Association between HDL-cholesterol subfractions and the risk of major adverse cardiac and cerebrovascular events in patients with acute myocardial infarction: a single-center retrospective observational study

Background: This study aimed to evaluate the association between high-density lipoprotein (HDL) subfractions and long-term major adverse cardiac and cerebrovascular events (MACCEs) in patients with acute myocardial infarction (AMI). Method: A total of 1,240 AMI patients admitted to Beijing Tsinghua Changgung Hospital between 2017 and 2023 were included. HDL subfractions, including HDL-2b and HDL-3, were quantified using microfluidic chip electrophoresis. Patients were stratified into tertiles according to HDL-3 levels. The primary endpoint was the occurrence of MACCEs. Kaplan-Meier analysis, Cox proportional hazards models, restricted cubic spline (RCS), and mediation analyses were performed to evaluate the associations between HDL subfractions and MACCEs. Higher HDL-3 levels were associated with improved event-free survival (HR = 0.58, 95% CI: 0.37-0.91) and demonstrated discriminative ability for MACCE risk (AUC = 0.62; 95% CI: 0.57-0.67), whereas HDL-C and HDL-2b were not significant. RCS analysis revealed a linear inverse association between HDL-3 and MACCEs (p for non-linearity = 0.356). The Gensini score partially mediated this relationship, accounting for 11.8% of the total effect. Conclusion: Lower HDL-3 levels were independently associated with a higher long-term risk of MACCEs in AMI patients. HDL-3 may represent a potential biomarker for residual cardiovascular risk stratification and a potential therapeutic target for improving post-infarction outcomes.