Sex-specific disparities in lipid-based prediction of major cardiovascular events

AIMS: Lipid-based markers have a profound prognostic potential concerning cardiovascular diseases. However, differences in lipid levels between women and men are evident, and it is unknown whether the differences also extend to the predictive power of the lipid markers. Therefore, this study aims to evaluate potential sex differences concerning the risk estimation of five topical lipid markers: low-density lipoprotein cholesterol (LDL-C), remnant cholesterol, apolipoprotein A-1 (ApoA-1), the triglyceride/HDL cholesterol (TG/HDL) ratio, and ceramide scores (CERT1 and CERT2). METHODS AND RESULTS: In this prospective cohort study, the lipid markers were obtained for patients with high cardiovascular risk, who were followed for major cardiovascular events (MACE) for up to 14 years. The risk estimation was done for women (n = 433) and age-matched men (n = 433) separately using multiple performance and discrimination metrics. Women showed higher LDL-C and ApoA-1 and lower remnant cholesterol and TG/HDL ratio. Also, CERT1, but not CERT2, differed between the sexes, with women scoring slightly higher. During follow-up, MACE occurred in 25% of women and 37% of men. While an adjusted Cox regression demonstrated that remnant cholesterol significantly predicted MACE in both sexes, the ApoA-1 and TG/HDL ratio was a predictor only in women, whereas ceramide-based scores predicted MACE solely in men. LDL-C showed no predictive potential in this high-risk cohort. CONCLUSION: To estimate cardiovascular risk, in several cases, a sex-specific adaptation of lipid markers seems warranted.