title: Walking disability in patients with peripheral artery disease is associated with arterial endothelial function.
abstract: 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, β-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.
authors.affiliation: Department of Surgery, University of California San Francisco, San Francisco, Calif; Department of Surgery, Veterans Affairs Medical Center, San Francisco, Calif; VIPERx Laboratory, San Francisco, Calif. Electronic address: marlene.grenon@ucsfmedctr.org.
authors.forename: S Marlene
authors.initials: SM
authors.lastname: Grenon
authors.affiliation: Department of Surgery, University of California San Francisco, San Francisco, Calif; VIPERx Laboratory, San Francisco, Calif.
authors.forename: Karen
authors.initials: K
authors.lastname: Chong
authors.affiliation: Department of Surgery, University of California San Francisco, San Francisco, Calif; VIPERx Laboratory, San Francisco, Calif.
authors.forename: Hugh
authors.initials: H
authors.lastname: Alley
authors.affiliation: Department of Surgery, University of California San Francisco, San Francisco, Calif; VIPERx Laboratory, San Francisco, Calif.
authors.forename: Emily
authors.initials: E
authors.lastname: Nosova
authors.affiliation: Department of Surgery, University of California San Francisco, San Francisco, Calif; Department of Surgery, Veterans Affairs Medical Center, San Francisco, Calif; VIPERx Laboratory, San Francisco, Calif.
authors.forename: Warren
authors.initials: W
authors.lastname: Gasper
authors.affiliation: Department of Surgery, University of California San Francisco, San Francisco, Calif.
authors.forename: Jade
authors.initials: J
authors.lastname: Hiramoto
authors.affiliation: Department of Biostatistics and Epidemiology, University of California San Francisco, San Francisco, Calif; Department of Medicine, University of California San Francisco, San Francisco, Calif.
authors.forename: W John
authors.initials: WJ
authors.lastname: Boscardin
authors.affiliation: Department of Surgery, University of California San Francisco, San Francisco, Calif; Department of Surgery, Veterans Affairs Medical Center, San Francisco, Calif; VIPERx Laboratory, San Francisco, Calif.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Owens
mesh_terms: D000368:Aged; D055109:Ankle Brachial Index; D062186:Arterial Pressure; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000503:physiopathology*; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D004185:Disability Evaluation; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007383:Intermittent Claudication / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D058729:Peripheral Arterial Disease / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology; D011237:Predictive Value of Tests; D012307:Risk Factors; D057566:Self Report; D012720:Severity of Illness Index; D014664:Vasodilation; D016138:Walking
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D002097:C-Reactive Protein