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Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality.

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.

SUBMITTER: Marklund M

PROVIDER: S-EPMC6582360 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality.

Marklund Matti M Wu Jason H Y JHY Imamura Fumiaki F Del Gobbo Liana C LC Fretts Amanda A de Goede Janette J Shi Peilin P Tintle Nathan N Wennberg Maria M Aslibekyan Stella S Chen Tzu-An TA de Oliveira Otto Marcia C MC Hirakawa Yoichiro Y Eriksen Helle Højmark HH Kröger Janine J Laguzzi Federica F Lankinen Maria M Murphy Rachel A RA Prem Kiesha K Samieri Cécilia C Virtanen Jyrki J Wood Alexis C AC Wong Kerry K Yang Wei-Sin WS Zhou Xia X Baylin Ana A Boer Jolanda M A JMA Brouwer Ingeborg A IA Campos Hannia H Chaves Paulo H M PHM Chien Kuo-Liong KL de Faire Ulf U Djoussé Luc L Eiriksdottir Gudny G El-Abbadi Naglaa N Forouhi Nita G NG Michael Gaziano J J Geleijnse Johanna M JM Gigante Bruna B Giles Graham G Guallar Eliseo E Gudnason Vilmundur V Harris Tamara T Harris William S WS Helmer Catherine C Hellenius Mai-Lis ML Hodge Allison A Hu Frank B FB Jacques Paul F PF Jansson Jan-Håkan JH Kalsbeek Anya A Khaw Kay-Tee KT Koh Woon-Puay WP Laakso Markku M Leander Karin K Lin Hung-Ju HJ Lind Lars L Luben Robert R Luo Juhua J McKnight Barbara B Mursu Jaakko J Ninomiya Toshiharu T Overvad Kim K Psaty Bruce M BM Rimm Eric E Schulze Matthias B MB Siscovick David D Skjelbo Nielsen Michael M Smith Albert V AV Steffen Brian T BT Steffen Lyn L Sun Qi Q Sundström Johan J Tsai Michael Y MY Tunstall-Pedoe Hugh H Uusitupa Matti I J MIJ van Dam Rob M RM Veenstra Jenna J Monique Verschuren W M WM Wareham Nick N Willett Walter W Woodward Mark M Yuan Jian-Min JM Micha Renata R Lemaitre Rozenn N RN Mozaffarian Dariush D Risérus Ulf U

Circulation 20190501 21

<h4>Background</h4>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.<h4>Methods</h4>We performed harmonize ...[more]

PMID: 30971107

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Project description:ObjectiveTo investigate associations between dietary omega-3 fatty acids and other fat intake, genes related to age-related macular degeneration (AMD), and progression to geographic atrophy (GA).DesignObservational analysis of a prospective cohort.ParticipantsA total of 2531 individuals from the Age-Related Eye Disease Study, among which 525 eyes progressed to GA and 4165 eyes did not.MethodsEyes without advanced AMD at baseline were evaluated for progression to GA. Behavioral data, including smoking and body mass index measurements, were collected at baseline using questionnaires. Dietary data were collected from food frequency questionnaires (FFQs) at baseline. Omega-3 fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]), omega-6 fatty acids, monounsaturated, saturated, polyunsaturated, and total fat were adjusted for sex and calories and divided into quintiles (Q). Eight single nucleotide polymorphisms in 7 genes (CFH, ARMS2/HTRA1, CFB, C2, C3, CFI, and LIPC) were genotyped. Cox proportional hazards models were used to test for associations between incident GA and intake of dietary lipids and interaction effects between dietary fat intake and genetic variation on risk of GA.Main outcome measuresAssociations between dietary fat intake reported from FFQs, genetic variants, and incident GA.ResultsIncreased intake of DHA was significantly associated with reduced risk of progression to GA in models with behavioral factors (model A) plus genetic variants (model B) (P trend = 0.01 and 0.03, respectively). Total omega-3 long chain polyunsaturated (DHA + EPA) fatty acid intake was significantly associated with reduced risk of progression in model B (P trend = 0.02). Monounsaturated fat was associated with increased risk in model A (P trend = 0.05). DHA intake was significantly associated with reduced risk of incident GA among those with the ARMS2/HTRA1 homozygous risk genotype (hazard ratio [HR] Q5 vs Q1, 0.4; P = 0.002; P for interaction between gene and fat intake = 0.05). DHA was not associated with reduced risk of GA among those with the homozygous ARMS2/HTRA1 nonrisk genotype (HR, 1.0; P = 0.90).ConclusionsIncreased self-reported dietary intake of omega-3 fatty acids is associated with reduced risk of GA and may modify genetic susceptibility for progression to GA.Financial disclosure(s)The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Project description:BackgroundAlthough omega-6 polyunsaturated fatty acids (n-6 PUFA) have been recommended to reduce coronary heart disease (CHD), controversy remains about benefits versus harms, including concerns over theorized proinflammatory effects of n-6 PUFA. We investigated associations of circulating n-6 PUFA including linoleic acid (the major dietary PUFA), γ-linolenic acid, dihomo-γ-linolenic acid, and arachidonic acid, with total and cause-specific mortality in the Cardiovascular Health Study, a community-based U.S. cohort.Methods and resultsAmong 2792 participants(aged ≥65 years) free of cardiovascular disease at baseline, plasma phospholipid n-6 PUFA were measured at baseline using standardized methods. All-cause and cause-specific mortality, and total incident CHD and stroke, were assessed and adjudicated centrally. Associations of PUFA with risk were assessed by Cox regression. During 34 291 person-years of follow-up (1992-2010), 1994 deaths occurred (678 cardiovascular deaths), with 427 fatal and 418 nonfatal CHD, and 154 fatal and 399 nonfatal strokes. In multivariable models, higher linoleic acid was associated with lower total mortality, with extreme-quintile hazard ratio =0.87 (P trend=0.005). Lower death was largely attributable to cardiovascular disease causes, especially nonarrhythmic CHD mortality (hazard ratio, 0.51; 95% confidence interval, 0.32-0.82; P trend=0.001). Circulating γ-linolenic acid, dihomo-γ-linolenic acid, and arachidonic acid were not significantly associated with total or cause-specific mortality (eg, for arachidonic acid and CHD death, the extreme-quintile hazard ratio was 0.97; 95% confidence interval, 0.70-1.34; P trend=0.87). Evaluated semiparametrically, linoleic acid showed graded inverse associations with total mortality (P=0.005). There was little evidence that associations of n-6 PUFA with total mortality varied by age, sex, race, or plasma n-3 PUFA. Evaluating both n-6 and n-3 PUFA, lowest risk was evident with highest levels of both.ConclusionsHigh circulating linoleic acid, but not other n-6 PUFA, was inversely associated with total and CHD mortality in older adults.

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Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality.

Publications

Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality.

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