Plasma phospholipid long-chain ω-3 fatty acids and total and cause-specific mortality in older adults: a cohort study

Ann Intern Med. 2013 Apr 2;158(7):515-25. doi: 10.7326/0003-4819-158-7-201304020-00003.

Abstract

Background: Long-chain ω-3 polyunsaturated fatty acids (ω3-PUFAs), including eicosapentaenoic acid (EPA) (20:5ω-3), docosapentaenoic acid (DPA) (22:5ω-3), and docosahexaenoic acid (DHA) (22:6ω-3), have been shown to reduce cardiovascular risk, but effects on cause-specific and total mortality and potential dose-responses remain controversial. Most observational studies have assessed self-reported dietary intake and most randomized trials have tested effects of adding supplements to dietary intake and evaluated secondary prevention, thus limiting inference for dietary ω3-PUFAs or primary prevention.

Objective: To investigate associations of plasma phospholipid EPA, DPA, DHA, and total ω3-PUFA levels with total and cause-specific mortality among healthy older adults not receiving supplements.

Design: Prospective cohort study.

Setting: 4 U.S. communities.

Participants: 2692 U.S. adults aged 74 years (±5 years) without prevalent coronary heart disease (CHD), stroke, or heart failure at baseline.

Measurements: Phospholipid fatty acid levels and cardiovascular risk factors were measured in 1992. Relationships with total and cause-specific mortality and incident fatal or nonfatal CHD and stroke through 2008 were assessed.

Results: During 30 829 person-years, 1625 deaths (including 570 cardiovascular deaths), 359 fatal and 371 nonfatal CHD events, and 130 fatal and 276 nonfatal strokes occurred. After adjustment, higher plasma levels of ω3-PUFA biomarkers were associated with lower total mortality, with extreme-quintile hazard ratios of 0.83 for EPA (95% CI, 0.71 to 0.98; P for trend = 0.005), 0.77 for DPA (CI, 0.66 to 0.90; P for trend = 0.008), 0.80 for DHA (CI, 0.67 to 0.94; P for trend = 0.006), and 0.73 for total ω3-PUFAs (CI, 0.61 to 0.86; P for trend < 0.001). Lower risk was largely attributable to fewer cardiovascular than noncardiovascular deaths. Individuals in the highest quintile of phospholipid ω3-PUFA level lived an average of 2.22 more years (CI, 0.75 to 3.13 years) after age 65 years than did those in the lowest quintile.

Limitation: Temporal changes in fatty acid levels and misclassification of causes of death may have resulted in underestimated associations, and unmeasured or imperfectly measured covariates may have caused residual confounding.

Conclusion: Higher circulating individual and total ω3-PUFA levels are associated with lower total mortality, especially CHD death, in older adults.

Primary funding source: National Institutes of Health.

Publication types

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

MeSH terms

  • Aged
  • Biomarkers / blood
  • Cause of Death*
  • Coronary Disease / mortality
  • Coronary Disease / prevention & control
  • Diet Records
  • Docosahexaenoic Acids / blood
  • Eicosapentaenoic Acid / blood
  • Fatty Acids, Omega-3 / blood*
  • Fatty Acids, Unsaturated / blood
  • Feeding Behavior*
  • Female
  • Humans
  • Male
  • Prospective Studies
  • Risk Assessment
  • Stroke / mortality
  • Stroke / prevention & control

Substances

  • Biomarkers
  • Fatty Acids, Omega-3
  • Fatty Acids, Unsaturated
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • docosapentaenoic acid