Omega-3 fatty acids, subclinical atherosclerosis, and cardiovascular events: Implications for primary prevention

Atherosclerosis. 2022 Jul;353:11-19. doi: 10.1016/j.atherosclerosis.2022.06.1018. Epub 2022 Jun 20.


Background and aims: High-dose eicosapentaenoic acid (EPA) therapy was beneficial in high-risk patients without clinical cardiovascular disease (CVD). Whether higher plasma levels of EPA and docosahexaenoic acid (DHA) have similar benefits in those without subclinical CVD is unclear. We aim to evaluate the interplay between plasma omega-3 fatty acids and coronary artery calcium (CAC) in relation to CVD events.

Methods: We examined 6568 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with plasma EPA and DHA levels and CAC measured at baseline. The primary outcome was incident CVD events (myocardial infarction, angina, cardiac arrest, stroke, CVD death). Hazard ratios for the primary outcome were adjusted for potential confounder using Cox regression.

Results: Mean ± SD age was 62.1 ± 10.2 years and 52.9% were females. The median follow-up time was 15.6 years. Higher loge(EPA) (adjusted hazard ratio, aHR = 0.83; 95% CI, 0.74-0.94) and loge(DHA) (aHR = 0.79; 95% CI, 0.66-0.96) were independently associated with fewer CVD events. The difference in absolute CVD event rates between lowest vs. highest EPA tertile increased at higher CAC levels. The adjusted HR for highest vs. lowest EPA tertile within CAC = 0 was 1.02 (95% CI, 0.72-1.46), CAC = 1-99 was 0.71 (95% CI, 0.51-0.99), and CAC≥100 was 0.67 (95% CI, 0.52-0.84). A similar association was seen in tertiles of DHA by CAC category.

Conclusions: In an ethnically diverse population free of clinical CVD, higher plasma omega-3 fatty acid levels were associated with fewer long-term CVD events. The absolute decrease in CVD events with higher omega-3 fatty acid levels was more apparent at higher CAC scores.

Keywords: Cardiovascular disease; Coronary artery calcium; Docosahexaenoic acid; Eicosapentaenoic acid; Primary prevention.

Publication types

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

MeSH terms

  • Aged
  • Atherosclerosis* / complications
  • Atherosclerosis* / diagnosis
  • Atherosclerosis* / prevention & control
  • Cardiovascular Diseases* / diagnosis
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / prevention & control
  • Coronary Artery Disease* / diagnosis
  • Coronary Artery Disease* / prevention & control
  • Disease Progression
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Fatty Acids, Omega-3*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Primary Prevention
  • Risk Factors


  • Fatty Acids, Omega-3
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid