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Title: Omega-3 polyunsaturated fatty acid biomarkers and coronary heart disease: Pooling project of 19 cohort studies

Author
item DEL GOBBO, LIANA - Stanford University School Of Medicine
item IMAMURA, FUMIAKI - Cambridge University
item ASLIBEKYAN, STELLA - University Of Alabama
item MARKLUND, MATTI - Uppsala University
item VIRTANEN, JYRKI - University Of Eastern Finland
item WENNBERG, MARIA - University Of Umea
item YAKOOB, MOHAMMAD - Stanford University School Of Medicine
item CHIUVE, STEPHANIE - Brigham & Women'S Hospital
item DELA GRUZ, LUICITO - Cancer Council Victoria
item FRAZIER-WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC)
item FRETTS, AMANDA - University Of Washington
item GUALLAR, ELISEO - Johns Hopkins School Of Public Health
item MATSUMOTO, CHISA - Tokyo Medical And Dental University
item PREM, KIESHA - National University Of Singapore
item TANAKA, TOSH - National Institute On Aging (NIA, NIH)
item WU, JASON - University Of Sydney
item ZHOU, XIA - University Of Minnesota
item HELMER, CATHERINE - Institut National De La Sante Et De La Recherche Medicale (INSERM)
item INGELSSON, ERIK - Stanford University School Of Medicine
item YUAN, JIAN - University Of Pittsburgh
item BARBERGER-GATEAU, PASCALE - Institut National De La Sante Et De La Recherche Medicale (INSERM)
item CAMPOS, HANNIA - Harvard School Of Public Health
item CHAVES, PAULO - Florida International University
item DJOUSSE, LUC - Brigham & Women'S Hospital
item GILES, GRAHAM - Cancer Council Victoria
item GOMEZ-ARACENA, JOSE - University Of Malaga
item HODGE, ALLISON - Cancer Council Victoria
item HU, FRANK - Brigham & Women'S Hospital
item JANSON, JAN - University Of Umea
item JOHANSSON, INGEGERD - University Of Umea
item KHAW, KAY - University Of Cambridge
item KOH, WOON - National University Of Singapore
item LEMAITRE, ROZENN - University Of Washington
item LIND, LARS - Uppsala University
item LUBEN, ROBERT - University Of Cambridge
item RIMM, ERIC - Brigham & Women'S Hospital
item RISERUS, ULF - Uppsala University
item SAMIERI, CECILIA - Institut National De La Sante Et De La Recherche Medicale (INSERM)
item FRANKS, PAUL - Lund University
item SISCOVICK, DAVID - New York Academy Of Medicine
item STAMPFER, MEIR - Harvard School Of Public Health
item STEFFEN, LYN - University Of Minnesota
item STEFFEN, BRIAN - University Of Minnesota
item TSAI, MICHAEL - University Of Minnesota
item VAN DAM, ROB - National University Of Singapore
item VOUTILAINEN, SARI - University Of Eastern Finland
item WILLETT, WALTER - Harvard School Of Public Health
item WOODWARD, MARK - Oxford University
item MOZAFFARIAN, DARIUSH - Tufts University

Submitted to: JAMA Internal Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/3/2016
Publication Date: 8/1/2016
Citation: Del Gobbo, L.C., Imamura, F., Aslibekyan, S., Marklund, M., Virtanen, J.K., Wennberg, M., Yakoob, M.Y., Chiuve, S.E., Dela Gruz, L., Frazier-Wood, A.C., Fretts, A.M., Guallar, E., Matsumoto, C., Prem, K., Tanaka, T., Wu, J.H., Zhou, X., Helmer, C., Ingelsson, E., Yuan, J.M., Barberger-Gateau, P., Campos, H., Chaves, P.H., Djousse, L., Giles, G.G., Gomez-Aracena, J., Hodge, A.M., Hu, F.B., Janson, J.H., Johansson, I., Khaw, K.T., Koh, W.P., Lemaitre, R.N., Lind, L., Luben, R.N., Rimm, E.B., Riserus, U., Samieri, C., Franks, P.W., Siscovick, D.S., Stampfer, M., Steffen, L.M., Steffen, B.T., Tsai, M.Y., Van Dam, R.M., Voutilainen, S., Willett, W.C., Woodward, M., Mozaffarian, D. 2016. Omega-3 polyunsaturated fatty acid biomarkers and coronary heart disease: Pooling project of 19 cohort studies. JAMA Internal Medicine. 176(8):1155-1166.

Interpretive Summary: Consumption of omega-3 polyunsaturated fatty acids (PUFAs) has been associated with a reduced risk of coronary heart disease (CHD), but the problem is that not all studies support this notion – many report no association making it unclear if dietary guidelines should emphasize omega-3 PUFA intake or not. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers, and since self-reported consumption can often be inaccurate, in this study we aimed to clarify the role of omega-3 PUFAs in health by evaluating the association of seafood-derived eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) and plant-derived a-linolenic acid (ALA) with incident CHD. We analyzed data from 19 studies across the globe and found that ALA, DPA, and DHA were associated with a lower risk of fatal CHD. DPA was associated with a lower risk of total CHD, other omega-3 PUFAs were not. These data suggest that biomarker concentrations of seafood and plant-derived omega-3 PUFAs are associated with a modestly lower incidence of fatal CHD, and so may be important to include in nutrition advice.

Technical Abstract: 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. This study sought to evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5 omega-3), docosapentaenoic acid (DPA; 22:5 omega-3), and docosahexaenoic acid (DHA; 22:6 omega-3) and plant-derived a-linolenic acid (ALA; 18:3 omega-3) for incident CHD, using data from a global consortium of 19 studies identified by November 2014. Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue omega-3 biomarkers and ascertained CHD were selected. 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. Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI) were measured. The 19 studies comprised 16 countries, 45,637 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. 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.