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
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.
-
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.”
Share this page with your colleagues and friends: