Ankle‐Brachial Index and Energy Production in People Without Peripheral Artery Disease: The BLSA

BACKGROUND: Lower ankle‐brachial index (ABI) values within the 0.90 to 1.40 range are associated with poorer mitochondrial oxidative capacity of thigh muscles in cross‐sectional analyses. Whether ABI decline is associated with greater declines in thigh muscle oxidative capacity with aging is unknown. METHOD AND RESULTS: We analyzed data from 228 participants (100 men) of the BLSA (Baltimore Longitudinal Study of Aging), aged 39 to 97 years, with an ABI between 0.9 and 1.40 at baseline and at follow‐up (mean follow‐up period of 2.8 years). We examined mitochondrial oxidative capacity of the left thigh muscle, by measuring the postexercise phosphocreatine recovery rate constant (kPCr) from phosphorus‐31 magnetic resonance spectroscopy. Greater kPCr indicated higher mitochondrial oxidative capacity. Although kPCr was available on the left leg only, ABI was measured in both legs. Longitudinal rates of change ((Change)) of left and right ABI and kPCr of the left thigh muscle were estimated using linear mixed effects models, and their association was analyzed by standardized multiple linear regressions. In multivariate analysis including sex, age, baseline kPCr, both left and right baseline ABI, and ABI change in both legs, (kPCr)(Change) was directly associated with ipsilateral (left) (ABI)(Change) (standardized [STD]‐β=0.14; P=0.0168) but not with contralateral (right) (ABI)(Change) (P=0.22). Adjusting for traditional cardiovascular risk factors, this association remained significant (STD‐β=0.18; P=0.0051). (kPCr)(Change) was steeper in White race participants (STD‐β=0.16; P=0.0122) and body mass index (STD‐β=0.13; P=0.0479). There was no significant association with current smoking status (P=0.63), fasting glucose (P=0.28), heart rate (P=0.67), mean blood pressure (P=0.78), and low‐density lipoprotein (P=0.75), high‐density lipoprotein (P=0.82), or triglycerides (P=0.15). CONCLUSIONS: In people without peripheral arterial disease, greater decline in ABI over time, but not baseline ABI, was associated with faster decline in thigh mitochondrial oxidative capacity in the ipsilateral leg. Further studies are needed to examine whether early interventions that improve lower extremity muscle perfusion can improve and prevent the decline of muscle energetics.