Serum Long-Chain n-3 Polyunsaturated Fatty Acids, Mercury, and Risk of Sudden Cardiac Death in Men: A Prospective Population-Based Study

Jyrki K Virtanen,Tomi-Pekka Tuomainen,Sari Voutilainen,Jaakko Mursu,Jari A Laukkanen,Ann M Moormann

doi:10.1371/journal.pone.0041046

Jyrki K Virtanen, Tomi-Pekka Tuomainen + Show 4 more

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https://doi.org/10.1371/journal.pone.0041046

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Journal: PloS one	Publication Date: Jul 16, 2012
Citations: 73	License type: CC BY 4.0

Affiliation: University of Eastern Finland

Abstract

ObjectivesFish consumption has been associated with reduced risk of cardiovascular diseases (CVD), especially sudden cardiac death (SCD). Fish is the major source of long-chain n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid and docosahexaenoic acid. It is also a major source of methylmercury, which was associated with increased risk of CVD in this study population. Impact of interaction between long-chain n-3 PUFA and methylmercury on the SCD risk is unknown.MethodsA total of 1857 men from the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor study, aged 42–60 years and free of CVD at baseline in 1984–1989, were studied. Serum long-chain n-3 PUFA was used as the marker for long-chain n-3 PUFA intake and hair mercury as the marker for mercury exposure.ResultsDuring the mean follow-up of 20.1 years, 91 SCD events occurred. In the multivariate Cox proportional hazards regression models, serum long-chain n-3 PUFA concentration was not associated with the risk of SCD until hair mercury was accounted for; then the hazard ratio (HR) in the highest vs. lowest tertile was 0.54 [95% confidence interval (CI) 0.32 to 0.91, p for trend = 0.046]. When the analyses were stratified by hair mercury content, among those with lower hair mercury, each 0.5 percentage unit increase in the serum long-chain n-3 PUFA was associated with HR of 0.77 (95% CI 0.64 to 0.93), whereas no association was seen among those with higher hair mercury (p for interaction = 0.01). Among the individual long-chain n-3 PUFA, docosahexaenoic acid was most strongly associated with the risk.ConclusionHigh exposure to mercury may reduce the benefits of long-chain n-3 PUFA on SCD.

Highlights

The benefits of fish consumption have been most strongly observed with reduction in fatal coronary heart disease (CHD) or sudden cardiac death (SCD) [1]
In the multivariate Cox proportional hazards regression models, serum long-chain n-3 polyunsaturated fatty acids (PUFA) concentration was not associated with the risk of SCD until hair mercury was accounted for; the hazard ratio (HR) in the highest vs. lowest tertile was 0.54 [95% confidence interval (CI) 0.32 to 0.91, p for trend = 0.046]
When the analyses were stratified by hair mercury content, among those with lower hair mercury, each 0.5 percentage unit increase in the serum long-chain n-3 PUFA was associated with HR of 0.77, whereas no association was seen among those with higher hair mercury (p for interaction = 0.01)

Summary

Introduction

The benefits of fish consumption have been most strongly observed with reduction in fatal coronary heart disease (CHD) or sudden cardiac death (SCD) [1]. As SCD is often preceded by ventricular arrhythmia [2], this has led to the hypothesis that longchain n-3 polyunsaturated fatty acids (PUFA) from fish may have an antiarrhythmic effect. This hypothesis is supported by animal and in vitro studies [3,4,5]. In observational studies in humans, consumption of fish or long-chain n-3 PUFA from fish, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has been associated with markedly reduced risk of SCD in participants without history of CHD [6,7,8,9] and in a general population [10], not all studies have found an association [11]. Benefits have not been observed in all trials, [15,16]

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