OBJECTIVES-To determine whether lower ankle brachial index (ABI) levels are associated with lower calf skeletal muscle area and higher calf muscle percentage fat in persons with and without lower extremity peripheral arterial disease (PAD). DESIGN-Cross-sectional.SETTING-Three Chicago-area medical centers. MEASUREMENTS-Calf muscle cross-sectional area and the percentage of fat in calf muscle were measured using computed tomography at 66.7% of the distance between the distal and proximal tibia. Physical activity was measured using an accelerometer. Functional measures included the 6-minute walk, 4-meter walking speed, and the Short Physical Performance Battery (SPPB). PARTICIPANTS-FourRESULTS-Adjusting for age, sex, race, comorbidities, and other potential confounders, lower ABI values were associated with lower calf muscle area (ABI<0.50, 5,193 mm 2 ; ABI 0.50-0.90, 5,536 mm 2 ; ABI 0.91-1.30, 5,941 mm 2 ; P for trend <.001). These significant associations remained after additional adjustment for physical activity. In participants with PAD, lower calf muscle area in the leg with higher ABI was associated with significantly poorer performance in usual-and fastpaced 4-meter walking speed and on the SPPB, adjusting for ABI, physical activity, percentage fat in calf muscle, muscle area in the leg with lower ABI, and other confounders (P<.05 for all comparisons). Although it is known that patients with lower extremity peripheral arterial disease (PAD) have greater functional impairment and faster rates of functional decline than persons without PAD, 1,2 mechanisms of functional impairment and decline in PAD are not well established.Ischemia-related pathological changes in calf skeletal muscle may contribute to functional impairment in patients with PAD, but associations between lower extremity ischemia, calf muscle characteristics, and lower extremity functioning in PAD are not well understood.The purpose of this study was to determine whether participants with lower ankle brachial index (ABI) levels have lower calf skeletal muscle area and greater calf muscle percentage fat than participants with higher ABI levels. Associations between calf muscle area and calf muscle percentage fat and the degree of functional impairment in persons with PAD were also evaluated. METHODS SubjectsThe institutional review board of Northwestern University Feinberg School of Medicine and Catholic Health Partners Hospitals approved the protocol. Participants gave informed consent. Participants included 325 persons attending their fourth annual follow-up visit in the Walking and Leg Circulation Study (WALCS) 1,2 and 379 individuals newly identified. Participation rates and exclusion criteria for the WALCS cohort have been described. 1,2 The 379 newly identified participants were recruited from among 1,804 contacted for participation. Of these 1,804, 176 (9.8%) met exclusion criteria, 131 (7.3%) refused participation, 1,021 (57%) did not respond to letters inviting their participation, and 74 (4.1%) did not attend their study appoin...

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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 Ն20% 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 Ͻ0.001) and lower calf muscle area (P for trendϭ0.039) 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; Pϭ0.003), 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; Pϭ0.015). 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.