Harris · Journal of clinical lipidology 2018 · prospective cohort study · n=2500

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

Cited 139 times in the scientific literature.

Level 3 - non-randomized controlled study

Prospective observational cohort study

PubMed 29559306 · doi:10.1016/j.jacl.2018.02.010 · record verified 2026-08-26

What was done

The authors evaluated the prospective association between red blood cell eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels (the Omega-3 Index) and clinical outcomes in 2,500 participants from the Framingham Heart Study Offspring cohort (mean age 66 years, 54% women) who were free of cardiovascular disease (CVD) at baseline. Outcomes included total mortality, cause-specific mortality (CVD, cancer, other), and incident CVD events over a median follow-up of 7.3 years. Multivariable Cox proportional hazards models adjusted for 18 demographic, clinical, therapeutic, and cardiovascular risk variables.

What was found

During follow-up, 350 deaths occurred (58 CVD, 146 cancer, 128 other known causes, 18 unknown causes) along with 245 incident CVD events. In multivariable-adjusted trend analyses across quintiles, higher Omega-3 Index was significantly associated with lower total mortality (P = .02), non-CVD/non-cancer mortality (P = .009), and total CVD events (P = .008). Comparing the highest quintile (>6.8%) to the lowest quintile (<4.2%), participants had a 34% lower risk of death from any cause and a 39% lower risk of incident CVD. Associations were stronger for DHA than for EPA. In comparative models, the Omega-3 Index remained significantly related to these outcomes, whereas total cholesterol did not.

Why it matters

This study provides prospective evidence from a well-characterized community cohort that higher objective biomarker levels of circulating omega-3 fatty acids are independently associated with lower cardiovascular morbidity and all-cause mortality.

Limits

The study is observational and cannot establish causality. Omega-3 levels were assessed from a single baseline blood sample rather than serial measurements, and the median follow-up duration (7.3 years) was relatively short. Generalizability may be limited to older populations similar to the Framingham Offspring cohort.

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