Association between mitochondrial DNA copy number and sudden cardiac death: Findings from the Atherosclerosis Risk in Communities study (ARIC)

Authors

Yiyi Zhang, Welch Center for Prevention Epidemiology and Clinical Research
Eliseo Guallar, Welch Center for Prevention Epidemiology and Clinical Research
Foram N. Ashar, Johns Hopkins Medicine
Ryan J. Longchamps, Johns Hopkins Medicine
Christina A. Castellani, Johns Hopkins MedicineFollow
John Lane, University of Minnesota Twin Cities
Megan L. Grove, University of Texas School of Public Health
Josef Coresh, Welch Center for Prevention Epidemiology and Clinical Research
Nona Sotoodehnia, University of Washington School of Medicine
Leonard Ilkhanoff, Northwestern University
Eric Boerwinkle, University of Texas School of Public Health
Nathan Pankratz, University of Minnesota Twin Cities
Dan E. Arking, Johns Hopkins Medicine

Document Type

Article

Publication Date

12-7-2017

Journal

European Heart Journal

Volume

38

Issue

46

First Page

3443

Last Page

3448

URL with Digital Object Identifier

10.1093/eurheartj/ehx354

Abstract

Aims Sudden cardiac death (SCD) is a major public health burden. Mitochondrial dysfunction has been implicated in a wide range of cardiovascular diseases including cardiomyopathy, heart failure, and arrhythmias, but it is unknown if it also contributes to SCD risk. We sought to examine the prospective association between mtDNA copy number (mtDNA-CN), a surrogate marker of mitochondrial function, and SCD risk. Methods and results We measured baseline mtDNA-CN in 11 093 participants from the Atherosclerosis Risk in Communities (ARIC) study. mtDNA copy number was calculated from probe intensities of mitochondrial single nucleotide polymorphisms (SNP) on the Affymetrix Genome-Wide Human SNP Array 6.0. Sudden cardiac death was defined as a sudden pulseless condition presumed due to a ventricular tachyarrhythmia in a previously stable individual without evidence of a non-cardiac cause of cardiac arrest. Sudden cardiac death cases were reviewed and adjudicated by an expert committee. During a median follow-up of 20.4 years, we observed 361 SCD cases. After adjusting for age, race, sex, and centre, the hazard ratio for SCD comparing the 1st to the 5th quintiles of mtDNA-CN was 2.24 (95% confidence interval 1.58-3.19; P-trend <0.001). When further adjusting for traditional cardiovascular disease risk factors, prevalent coronary heart disease, heart rate, QT interval, and QRS duration, the association remained statistically significant. Spline regression models showed that the association was approximately linear over the range of mtDNA-CN values. No apparent interaction by race or by sex was detected. Conclusion In this community-based prospective study, mtDNA-CN in peripheral blood was inversely associated with the risk of SCD.