The ankle–brachial index, gastrocnemius mitochondrial respirometry, and walking performance in people with and without peripheral artery disease

Author:

McDermott Mary M12ORCID,Dayanidhi Sudarshan3,Leeuwenburgh Christiaan4,Wohlgemuth Stephanie E4,Ferrucci Luigi5,Peterson Charlotte A6,Tian Lu7,Sufit Robert8,Zhao Lihui2,Slysz Joshua19ORCID,Polonsky Tamar S10,Guralnik Jack M11,Kibbe Melina R12ORCID,Ho Karen J13ORCID,Criqui Michael H14,Zhang Dongxue1,Xu Shujun1,Greenland Philip12

Affiliation:

1. Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

2. Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

3. Shirley Ryan AbilityLab, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

4. Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA

5. Division of Intramural Research, National Institute on Aging, Baltimore, MD, USA

6. Center for Muscle Biology, University of Kentucky, Lexington, KY, USA

7. Department of Health Research and Policy, Stanford University, Stanford, CA, USA

8. Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

9. Current: Department of Physiology and Biophysics, Dalhousie University, Nova Scotia, Canada

10. Department of Medicine, University of Chicago, Chicago, IL, USA

11. Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA

12. Department of Surgery and Biomedical Engineering, University of Virginia School of Medicine, Charlottesville, VA, USA

13. Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

14. Department of Preventive Medicine, Family Medicine and Public Health, University of San Diego California, San Diego, CA, USA

Abstract

Background: Mitochondrial abnormalities exist in lower-extremity peripheral artery disease (PAD), yet the association of the ankle–brachial index (ABI) with mitochondrial respiration in gastrocnemius muscle is unknown. The association of gastrocnemius mitochondrial respiration with 6-minute walk distance in PAD is unknown. Objective: To describe associations of the ABI with mitochondrial respiratory function in gastrocnemius muscle biopsies and associations of gastrocnemius mitochondrial respirometry with 6-minute walk distance in people with and without PAD. Methods: People with (ABI ⩽ 0.90) and without (ABI 1.00–1.40) PAD were enrolled. ABI and 6-minute walk distance were measured. Mitochondrial function of permeabilized myofibers from gastrocnemius biopsies was measured with high-resolution respirometry. Results: A total of 30 people with PAD (71.7 years, mean ABI: 0.64) and 68 without PAD (71.8 years, ABI: 1.17) participated. In non-PAD participants, higher ABI values were associated significantly with better mitochondrial respiration (Pearson correlation for maximal oxidative phosphorylation PCI+II: +0.29, p = 0.016). In PAD, the ABI correlated negatively and not significantly with mitochondrial respiration (Pearson correlation for PCI+II: –0.17, p = 0.38). In people without PAD, better mitochondrial respiration was associated with better 6-minute walk distance (Pearson correlation: +0.51, p < 0.001), but this association was not present in PAD (Pearson correlation: +0.10, p = 0.59). Conclusions: Major differences exist between people with and without PAD in the association of gastrocnemius mitochondrial respiration with ABI and 6-minute walk distance. Among people without PAD, ABI and walking performance were positively associated with mitochondrial respiratory function. These associations were not observed in PAD.

Funder

American Heart Association

Publisher

SAGE Publications

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