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Title: Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality.
Authors: Marklund, Matti
Wu, Jason HY
Imamura, Fumiaki
Del Gobbo, Liana C
Fretts, Amanda
de Goede, Janette
Shi, Peilin
Tintle, Nathan
Wennberg, Maria
Aslibekyan, Stella
Chen, Tzu-An
de Oliveira Otto, Marcia C
Hirakawa, Yoichiro
Eriksen, Helle Højmark
Kröger, Janine
Laguzzi, Federica
Lankinen, Maria
Murphy, Rachel A
Samieri, Cécilia
Virtanen, Jyrki
Wood, Alexis C
Wong, Kerry
Yang, Wei-Sin
Zhou, Xia
Baylin, Ana
Boer, Jolanda MA
Brouwer, Ingeborg A
Campos, Hannia
Chaves, Paulo HM
Chien, Kuo-Liong
de Faire, Ulf
Djoussé, Luc
Eiriksdottir, Gudny
El-Abbadi, Naglaa
Forouhi, Nita G
Michael Gaziano, J
Geleijnse, Johanna M
Gigante, Bruna
Giles, Graham
Guallar, Eliseo
Gudnason, Vilmundur
Harris, Tamara
Harris, William S
Helmer, Catherine
Hellenius, Mai-Lis
Hodge, Allison
Hu, Frank B
Jacques, Paul F
Jansson, Jan-Håkan
Kalsbeek, Anya
Khaw, Kay-Tee
Laakso, Markku
Leander, Karin
Lin, Hung-Ju
Lind, Lars
Luben, Robert
Luo, Juhua
McKnight, Barbara
Mursu, Jaakko
Ninomiya, Toshiharu
Overvad, Kim
Psaty, Bruce M
Rimm, Eric
Schulze, Matthias B
Siscovick, David
Skjelbo Nielsen, Michael
Smith, Albert V
Steffen, Brian T
Steffen, Lyn
Sun Qi
Sundström, Johan
Tsai, Michael Y
Tunstall-Pedoe, Hugh
Uusitupa, Matti IJ
Veenstra, Jenna
Monique Verschuren, WM
Wareham, Nick
Willett, Walter
Woodward, Mark
Micha, Renata
Lemaitre, Rozenn N
Mozaffarian, Dariush
Risérus, Ulf
Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCE)
Keywords: arachidonic acid
cardiovascular diseases
linoleic acid
primary prevention
Issue Date: 21-May-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Citation: Marklund, Matti, Wu, Jason HY, Imamura, Fumiaki, Del Gobbo, Liana C, Fretts, Amanda, de Goede, Janette, Shi, Peilin, Tintle, Nathan, Wennberg, Maria, Aslibekyan, Stella, Chen, Tzu-An, de Oliveira Otto, Marcia C, Hirakawa, Yoichiro, Eriksen, Helle Højmark, Kröger, Janine, Laguzzi, Federica, Lankinen, Maria, Murphy, Rachel A, KIESHA PREM, Samieri, Cécilia, Virtanen, Jyrki, Wood, Alexis C, Wong, Kerry, Yang, Wei-Sin, Zhou, Xia, Baylin, Ana, Boer, Jolanda MA, Brouwer, Ingeborg A, Campos, Hannia, Chaves, Paulo HM, Chien, Kuo-Liong, de Faire, Ulf, Djoussé, Luc, Eiriksdottir, Gudny, El-Abbadi, Naglaa, Forouhi, Nita G, Michael Gaziano, J, Geleijnse, Johanna M, Gigante, Bruna, Giles, Graham, Guallar, Eliseo, Gudnason, Vilmundur, Harris, Tamara, Harris, William S, Helmer, Catherine, Hellenius, Mai-Lis, Hodge, Allison, Hu, Frank B, Jacques, Paul F, Jansson, Jan-Håkan, Kalsbeek, Anya, Khaw, Kay-Tee, KOH WOON PUAY, Laakso, Markku, Leander, Karin, Lin, Hung-Ju, Lind, Lars, Luben, Robert, Luo, Juhua, McKnight, Barbara, Mursu, Jaakko, Ninomiya, Toshiharu, Overvad, Kim, Psaty, Bruce M, Rimm, Eric, Schulze, Matthias B, Siscovick, David, Skjelbo Nielsen, Michael, Smith, Albert V, Steffen, Brian T, Steffen, Lyn, Sun Qi, Sundström, Johan, Tsai, Michael Y, Tunstall-Pedoe, Hugh, Uusitupa, Matti IJ, ROB MARTINUS VAN DAM, Veenstra, Jenna, Monique Verschuren, WM, Wareham, Nick, Willett, Walter, Woodward, Mark, YUAN JIAN-MIN, Micha, Renata, Lemaitre, Rozenn N, Mozaffarian, Dariush, Risérus, Ulf, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCE) (2019-05-21). Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality.. Circulation 139 (21) : 2422-2436. ScholarBank@NUS Repository.
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.
Source Title: Circulation
ISSN: 00097322
DOI: 10.1161/CIRCULATIONAHA.118.038908
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