Non-HDL Cholesterol, ApoB, Standard Lipid Measures, and CRP as Risk Factors for Cardiovascular Disease in Women

The Women’s Health Study enrolled 15,632 initially healthy women and followed them prospectively for cardiovascular events. This analysis compared the predictive value of standard lipid measures, non-HDL cholesterol, apolipoproteins, lipid ratios, and C-reactive protein (CRP) for incident cardiovascular events.

Non-HDL cholesterol and the total cholesterol/HDL-C ratio were the strongest lipid predictors — outperforming LDL-C with hazard ratios of 2.51 and 2.95 versus 1.62 in the highest versus lowest quintile comparisons. ApoB was also a strong predictor and comparable to non-HDL-C in predictive performance. CRP added independent prognostic information beyond all lipid measures: after adjustment for the strongest lipid predictors, CRP remained significantly associated with cardiovascular events.

The women-only cohort is particularly important. Women have systematically different lipid profiles and cardiovascular risk patterns than men, and the evidence for risk predictors in women has historically been derived from predominantly male cohorts. This study established that in women, non-HDL-C and lipid ratios are more informative than LDL-C, and that CRP contributes independently — findings that shaped the Reynolds Risk Score for women and the JUPITER trial design.

For female patients with LDL-C in the normal range but elevated non-HDL-C or CRP, this analysis provides the evidence basis for more aggressive risk assessment and consideration of therapy.

We rate the evidence strong. A large, well-conducted prospective cohort establishing non-HDL-C and CRP as superior risk predictors in women — directly informing women-specific cardiovascular risk assessment algorithms.