Abstract

Background: Recent trials have raised questions about the role of seafood-derived long-chain omega-3 fatty acids for prevention of CHD; and evidence linking intermediate-chain omega-3 fatty acids to CHD remains weak. Methods: We developed a global consortium of 17 prospective (cohort or nested case-control) and retrospective studies having circulating or tissue biomarker measures of eicosapentaenoic (EPA; 20:5n-3), docosapentaenoic (DPA; 22:5n-3), docosahexaenoic acid (DHA; 22:6n-3), and α-linolenic acid (ALA; 18:3n-3). Each study ascertained CHD risk, including total CHD, nonfatal MI, and/or fatal CHD. Associations of each omega-3 fatty acid biomarker with CHD were evaluated within each cohort using standardized models, exposures, outcomes, and covariates across studies. Omega-3 fatty acid levels were analyzed continuously (per SD) and categorically (quintiles), and study-specific estimates were centrally pooled using fixed effects meta-analysis. Results: Current findings (Oct 2013) were based on 13 of 17 participating studies, including 7105 total CHD, 4926 nonfatal MI, and 2466 fatal CHD events. In both continuous and categorical multivariable-adjusted analyses, each omega-3 biomarker was inversely associated with fatal CHD. For each 1 SD unit increment, ALA was associated with 9% lower risk [HR 0.91 (95% CI 0.84-0.99)]; EPA, with 8% lower risk [HR 0.92 (95% CI 0.85-1.00)]; DPA, with 8% lower risk [HR: 0.92 (0.87-0.98)]; and DHA, with 9% lower risk [HR: 0.91 (0.86-0.96)] (Figure). Associations with total CHD and nonfatal MI were generally weaker and non-significant, except for EPA and nonfatal MI [HR: 0.93 (0.89-0.98)] and DHA and nonfatal MI [HR: 0.95 (0.91-0.99)]. Conclusions: Based on all available studies from around the world, both long and intermediate-chain omega-3 fatty acids, measured using objective biomarkers, are associated with lower risk of fatal CHD. These findings support potential benefit of omega-3 fatty acids for reducing CHD death.

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