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dc.contributor.authorMarklund, Matti*
dc.contributor.authorWu, Jason H Y*
dc.contributor.authorImamura, Fumiaki*
dc.contributor.authorDel Gobbo, Liana C*
dc.contributor.authorFretts, Amanda*
dc.contributor.authorde Goede, Janette*
dc.contributor.authorShi, Peilin*
dc.contributor.authorTintle, Nathan*
dc.contributor.authorWennberg, Maria*
dc.contributor.authorAslibekyan, Stella*
dc.contributor.authorChen, Tzu-An*
dc.contributor.authorde Oliveira Otto, Marcia C*
dc.contributor.authorHirakawa, Yoichiro*
dc.contributor.authorEriksen, Helle Højmark*
dc.contributor.authorKröger, Janine*
dc.contributor.authorLaguzzi, Federica*
dc.contributor.authorLankinen, Maria*
dc.contributor.authorMurphy, Rachel A*
dc.contributor.authorPrem, Kiesha*
dc.contributor.authorSamieri, Cécilia*
dc.contributor.authorVirtanen, Jyrki*
dc.contributor.authorWood, Alexis C*
dc.contributor.authorWong, Kerry*
dc.contributor.authorYang, Wei-Sin*
dc.contributor.authorZhou, Xia*
dc.contributor.authorBaylin, Ana*
dc.contributor.authorBoer, Jolanda M A*
dc.contributor.authorBrouwer, Ingeborg A*
dc.contributor.authorCampos, Hannia*
dc.contributor.authorChaves, Paulo H M*
dc.contributor.authorChien, Kuo-Liong*
dc.contributor.authorDe Faire, Ulf*
dc.contributor.authorDjoussé, Luc*
dc.contributor.authorEiriksdottir, Gudny*
dc.contributor.authorEl-Abbadi, Naglaa*
dc.contributor.authorForouhi, Nita G*
dc.contributor.authorGaziano, J Michael*
dc.contributor.authorGeleijnse, Johanna M*
dc.contributor.authorGigante, Bruna*
dc.contributor.authorGiles, Graham*
dc.contributor.authorGuallar, Eliseo*
dc.contributor.authorGudnason, Vilmundur*
dc.contributor.authorHarris, Tamara*
dc.contributor.authorHarris, William S*
dc.contributor.authorHelmer, Catherine*
dc.contributor.authorHellénius, Mai-Lis*
dc.contributor.authorHodge, Allison*
dc.contributor.authorHu, Frank B*
dc.contributor.authorJacques, Paul F*
dc.contributor.authorJansson, Jan-Håkan*
dc.contributor.authorKalsbeek, Anya*
dc.contributor.authorKhaw, Kay-Tee*
dc.contributor.authorKoh, Woon-Puay*
dc.contributor.authorLaakso, Markku*
dc.contributor.authorLeander, Karin*
dc.contributor.authorLin, Hung-Ju*
dc.contributor.authorLind, Lars*
dc.contributor.authorLuben, Robert*
dc.contributor.authorLuo, Juhua*
dc.contributor.authorMcKnight, Barbara*
dc.contributor.authorMursu, Jaakko*
dc.contributor.authorNinomiya, Toshiharu*
dc.contributor.authorOvervad, Kim*
dc.contributor.authorPsaty, Bruce M*
dc.contributor.authorRimm, Eric*
dc.contributor.authorSchulze, Matthias B*
dc.contributor.authorSiscovick, David*
dc.contributor.authorSkjelbo Nielsen, Michael*
dc.contributor.authorSmith, Albert V*
dc.contributor.authorSteffen, Brian T*
dc.contributor.authorSteffen, Lyn*
dc.contributor.authorSun, Qi*
dc.contributor.authorSundström, Johan*
dc.contributor.authorTsai, Michael Y*
dc.contributor.authorTunstall-Pedoe, Hugh*
dc.contributor.authorUusitupa, Matti I J*
dc.contributor.authorvan Dam, Rob M*
dc.contributor.authorVeenstra, Jenna*
dc.contributor.authorVerschuren, W M Monique*
dc.contributor.authorWareham, Nicholas*
dc.contributor.authorWillett, Walter*
dc.contributor.authorWoodward, Mark*
dc.contributor.authorYuan, Jian-Min*
dc.contributor.authorMicha, Renata*
dc.contributor.authorLemaitre, Rozenn N*
dc.contributor.authorMozaffarian, Dariush*
dc.contributor.authorRisérus, Ulf*
dc.date.accessioned2019-04-26T08:05:45Z
dc.date.available2019-04-26T08:05:45Z
dc.date.issued2019-04-11
dc.identifier.issn1524-4539
dc.identifier.pmid30971107
dc.identifier.doi10.1161/CIRCULATIONAHA.118.038908
dc.identifier.urihttp://hdl.handle.net/10029/623037
dc.description.abstractGlobal 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. 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 (CHD), ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytical plan. Levels of LA and AA, measured as % of total fatty acids, were evaluated linearly according to their interquintile range (i.e., the range between the mid-point 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, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available). 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 CHD 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; comparing 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. 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.en_US
dc.language.isoenen_US
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectArachidonic aciden_US
dc.subjectLinoleic aciden_US
dc.subjectPooled analysisen_US
dc.subjectdiet and nutritionen_US
dc.titleBiomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies.en_US
dc.typeArticleen_US
dc.identifier.journalCirculation 2019; 139(21):2422-36en_US
dc.source.journaltitleCirculation


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