Dariush Mozaffarian, MD, DrPH; Rozenn N. Lemaitre, PhD, MPH; Irena B. King, PhD; Xiaoling Song, PhD; Hongyan Huang, PhD; Frank M. Sacks, MD; Eric B. Rimm, ScD; Molin Wang, PhD; David S. Siscovick, MD, MPH
Acknowledgment: The authors thank all CHS participants, CHS investigators, and institutions (see www.chs-nhlbi.org); Donna Spiegelman, ScD, for invaluable guidance on the analyses of life-years lost and measurement error correction; and Fumiaki Imamura, PhD, for assistance with performing regression dilution bias and measurement error correction analyses.
Grant Support: This investigation was supported by the National Heart, Lung, and Blood Institute (NHLBI) and the Office of Dietary Supplements of the National Institutes of Health (R01-HL-085710). The CHS was supported by NHLBI contracts HHSN268201200036C, N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, and N01-HC-45133 and NHLBI grant HL080295, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the National Institute on Aging. See www.chs-nhlbi.org/pi.htm.
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M12-1795.
Reproducible Research Statement: Study protocol: Available from Dr. Mozaffarian (e-mail, firstname.lastname@example.org). Statistical code: Not available. Data set: Not available from the authors. Interested readers can review the CHS procedures for outside investigators to obtain and analyze data (www.chs-nhlbi.org/CHS_DistribPolicy.htm).
Requests for Single Reprints: Dariush Mozaffarian, MD, DrPH, Harvard School of Public Health, 665 Huntington Avenue, Building 2-319, Boston, MA 02115; e-mail, email@example.com.
Current Author Addresses: Dr. Mozaffarian: Harvard School of Public Health, 665 Huntington Avenue, Building 2-319, Boston, MA 02115.
Drs. Lemaitre and Siscovick: Cardiovascular Health Research Unit, 1730 Minor Avenue, Suite 1360, Seattle, WA 98101.
Dr. King: University of New Mexico, 2703 Frontier Avenue NE, Suite 190, Albuquerque, NM 87131.
Dr. Song: Fred Hutchinson Cancer Research Center, M5-A864, 1100 Fairview Avenue N, Seattle, WA 98109.
Drs. Huang, Sacks, Rimm, and Wang: Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115.
Author Contributions: Conception and design: D. Mozaffarian, I.B. King, D.S. Siscovick.
Analysis and interpretation of the data: D. Mozaffarian, X. Song, H. Huang, F.M. Sacks, M. Wang, D.S. Siscovick.
Drafting of the article: D. Mozaffarian.
Critical revision of the article for important intellectual content: D. Mozaffarian, R.N. Lemaitre, H. Huang, F.M. Sacks, E.B. Rimm, D.S. Siscovick.
Final approval of the article: D. Mozaffarian, R.N. Lemaitre, I.B. King, X. Song, H. Huang, F.M. Sacks, M. Wang, D.S. Siscovick.
Statistical expertise: D. Mozaffarian, H. Huang, M. Wang.
Obtaining of funding: D. Mozaffarian, R.N. Lemaitre, I.B. King, D.S. Siscovick.
Administrative, technical, or logistic support: X. Song.
Collection and assembly of data: D. Mozaffarian, X. Song, D.S. Siscovick.
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.
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.
Prospective cohort study.
4 U.S. communities.
2692 U.S. adults aged 74 years (±5 years) without prevalent coronary heart disease (CHD), stroke, or heart failure at baseline.
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.
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.
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.
Higher circulating individual and total ω3-PUFA levels are associated with lower total mortality, especially CHD death, in older adults.
National Institutes of Health.
Mozaffarian D, Lemaitre RN, King IB, Song X, Huang H, Sacks FM, et al. Plasma Phospholipid Long-Chain ω-3 Fatty Acids and Total and Cause-Specific Mortality in Older Adults: A Cohort Study. Ann Intern Med. 2013;158:515–525. doi: 10.7326/0003-4819-158-7-201304020-00003
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Published: Ann Intern Med. 2013;158(7):515-525.
Cardiology, Coronary Risk Factors, Geriatric Medicine, Prevention/Screening.
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