Higher circulating levels of EPA, but not DHA, associated with lower MACE risk
In an observational cohort study, higher plasma levels of eicosapentaenoic acid (EPA), but not docosahexaenoic acid (DHA), were associated with a lower 10-year risk of MACE. Adjustment for DHA level increased the protective effect of higher EPA levels.
Higher docosahexaenoic acid levels lower the protective impact of eicosapentaenoic acid on long-term major cardiovascular eventsLiterature - 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
Background
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.
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Methods
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.
Outcome
The primary endpoint was the occurrence of MACE, defined as all-cause mortality, MI, stroke, or HF hospitalization, after 10 years.
Main results
- The 10-year MACE rate was associated with lower levels of EPA (unadjusted P=0.0002, adjusted P=0.0005) but not DHA (unadjusted P=0.43; adjusted P=0.52).
- Of the individual components of the primary endpoint, only all-cause mortality was associated with EPA (unadjusted P<0.0001; adjusted P=0.0003).
- Subjects in the highest quartile of EPA level showed a reduced 10-year MACE rate compared with those in the lowest EPA quartile (22.8% vs. 40.5%; unadjusted HR: 0.48; 95%CI: 0.35–0.67). Adjustment for both DHA level and significant baseline differences lowered the HR to 0.36 (95%CI: 0.22–0.58).
- For DHA, the unadjusted HR for 10-year MACE risk for the highest versus lowest quartile was not significantly different (27.6% vs. 33.6%; HR: 0.78; 95%CI: 0.56–1.01). Adjustment for EPA level resulted in a significantly higher risk of 10-year MACE (HR: 1.81; 95%CI: 1.14–2.90), but after additional adjustment for significant baseline differences, there was no difference between the highest and lowest DHA quartiles (HR: 1.37; 95%CI: 0.85–2.20).
- Subgroup analyses showed that higher levels of EPA are associated with lower 10-year MACE risk in patients with severe coronary artery disease at baseline (adjusted HR: 0.35; 95%CI: 0.18-0.68) and in patients with no, mild, or moderate coronary artery disease at baseline (adjusted HR: 0.42; 95%CI: 0.20-0.85). There were no significant associations when stratifying for prior HF, age ≥75 years, or triglycerides ≥200 mg/dL.
- Subjects with an EPA/DHA ratio >1 had a lower 10-year MACE risk compared with those who had an EPA/DHA ratio ≤1 (27.3% vs. 36.7%; adjusted HR: 0.75; 95%CI: 0.60–0.94).
Conclusion
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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