which included exercise (180 minutes/week) reduced systolic blood pressure 1.2 mm Hg in African-American women and 4.5 mm Hg in non–African-American women with above-optimal blood pressure or stage I hypertension (18).

Weight loss prevented hypertension in the Trials of Hypertension Prevention, Phase II. Among 381 women randomized to a weight loss intervention of dietary change, physical activity, and social support, or no intervention, those with the greatest weight loss had the largest reductions in diastolic blood pressure. For the entire cohort of men and women, the risk of
developing hypertension was lower in the intervention group (risk ratio 0.79, 95% CI 0.65–0.96) (19).

The current popularity of low-carbohydrate diets has increasing interest in their impact on plasma lipids. Isocaloric low-fat and very-low-carbohydrate diets were compared in normal weight, normolipemic women (20). The low-fat diet contained less than 10% of calories from saturated fat and less than 300 mg of daily cholesterol. The very-low-carbohydrate diet contained 30% of calories from protein, 60% from fat, and 10% from carbohydrates. LDL-C, HDL-C, and triglycerides were not changed after 4 weeks on the low-fat diet. In contrast, LDL-C increased 15% after 4 weeks on the very-low-carbohydrate diet; HDL-C increased 33% and triglycerides fell 33% (all p < .05). LDL-C subclasses and C-reactive protein levels were not affected by either diet.

Although less effective than lifestyle modification, metformin reduced progression to diabetes by 28% (95% CI 10%–43%) among women with prediabetes (17). In a post hoc analysis from the Heart Outcomes Prevention Evaluation trial, 27 of 1,201 women assigned to placebo developed diabetes compared with 16 of 1,279 women in the ramipril group (relative risk 0.57, 95% CI 0.31–1.07) (21). Incidence of diabetes was also reduced by conjugated estrogens with medroxyprogesterone acetate in post hoc analysis from the Women’s Health Initiative randomized trial (hazard ratio 0.79, 95% CI 0.67–0.93) (22). Neither ramipril nor postmenopausal hormone therapy (HT) is currently recommended, however, for the primary prevention of type 2 diabetes.

Primary prevention interventions delay or prevent onset of disease.