Physicians' Academy for Cardiovascular Education

Higher circulating levels of EPA, but not DHA, associated with lower MACE risk

Higher docosahexaenoic acid levels lower the protective impact of eicosapentaenoic acid on long-term major cardiovascular events

Literature - Le VT, Knight S, Watrous JD, et al - Front Cardiovasc Med. 2023 Aug 23;10:1229130. doi: 10.3389/fcvm.2023.1229130

Introduction and methods


Several meta-analyses have shown that omega-3 fatty acid supplements do not reduce the risk of MACE [1-5]. More recent meta-analyses have demonstrated inverse relationships of both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) circulating levels and supplementation dose with mortality and CV events [6,7]. Remarkably, 5 contemporary RCTs indicated that supplementation with only EPA reduces the occurrence of MACE, while the combination of EPA and DHA does not [8-12].

Aim of the study

The authors evaluated the associations between EPA and DHA levels and long-term MACE, and the potential interaction between EPA and DHA in these associations.



For this prospective observational cohort study, data were collected from 987 randomly selected individuals enrolled in the INSPIRE Biobank Registry who underwent their first coronary angiography at a center affiliated with Intermountain Healthcare, an American not-for-profit healthcare system, from January 1994 through December 2012. EPA and DHA plasma levels were assessed in blood samples taken at the time of the coronary angiography. Mean ± SD follow-up time was 12 ± 5 years. The significance level was set at 0.01.


The primary endpoint was the occurrence of MACE, defined as all-cause mortality, MI, stroke, or HF hospitalization, after 10 years.

Main results


This prospective observational cohort study of individuals undergoing coronary angiography showed that higher plasma levels of EPA, but not DHA, were associated with a lower 10-year risk of MACE. Adjustment for DHA level increased the estimated protective effect of higher EPA levels. In addition, an EPA/DHA ratio >1 was associated with a lower 10-year MACE risk compared with an EPA/DHA ratio ≤1. According to the authors, “these observations are consistent with a proposed anti-inflammatory/membrane-stabilizing effect of EPA, which, in part, is neutralized by increasing levels of DHA.”


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Find this article online at Front Cardiovasc Med.

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