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Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia;Univ New South Wales, Fac Med, Sydney, NSW, Australia.
Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia;Univ New South Wales, Fac Med, Sydney, NSW, Australia.
Univ Cambridge, MRC, Epidemiol Unit, Cambridge, England.
Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA.
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2019 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, no 21, p. 2422-2436Article in journal (Refereed) Published
Abstract [en]

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, 15198 incident cardiovascular events occurred among 68659 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.

Place, publisher, year, edition, pages
2019. Vol. 139, no 21, p. 2422-2436
Keywords [en]
arachidonic acid, biomarkers, cardiovascular diseases, diet, epidemiology, linoleic acid, primary prevention
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:uu:diva-387592DOI: 10.1161/CIRCULATIONAHA.118.038908ISI: 000469018300011PubMedID: 30971107OAI: oai:DiVA.org:uu-387592DiVA, id: diva2:1331295
Available from: 2019-06-26 Created: 2019-06-26 Last updated: 2019-06-26Bibliographically approved

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Marklund, MattiLind, LarsSundström, JohanRisérus, Ulf

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