ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies - PubMed (original) (raw)

. 2016 Aug 1;176(8):1155-66.

doi: 10.1001/jamainternmed.2016.2925.

Fumiaki Imamura 2, Stella Aslibekyan 3, Matti Marklund 4, Jyrki K Virtanen 5, Maria Wennberg 6, Mohammad Y Yakoob 1, Stephanie E Chiuve 7, Luicito Dela Cruz 8, Alexis C Frazier-Wood 9, Amanda M Fretts 10, Eliseo Guallar 11, Chisa Matsumoto 12, Kiesha Prem 13, Tosh Tanaka 14, Jason H Y Wu 15, Xia Zhou 16, Catherine Helmer 17, Erik Ingelsson 18, Jian-Min Yuan 19, Pascale Barberger-Gateau 17, Hannia Campos 20, Paulo H M Chaves 21, Luc Djoussé 22, Graham G Giles 8, Jose Gómez-Aracena 23, Allison M Hodge 8, Frank B Hu 24, Jan-Håkan Jansson 6, Ingegerd Johansson 25, Kay-Tee Khaw 26, Woon-Puay Koh 27, Rozenn N Lemaitre 28, Lars Lind 29, Robert N Luben 26, Eric B Rimm 24, Ulf Risérus 4, Cecilia Samieri 17, Paul W Franks 30, David S Siscovick 31, Meir Stampfer 24, Lyn M Steffen 16, Brian T Steffen 16, Michael Y Tsai 32, Rob M van Dam 33, Sari Voutilainen 5, Walter C Willett 24, Mark Woodward 34, Dariush Mozaffarian 35; Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCe)

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ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies

Liana C Del Gobbo et al. JAMA Intern Med. 2016.

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Abstract

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; 20:5ω-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.

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 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. 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.

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Conflict of interest statement

Disclosures: Dr Barberger-Gateau reported receiving grants and nonfinancial support from Danone Research, Vifor Pharma, and Groupe Lipides et Nutrition; personal fees and nonfinancial support from Nutricia, ILSI Europe, and PiLeJe; and a grant from the Centre National Interprofessionnel de l’Industrie Laitière. Dr Del Gobbo reported receiving ad hoc consulting fees from the Life Sciences Research Organization. Dr Djoussé reported receiving investigator-initiated grants from Merck, Amarin Pharma Inc, California Walnut Commission, and the National Institutes of Health and serving as ad hoc consultant for Amarin Pharma Inc. Dr Helmer reported receiving fees for a conference from Novartis. Dr Mozaffarian reported receiving ad hoc honoraria from Bunge, Pollock Institute, and Quaker Oats; ad hoc consulting for Foodminds, Life Sciences Research Organization, Nutrition Impact, Amarin, AstraZeneca, Winston, and Strawn LLP; membership in Unilever North America Scientific Advisory Board; and chapter royalties from UpToDate. Dr Woodward reported receiving consulting fees from Amgen and Novartis and research funding from Sanofi. No other disclosures were reported.

Figures

Figure 1

Figure 1

Relative Risk (RR) of Fatal Coronary Heart Disease (CHD) per 1-SD Increase in the Biomarkers α-Linolenic Acid (ALA; 18:3ω-3) and Eicosapentaenoic Acid (EPA; 20:5ω-3) Estimates were pooled using random effects meta-analysis. See eFigure 1 in the Supplement for results using inverse-variance weights. CHS indicates Cardiovascular Health Study; EPIC-Norfolk, European Prospective Investigation of Cancer (Norfolk); HPFS, Health Professionals Follow-up Study; KIHD, Kuopio Ischaemic Heart Disease Risk Factor Study; MCCS, Melbourne Collaborative Cohort Study; MESA, Multi-Ethnic Study of Atherosclerosis; NHS, Nurses’ Health Study; NSHDS, Northern Sweden Health and Disease Study,; PHS, Physician’s Health Study; SCHS, Singapore Chinese Health Study; and ULSAM, Uppsala Longitudinal Study of Adult Men.

Figure 2

Figure 2

Relative Risk (RR) of Fatal Coronary Heart Disease (CHD) per 1-SD Increase in the Biomarkers Docosapentaenoic Acid (DPA; 22:5ω-3) and Docosahexaenoic Acid (DHA; 22:6ω-3) Estimates were pooled using random effects meta-analysis. See eFigure 1 in the Supplement for results using inverse-variance weights. CHS indicates Cardiovascular Health Study; EPIC-Norfolk, European Prospective Investigation of Cancer (Norfolk); HPFS, Health Professionals Follow-up Study; KIHD, Kuopio Ischaemic Heart Disease Risk Factor Study; MCCS, Melbourne Collaborative Cohort Study; MESA, Multi-Ethnic Study of Atherosclerosis; NHS, Nurses’ Health Study; NSHDS, Northern Sweden Health and Disease Study,; PHS, Physician’s Health Study; SCHS, Singapore Chinese Health Study; SHHEC, Scottish Heart Health Extended Chart; and ULSAM, Uppsala Longitudinal Study of Adult Men.

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