Association of omega-3 fatty acids with improved prognosis after myocardial infarction: the role of red cell distribution width—an EHR study

TL;DR

Higher levels of omega-3 fatty acids are linked to lower red cell distribution width (RDW) and better survival after heart attacks, suggesting RDW may mediate the protective effects of omega-3s.

Contribution

This study is the first to investigate the mediating role of RDW in the relationship between omega-3 fatty acids and post-MI prognosis using electronic health records.

Findings

Dietary and blood omega-3 fatty acids are inversely associated with RDW in post-MI patients.

RDW partially mediates the relationship between blood omega-3 biomarkers and 5-year mortality.

Higher omega-3 levels are associated with improved prognosis after myocardial infarction.

Abstract

A high red cell distribution width (RDW) reflects an inflammatory state and abnormal red blood cell function, which has been associated with poor prognosis in patients with prior myocardial infarction (MI). Omega-3 fatty acids (n-3 FAs) are inversely related to RDW in the general population but have not been studied in post-MI patients. We aimed to explore associations between n-3 FAs, RDW and prognosis in individuals with prior MI by analyzing electronic health records (EHRs).

This study analyzed two cohorts from the National Health and Nutrition Examination Survey (NHANES) and the UK Biobank databases. In the NHANES cohort, associations between dietary n-3 FA intake, RDW, and mortality were explored using multivariable Cox proportional hazards regression and restricted cubic splines (RCSs). In the UK Biobank cohort, associations between n-3 blood biomarkers, RDW, and 5 year mortality were examined through Spearman correlations, multivariate Cox proportional hazards regression, RCSs, and Karlson–Holm–Breen (KHB) mediation analysis. Finally, in the internal dataset, this study explored the potential role of RDW in the association between plasma eicosapentaenoic acid (EPA) level and the 6 month major adverse cardiovascular events (MACE) incidence using KHB mediation analysis.

RDW was positively associated with mortality in both cohorts from public databases. Dietary n-3 FA intake were inversely associated with RDW. Blood n-3 biomarkers were significantly inversely associated with RDW and 5 year mortality. Moreover, RDW appears to partially mediate the relationship between n-3 blood biomarkers and 5 year mortality. The internal dataset also suggested that RDW may modestly influence the association between plasma EPA level and 6-month MACE incidence.

Both dietary and blood levels of n-3 FAs are negatively associated with RDW in individuals with prior MI. The findings are consistent with the hypothesis that RDW may play a potential mediating role in the association between n-3 FAs and mortality risk. Given that a high RDW signifies an inflammatory state and abnormal erythrocyte function, the observed association between higher blood levels of n-3 FAs and improved prognosis after MI aligns with potential underlying mechanisms: attenuated inflammation and enhanced erythrocyte function.

The online version contains supplementary material available at 10.1186/s40001-026-03909-9.

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