Omega-3 fatty acids in adipose tissue and risk of atrial fibrillation.

BACKGROUND: The aim of the present study was to examine the relation between adipose tissue content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the risk of incident atrial fibrillation (AF). METHODS: In this case-cohort study based on data from the Danish Diet, Cancer and Health cohort, a total of 5255 incident cases of AF was identified during 16.9 years of follow-up. Adipose tissue biopsies collected at baseline from all cases and from a randomly drawn subcohort of 3440 participants were determined by gas chromatography. Data were analysed using weighted Cox regression. RESULTS: Data were available for 4741 incident cases of AF (2920 men and 1821 women). Participants in the highest vs. the lowest quintile of EPA experienced a 45% lower risk of AF (men HR 0.55 (95% CI 0.41-0.69); women HR 0.55 (0.41-0.72)). For DHA, no clear association was found in men, whereas in women, participants in the highest quintile of DHA in adipose tissue had a 30% lower risk of incident AF (HR 0.70 (0.54-0.91)) compared to participants in the lowest quintile. CONCLUSIONS: A monotonous inverse association was found for the content of EPA in adipose tissue and risk of AF in both men and women. The content of DHA was inversely associated with the risk of AF in women, whereas no clear association was found for men.

Patterns of adipose tissue fatty acids and the risk of atrial fibrillation: A case-cohort study.

Fatty acids in adipose tissue share dietary sources and metabolic pathways and therefore occur in patterns. The aim of the present study was to investigate the association between adipose tissue fatty acid patterns identified by the data-driven dimension-reducing method treelet transform and the risk of atrial fibrillation. A total of 57,053 Danish men and women aged 50-64 years participating in the Diet, Cancer and Health cohort had an adipose tissue biopsy taken at baseline. During a median follow-up of 14.6 years, a total of 4,710 participants developed atrial fibrillation or atrial flutter. Adipose tissue biopsies were analysed for fatty acid content by gas chromatography for all cases of atrial fibrillation and for a randomly drawn subcohort (n = 3,500) representative for the entire cohort. Hazard ratios with 95% confidence intervals for atrial fibrillation according to quintiles of factor scores were determined by weighted Cox proportional hazards regression analyses for men and women separately. From the 32 fatty acids measured, 7 major factors/patterns of fatty acids were identified using treelet transform. We found that a pattern consisting of n-6 polyunsaturated fatty acids (PUFA) (except linoleic acid) was associated with a lower hazard of atrial fibrillation. Patterns consisting of marine n-3 PUFA and containing n-9 fatty acids were associated with a lower hazard of atrial fibrillation in women. In conclusion, patterns of fatty acids in adipose tissue identified by treelet transform may be differentially associated with the risk of atrial fibrillation.

Effect of Dietary Intake of Saturated Fatty Acids on the Development of Atrial Fibrillation and the Effect of Replacement of Saturated With Monounsaturated and Polyunsaturated Fatty Acids.

The aim of the present study was to explore substitution of intake of saturated fatty acids (FAs) with monounsaturated and polyunsaturated FAs and incident atrial fibrillation (AF) in men and women. A total of 57,053 Danish participants aged 50 to 64 years were enrolled in the Diet, Cancer and Health cohort study in 1993 to 1997 and completed a semiquantitative food frequency questionnaire at baseline. Follow-up was registry-based and data were analyzed using Cox proportional hazards regression. The statistical model was formulated in such a way that 1 g/day of saturated FAs was replaced with 1 g/day of monounsaturated or polyunsaturated FAs while keeping total fat intake, total energy intake, and energy intake from protein and carbohydrates constant. During a median follow-up of 17 years, 5,175 incident cases of AF occurred. In men, there was a higher hazard of AF when total n-3 polyunsaturated FAs replaced dietary saturated FAs-hazard ratio per 1-g substitution of FAs of 1.08 (95% confidence interval 1.02 to 1.14) in a model adjusted for lifestyle factors. For other substitutions of FAs (monounsaturated, total or n-6 polyunsaturated FAs), no consistent nor statistically significant associations were found. In conclusion, we found a moderately higher risk of AF in men, but not in women, when total n-3 polyunsaturated FAs replaced dietary saturated FAs. Substitution of saturated FAs with monounsaturated, total or n-6 polyunsaturated FAs was not associated with the risk of AF.

Marine n-3 fatty acids in adipose tissue and development of atrial fibrillation: a Danish cohort study.

OBJECTIVE: Consumption of fish and marine n-3 polyunsaturated fatty acids (PUFA) may be associated with a lower risk of atrial fibrillation (AF), but results have been inconsistent. The aim was to investigate this further by measurements of marine n-3 PUFA in adipose tissue. DESIGN: Cohort study. SETTING: A total of 57 053 Danish participants 50-64 years of age were enrolled into the Diet, Cancer and Health Cohort Study. PATIENTS: A randomly drawn subcohort of 3440 participants with available data from baseline adipose tissue biopsies. INTERVENTIONS: Exposure was the adipose tissue content of marine n-3 PUFA, which reflects the endogenous exposure and is also an objective marker of the long-term dietary intake. MAIN OUTCOME MEASURES: Incident AF during follow-up. RESULTS: 179 cases of AF occurred over 13.6 years. Multivariate, sex-stratified Cox proportional hazards regression analyses using cubic splines showed a monotonic, negative, dose-response trend, but not statistically significant association, between total marine n-3 PUFA in adipose tissue and incident AF. A similar trend towards a lower risk of AF was seen in the second (HR 0.87, 95% CI 0.60 to 1.24) and third tertiles (HR 0.77, 95% CI 0.53 to 1.10) of marine n-3 PUFA compared with the lowest tertile. Similar trends, but also not statistically significant, were found separately for eicosapentaenoic, docosahexaenoic and docosapentaenoic acids. CONCLUSIONS: There was no statistically significant association between the content of marine n-3 PUFA in adipose tissue and the development of AF; however, data showed a monotonic, negative dose-response trend suggestive of a negative association.

Fish, Marine n-3 Fatty Acids, and Atrial Fibrillation - Experimental Data and Clinical Effects.

Marine n-3 polyunsaturated fatty acids (PUFA) may have beneficial effects in relation to atrial fibrillation (AF) with promising data from experimental animal studies, however, results from studies in humans have been inconsistent. This review evaluates the mechanisms of action of marine n-3 PUFA in relation to AF based on experimental data and provides a status on the evidence obtained from observational studies and interventional trials. In conclusion, there is growing evidence for an effect of marine n-3 PUFA in prevention and treatment of AF. However, further studies are needed to establish which patients are more likely to benefit from n-3 PUFA, the timing of treatment, and dosages.

Validity of the diagnoses atrial fibrillation and atrial flutter in a Danish patient registry.

OBJECTIVES: To assess the validity of the diagnoses of atrial fibrillation (AF) and atrial flutter (AFL) for men and women recorded in the Danish National Patient Registry, and to assess the relative distribution of AF and AFL. DESIGN: Review of medical records for incident cases of AF and/or AFL in the Diet, Cancer, and Health cohort study. Participants were enrolled in 1993-97 with 13.6 years of follow-up until 30 December, 2009. RESULTS: The positive predictive value of the combined diagnosis of AF and/or AFL was 92.6% (95% CI 88.8%; 95.2%) with no significant difference between sexes (men 93.7% (133/142), women 90.8% (129/142)). The proportion of AFL either alone or in combination with AF was significantly higher in men than in women (13.5% (18/133) vs. 5.4% (7/129), p =0.03). The positive predictive value of the specified diagnosis of AFL was 57.5% for men (46/80) and 29.6% for women (8/27). CONCLUSIONS: This study shows that the validity of the diagnosis of AF and/or AFL is high and may be used for registry-based studies. A specified diagnosis of AFL was rarely used and was not reliable to distinguish between cases of AF and AFL.