Abstract 4370430: Sex-Specific Association of Lipoprotein(a) Concentrations with Atherosclerotic Cardiovascular Disease Risk: A Systematic Review and Meta-Analysis

Background: Elevated lipoprotein(a) [Lp(a)] is recognized as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). However, the precise magnitude of this association at different Lp(a) concentrations and potential differences between sexes warrant further elucidation. Objective: This meta-analysis evaluated the association between various Lp(a) thresholds and ASCVD risk, stratified by sex. Methods: We systematically searched PubMed and Google Scholar databases from inception until May 2025. Studies reporting on Lp(a) levels predicting ASCVD risk were included for analysis. Pooled adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for ASCVD were calculated using a DerSimonian–Laird random-effects models for predefined Lp(a) thresholds (>20, >30, >50, and >100 mg/dL) compared to lower levels, separately for men and women. Results: Out of 1,135 studies screened, 5 studies comprising participants were 111,246 included. The mean age was 58.7 ± 12.04 years. Elevated Lp(a) was significantly associated with increased ASCVD risk in men (AOR 1.47 [1.24-1.74], I2:97.98%) and women (AOR 1.39 [1.21-1.59], I2:94.03%), both p<0.001. A dose-response relationship was evident in both sexes. In men, significant risk emerged at Lp(a) >30 mg/dL (AOR 1.18 [1.13-1.22], p<0.001), increasing to an AOR of 2.04 [1.22-3.40] (p=0.01) for levels >100 mg/dL. In women, significant risk was apparent at Lp(a) >50 mg/dL (AOR 1.48 [1.26-1.72], p<0.001), reaching an AOR of 1.74 [1.22-2.48] (p<0.001) for levels >100 mg/dL. A leave-one-out sensitivity analysis demonstrated that the direction and significance of these pooled estimates were not dependent on any single study. Conclusion: This meta-analysis confirms a significant and dose-dependent association between elevated Lp(a) concentrations and increased ASCVD risk in both men and women. While overall risk estimates at high Lp(a) concentrations showed considerable overlap, significant ASCVD risk appeared at Lp(a) concentrations >30 mg/dL in men, whereas in women, this was evident at concentrations >50 mg/dL. These findings underscore the importance of Lp(a) as a key cardiovascular risk factor in both sexes and may inform sex-specific considerations in risk stratification and future guideline development for ASCVD prevention.