A distinct gender difference exists in cardiovascular disease (CVD) risk. 1 Although CVD is seen 2 to 5 times more often in middle-aged men than in women the same age, CVD is the leading killer of women in the United States. Coronary heart disease (CHD) is the leading cause of CVD death in women, and two thirds of the women who die of CHD had no previous symptoms. 2,3

When CHD symptoms are present in women, they often differ from the "traditional" CHD symptoms observed in men. 2,3 One CVD risk area, lipid and lipoprotein profiles, is increasingly recognized as an area in which women differ from men. For example, low-density lipoprotein cholesterol (LDL-C) is less important as a risk factor in premenopausal women, perhaps because estrogen has an impact on HDL-C until menopause. 4 After menopause, LDL-C rises dramatically, whereas HDL-C falls somewhat. In addition, HDL-C levels are a much stronger CVD predictor in women than in men. Blood triglyceride levels in postmenopausal women also are an independent CVD factor. 4

In recent years, the many factors that influence lipid synthesis and catabolism have become better understood with regard to men, and to a lesser extent with regard to women. Until the early 1990s, few studies specifically considered the effects of plasma lipid and lipoprotein profiles on women's CVD risk. 3 Assumptions about women's risk were extrapolated from studies of men, with little thought given to the genetic, hormonal, lifestyle, and other differences between men and women. More recent studies focused specifically on the lipid and lipoprotein profiles of women have contributed to an understanding of the risks and protective factors for women in this important area. It is now understood, for example, that physical activity has a beneficial effect on the plasma lipid and lipoprotein profiles of both men and women, a fact not widely recognized until recent years. 5,6

For many years, men participated in cardiac rehabilitation programming at higher rates than women. 7 In this issue of JCR, Savage et al 8 report gender-specific HDL-C responses to cardiac rehabilitation. In their study, women experienced a greater HDL-C improvement after exercise training (14% for women and 7.1% for men). The patients were divided into four groups based on gender and initial HDL-C levels. The NCEP ATP III guidelines were used to divide the men and women into low (<40 mg/dL) and high (>40 mg/dL) HDL-C groups. After 12 weeks of exercise training, the women who had high initial HDL-C improved their HDL-C levels (8.40%), whereas the men who had high initial HDL-C did not (0.9%). In the groups with low initial HDL-C, the women experienced a greater improvement than the men (15.3% and 11.5%, respectively).

Warner et al 9 followed cardiac rehabilitation patients for 5 years and found that HDL-C changes were greater for women than for men. After 1 year of cardiac rehabilitation, women and men showed respective HDL-C increases of approximately 7% and 10%. However, only the women had continued HDL-C increases over the 5-year follow-up period (20% and 5%, respectively). Furthermore, the changes in the total cholesterol to HDL-C ratios were far more favorable for the women, with a 38% decrease over the 5 years, as compared with only a 20% decrease for the men.

Stevenson et al 10 evaluated pre- and postmenopausal sedentary women and pre- and postmenopausal physically active women. Their results support the view that the adverse changes in plasma lipids and lipoproteins that occur with age result from a sedentary lifestyle and are not observed in women who regularly perform endurance exercise. Furthermore, these findings also indicate that the unfavorable changes in the plasma lipid and lipoprotein profile associated with an increased CVD risk are not an inevitable consequence of the aging process in physically active women.

Scientists once believed that because premenopausal women already had higher HDL-C, exercise training intervention would not further increase HDL-C. However, Goodyear et al 11 increased the miles run by a group of recreational runners approximately 30 to more than 60 miles per week. The HDL-C levels in these premenopausal women increased from 59 to 76 mg/dL, an increase of 29%, after only 8 weeks of exercise training.

Lifestyle factors that influence HDL-C change are not limited to exercise. Many environmental factors can contribute to HDL-C change, and the amount of change can vary by gender and risk factor. Ellison et al, 12 using data from the National Heart, Lung, and Blood Institute Family Heart Study, reported that alcohol consumption accounted for 29% of the HDL-C variance among women and 50% of the variance among men, with smoking accounting for 7% and 3%, and physical activity accounting for 3% and 4%, respectively.

The data from Savage et al 8 show that women undergo greater improvements in HDL-C with cardiac rehabilitation than men despite the same physical fitness and body composition changes. Recently, the American Heart Association published its guidelines for cardiovascular disease prevention in women. 3 Major lifestyle interventions recommended in the guidelines include smoking cessation, increased physical activity/cardiac rehabilitation, a heart-healthy diet, and weight maintenance/reduction programs. Major risk factor interventions recommended include blood pressure, lipid and lipoprotein, and diabetes programming. The guidelines make clear that CVD prevention activities once recommended primarily for men are equally important for women. Physicians and other healthcare providers should use this information in conjunction with other CVD risk factor information to optimize the risk factor reduction and cardiac rehabilitation plans for their female patients. The more aggressive the staff can make the rehabilitation plan, the greater its impact and the better its likelihood of reducing the risk for future CVD events.

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