Walking disability in patients with peripheral artery disease is associated with arterial endothelial function

Objective: Patients with peripheral artery disease (PAD) have varying degrees of walking disability that do not completely correlate with ankle-brachial index (ABI) or angiographic anatomy. We hypothesized that endothelial function (EF) is an independent predictor of symptom severity in PAD patients. Methods: This was a cross-sectional study of 100 PAD patients presenting to a vascular surgery clinic. All patients received ABI testing and brachial artery flow-mediated, endothelium-dependent vasodilation (FMD) to assess arterial EF. Symptom severity and walking disability reported by Rutherford category was based on the patient's self-report during the clinic visit and recorded by the investigator-vascular surgeons. Demographic, biochemical, and physiologic parameters were entered into regression equations to determine association with symptom severity. Results: Patients were a mean age of 66 +/- 8 years, and 43% had diabetes. Mean FMD was 7.4%, indicating impaired EF. EF progressively declined as Rutherford category increased (P=.01). Brachial artery FMD, ABI, systolic blood pressure, C-reactive protein, low-density lipoprotein, high-density lipoprotein, beta-blocker use, and a history of diabetes or coronary artery disease were all associated with Rutherford category (all P<.05). Multivariable regression showed EF (P<.02) and ABI (P<.0001) were independently associated with walking disability. When the cohort was restricted to claudicant patients (n=73), EF remained associated with walking disability after adjustment for other covariates (P=.0001). Conclusions: Symptom severity in PAD is multifactorial, reflecting impaired hemodynamics and vascular dysfunction. This is the first report demonstrating that walking disability in PAD is associated with arterial EF. The mechanistic link underlying these observations remains to be defined.