Association Between Omega-3 Fatty Acid Levels and Risk for Incident Major Bleeding Events and Atrial Fibrillation: MESA

J Am Heart Assoc. 2021 Jun;10(11):e021431. doi: 10.1161/JAHA.121.021431. Epub 2021 May 27.


Background Randomized trials of pharmacologic strength omega-3 fatty acid (n3-FA)-based therapies suggest a dose-dependent cardiovascular benefit. Whether blood n3-FA levels also mediate safety signals observed in these trials, such as increased bleeding and atrial fibrillation (AF), remains uncertain. We hypothesized that higher baseline n3-FA levels would be associated with incident bleeding and AF events in MESA (Multi-Ethnic Study of Atherosclerosis), which included a population free of clinical cardiovascular disease at baseline. Methods and Results We examined the association between baseline plasma n3-FA levels (expressed as percent mass of total fatty acid) with incident bleeding and AF in MESA, an ongoing prospective cohort study. Bleeding events were identified from review of hospitalization International Classification of Diseases, Ninth Revision (ICD-9), and International Classification of Diseases, Tenth Revision (ICD-10), codes, and AF from participant report, discharge diagnoses, Medicare claims data, and study ECGs performed at MESA visit 5. Separate multivariable Cox proportional hazard modeling was used to estimate hazard ratios of the association of continuous n3-FA (log eicosapentaenoic acid [EPA], log docosahexaenoic acid [DHA], log [EPA+DHA]) and incident hospitalized bleeding events and AF. Among 6546 participants, the mean age was 62.1 years and 53% were women. For incident bleeding, consistent statistically significant associations with lower rates were seen with increasing levels of EPA and EPA+DHA in unadjusted and adjusted models including medications that modulate bleeding risk (aspirin, NSAIDS, corticosteroids, and proton pump inhibitors). For incident AF, a significant association with lower rates was seen with increasing levels of DHA, but not for EPA or EPA+DHA. Conclusions In MESA, higher plasma levels of n3-FA (EPA and EPA+DHA, but not DHA) were associated with significantly fewer hospitalized bleeding events, and higher DHA levels (but not EPA or EPA+DHA) with fewer incident AF events.

Keywords: arrhythmia; atrial fibrillation; bleeding; docosahexaenoic acid; eicosapentaenoic acid; omega‐3.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Atrial Fibrillation / blood
  • Atrial Fibrillation / complications*
  • Atrial Fibrillation / ethnology
  • Biomarkers / blood
  • Ethnicity*
  • Fatty Acids, Omega-3 / blood*
  • Female
  • Follow-Up Studies
  • Hemorrhage / blood*
  • Hemorrhage / etiology
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Prospective Studies
  • United States / epidemiology


  • Biomarkers
  • Fatty Acids, Omega-3

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