SEX DIFFERENCES IN MYOCARDIAL INFARCTION RISK AMONG INDIVIDUALS WITH HIGH LIPOPROTEIN(A): A META-ANALYSIS

Therapeutic Area

ASCVD/CVD Risk Assessment

Background

Lipoprotein(a) [Lp(a)] is a well-established causal risk factor for cardiovascular morbidity and mortality. Despite this, little is known about how sex influences the risk of myocardial infarction (MI) in individuals with high Lp(a) levels.

Methods

We conducted a comprehensive search of multiple databases up to March 25, 2025. Statistical analysis was performed using RevMan 5.4, applying a random-effects model to pool dichotomous outcomes as risk ratios (RR) with corresponding 95% confidence intervals (CI). The degree of heterogeneity among studies was assessed using Higgins I2 statistic. High Lp(a) levels were defined as median levels of ≥30 mg/dL. The protocol for this study has been submitted to PROSPERO for registration (CRD 1022715).

Results

Our final analysis included 14 observational studies examining the influence of sex on Lp(a) levels and the risk of MI, with a total of 66,124 patients (46% females), an average age of 57 years, and an average follow-up period of 7.6 years. The narrative synthesis of the included studies indicated a positive association between elevated Lp(a) levels and an increased risk of MI in both females and males. However, the pooled analysis showed no statistically significant difference in the risk of MI between females and males with high Lp(a) levels, with an RR of 1.01 (95% CI: 0.77–1.31; p = 0.96; I2 = 98%), and high heterogeneity was observed. Additionally, some studies reported a significant increase in Lp(a) levels in women after the age of 50.

Conclusions

Our analysis found no sex-based difference in the risk of MI associated with high Lp(a) levels. However, further studies are needed to explore sex-specific thresholds in the clinical evaluation of cardiovascular disease risk based on Lp(a) levels, which could improve personalized cardiovascular risk assessment.