Lower extremity ischemia, calf skeletal muscle characteristics, and functional impairment in peripheral arterial disease

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. PARTICIPANTS: Four hundred thirty-nine persons with PAD (ABI<0.90) and 265 without PAD (ABI 0.90-1.30). 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). RESULTS: 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 mm²; ABI 0.50-0.90, 5,536 mm²; ABI 0.91-1.30, 5,941 mm²; 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 fast-paced 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). CONCLUSION: These data support the hypothesis that lower extremity ischemia has a direct adverse effect on calf skeletal muscle area. This association may mediate previously established relationships between PAD and functional impairment.