Coronary calcium score adds prognostic value over Lp(a) in men but not women, MESA analysis of 4,651 participants finds (Circ Cardiovasc Imaging 2025)

Background: Lp(a) (lipoprotein [a]) and coronary artery calcium score (CACS) are independently associated with atherosclerotic cardiovascular disease (ASCVD) risk. This study aimed to investigate sex-specific prognostic differences between Lp(a) and CACS in ASCVD risk.

Methods: We analyzed 4651 participants from the Multi-Ethnic Study of Atherosclerosis, grouped by sex. Multivariable Cox regression analysis was performed to evaluate the prognostic value of Lp(a) and CACS for ASCVD risk in both sexes. The predictive performance of these factors was compared in men and women.

Results: During a median follow-up of 13.84 years, 465 ASCVD events were recorded (272 in men and 193 in women). Multivariable Cox regression analysis revealed that both elevated Lp(a) and CACS were independent predictors of ASCVD risk in both sexes. The C-index analysis demonstrated that CACS provided incremental prognostic value over Lp(a) in men (C-index: 0.732 versus 0.714; P=0.011), but not in women (C-index: 0.776 versus 0.762; P=0.069). Notably, in men with CACS >400, elevated Lp(a) levels (adjusted hazard ratio, 1.822 [95% CI, 1.041-3.189]; P=0.036) were associated with higher ASCVD risk, although no such association was observed in those with CACS ≤400. In women, elevated Lp(a) levels were associated with increased ASCVD risk in those with CACS >100 (adjusted hazard ratio, 1.877 [95% CI, 1.130-3.118]; P=0.015).

Conclusions: Although both Lp(a) and CACS independently predict ASCVD risk in both sexes, the predictive value of Lp(a) varies significantly between men and women across different CACS categories. These findings may inform sex-specific strategies for primary prevention of ASCVD.