Abstract 4143433: Vascular Determinants of Functional Capacity in Peripheral Artery Disease

Background: Patients with peripheral artery disease (PAD) experience walking impairment that is incompletely explained by conduit artery atherosclerotic occlusive disease and ankle-brachial index (ABI). Microvascular dysfunction is associated with adverse outcomes including amputation but its effect on ambulation is unknown. We tested whether calf skeletal muscle microvascular function independently associates with walking distance and with ambulatory improvement following exercise therapy or revascularization. Hypothesis: Calf skeletal muscle microvascular function predicts walking distance after adjusting for conduit artery function and ABI. Methods: Sixty-eight participants, including 50 with PAD (ABI < 0.85) and 18 controls underwent vascular function assessment after sphygmomanometer cuff-induced calf ischemia using magnetic resonance imaging (MRI) measures of blood-oxygenation-level-dependent (BOLD) perfusion-dependent reactivity and arterial-spin labeling-based perfusion reactivity. Functional status was assessed using 6-minute walk testing (6MWT). A subgroup of PAD patients underwent repeat testing after exercise therapy (n=14) or revascularization (n=14). Multivariable regression models were used to assess the association of microvascular function with 6MWT distance controlling for age, sex, diabetes, ABI, and macrovascular function. Results: Resting conduit artery pressure by ABI (R=0.74, p<0.001), BOLD macrovascular reactive hyperemic blood flow (R=0.40, p<0.001), and skeletal muscle microvascular BOLD maximal reactivity (R=0.66; p<0.001) significantly correlated with 6MWT distance in univariable vascular testing (Figure 1A-C). In multivariable analysis of each vascular parameter, calf skeletal muscle microvascular reactivity most strongly associated with 6MWT (b=825.3, p=0.023). In those with repeat testing after intervention, the change in microvascular BOLD reactivity, but not ABI or macrovascular BOLD blood flow, significantly correlated with change in 6MWT distance (R=0.46, p=0.014, Figure 1D-F). Conclusions: Skeletal muscle microvascular function directly associates with walking distance independent of conduit artery blood flow and correlates with ambulatory improvement following PAD interventions.