Abstract Background Acute myocardial infarction (AMI) remains a major cause of morbidity and readmission due to recurrent cardiovascular events. LDL-C levels are highly heritable, and polygenic risk scores (PRS) have been shown to predict CVD risk. However, their role in secondary prevention, particularly in AMI patients, remains unclear. Purpose This study aims to assess the association between low-density lipoprotein cholesterol polygenic risk score (LDL-C PRS) and the risk of recurrent cardiovascular disease (CVD) events in an AMI cohort. Methods Genome-wide genotyping was completed in 970 AMI patients consecutively recruited from Peking University First Hospital. Weighted LDL-C PRS comprising 84 alleles was calculated. Multivariable linear fitting was used to test the correlation between LDL-C PRS and LDL-C. Cox proportional hazard model was used to evaluate the association between LDL-C PRS and recurrent CVD events (nonfatal myocardial infarction, nonfatal stroke, CVD death, rehospitalization for heart failure or unstable angina). Models’ performance was evaluated by C-statistic, net reclassification index (NRI) and integrated discrimination improvement (IDI). Results The study demonstrated a significant correlation between LDL-C PRS and LDL-C levels (Pearson coefficient = 0.192, p 0.001), with LDL-C PRS accounting for 3.08% of LDL-C variance. During a median follow-up of 4.59 years, 44.53% of patients experienced recurrent cardiovascular events. Multivariable Cox regression revealed that a 1-SD increase in LDL-C PRS was associated with a 53% higher risk of CVD recurrence (HR: 1.53, 95% CI: 1.11-2.11, p = 0.009). When stratified into tertiles, patients in T2 (HR: 1.41, 95%CI: 1.03-1.95, p = 0.037) and T3 (HR: 1.51, 95%CI: 1.10-2.08, p = 0.011) had significantly higher recurrence risk than those in T1. RCS curve depicted linear increase of adjusted HR in relation to LDL-C PRS (p for nonlinear = 0.355), and Kaplan-Meier analysis confirmed that individuals with higher LDL-C PRS were more prone to recurrent CVD (log-rank p = 0.046). Subgroup analysis revealed a stronger predictive value of LDL-C PRS in younger patients (65 years) (p for interaction = 0.024). Nevertheless, prediction model for two-year recurrent CVD was not optimized by introducing LDL-C PRS to traditional risk factors when measured by C-statistic (old model vs new model: 0.670 vs 0.676, p = 0.706), NRI (estimate: 0.072, 95%CI: -0.009 to 0.110, p = 0.190) or IDI (estimate: 0.006, 95%CI: -0.002 to 0.019, p = 0.206). Conclusion Polygenic susceptibility of hypercholesterolemia poses extra risk of CVD recurrence in AMI patients, especially in younger individuals, highlighting LDL-C PRS as a potential tool for refined risk stratification in AMI secondary prevention. Nevertheless, integration of LDL-C PRS contributed to little improvement for residual risk evaluation.Figure 2
Wang et al. (Sat,) studied this question.