J Am Heart Assoc. , 2021, Apr 20;10(8):e017401. doi: 10.1161/JAHA.120.017401.

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

Zelniker TA Morrow DA Scirica BM et al.

Abstract

Background Plasma omega-3 polyunsaturated fatty acids (ω3-PUFAs) have been shown to be inversely correlated with the risk of cardiovascular death in primary prevention. The risk relationship in the setting of an acute coronary syndrome is less well established. Methods and Results Baseline plasma ω3-PUFA composition (α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) was assessed through gas chromatography with flame ionization detection in a case-cohort study involving 203 patients with cardiovascular death, 325 with myocardial infarction, 271 with ventricular tachycardia, and 161 with atrial fibrillation, and a random sample of 1612 event-free subjects as controls from MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation-Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 36), a trial of patients hospitalized with non-ST-segment-elevation -acute coronary syndrome. After inverse-probability-weighted multivariable adjustment including all traditional risk factors, a higher relative proportion of long-chain ω3-PUFAs (eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid) were associated with 18% lower odds of cardiovascular death (adjusted [adj] odds ratio [OR] per 1 SD, 0.82; 95% CI, 0.68-0.98) that was primarily driven by 27% lower odds of sudden cardiac death (adj OR per 1 SD, 0.73; 95% CI, 0.55-0.97). Long-chain ω3-PUFA levels in the top quartile were associated with 51% lower odds of cardiovascular death (adj OR 0.49; 95% CI, 0.27-0.86) and 63% lower odds of sudden cardiac death (adj OR, 0.37; 95% CI, 0.16-0.56). An attenuated relationship was seen for α-linolenic acid and subsequent odds of cardiovascular (adj OR, 0.92; 95% CI, 0.74-1.14) and sudden cardiac death (adj OR, 0.91; 95% CI, 0.67-1.25). No significant relationship was observed between any ω3-PUFAs and the odds of cardiovascular death unrelated to sudden cardiac death, myocardial infarction, atrial fibrillation, or early post-acute coronary syndrome ventricular tachycardia. Conclusions In patients after non-ST-segment-elevation-acute coronary syndrome, plasma long-chain ω3-PUFAs are inversely associated with lower odds of sudden cardiac death, independent of traditional risk factors and lipids.

 

Link to Full Text

Key Points

In the current study, although the individual subtypes of long-chain ω3-PUFAs showed a directionally concordant relationship with sudden cardiac death, the relationship appeared to be more attenuated for ALA. However, the proportion of omega-3 fatty acids represented by ALA, as with the other subtypes, was relatively small and therefore underpowered. ALA also serves as a biologic precursor to the long chain ω3-PUFAs; therefore, marine-sourced intake is not required to increase long-chain ω3-PUFA content.

The relationship between ALA and risk of sudden cardiac death appeared stronger when assessed in fasting samples. Nonetheless, evidence on ALA has been more limited, and previous observational studies and clinical trials provide conflicting evidence on its protective effects.

In patients with non–ST‐segment–elevation–acute coronary syndromes, a higher relative proportion of long‐chain omega‐3 polyunsaturated fatty acid (ω3‐PUFAs) content in plasma is associated with lower odds of cardiovascular and sudden cardiac death, independent of traditional risk factors and lipids. Although directional consistency was seen across the ω3 subtypes, the magnitude of the effect appeared to be greatest for the long‐chain marine‐based ω3‐PUFAs including docosahexaenoic acid, docosapentaenoic acid, and eicosapentaenoic acid.

These data lend support to the theory that certain types of ω3 supplementation may reduce the risk of adverse cardiovascular outcomes in higher‐risk populations.