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J Clin Lipidol. 2018 May - Jun;12(3):718-727.e6. doi: 10.1016/j.jacl.2018.02.010. Epub 2018 Mar 2.

Erythrocyte long-chain omega-3 fatty acid levels are inversely associated with mortality and with incident cardiovascular disease: The Framingham Heart Study.

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Department of Internal Medicine, Sanford School of Medicine, University of South Dakota; and OmegaQuant Analytics, LLC, Sioux Falls, SD, USA. Electronic address:
Department of Mathematics & Statistics, Dordt College, Sioux Center, IA, USA.
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
National Heart Lung and Blood Institute's, Boston University's Framingham Heart Study, Framingham, MA, USA; Departments of Cardiology and Preventive Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.



The extent to which omega-3 fatty acid status is related to risk for death from any cause and for incident cardiovascular disease (CVD) remains controversial.


To examine these associations in the Framingham Heart Study.


Prospective and observational.


Framingham Heart Study Offspring cohort.


The exposure marker was red blood cell levels of eicosapentaenoic and docosahexaenoic acids (the Omega-3 Index) measured at baseline. Outcomes included mortality (total, CVD, cancer, and other) and total CVD events in participants free of CVD at baseline. Follow-up was for a median of 7.3 years. Cox proportional hazards models were adjusted for 18 variables (demographic, clinical status, therapeutic, and CVD risk factors).


Among the 2500 participants (mean age 66 years, 54% women), there were 350 deaths (58 from CVD, 146 from cancer, 128 from other known causes, and 18 from unknown causes). There were 245 CVD events. In multivariable-adjusted analyses, a higher Omega-3 Index was associated with significantly lower risks (P-values for trends across quintiles) for total mortality (P = .02), for non-CVD and non-cancer mortality (P = .009), and for total CVD events (P = .008). Those in the highest (>6.8%) compared to those in the lowest Omega-3 Index quintiles (<4.2%) had a 34% lower risk for death from any cause and 39% lower risk for incident CVD. These associations were generally stronger for docosahexaenoic acid than for eicosapentaenoic acid. When total cholesterol was compared with the Omega-3 Index in the same models, the latter was significantly related with these outcomes, but the former was not.


Relatively short follow-up time and one-time exposure assessment.


A higher Omega-3 Index was associated with reduced risk of both CVD and all-cause mortality.


Docosahexaenoic acid; Eicosapentaenoic acid; Epidemiology; Omega-3 fatty acids; Prospective cohort study

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