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

• Published in: European heart journal 2017-12, Vol.38 (46), p.3443-3448
• Main Authors: Zhang, Yiyi, Guallar, Eliseo, Ashar, Foram N, Longchamps, Ryan J, Castellani, Christina A, Lane, John, Grove, Megan L, Coresh, Josef, Sotoodehnia, Nona, Ilkhanoff, Leonard, Boerwinkle, Eric, Pankratz, Nathan, Arking, Dan E
• Format: Article
• Language: English
• Subjects: Clinical Research; Coronary Artery Disease - etiology; Death, Sudden, Cardiac - etiology; DNA Copy Number Variations - physiology; DNA, Mitochondrial - physiology; Female; Humans; Male; Middle Aged; Prospective Studies; Risk Factors
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/ehx354

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. 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