Mitochondrial DNA copy number and incident heart failure: The Atherosclerosis Risk in Communities (ARIC) study

Background The association between mitochondrial DNA-copy number (mtDNA-CN) and incident heart failure (HF) in the general population is unclear. Methods We examined the association between mtDNA-CN and the risk of incident HF among 10,802 participants free of HF at baseline from the Atherosclerosis Risk in Communities (ARIC) study, a large bi-racial population-based cohort. mtDNA-CN was estimated using probe intensities on the Affymetrix Genome-Wide Human single nucleotide polymorphisms Array 6.0. Incident HF events were identified through hospital discharge codes from 1987 until 2005 and through adjudication by the ARIC HF Classification Committee since 2005. Results During a median follow-up of 23.1 years, there were 2,227 incident HF events (incidence rate 10.3 per 1000 person-years). In fully adjusted models, the hazard ratios (95% confidence intervals) for HF comparing the 2 nd through 5 th quintiles of mtDNA-CN to the 1 st quintile were 0.91 (0.80–1.04), 0.82 (0.72–0.93), 0.81 (0.71–0.92), and 0.74 (0.65–0.85), respectively ( P for trend < 0.001). In stratified analyses, the associations between mtDNA-CN and HF were similar across examined subgroups. The inverse association between mtDNA-CN and incident HF was stronger in HF with reduced ejection fraction (HFrEF) than in HF with preserved ejection fraction (HFpEF). Conclusions In this prospective cohort, mtDNA-CN was inversely associated with the risk of incident HF suggesting that reduced levels of mtDNA-CN, a biomarker of mitochondrial dysfunction, could reflect early susceptibility to HF.