Serum free eicosapentaenoic acid-to-arachidonic acid ratio and long-term risk of major adverse cardiovascular events in patients with coronary artery disease

Abstract

The eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio reflects the balance between n-3 and n-6 polyunsaturated fatty acids. We examined the association between the serum free (non-esterified) EPA/AA ratio and long-term major adverse cardiovascular events (MACE) in patients with angiographically confirmed coronary artery disease (CAD). This single-center retrospective cohort study included 308 patients with CAD. Serum free fatty acids were quantified by LC-MS/MS, and the free EPA/AA ratio was evaluated as the primary fatty-acid biomarker. Cox proportional hazards models were used to estimate hazard ratios (HRs), and principal component analysis (PCA) was used to explore fatty-acid patterns. During a median follow-up of 48.7 months, 201 first MACE events occurred. In the fully adjusted primary analysis, each 1-SD increase in the free EPA/AA ratio was associated with a lower risk of MACE (HR = 0.82, 95% CI 0.70–0.96, P  = 0.011; FDR-adjusted P  = 0.049). The association was attenuated after additional adjustment for analytical batch (HR = 0.92, 95% CI 0.77–1.10, P  = 0.375) and in a Cox model stratified by batch (HR = 0.92, 95% CI 0.77–1.11, P  = 0.398). A higher serum free EPA/AA ratio was associated with a lower risk of MACE in the primary multivariable analysis, but the association was attenuated in additional sensitivity analyses. These findings should be interpreted cautiously and require validation in independent cohorts.