Introduction:
Long-chain n-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-arrhythmic effects in experimental studies and blood levels of EPA + DHA, an objective marker of intake, have been associated with lower risk of sudden cardiac death (SCD) in healthy populations. However, data from observational studies and clinical trials of n-3 PUFAs in secondary prevention have been mixed.
Methods:
We conducted a nested, case-control study among individuals from 6 prospective cohort studies. RBC levels of α-linolenic acid (ALA), EPA, docosapentaenoic acid (DPA), and DHA were measured in 442 cases of SCD and 852 controls matched on age, sex, race, smoking status, fasting status and prevalent and incident CVD using risk-set sampling. The Omega-3 Index was estimated as EPA + DHA. Multivariable conditional logistic regression was used to estimate the relative risk (RR) separately in each cohort. The RRs were combined using random effect meta-analyses and stratified by presence of absence of known CVD prior to SCD.
Results:
In this population, the mean age was 64 years, 51% were women and 41% had prior CVD. Higher EPA and DHA levels, as summarized by the Omega-3 Index, were associated with lower risk of SCD in the entire population (Table). Compared to the lowest quintile, the RR in the highest quintile of the Omega-3 Index was 0.40 (95%CI, 0.21-0.77; P, trend= 0.04). When stratified by history of prior CVD, this association was restricted to individuals without prior CVD (Table, P, trend = 0.03). Neither DPA nor ALA was associated with risk of SCD in those with or without CVD.
Conclusions:
In this prospective nested, case-control study, the inverse association between long-chain n-3 PUFAs and SCD was limited to individuals without prior CVD. These data suggest that the utility of n-3 PUFAs as markers of SCD and/or as preventative dietary supplements may be greater in a primary prevention population.
Risk of Out-of-Hospital Sudden Cardiac Death in Users of Domperidone, Proton Pump Inhibitors, or Metoclopramide: A Population-Based Nested Case-Control Study