Omega-3 Fatty Acids and Risk of Ischemic Stroke in REGARDS

We examined associations between lipidomic profiles and incident ischemic stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Plasma lipids (n = 195) were measured from baseline blood samples, and lipids were consolidated into underlying factors using exploratory factor analysis. Cox proportional hazards models were used to test associations between lipid factors and incident stroke, linear regressions to determine associations between dietary intake and lipid factors, and the inverse odds ratio weighting (IORW) approach to test mediation. The study followed participants over a median (IQR) of 7 (3.4–11) years, and the case-cohort substudy included 1075 incident ischemic stroke and 968 non-stroke participants. One lipid factor, enriched for docosahexaenoic acid (DHA, an omega-3 fatty acid), was inversely associated with stroke risk in a base model (HR = 0.84; 95%CI 0.79–0.90; P = 8.33 × 10⁻⁸) and fully adjusted model (HR = 0.88; 95%CI 0.83–0.94; P = 2.79 × 10⁻⁴). This factor was associated with a healthy diet pattern (β = 0.21; 95%CI 0.12–0.30; P = 2.06 × 10⁻⁶), specifically with fish intake (β = 1.96; 95%CI 0.95–2.96; P = 1.36 × 10⁻⁴). DHA was a mediator between fish intake and incident ischemic stroke (30% P = 5.78 × 10⁻³). Taken together, DHA-containing plasma lipids were inversely associated with incident ischemic stroke and mediated the relationship between fish intake and stroke risk.