04101nas a2200685 4500000000100000008004100001100001000042700001400052700001200066700001700078700001300095700001800108700001000126700001500136700001200151700001900163700001700182700001400199700001600213700001200229700001500241700001400256700001500270700001200285700001400297700001500311700001700326700001500343700001800358700001600376700001600392700001600408700001400424700001700438700002000455700001400475700001700489700001200506700001200518700002400530700001400554700001400568700002100582700001300603700001500616700001700631700001100648700001200659700001300671700001500684700001500699700001600714700001500730700001900745700001500764245011500779250001500894520245500909020005103364 2016 d1 aHu F.1 aFranks P.1 aRimm E.1 aIngelsson E.1 aGiles G.1 aWoodward Mark1 aWu J.1 avan Dam R.1 aZhou X.1 aMozaffarian D.1 aSiscovick D.1 aHelmer C.1 aLemaitre R.1 aKhaw K.1 aDjousse L.1 aTanaka T.1 aSteffen L.1 aTsai M.1 aChiuve S.1 aGuallar E.1 aDel Gobbo L.1 aImamura F.1 aAslibekyan S.1 aMarklund M.1 aVirtanen J.1 aWennberg M.1 aYakoob M.1 aL. Cruz Dela1 aFrazier-Wood A.1 aFretts A.1 aMatsumoto C.1 aPrem K.1 aYuan J.1 aBarberger-Gateau P.1 aCampos H.1 aChaves P.1 aGomez-Aracena J.1 aHodge A.1 aJansson J.1 aJohansson I.1 aKoh W.1 aLind L.1 aLuben R.1 aRiserus U.1 aSamieri C.1 aStampfer M.1 aSteffen B.1 aVoutilainen S.1 aWillett W.00aomega-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies a2016/07/013 a

Importance: The role of omega-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. Objective: To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5omega-3), docosapentaenoic acid (DPA; 22:5omega-3), and docosahexaenoic acid (DHA; 22:6omega-3) and plant-derived alpha-linolenic acid (ALA; 18:3omega-3) for incident CHD. Data Sources: A global consortium of 19 studies identified by November 2014. Study Selection: Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue omega-3 biomarkers and ascertained CHD. Data Extraction and Synthesis: Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, omega-6 levels, and FADS desaturase genes. Main Outcomes and Measures: Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). Results: The 19 studies comprised 16 countries, 45637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with omega-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the omega-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. Conclusions and Relevance: On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived omega-3 fatty acids are associated with a modestly lower incidence of fatal CHD.

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