Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies
Journal
Circulation
Journal Volume
139
Journal Issue
21
Pages
2422-2436
Date Issued
2019
Author(s)
Wu J.H.Y.
Imamura F.
Del Gobbo L.C.
Fretts A.
De Goede J.
Shi P.
Tintle N.
Wennberg M.
Aslibekyan S.
Chen T.-A.
De Oliveira Otto M.C.
Hirakawa Y.
Eriksen H.Hø.
Kröger J.
Laguzzi F.
Lankinen M.
Murphy R.A.
Prem K.
Samieri C.
Virtanen J.
Wood A.C.
Wong K.
Yang W.-S.
Zhou X.
Baylin A.
Boer J.M.A.
Brouwer I.A.
Campos H.
Chaves P.H.M.
Chien K.-L.
De Faire U.
Djoussé L.
Eiriksdottir G.
El-Abbadi N.
Forouhi N.G.
Michael Gaziano J.
Geleijnse J.M.
Gigante B.
Giles G.
Guallar E.
Gudnason V.
Harris T.
Harris W.S.
Helmer C.
Hellenius M.-L.
Hodge A.
Hu F.B.
Jacques P.F.
Jansson J.-H.
Kalsbeek A.
Khaw K.-T.
Koh W.-P.
Laakso M.
Leander K.
Lind L.
Luben R.
Luo J.
Mcknight B.
Mursu J.
Ninomiya T.
Overvad K.
Psaty B.M.
Rimm E.
Schulze M.B.
Siscovick D.
Skjelbo Nielsen M.
Smith A.V.
Steffen B.T.
Steffen L.
Sun Q.
Sundström J.
Tsai M.Y.
Tunstall-Pedoe H.
Uusitupa M.I.J.
Van Dam R.M.
Veenstra J.
Monique Verschuren W.M.
Wareham N.
Willett W.
Woodward M.
Yuan J.-M.
Micha R.
Lemaitre R.N.
Mozaffarian D.
Risérus U.
Abstract
Background: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies. Methods: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available). Results: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships. Conclusions: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention. ? 2019 American Heart Association, Inc.
SDGs
Other Subjects
acetylsalicylic acid; acyl coenzyme A desaturase 1; arachidonic acid; hydroxymethylglutaryl coenzyme A reductase inhibitor; linoleic acid; omega 3 fatty acid; arachidonic acid; biological marker; linoleic acid; adipose tissue; adult; aged; Article; Australia; brain ischemia; cardiovascular disease; cardiovascular mortality; clinical article; cohort analysis; Costa Rica; Denmark; diabetes mellitus; drug use; fat intake; fatty acid blood level; female; Finland; follow up; France; Germany; human; Iceland; ischemic heart disease; Japan; male; middle aged; Netherlands; observational study; priority journal; prospective study; race; retrospective study; Singapore; Sweden; Taiwan; United Kingdom; United States; administration and dosage; blood; cardiovascular disease; clinical trial; dietary reference intake; fat intake; meta analysis; mortality; multicenter study; nutritional value; primary prevention; procedures; protection; risk assessment; risk factor; risk reduction; Aged; Arachidonic Acid; Biomarkers; Cardiovascular Diseases; Diet, Healthy; Dietary Fats; Female; Humans; Linoleic Acid; Male; Middle Aged; Nutritive Value; Observational Studies as Topic; Primary Prevention; Protective Factors; Recommended Dietary Allowances; Risk Assessment; Risk Factors; Risk Reduction Behavior
Publisher
Lippincott Williams and Wilkins
Type
journal article