P6429Prognostic value of mitochondrial DNA4977 deletion and mitochondrial DNA copy number in patients with coronary artery disease

ABSTRACTAmong cardiovascular disease (CVD) biomarkers, the mitochondrial DNA copy number (mtDNAcn) is a promising candidate. A growing attention has been also dedicated to trimethylamine-N-oxide (TMAO), an oxidative derivative of the gut metabolite trimethylamine (TMA). With the aim to identify biomarkers predictive of CVD, we investigated TMA, TMAO and mtDNAcn in a population of 389 coronary artery disease (CAD) patients and 151 healthy controls, in association with established risk factors for CVD (gender, age, hypertension, smoking, diabetes, glomerular filtration rate (GFR)). MtDNAcn was significantly lower in CAD patients and in hypertensive subjects; it correlates with GFR and TMA, but not with TMAO. A biomarker including mtDNAcn, gender, and hypertension (but neither TMA nor TMAO) emerged as a good predictor of CAD. Our findings support the usage of mtDNAcn as a plastic biomarker to monitor the exposure to risk factors and the efficacy of preventive interventions for a personalized CAD risk reduction.Highlights-mtDNAcn measured in whole blood is associated to the cardiovascular health status in humans;-mtDNAcn is reduced in CAD and hypertension, and inversely correlates with GFR;-mtDNA, gender and hypertension together represent a good predictive biomarker for CAD;-TMA metabolism is different in healthy and CAD subjects;-TMA and TMAO are not good predictors of CAD.

Download Full-text

Peripheral artery disease, calf skeletal muscle mitochondrial DNA copy number, and functional performance

Vascular Medicine ◽

10.1177/1358863x18765667 ◽

2018 ◽

Vol 23 (4) ◽

pp. 340-348 ◽

Cited By ~ 13

Author(s):

Mary M McDermott ◽

Charlotte A Peterson ◽

Robert Sufit ◽

Luigi Ferrucci ◽

Jack M Guralnik ◽

...

Keyword(s):

Mitochondrial Dna ◽

Copy Number ◽

Functional Performance ◽

Dna Copy Number ◽

Walk Distance ◽

Mitochondrial Dna Copy Number ◽

Walking Velocity ◽

Artery Disease ◽

Minute Walk Distance ◽

Minute Walk

In people without lower extremity peripheral artery disease (PAD), mitochondrial DNA copy number declines with aging, and this decline is associated with declines in mitochondrial activity and functional performance. However, whether lower extremity ischemia is associated with lower mitochondrial DNA copy number and whether mitochondrial DNA copy number is associated with the degree of functional impairment in people with PAD is unknown. In people with and without PAD, age 65 years and older, we studied associations of the ankle–brachial index (ABI) with mitochondrial DNA copy number and associations of mitochondrial DNA copy number with functional impairment. Calf muscle biopsies were obtained from 34 participants with PAD (mean age: 73.5 years (SD 6.4), mean ABI: 0.67 (SD 0.15), mean 6-minute walk distance: 1191 feet (SD 223)) and 10 controls without PAD (mean age: 73.1 years (SD 4.7), mean ABI: 1.14 (SD 0.07), mean 6-minute walk distance: 1387 feet (SD 488)). Adjusting for age and sex, lower ABI values were associated with higher mitochondrial DNA copy number, measured in relative copy number (ABI<0.60: 914, ABI 0.60–0.90: 731, ABI 0.90–1.50: 593; p trend=0.016). The association of mitochondrial DNA copy number with the 6-minute walk distance and 4-meter walking velocity differed significantly between participants with versus without PAD ( p-value for interaction=0.001 and p=0.015, respectively). The correlation coefficient between mitochondrial DNA copy number and the 6-minute walk distance was 0.653 ( p=0.056) among people without PAD and –0.254 ( p=0.154) among people with PAD and ABI < 0.90. In conclusion, lower ABI values are associated with increased mitochondrial DNA copy number. Associations of mitochondrial DNA copy number with the 6-minute walk distance and 4-meter walking velocity significantly differed between people with versus without PAD, with stronger positive associations observed in people without PAD than in people with PAD. The cross-sectional and exploratory nature of the analyses precludes conclusions regarding causal inferences. ClinicalTrials.gov Identifier: NCT02246660

Download Full-text