Women

CHD is a major cause of death in women as well as men and it ultimately kills as many women as men. However, the onset of CHD is delayed by some 10-15 years in women compared to men; thus ATP III defines age as a risk factor in women at age 55, compared to age 45 for men. Since the onset of CHD is delayed by 10-15 years in women compared to men, it seems appropriate to include comments on treatment of women up to age 45 under younger adults and to restrict comments for older persons to women age >75 years. Thus comments in this section will apply to women in the age range of 45 to 75 years. It is only at age 75 and above that CHD rates of women approximate those of men. Because there are more older women than older men, the lifetime risk of CHD is almost as high in women as in men. The reasons for the disparity in ages of onset of CHD between women and men are not fully understood. The Framingham Heart Study could not explain the gender disparity solely on the basis of the major risk factors. Nonetheless, patterns of risk factors often differ between men and women. For example, blood pressure, LDL cholesterol, and triglycerides rise at an earlier age in men than in women. Moreover, HDL-cholesterol levels are on average some 10 mg/dL lower in adult men than in women. This latter difference is established at puberty when HDL-cholesterol levels decrease in males but not in females. Since a 10-mg/dL difference in HDL cholesterol is projected to account for a 20-30 percent difference in CHD event rates over the short term, this difference over the adult lifespan could account for a significant portion of the gender disparity between men and women.

Although the magnitude of risk factors on average may vary between women and men, all of the major risk factors raise the risk for CHD in women. This is true for lipid risk factors including LDL cholesterol and HDL cholesterol. Moreover, triglycerides appear to be an even more powerful risk factor in women than in men.

A commonly cited reason for the gender difference is a protective effect of estrogen in women. Data in support, however, are open to varying interpretations. For example, while oral estrogens increase HDL cholesterol and decrease LDL cholesterol, they also increase the potential for coagulation and possibly for inflammation. Oral estrogens do not mimic the physiologic role of endogenous estrogen, which is released into the systemic rather than the portal circulation. When given through the transcutaneous route, estrogen does not in fact increase HDL cholesterol and has a more modest effect on LDL cholesterol and on coagulation factors than oral estrogen. There is no acceleration of CHD rates at about the age of menopause as endogenous estrogen levels wane; but as in males, the rates simply increase in a log-linear fashion with age. There is very little or no decrease in HDL cholesterol in cohorts followed across the transition through the menopause. Observational studies have consistently suggested that postmenopausal estrogen users are at lower risk of CHD than non-users. However, these studies are confounded by a number of powerful biases that may account for a large overestimation of potential benefit.