Lower Mitochondrial Energy Production of the Thigh Muscles in Patients With Low‐Normal Ankle‐Brachial Index

Abstract

BackgroundLower muscle mitochondrial energy production may contribute to impaired walking endurance in patients with peripheral arterial disease. A borderline ankle‐brachial index (ABI) of 0.91 to 1.10 is associated with poorer walking endurance compared with higher ABI. We hypothesized that in the absence of peripheral arterial disease, lower ABI is associated with lower mitochondrial energy production.Methods and ResultsWe examined 363 men and women participating in the Baltimore Longitudinal Study of Aging with an ABI between 0.90 and 1.40. Muscle mitochondrial energy production was assessed by post‐exercise phosphocreatine recovery rate constant (kPCr) measured by phosphorus magnetic resonance spectroscopy of the left thigh. A lower post‐exercise phosphocreatine recovery rate constant reflects decreased mitochondria energy production.The mean age of the participants was 71±12 years. A total of 18.4% had diabetes mellitus and 4% were current and 40% were former smokers. Compared with participants with an ABI of 1.11 to 1.40, those with an ABI of 0.90 to 1.10 had significantly lower post‐exercise phosphocreatine recovery rate constant (19.3 versus 20.8 ms−1, P=0.015). This difference remained significant after adjusting for age, sex, race, smoking status, diabetes mellitus, body mass index, and cholesterol levels (P=0.028). Similarly, post‐exercise phosphocreatine recovery rate constant was linearly associated with ABI as a continuous variable, both in the ABI ranges of 0.90 to 1.40 (standardized coefficient=0.15, P=0.003) and 1.1 to 1.4 (standardized coefficient=0.12, P=0.0405).ConclusionsAn ABI of 0.90 to 1.10 is associated with lower mitochondrial energy production compared with an ABI of 1.11 to 1.40. These data demonstrate adverse associations of lower ABI values with impaired mitochondrial activity even within the range of a clinically accepted definition of a normal ABI. Further study is needed to determine whether interventions in persons with ABIs of 0.90 to 1.10 can prevent subsequent functional decline.

Skeletal muscle ex vivo mitochondrial respiration parallels decline in vivo oxidative capacity, cardiorespiratory fitness, and muscle strength: The Baltimore Longitudinal Study of Aging

“…Recently, we have shown that (i) mitochondrial function correlates with insulin resistance and its severity in nondiabetic older persons, suggesting that decline in mitochondrial function occur in the early stage of development of diabetes type 2 (Fabbri et al., ) and (ii) that part of the decline in mitochondrial function is due to reduced perfusion as indicated by lower values of the ankle brachial index (ABI), although within the normal limits (AlGhatrif et al., ). Taken together, these two studies suggest that decline in mitochondrial function occur early in the pathways to metabolic dysregulation and disability.…”

The Rise of Mitochondria in Peripheral Arterial Disease Physiopathology: Experimental and Clinical Data

“…Mitochondrial energy metabolism was shown to decrease in PAD patients compared to controls [36,37]. In contrast, Hou et al found similar mitochondrial ATP production rate in both PAD patients and healthy controls [38].…”

Cardiovascular Magnetic Resonance in the Oncology Patient

“…One involves using multinuclear phosphorus spectroscopy to assess myocardial adenosine triphosphate/phosphocreatine ratio as a measure of bioenergetics in the heart ( 137 ). The second opportunity involves similar phosphorus bioenergetic assessments in the skeletal muscle ( 138 ). Perhaps disorders of skeletal muscle energetics could be contributing to exercise intolerance experienced by patients with cancer.…”