Primary prevention of coronary heart disease in postmenopausal women.

The recent Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) demonstrated the clinical benefits of lipid-lowering treatment in postmenopausal women and reinforced the need to identify and treat postmenopausal women at risk for coronary heart disease (CHD). Based on these results, some investigators have questioned whether the National Cholesterol Education Program (NCEP) cutpoint strategy for selecting candidates for drug therapy misses additional candidates for primary prevention. Although the absolute CHD event rate observed in the placebo-treated group in the AFCAPS/TexCAPS trial was lower than that seen in high-risk primary prevention studies, cholesterollowering drug therapy achieved a similar $30% reduction in CHD event rates. Extrapolating these results to the general population, CHD event rates for the nation would likely be cut by one third if drug therapy were offered to those with more modest low-density lipoprotein (LDL) elevations. Applying lower LDL cutpoints to postmenopausal women would select many women but would not necessarily identify a subset at higher immediate risk for CHD. More than 60% of postmenopausal women have LDL cholesterol (LDL-C) levels .130 mg/dL, yet these women have low event rates until they reach their late 70s. An alternative to lowering the cutpoint for drug therapy in postmenopausal women would be to improve the strategies for selecting those at higher risk of CHD. The NCEP has provided an algorithm for classifying individuals into one of three CHD risk categories. Treating individuals at higher risk for CHD more aggressively than individuals at lower risk is the fundamental strategy. This strategy reduces the number of candidates for drug therapy and also is cost-effective. Minor modifications to the NCEP guidelines can be made to place more postmenopausal women into a higher risk category. These proposed algorithm changes allow more aggressive therapy of postmenopausal women (Table 1). Hypertension, a family history of premature CHD, and hypercholesterolemia are prevalent in the postmenopausal population, and epidemiologic observations suggest that postmenopausal women with these risk factors have the same risk as men of the same age. Therefore, targeting the aggressiveness of LDL lowering to whether a woman has hypertension or a family history of premature CHD, as detailed in the NCEP guidelines, is appropriate. The NCEP guidelines identify cigarette smoking as an important risk factor for CHD. Two observational studies confirmed the hazards of smoking in postmenopausal women and estimated a relative CHD risk of 1.6 in postmenopausal smokers. Although both studies suggested that the cardiovascular risk of smoking disappears at any age when a woman quits smoking, many women cannot or will not quit. In the AFCAPS/TexCAPS trial, cholesterol lowering in smokers reduced the rate of cardiovascular events by .50%. In the United States, 10 – 15% of postmenopausal women continue to smoke. Rather than counting smoking as a single risk factor, the NCEP guidelines should be modified to include postmenopausal women who smoke in the category of those at highest risk for CHD and should target LDL lowering to ,100 mg/dL. Postmenopausal women comprise a subset of the elderly, who are at greatest risk for CHD. The change in estrogen status that occurs at menopause does not result in an increased risk for CHD, but the risk appears to increase with age. Targeting age .55 years in women as a risk factor for CHD without reference to estrogen status, as recommended in the current NCEP guidelines, is appropriate. In the Nurses’ Health Study, a body mass index (BMI) of .30 kg/m imparted a relative CHD risk of 2.6 compared with a BMI of ,21 kg/m. This report confirmed that obesity remains a risk factor among smokers, and patients with hypertension, hypercholesterolemia, and diabetes. Approximately 20% of the postmenopausal population are obese. The NCEP guidelines should include BMI .30 kg/m as a risk factor for CHD. Because of the lack of a quick, inexpensive, and inclusive measure of physical activity, this parameter was not included in the NCEP algorithm. Instead, the NCEP relied on high-density lipoprotein cholesterol (HDL-C) levels as a surrogate measure of physical activity. Exclusion of physical activity from the current NCEP guidelines is acceptable, but BMI .30 kg/m, HDL-C ,40 mg/ dL, and serum triglycerides .200 mg/dL should be added as surrogate measures of physical inactivity. Low HDL-C levels, hypertriglyceridemia, and type 2 diabetes impart a greater risk of CHD to women than to men. The NCEP guidelines currently define low HDL-C From the Department of Internal Medicine, Center for Human Nutrition, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA. Reprints are not available. Correspondence should be addressed to Margo A. Denke, MD, The University of Texas Southwestern Medical Center at Dallas, Center for Human Nutrition, Department of Internal Medicine, 5323 Harry Hines Boulevard, Dallas, Texas 75235-9052.