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

Mary M. McDermott*, Charlotte A. Peterson, Robert Sufit, Luigi Ferrucci, Jack M. Guralnik, Melina R Kibbe, Tamar S. Polonsky, Lu Tian, Michael H. Criqui, Lihui Zhao, James H. Stein, Lingyu Li, Christiaan Leeuwenburgh

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)340-348
Number of pages9
JournalVascular Medicine (United Kingdom)
Volume23
Issue number4
DOIs
StatePublished - Aug 1 2018

Keywords

  • functional performance
  • mitochondria
  • peripheral artery disease (PAD)
  • vascular medicine

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    McDermott, M. M., Peterson, C. A., Sufit, R., Ferrucci, L., Guralnik, J. M., Kibbe, M. R., Polonsky, T. S., Tian, L., Criqui, M. H., Zhao, L., Stein, J. H., Li, L., & Leeuwenburgh, C. (2018). Peripheral artery disease, calf skeletal muscle mitochondrial DNA copy number, and functional performance. Vascular Medicine (United Kingdom), 23(4), 340-348. https://doi.org/10.1177/1358863X18765667