Abstract 19318: Mitochondrial DNA Copy Number as a Predictor of Cardiovascular Disease
Mitochondrial dysfunction is a core component of cardiovascular disease (CVD) and is associated with several CVD risk factors (diabetes, cigarette smoke exposure, and hypertension). We therefore explored the association of mitochondrial DNA copy number, which reflects oxidative stress, with prevalent and incident CVD, and its potential utility as a novel clinical biomarker of CVD.
We determined mtDNA copy number in DNA extracted from whole blood in 16,401 samples from two large multi-center prospective studies_the Cardiovascular Health Study (CHS) and the Atherosclerosis Risk in Communities (ARIC) study. Lower mtDNA copy number was associated with increased prevalence of CVD in 4,109 white participants from CHS (OR for lowest quintile [Q1] to highest quintile [Q5] of mtDNA copy number=2.35, 95% CI=1.74-3.19, P<0.0001), and in 11,165 participants from ARIC (OR for Q1 to Q5 in whites= 1.64, 95% CI=1.27-2.11, P=0.0001; OR in blacks=1.95, 95% CI=1.21-3.20, P=0.007). Additionally, lower mtDNA copy number was associated with an increased risk of incident hard CVD events (MI, fatal coronary heart disease, fatal and non-fatal stroke) in ARIC (HR for Q1 to Q5=1.88, 95% CI=1.53-2.22, P<0.0001). Furthermore, we show that incorporating mtDNA copy number in the recently released AHA/ACC 10-yr ASCVD Risk Score improves discrimination of the model by 0.018 (95% CI= 0.013-0.023, P< 0.001) with a net reclassification improvement of 3.95% (P<0.001) for the predicted 10-year risk categories of “low” (<7.5%) and “high” (>7.5%) risk. While we do not see the association with incident CVD in samples from CHS, this finding may reflect underlying differences in participants’ ages between the cohorts. The mean age in CHS is 72.4 years versus 58.1 years in ARIC suggesting that the association of mtDNA copy number with incident CVD may weaken with age. Given the magnitude of the effect we observe in
ARIC, and the ease and low cost of the assay, we suggest that assessment of mtDNA copy number may have clinical utility for CVD risk classification warranting further validation in additional large prospective cohorts.
Author Disclosures: F.N. Ashar: None. Y. Zhang: None. A. Moes: None. M.L. Grove: None. A.G. Wilsdon: None. P.H. Chaves: None. J. Coresh: None. A.B. Newman: None. K. Bandeen-Roche: None. E. Boerwinkle: None. J.D. Walston: None. E. Guallar: None. D.E. Arking: None.
- © 2014 by American Heart Association, Inc.