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Omega-6 fatty acid biomarkers and incident atrial fibrillation: an individual participant-level pooled analysis of 11 international prospective studies.

P. Garg,Weihua Guan,Sarah O. Nomura,Natalie L. Weir,N. Tintle,J. Virtanen,Y. Hirakawa,Frank Qian,Qi Sun,E. Rimm,R. Lemaitre,P. Jensen,S. Heckbert,F. Imamura,M. Steur,K. Leander,F. Laguzzi,T. Voortman,T. Ninomiya,D. Mozaffarian,William S. Harris,D. Siscovick,M. Tsai

Published 2023 in American Journal of Clinical Nutrition

ABSTRACT

BACKGROUND The presence of atrial fibrillation (AF) is associated with an over two-fold increased risk of stroke, heart failure, and cardiovascular mortality. Long chain omega-6 polyunsaturated fatty acids (n-6 PUFAs) have been suggested to have a variety of beneficial biologic effects that may reduce AF development; however, prior studies evaluating this relationship are limited. OBJECTIVE We prospectively evaluated the association between circulating levels of linoleic acid (LA) and arachidonic acid (AA) with incident AF. METHODS We used participant-level data from a global consortium of 11 prospective cohort studies with measurements of LA and AA in adults (age≥18). Participating studies conducted de novo analyses using a prespecified analytical plan with harmonized definitions for exposures, outcomes, covariates, and subgroups. Associations were pooled using inverse-variance weighted meta-analysis. RESULTS Among 41,335 participants, 6,173 incident cases of AF were ascertained, with median follow-up time of 14 years. In multivariable analysis, per interquintile range (difference between the 10th and 90th percentiles for each fatty acid), circulating omega-6 levels were not associated with incident AF. For LA, the hazard ratio (95% confidence interval) per interquintile range was 0.96 (0.89, 1.04), and for AA, 1.02 (0.94, 1.10), with little evidence of heterogeneity between cohorts. Associations were similarly nonsignificant across subgroups of age, race, and biomarker fraction. CONCLUSIONS Biomarkers of n-6 fatty acids including LA and AA were not associated with incident AF. These findings suggest that overall effects of n-6 PUFAs on influencing AF development are neutral.

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