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.
| Original language | English |
|---|---|
| Pages (from-to) | 2422-2436 |
| Number of pages | 15 |
| Journal | Circulation |
| Volume | 139 |
| Issue number | 21 |
| DOIs | |
| Publication status | Published - 21 May 2019 |
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Keywords
- arachidonic acid
- biomarkers
- cardiovascular diseases
- diet
- epidemiology
- linoleic acid
- primary prevention
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Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality. / Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCE).
In: Circulation, Vol. 139, No. 21, 21.05.2019, p. 2422-2436.Research output: Contribution to Journal › Article › Academic › peer-review
TY - JOUR
T1 - Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality
AU - Marklund, Matti
AU - Wu, Jason H.Y.
AU - Imamura, Fumiaki
AU - Del Gobbo, Liana C.
AU - Fretts, Amanda
AU - de Goede, Janette
AU - Shi, Peilin
AU - Tintle, Nathan
AU - Wennberg, Maria
AU - Aslibekyan, Stella
AU - Chen, Tzu An
AU - de Oliveira Otto, Marcia C.
AU - Hirakawa, Yoichiro
AU - Eriksen, Helle Højmark
AU - Kröger, Janine
AU - Laguzzi, Federica
AU - Lankinen, Maria
AU - Murphy, Rachel A.
AU - Prem, Kiesha
AU - Samieri, Cécilia
AU - Virtanen, Jyrki
AU - Wood, Alexis C.
AU - Wong, Kerry
AU - Yang, Wei Sin
AU - Zhou, Xia
AU - Baylin, Ana
AU - Boer, Jolanda M.A.
AU - Brouwer, Ingeborg A.
AU - Campos, Hannia
AU - Chaves, Paulo H.M.
AU - Chien, Kuo Liong
AU - de Faire, Ulf
AU - Djoussé, Luc
AU - Eiriksdottir, Gudny
AU - El-Abbadi, Naglaa
AU - Forouhi, Nita G.
AU - Michael Gaziano, J.
AU - Geleijnse, Johanna M.
AU - Gigante, Bruna
AU - Giles, Graham
AU - Guallar, Eliseo
AU - Gudnason, Vilmundur
AU - Harris, Tamara
AU - Harris, William S.
AU - Helmer, Catherine
AU - Hellenius, Mai Lis
AU - Hodge, Allison
AU - Hu, Frank B.
AU - Jacques, Paul F.
AU - Jansson, Jan Håkan
AU - Kalsbeek, Anya
AU - Khaw, Kay Tee
AU - Koh, Woon Puay
AU - Laakso, Markku
AU - Leander, Karin
AU - Lin, Hung Ju
AU - Lind, Lars
AU - Luben, Robert
AU - Luo, Juhua
AU - McKnight, Barbara
AU - Mursu, Jaakko
AU - Ninomiya, Toshiharu
AU - Overvad, Kim
AU - Psaty, Bruce M.
AU - Rimm, Eric
AU - Schulze, Matthias B.
AU - Siscovick, David
AU - Skjelbo Nielsen, Michael
AU - Smith, Albert V.
AU - Steffen, Brian T.
AU - Steffen, Lyn
AU - Sun, Qi
AU - Sundström, Johan
AU - Tsai, Michael Y.
AU - Tunstall-Pedoe, Hugh
AU - Uusitupa, Matti I.J.
AU - van Dam, Rob M.
AU - Veenstra, Jenna
AU - Monique Verschuren, W. M.
AU - Wareham, Nick
AU - Willett, Walter
AU - Woodward, Mark
AU - Yuan, Jian Min
AU - Micha, Renata
AU - Lemaitre, Rozenn N.
AU - Mozaffarian, Dariush
AU - Risérus, Ulf
AU - Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCE)
PY - 2019/5/21
Y1 - 2019/5/21
N2 - 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.
AB - 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.
KW - arachidonic acid
KW - biomarkers
KW - cardiovascular diseases
KW - diet
KW - epidemiology
KW - linoleic acid
KW - primary prevention
UR - http://www.scopus.com/inward/record.url?scp=85066456162&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85066456162&partnerID=8YFLogxK
U2 - 10.1161/CIRCULATIONAHA.118.038908
DO - 10.1161/CIRCULATIONAHA.118.038908
M3 - Article
VL - 139
SP - 2422
EP - 2436
JO - Circulation
JF - Circulation
SN - 1524-4539
IS - 21
ER -