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Eur Heart J. 2017 Dec 7;38(46):3443-3448. doi: 10.1093/eurheartj/ehx354.

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

Author information

1
Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, 2024 E. Monument St.. Room 2-645, Baltimore, MD 21205, USA.
2
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Miller Research Building, Room 459, Baltimore, MD 21205, USA.
3
Department of Laboratory Medicine and Pathology, University of Minnesota, Room 1-156, Moos Tower, 515 Delaware Street SE, Minneapolis, MN 55455, USA.
4
Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
5
Department of Medicine, Division of Cardiology, Cardiovascular Health Research Unit, University of Washington, 1730 Minor Ave, Suite 1360, Seattle, Washington 98101, USA.
6
Department of Medicine, Division of Cardiology, Electrophysiology Section, Northwestern University, 676 N. St. Clair, Suite 600, Chicago, Illinois, USA.
7
Inova Heart and Vascular Institute, 3300 Gallows Rd, Falls Church, VA 22042, USA.
8
Baylor College of Medicine, Human Genome Sequencing Center, One Baylor Plaza, Alkek N1419, MS: BCM226, Houston, TX 77030-3411, USA.

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.

KEYWORDS:

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

PMID:
29020391
PMCID:
PMC5837579
DOI:
10.1093/eurheartj/ehx354
[Indexed for MEDLINE]
Free PMC Article

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