Background—Associations of pathophysiological calf muscle characteristics with functional decline in people with lower extremity peripheral arterial disease are unknown.

Methods and Results—Three hundred seventy participants with peripheral arterial disease underwent baseline measurement of calf muscle area, density, and percent fat with the use of computed tomography. Participants were followed up annually for 2 years. The outcome of mobility loss was defined as becoming unable to walk 1/4 mile or walk up and down 1 flight of stairs without assistance among those without baseline mobility limitations. Additional outcomes were 20% decline in 6-minute walk distance and becoming unable to walk for 6 minutes continuously among participants who walked continuously for 6 minutes at baseline. With adjustment for age, sex, race, body mass index, the ankle-brachial index, smoking, physical activity, relevant medications, and comorbidities, lower calf muscle density (P for trend <0.001) and lower calf muscle area (P for trend=0.039) were each associated with increased mobility loss rates. Compared with participants in the highest baseline tertiles, participants in the lowest tertile of calf muscle percent fat had a hazard ratio of 0.18 for incident mobility loss (95% confidence interval, 0.06 to 0.55; P=0.003), and participants in the lowest tertile of muscle density had a 3.50 hazard ratio for incident mobility loss (95% confidence interval, 1.28 to 9.57; P=0.015). No significant associations of calf muscle characteristics with 6-minute walk outcomes were observed.

Conclusions—Our findings suggest that interventions to prevent mobility loss in peripheral arterial disease should focus on reversing pathophysiological findings in calf muscle.