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Dietary omega-3 fatty acids and susceptibility to ventricular fibrillation: lack of protection and a proarrhythmic effect.

ABSTRACT: BACKGROUND:Recent clinical studies that evaluated the effects of supplemental omega-3 polyunsaturated fatty acids (n-3 PUFAs) on sudden cardiac death have yielded conflicting results. Our aim was to clarify this issue using an established and clinical relevant canine model of sudden cardiac death. METHODS AND RESULTS:Susceptibility to ventricular fibrillation (VF) was evaluated using a 2-minute left circumflex artery occlusion during the last minute of an exercise test in 76 dogs (from 2 independent studies) with healed myocardial infarctions (MI); 44 developed VF (susceptible, VF+), whereas 32 did not (resistant, VF-). These dogs were then randomly assigned to either placebo (1 g/d, corn oil; 15 VF+, 11 VF-) or n-3 PUFA (1-4 g/d, docosahexaenoic acid+eicosapentaenoic acid ethyl esters, 29 VF+, 21 VF-) groups. Seven sham (no-MI) dogs were also treated with n-3 PUFA (4 g/d). After treatment (3 months), the exercise+ischemia test was repeated. Dietary n-3 PUFAs produced significant (P<0.01) increases in red blood cell and left ventricular n-3 PUFA levels. Nine post-MI (5 placebo versus 4 n-3 PUFA) and 2 sham dogs died suddenly during the 3-month treatment period. The n-3 PUFA treatment failed to prevent arrhythmias in VF+ dogs (decreased in 27% placebo versus 24% n-3 PUFA, P=0.5646) but induced VT/VF in VF- animals (n-3 PUFA 33% versus placebo 0%, P=0.0442). CONCLUSIONS:Despite large increases in cardiac tissue n-3 PUFA content, dietary n-3 PUFAs did not prevent ischemia-induced VF and actually increased arrhythmia susceptibility in both noninfarcted and low-risk post-MI dogs.

SUBMITTER: Billman GE

PROVIDER: S-EPMC3380163 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Dietary omega-3 fatty acids and susceptibility to ventricular fibrillation: lack of protection and a proarrhythmic effect.

Billman George E GE Carnes Cynthia A CA Adamson Philip B PB Vanoli Emilio E Schwartz Peter J PJ

Circulation. Arrhythmia and electrophysiology 20120214 3

<h4>Background</h4>Recent clinical studies that evaluated the effects of supplemental omega-3 polyunsaturated fatty acids (n-3 PUFAs) on sudden cardiac death have yielded conflicting results. Our aim was to clarify this issue using an established and clinical relevant canine model of sudden cardiac death.<h4>Methods and results</h4>Susceptibility to ventricular fibrillation (VF) was evaluated using a 2-minute left circumflex artery occlusion during the last minute of an exercise test in 76 dogs ...[more]

PMID: 22333345

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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:BackgroundGlobal 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.MethodsWe 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).ResultsIn 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.ConclusionsIn 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.

Dataset Information

Dietary omega-3 fatty acids and susceptibility to ventricular fibrillation: lack of protection and a proarrhythmic effect.

Publications

Dietary omega-3 fatty acids and susceptibility to ventricular fibrillation: lack of protection and a proarrhythmic effect.

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