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

Yiyi Zhang, Eliseo Guallar, Foram N. Ashar, Ryan J. Longchamps, Christina A. Castellani, John Lane, Megan L. Grove, Josef Coresh, Nona Sotoodehnia, Leonard Ilkhanoff, Eric Boerwinkle, Nathan Pankratz, Dan E. Arking

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)3443-3448
Number of pages6
JournalEuropean heart journal
Volume38
Issue number46
DOIs
StatePublished - Dec 7 2017

Keywords

  • Cardiovascular disease
  • Mitochondrial DNA
  • Mitochondrial copy number
  • Risk factor
  • Sudden cardiac death

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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