Association between ratio of serum eicosapentaenoic acid to arachidonic acid and risk of cardiovascular disease: the Hisayama Study

Atherosclerosis. 2013 Dec;231(2):261-7. doi: 10.1016/j.atherosclerosis.2013.09.023. Epub 2013 Oct 5.


Objective: We examined the association between the ratio of serum eicosapentaenoic acid to arachidonic acid (EPA/AA) or the docosahexaenoic acid (DHA)/AA and the development of cardiovascular disease in a general Japanese population.

Methods: A total of 3103 community-dwelling Japanese individuals aged ≥40 years were followed up for an average of 5.1 years. Serum EPA/AA ratios were categorized into quartiles. The risk estimates were computed using a Cox proportional hazards model.

Results: During the follow-up period, 127 subjects experienced cardiovascular events. Age- and sex-adjusted incidence rates of cardiovascular disease increased with lower serum EPA/AA ratios in individuals with high-sensitivity C-reactive protein (HS-CRP) of ≥1.0 mg/L (p for trend = 0.006), whereas no clear association was observed in those with HS-CRP of <1.0 mg/L (p for trend = 0.27). The multivariable-adjusted risk of cardiovascular disease increased significantly, by 1.52 times (95% confidence interval 1.12-2.04) per 0.20 decrement in serum EPA/AA ratio in subjects with HS-CRP of ≥1.0 mg/L. A lower serum EPA/AA ratio was significantly associated with an increased risk of coronary heart disease, but there was no evidence of an association with stroke. The magnitude of the influence of the serum EPA/AA ratio on the cardiovascular risk increased significantly with elevating HS-CRP levels taken as a continuous variable (p for heterogeneity = 0.007). However, no such association was observed for DHA/AA ratio.

Conclusion: Our findings suggest that a lower serum EPA/AA ratio is associated with a greater risk of cardiovascular disease, especially coronary heart disease, among subjects with higher HS-CRP levels in the general Japanese population.

Keywords: AA; CI; Cardiovascular disease; DHA; EPA; Eicosapentaenoic acid; HDL; HR; HS-CRP; High sensitivity C-reactive protein; PUFA; Prospective cohort study; arachidonic acid; confidence interval; docosahexaenoic acid; eicosapentaenoic acid; hazard ratio; high-density lipoprotein; high-sensitivity C-reactive protein; polyunsaturated fatty acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arachidonic Acid / blood*
  • Biomarkers / blood*
  • Cardiovascular Diseases / blood*
  • Coronary Disease / blood*
  • Eicosapentaenoic Acid / blood*
  • Fatty Acids / blood
  • Female
  • Follow-Up Studies
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Proportional Hazards Models
  • Risk Factors


  • Biomarkers
  • Fatty Acids
  • Arachidonic Acid
  • Eicosapentaenoic Acid