Eicosapentaenoic acid ethyl ester, cardiac metabolomic and lipidomic signatures, and cardioprotection in myocardial infarction

In this issue, we highlight a recent translational study from the group of Prof. Vilahur at the Research Institute Sant Pau (IR Sant Pau) published in Eur Heart J exploring whether eicosapentaenoic acid ethyl ester (EPA E) can directly protect the myocardium in the setting of hypertriglyceridaemia and acute myocardial infarction.

Why this paper matters

Hypertriglyceridaemia is highly prevalent in Europe and confers substantial residual cardiovascular risk, even when LDL C is well controlled. While REDUCE IT showed that EPA E reduces major adverse cardiovascular events in statin treated patients with hypertriglyceridaemia, the mechanisms underlying these benefits, and whether EPA E confers direct cardioprotection at the time of myocardial infarction, have remained unclear.

Using a diet induced rat model of hypertriglyceridaemia associated with an atherogenic lipid profile and left ventricular dysfunction, Alcover et al. assessed the impact of a human equivalent 2 week course of oral EPA E before transient LAD occlusion and 24 hour reperfusion. The main findings of the authors are the following:
- EPA E reduced circulating triglycerides and favourably remodelled the atherogenic lipid profile, while preventing hypertriglyceridaemia induced LV impairment before MI.
- EPA E–treated animals developed significantly smaller infarcts than both untreated hypertriglyceridaemic and control diet groups, with a trend towards lower MI related mortality, independently of circulating triglyceride levels.
- Cardioprotection was linked to reduced cardiolipotoxicity and apoptosis, less oxidative stress and mitochondrial dysfunction, and attenuated fibrosis in the infarcted myocardium.
- EPA E promoted a pro resolving inflammatory milieu (fewer neutrophils/macrophages, more CD206⁺ macrophages, higher resolvin E1 and IL 4) and an EPA enriched lipidomic profile with a higher EPA/AA ratio and improved systemic metabolomic signatures.

Together, these data provide mechanistic support for the benefits observed in clinical EPA E trials and reinforce its potential as an adjunct cardiometabolic therapy for secondary prevention in high risk patients with hypertriglyceridaemia and established ASCVD.