Abstract Body: Background: Recent observational studies in the UK Biobank (UKBB) concluded that self-reported fish oil supplement (FOS) use is associated with an increased risk for incident atrial fibrillation (AF). This lies in contradiction with a globally representative meta-analysis, which found an inverse relationship between blood levels of omega-3 fatty acids (n-3 FAs) and risk of AF. The extent to which plasma levels of n-3 FAs are related to risk of AF in UKBB has yet to be reported.

Objectives: We have leveraged data from the UKBB to 1) determine the relationship between plasma levels of n-3 FAs and incident AF and 2) to further explore the previously reported association between FOS use and incident AF.

Methods: Within the UKBB, we identified 266,477 individuals with data on blood plasma n-3 FAs and relevant covariates, and 433,607 individuals with data on self-reported FOS use. The primary outcome was incident AF during the follow-up period (median 12.7y). Multivariable-adjusted hazard ratios (95% CIs) for FAs were computed continuously (per inter-quintile range [IQ₅R]) and by quintile (Q). HRs were computed for dichotomous FOS use. Covariates included: age, sex, ethnicity, education, physical exercise, smoking, alcohol use, BMI, use of beta-blocker, drugs for hypertension or cholesterol, prevalent diabetes, CVD or heart failure, and plasma linoleic acid levels. Notably, in our analyses we adjusted for age as a continuous variable to more completely account for age-related risk of AF, compared to previous analyses which adjusted for age as a dichotomous variable (i.e., 65+ vs <65) in their assessment of FOS and risk of AF.

Results: Total n-3 levels in blood plasma were inversely associated with incident AF (HR per IQ₅R = 0.90 [95% CI 0.86, 0.93]), and HR=0.87 (0.83, 0.91) in Q5 (vs Q1). FOS use was reported by 31% of the cohort, with higher use reported in older individuals. After adjusting for age continuously, there was no association between FOS use and risk of AF risk (HR=1.00 [097, 1.02]).

Conclusion: In agreement with recent biomarker-based meta-analyses, higher circulating blood levels of n-3 FA were associated with reduced risk for AF in the UKBB. Secondly, this study reassessed the relationship between FOS use and risk of AF in the UKBB, and if age is adjusted for in a continuous fashion, the association between FOS and AF disappears. These findings indicate previous analyses may have insufficiently adjusted for the age-related risk of AF.