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. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00099788.