Multivariate assessment of lipid parameters as predictors of coronary heart disease among postmenopausal women: Potential implications for clinical guidelines

Background - Over the past decade, lipid measurements have been significantly improved and standardized. We evaluated the usefulness of multiple plasma lipid parameters in predicting coronary heart diseases (CHD) among women. Methods and Results - Among 32 826 women from the Nurses' Health Study who provided blood samples at baseline, 234 CHD events were documented during 8 years of follow-up. In a nested study, these cases were matched to controls (1:2) for age, smoking, fasting status, and month of blood draw. We estimated the relative risk (RR) for each lipid parameter, adjusted for C-reactive protein, homocysteine, body mass index, family history, hypertension, diabetes, postmenopausal hormone use, physical activity, alcohol intake, and blood draw parameters. The RRs associated with an increase of ≈1 SD (mg/dL) were as follows: HDL cholesterol (HDL-C) (RR=0.6 [0.5 to 0.8], SD=17), apolipoprotein B₁₀₀ (apoB₁₀₀) (RR=1.7 [1.4 to 2.1], SD=32), LDL cholesterol (LDL-C) (RR=1.4 [1.1 to 1.7], SD=36), total cholesterol (TC) (RR=1.4 [1.1 to 1.6], SD=40), and triglycerides (RR=1.3 [1.0 to 1.5], SD=80). Among the lipid indexes, the RRs were: apoB₁₀₀/HDL-C (RR=1.5 [1.4 to 2.1], SD=1.0), TC/HDL-C (RR=1.6 [1.3 to 1.9], SD=1.3), LDL-C/HDL-C (RR=1.5 [1.3 to 1.9], SD=1.0), and non-HDL-C (RR=1.6 [1.3 to 1.9], SD=42 mg/dL). After simultaneous control for several lipid biomarkers, HDL-C was the primary contributor of the variation in multivariate models (P=0.01), followed by LDL-C (P=0.01), whereas triglycerides and apoB₁₀₀ did not contribute further information. HDL-C-related ratios were the strongest contributors to predicting CHD (P<0.0001). Conclusions - Lower levels of HDL-C may be a key discriminator of higher CHD events among postmenopausal women. HDL-C-related ratios (such as TC/HDL-C) provide a powerful predictive tool independently of other known CHD risk factors.