ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease
Authors: Liana C. Del Gobbo, Fumiaki Imamura, Stella Aslibekyan, Matti Marklund, Jyrki K. Virtanen, Maria Wennberg, Mohammad Y. Yakoob, Stephanie E. Chiuve, Luicito dela Cruz, Alexis C. Frazier-Wood, Amanda M. Fretts, Eliseo Guallar, Chisa Matsumoto, Kiesha Prem, Tosh Tanaka, Jason H. Y. Wu, Xia Zhou, Catherine Helmer, Erik Ingelsson, Jian-Min Yuan, Pascale Barberger-Gateau, Hannia Campos, Paulo H. M. Chaves, Luc Djoussé, Graham G. Giles, Jose Gómez-Aracena, Allison M. Hodge, Frank B. Hu, Jan-Håkan Jansson, Ingegerd Johansson, Kay-Tee Khaw, Woon-Puay Koh, Rozenn N. Lemaitre, Lars Lind, Robert N. Luben, Eric B. Rimm, Ulf Risérus, Cecilia Samieri, Paul W. Franks, David S. Siscovick, Meir Stampfer, Lyn M. Steffen, Brian T. Steffen, Michael Y. Tsai, Rob M. van Dam, Sari Voutilainen, Walter C. Willett, Mark Woodward, Dariush Mozaffarian
Journal: JAMA Internal Medicine (2016)

<h3>Importance</h3> 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. <h3>Objective</h3> 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. <h3>Data Sources</h3> A global consortium of 19 studies identified by November 2014. <h3>Study Selection</h3> Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue ω-3 biomarkers and ascertained CHD. <h3>Data Extraction and Synthesis</h3> 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<i>FADS</i>desaturase genes. <h3>Main Outcomes and Measures</h3> Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). <h3>Results</h3> 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. <h3>Conclusions and Relevance</h3> 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.