Inverse association between plasma long-chain omega-3-PUFAs content and sudden cardiac death after ACS

Plasma Omega-3 Fatty Acids and the Risk of Cardiovascular Events in Patients After an Acute Coronary Syndrome in MERLIN-TIMI 36

Literature - Zelniker TA, Morrow DA, Scirica BM et al. - J Am Heart Assoc 2021, DOI: 10.1161/JAHA.120.017401

Introduction and methods

Long-chain omega-3 polyunsaturated fatty acids (PUFAs) include eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosaheaenoic acid (DHA), which are primarily obtained from marine sources. α-Linolenic acid (ALA) is obtained through plant-derived intake. Studies, both randomized controlled trials on CV markers and experimental studies [1,2], have shown many CV benefits of supplementation with omega-3-PUFAs, but clinical outcome trials have shown inconsistent findings [3-8]. In absence of supplementation, it was shown that higher omega-3-PUFAs content was associated with lower risk of CV and sudden cardiac death and weaker associated with risk of MI or stroke [9,10]. Therefore, supplementation of omega-3-PUFAs may provide benefit after ACS, when patients have increased risk of arrhythmic events.

In this study, the association between omega-3-PUFAs content and risk of CV events, including arrhythmic events, was investigated in a large clinical trial population with ACS (the MERLIN-TIMI 36 trial).

The MERLIN-TIMI 36 trial enrolled 6560 patients hospitalized with a non-ST-segment-elevation ACS within 48 hours of onset of symptoms. Plasma sample was drawn at randomization. The present metabolomics array study was a case-cohort study and included 2407 patients (203 subjects with CV death, 325 patients with MI, 271 with ventricular tachycardia, and 161 with AF events as cases and 1612 event-free subjects as controls). Baseline plasma omega-3-PUFAs composition including ALA and the long-chain marine-based omega-3-PUFAs EPA, DPA and DHA was assessed by gas chromatography. The composition of omega-3-PUFAs is expressed as the percentage of the total fatty acid content by weight.

Main results

  • Omega-3-PUFAs comprised 3.8% of all fatty acids. Among the omega-3-PUFAs, DHA contributed 52.5% to the total omega-3 content, followed by EPA (19.6%), ALA (14.4%) and DPA (13.5%).
  • Higher plasma content of the long-chain omega-3-PUFAs was associated with reduced CV death (adjusted OR per 1 SD: 0.82, 95%CI: 0.68-0.98), which appeared to be driven by 27% lower risk of sudden cardiac death (adjusted OR per 1 SD: 0.73, 95%CI: 0.55-0.97).
  • The magnitude of the relationship was not as strong for ALA (adjusted OR per 1 SD: 0.92, 95%CI:0.74-1.14) compared to the long chain omega-3-PUFAs.
  • There was a stepwise decrease in risk of sudden cardiac death with higher long-chain omega-3-PUFA content (Ptrend=0.025).
  • A consistent, nearly linear decrease in the probability of sudden cardiac death was observed for increasing proportions of the long-chain omega-3-PUFAs by adjusted natural cubic regression splines.
  • No association was found for any of the omega-3-PUFAs with any of the other outcomes of interest, including MI, atrial fibrillation, or early post-ACS ventricular tachycardia.


In this case-control study using data of a large clinical trial population of patients after ACS, higher content of plasma long-chain omega-3-PUFAs was associated with reduced risk of sudden cardiac death independent of traditional risk factors.


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Find this article online at J Am Heart Assoc

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