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

Date Published: 2026-09-29

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.

Introduction:
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).

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