Association of High-Density Lipoprotein Cholesterol With Incident Cardiovascular Events in Women, by Low-Density Lipoprotein Cholesterol and Apolipoprotein B100 Levels: A Cohort Study

Study Questions:

Is there an association between high-density lipoprotein cholesterol (HDL-C) (or apolipoprotein [apo] A-I level) and cardiovascular disease (CVD) across a range of low-density lipoprotein cholesterol (LDL-C) levels in women?


Data from the Women’s Health Study, a prospective study of female health professionals, ages 45 years or older (at entry 1992-1995), were followed for occurrence of CV events. All women were free of CVD and cancer at baseline. Baseline lipids were measured directly, and apolipoprotein was measured with immunoassays. Outcomes of interest included incident total CVD, coronary events, and stroke.


A total of 26,861 women were included in the present analysis. Over a mean follow-up period of 11 years, the cohort experienced 929 total incident CVD events, of which 602 were coronary events and 319 were strokes. Mean age of the women was 54.5 years. Mean HDL-C concentration was 1.40 mmol/L (standard deviation [SD], 0.39) (54 mg/dl [SD, 15]) and mean apo A-I concentration was 1.51 g/L (SD, 26). HDL-C levels were inversely associated with baseline prevalence of CV risk factors. In multivariable analyses, HDL-C and apo A-I levels were inversely associated with CVD and coronary events, but not stroke. Adjusted coronary hazard ratios for decreasing quintiles of HDL-C were 1.00 (reference), 1.23 (95% confidence interval [CI], 0.85-1.78), 1.42 (CI, 0.98-2.06), 1.90 (CI, 1.33-2.71), and 2.19 (CI, 1.51-3.19) (p for linear trend < 0.001). A similar pattern, although weaker, was observed for apo A-I. Consistent inverse associations were found for HDL-C with coronary events across a range of LDL-C values, including among women with low LDL-C levels. No associations were noted for HDL-C or apo A-I among women with low apo B100 values (<0.90 g/L).


The authors concluded that an inverse association between HDL-C and incident coronary events is present across a range of LDL-C levels. Among women with low total atherogenic particle burden, few events were observed; thus, no associations between HDL and CV events were noted.


These data provide evidence that low HDL-C is associated with increased risk of coronary events, but not for stroke, across a range of LDL levels. Clinicians can use this information to counsel their patients regarding lifestyle modification (healthy weight and regular physical activity), which will assist patients in preventing or improving low HDL levels.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Lipid Metabolism, Nonstatins

Keywords: Stroke, Life Style, Neoplasms, Atherosclerosis, Body Weight, Women's Health, Apolipoprotein A-I, Cholesterol, Dyslipidemias, Cardiology, Cardiovascular Diseases, Apolipoprotein B-100, Motor Activity, Confidence Intervals

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