Background:
Atrial fibrillation (AF) is the most common clinical arrhythmia. Molecular studies suggest that mitochondrial dysfunction is associated with increased risk of AF through reduced production of adenosine triphosphate and increased production of reactive oxidative species. Mitochondrial DNA copy number (mtDNA CN), a marker of mitochondrial function, has been found to be associated with sudden cardiac death and cardiovascular disease (CVD) in ARIC. However, the association between mtDNA CN and incident AF in the general population is unknown.
Objective:
To examine the prospective association between mtDNA CN and the risk of incident AF.
Methods:
Cohort study of 10,764 ARIC participants without AF at baseline (1987-89) and followed through December 31, 2014. AF were identified through electrocardiograms, review of hospital discharge codes, and death certificates. DNA samples were isolated from buffy coat. mtDNA CN was calculated from probe intensities on the Affymetrix Genome-Wide Human single nucleotide polymorphisms (SNP) Array and standardized using the residual method. Cox proportional hazards models adjusted for demographics and CVD risk factors were used to estimate hazard ratios (HR) for AF comparing the four lowest quintiles of mtDNA CN to the highest quintile.
Results:
The mean (SD) age was 57.4 (6.0) years. During 21 years of median follow-up, 1,946 participants developed AF. In fully-adjusted models, the HRs (95% CI) for AF comparing quintiles 1 - 4 to quintile 5 of mtDNA CN were 1.17 (1.00, 1.37), 1.17 (0.99, 1.37), 0.92 (0.78, 1.10) and 1.05 (0.89, 1.24), respectively (p-trend 0.044; Figure). The HR for AF comparing 10
th
vs 90
th
percentile of mtDNA-CN was 1.16 (1.04, 1.30).
Conclusions:
mtDNA CN was inversely associated with the risk of AF independent of traditional CVD risk factors. Decline in mitochondrial function may be a novel mechanism underlying biological changes that increase the risk of AF in the general population. mtDNA CN may provide potential for novel AF prevention strategies.
The Amyloid β Protein Induces Oxidative Damage of Mitochondrial DNA