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ω-3 Polyunsaturated fatty acid biomarkers and coronary heart disease : Pooling project of 19 cohort studies

  • 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
Publishing year: 2016-08-01
Language: English
Pages: 1155-1166
Publication/Series: JAMA Internal Medicine
Volume: 176
Issue: 8
Document type: Journal article
Publisher: American Medical Association

Abstract english

Importance: 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. Objective: To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5 ω-3), docosapentaenoic acid (DPA; 22:5 ω-3), and docosahexaenoic acid (DHA; 22:6 ω-3) and plant-derived α-linolenic acid (ALA; 18:3 ω-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 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). Results: 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 baselinewas 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 DHAwere 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 MIwere 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 ω-3 fatty acids are associated with a modestly lower incidence of fatal CHD.


  • Cardiac and Cardiovascular Systems


  • Genetic and Molecular Epidemiology
  • ISSN: 2168-6106
Paul Franks
E-mail: paul [dot] franks [at] med [dot] lu [dot] se

Principal investigator

Genetic and Molecular Epidemiology

+46 40 39 11 49



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