Elsevier

Resuscitation

Volume 78, Issue 3, September 2008, Pages 258-264
Resuscitation

Clinical paper
Low levels of cellular omega-3 increase the risk of ventricular fibrillation during the acute ischaemic phase of a myocardial infarction

https://doi.org/10.1016/j.resuscitation.2008.04.007Get rights and content

Summary

Aim of the study

Animal studies have demonstrated evidence of an anti-arrhythmic effect of marine n-3 fatty acids (FAs). In humans the same mechanism may explain the observed reduction in sudden cardiac death (SCD) associated with intake of fish. Whether high levels of n-3 FAs could protect against ventricular fibrillation (VF) during the acute ischaemic phase of a myocardial infarction (MI) is, however, not known.

Materials and methods

We measured red blood cell content of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) expressed as a percentage of total FAs (the omega-3 index) at admission in 460 patients hospitalised with an acute coronary syndrome. Out of 265 patients suffering their first MI, 10 (cases) experienced an episode of VF during the initial 6 h of symptom onset. The omega-3 index of these patients was compared to that of 185 first-MI patients (controls) free of VF for at least 30 days post-admission.

Results

The median value of the omega-3 index in the VF cases was 4.88% as compared to 6.08% in the controls (p = 0.013). After adjustment for age, sex, ejection fraction, high-sensitivity C-reactive protein, use of beta-blocker, differences of infarct characteristics and previous angina pectoris, a 1% increase of the omega-3 index was associated with a 48% reduction in risk of VF (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.28–0.96; p = 0.037).

Conclusion

Our study supports an anti-arrhythmic effect of n-3 FAs through their incorporation into myocardial cell membranes, reducing the risk of VF during ischaemia.

Introduction

Despite significant progress in the understanding and treatment of heart diseases, sudden cardiac death (SCD) still remains a major cause of death in industrialised countries. Incidence rates ranging from 36 to 128 per 100,000 inhabitants per year have been reported,1 increasing with age and being more frequent in men than in women.2 60–80% of sudden deaths are cardiac in origin, primarily due to underlying coronary artery disease (CAD) with acute myocardial ischaemia.2, 3, 4 With the possible exception of high-sensitivity C-reactive protein (hsCRP)5 and a history of familial sudden death,6 traditional clinical and biochemical risk factors for atherosclerosis and myocardial infarction (MI) do not seem to explain the risk of SCD. A recent meta-analysis on risk factors for ventricular fibrillation (VF), the most prevalent mechanism of SCD, could only demonstrate ST-elevation and time from onset of symptoms as independent risk factors for VF during the course of an acute MI.7 Previous studies have also indicated a greater risk associated with occlusion of the left coronary artery as compared to the right coronary artery,8 and a protective effect of pre-infarction angina pectoris9, 10 and use of beta-blocker.11 Most of these identified risk factors are, however, un-modifiable characteristics of the actual MI and not useful for risk stratification prior to the event. The overall survival rate of SCD is only 6–23%,12 and in more than half of the cases, the first symptom of CAD.3 Accordingly, better methods of identifying individuals at risk, prior to their MI, are critically important for reducing the incidence of this devastating event.

Epidemiological studies and interventional trials have revealed a protective effect from fish on risk of fatal CAD.13 Increasing fish intake,14 supplementation with fish-oil capsules,15 and elevated blood levels of n-3 fatty acids (FAs)16, 17 have all been related to a reduced incidence of cardiac death. The proportionately larger decrease in risk of SCD as compared to total cardiac death and non-fatal MI seen in the GISSI-Prevenzione study,15 has suggested that fish oil might have anti-arrhythmic properties, protecting against serious ventricular arrhythmias during the course of a MI.

Supplementation with fish oil has been found to enrich myocyte membranes with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).18, 19, 20 The favourable effects on the electrophysiological properties of myocardial cells (e.g. increased electrical stabilisation21, 22, 23) are thought to be a result of this altered membrane composition of FAs. According to this hypothesis, the level of EPA and DHA in myocyte membranes could provide information on the risk of SCD. As opposed to other established risk factors, this could also be modified. Direct measurement of FAs in myocardial biopsies is clearly not an option. Both Harris et al.18 and Owen et al.19 have, however, shown that red blood cell (RBC) EPA + DHA (expressed as weight percentage of total FAs; hereafter termed the omega-3 index) can serve as a surrogate of cardiac omega-3 FA content.

The aim of our study was to test the hypothesis that patients experiencing VF during the acute ischaemic phase of their MI, had a lower omega-3 index than MI patients free of arrhythmia.

Section snippets

Study subjects

This study was performed at Stavanger University Hospital, Norway, as part of the Risk factors in Acute Coronary Syndrome (RACS) study, designed to identify early risk markers for development of troponin-T (TnT)-positive coronary events following hospitalisation with chest pain or otherwise suspected acute coronary syndrome (ACS). The only exclusion criteria were previous inclusion in the same study and unwillingness to participate.

Between November 2002 and October 2003, 871 patients over the

Patient characteristics

Only 1 out of 10 case patients had any previous evidence of angina pectoris; for the remaining cases this dramatic event of SCA appeared during their initial presentation of CAD. Except for one patient who died from a non-arrhythmic cardiac cause 7 days after hospitalisation, all cases survived until discharge. One non-sudden cardiac death also appeared among controls during hospitalisation. The only statistically significant differences between the 10 cases and the 185 control patients were in

Discussion

In our study we have demonstrated a lower level of the omega-3 index in patients suffering a VF during the acute ischaemic phase of their MI as compared to MI-patients without such an event. This supports previous observations of a reduced risk of fatal CAD associated with high intake of fish or fish-oil supplements.13 After adjustment for other potential predictors of risk, our analyses suggest a 48% (95% CI 4–72%) reduction in risk of VF associated with an increase of 1% of the omega-3 index.

Conclusion

Our study supports a protective effect of n-3 FAs against VF during the acute ischaemic phase of a MI. If our results are verified in larger studies, recommendations of increased intake of n-3 FAs could reduce the incidence of SCD, with a number of lives being saved every year.

Conflict of interest statement

The analyses of the omega-3 index are performed by William S. Harris who is a consultant to companies with interests in omega-3 fatty acids, including Reliant Pharmaceuticals, Monsanto Company, and OmegaMetrix, LLC. There are otherwise no financial or other relationships associated with the manuscript that might lead to a conflict of interest.

Acknowledgment

The main author was supported with grants from the Regional Health Authorities in Western Norway.

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    A Spanish translated version of the summary of this article appears as Appendix in the final online version at doi:10.1016/j.resuscitation.2008.04.007.

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