The role of ω-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.
To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5ω-3), docosapentaenoic acid (DPA; 22:5ω-3), and docosahexaenoic acid (DHA; 22:6ω-3) and plant-derived α-linolenic acid (ALA; 18:3ω-3) for incident CHD.
A global consortium of 19 studies identified by November 2014.
Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue ω-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, ω-6 levels, and FADS desaturase genes.
Main Outcomes and Measures
Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI).
The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with ω-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 ω-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 per 1 SD. Across quintiles, lower risk of nonfatal MI was evident with EPA (RR, 0.71; 95% CI, 0.56-0.90) and ALA (RR, 0.87; 95% CI, 0.78-0.97), and lower risk of fatal CHD was evident with DPA (RR, 0.76; 95% CI, 0.65-0.90) and DHA (RR, 0.77; 95% CI, 0.64-0.89). 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 ω-3 fatty acids are associated with a lower incidence of fatal CHD.
Del Gobbo LC, Imamura F, Aslibekyan S, Marklund M, Virtanen JK, Wennberg M, Yakoob MY, Chiuve SE, dela Cruz L, Frazier-Wood AC, Fretts AM, Guallar E, Matsumoto C, Prem K, Tanaka T, Wu JHY, Zhou X, Helmer C, Ingelsson E, Yuan J, Barberger-Gateau P, Campos H, Chaves PHM, Djoussé L, Giles GG, Gómez-Aracena J, Hodge AM, Hu FB, Jansson J, Johansson I, Khaw K, Koh W, Lemaitre RN, Lind L, Luben RN, Rimm EB, Risérus U, Samieri C, Franks PW, Siscovick DS, Stampfer M, Steffen LM, Steffen BT, Tsai MY, van Dam RM, Voutilainen S, Willett WC, Woodward M, Mozaffarian D, for the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCe). ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart DiseasePooling Project of 19 Cohort Studies. JAMA Intern Med. 2016;176(8):1155-1166. doi:10.1001/jamainternmed.2016.2925