Limb hemodynamics are not predictive of functional capacity in patients with PAD

Abstract

improvements in ankle pressures, CBF, and symptoms. 5 Moreover, the approach toward development of novel treatments, such as therapeutic angiogenesis, is Abstract: To the practicing clinician, it seems obvious that limb hemodynamics would be the primary determinant of walking distance. However, other determinants, such as skeletal muscle metabolism, may play a role. Accordingly, in the current study, we examined the relationship between measures of limb hemodynamics and walking capacity in patients with peripheral arterial disease (PAD). We measured toe and ankle pressures for calculation of toe-(TBI) and ankle (ABI)-brachial indices; basal and hyperemic calf blood flow (CBF; by plethysmography); and initial (ICT) and absolute (ACT) claudication time using the Skinner-Gardner protocol. As expected, PAD patients had impaired limb hemodynamics with reduced TBI, ABI and a reduction in ABI post-exercise. However, there was no relationship between any of the hemodynamic variables (including ABI, ABI reduction post-exercise, TBI, baseline or maximal CBF) and walking distance as assessed by ICT or ACT. A subset of PAD patients with an ACT Ͼ750 s (n ϭ 16; 'long claudicators') were compared with a subset of PAD patients with an ACT Ͻ260 s (n ϭ 16; 'short claudicators'). The average ACT in the long claudicants was over fivefold greater than the short claudicators. Surprisingly, there were no differences between the two groups in any of the hemodynamic variables. There was also no relationship between the initial ABI, TBI, toe pressure, baseline or hyperemic CBF, and the improvement in ACT over the 3-month course of the study. This study found little relationship between hemodynamic variables and functional capacity in PAD. Accordingly, to assess the response to therapeutic interventions, exercise performance and functional status need to be directly measured, and cannot be predicted from hemodynamic measurements.

Pathophysiology of Intermittent Claudication in Peripheral Artery Disease

“…Magnetic resonance imaging-based measurement of calf blood flow was moderately related to walking distance, 43 but plethysmography-based calf blood flow showed no association with treadmill walking or change in walking time. 42 Prospective studies confirm that individuals with an abnormal ABI have a greater decline in walking ability at 2-year follow-up. 44 However, the association between the magnitude of the reduction in ABI and functional outcomes is less clear.…”

“…7, 39 Yet some studies have shown just modest correlation between ABI and walking ability, 40,41 and other studies have found no association between ABI and the magnitude of functional limitation. 42 Limb blood flow, assessed by other techniques, has shown inconsistent associations with functional measures. Magnetic resonance imaging-based measurement of calf blood flow was moderately related to walking distance, 43 but plethysmography-based calf blood flow showed no association with treadmill walking or change in walking time.…”

Reactive hyperemia and BOLD MRI demonstrate that VEGF inhibition, age, and atherosclerosis adversely affect functional recovery in a murine model of peripheral artery disease

“…Based on preliminary histologic analysis, it is also unlikely that femoral artery ligation was a less severe ischemic insult compared with YNG mice (data not shown). This leads us to hypothesize that the decrease from baseline is multifactorial and may indicate limited NOmediated vasodilation or metabolic adaptation (33). In future murine or human studies, the methodology presented herein may be sensitive enough to define the physiologic relevance of this portion of the RH response, as has been attempted for TTP and PH (15,20).…”

Outcomes for Clinical Studies Assessing Drug and Revascularization Therapies for Claudication and Critical Limb Ischemia in Peripheral Artery Disease

“…In studies of PAD patients not receiving revascularization, ABI, a measure integrating the impact of all stenoses in a limb, is poorly associated with function. 44,45 Although measures of plaque burden correlate with walking distance, 46,47 improvement in function occurs with exercise training despite no change in ABI. 23,28,48 Other factors such as the development of collaterals and improvements in endothelial function and skeletal muscle bioenergetics may maintain function in the presence of arterial restenosis or occlusion.…”