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

Am J Clin Nutr. 2023 Nov;118(5):921-929. doi: 10.1016/j.ajcnut.2023.09.008. Epub 2023 Sep 26.


Background: The presence of atrial fibrillation (AF) is associated with an over 2-fold increased risk of stroke, heart failure, and cardiovascular mortality. Long chain 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.

Objectives: 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 (aged ≥18 y). 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, 6173 incident cases of AF were ascertained, with median follow-up time of 14 y. In multivariable analysis, per interquintile range (difference between the 10th and 90th percentiles for each fatty acid), circulating n-6 levels were not associated with incident AF. For LA, the hazard ratio per interquintile range was 0.96 (95% confidence interval [CI]: 0.89, 1.04), and for AA, 1.02 (95% CI: 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 are not associated with incident AF. These findings suggest that overall effects of n-6 PUFAs on influencing AF development are neutral.

Keywords: Fatty Acids and Outcomes Research Consortium; atrial arrhythmia; cardiovascular disease; polyunsaturated fatty acids; primary prevention; prospective cohorts.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arachidonic Acid
  • Atrial Fibrillation* / diagnosis
  • Atrial Fibrillation* / epidemiology
  • Biomarkers
  • Fatty Acids, Omega-6*
  • Fatty Acids, Unsaturated
  • Humans
  • Incidence
  • Linoleic Acid
  • Prospective Studies
  • Risk Factors


  • Fatty Acids, Omega-6
  • Fatty Acids, Unsaturated
  • Linoleic Acid
  • Arachidonic Acid
  • Biomarkers