title: Potential vascular mechanisms of ramipril induced increases in walking ability in patients with intermittent claudication.
abstract: BACKGROUND
  We recently reported that ramipril more than doubled maximum walking times in patients with peripheral artery disease with intermittent claudication.
  
  
  OBJECTIVE
  Our aim was to conduct exploratory analyses of the effects of ramipril therapy on circulating biomarkers of angiogenesis/arteriogenesis, thrombosis, inflammation, and leukocyte adhesion in patients with intermittent claudication.
  
  
  RESULTS
  One hundred sixty-five patients with intermittent claudication (mean, 65.3 [SD, 6.7] years) were administered ramipril 10 mg per day (n=82) or matching placebo (n=83) for 24 weeks in a randomized, double-blind study. Plasma biomarkers of angiogenesis/arteriogenesis (vascular endothelial growth factor-A, fibroblast growth factor-2), thrombosis (D-dimer, von Willebrand factor, thrombin-antithrombin III), inflammation (high-sensitivity C-reactive protein, osteopontin), and leukocyte adhesion (soluble vascular cell adhesion molecule-1, soluble intracellular adhesion molecule-1) were measured at baseline and 24 weeks. Relative to placebo, ramipril was associated with increases in vascular endothelial growth factor-A by 38% (95% confidence interval [CI], 34%-42%) and fibroblast growth factor-2 by 64% (95% CI, 44-85%; P<0.001 for both), and reductions in D-dimer by 24% (95% CI, -30% to -18%), von Willebrand factor by 22% (95% CI, -35% to -9%), thrombin-antithrombin III by 16% (95% CI, -19% to -13%), high-sensitivity C-reactive protein by 13% (95% CI, -14% to -9%), osteopontin by 12% (95% CI, -14% to -10%), soluble vascular cell adhesion molecule-1 by 14% (95% CI, -18% to -10%), and soluble intracellular adhesion molecule-1 by 15% (95% CI, -17% to -13%; all P<0.001). With the exception of von Willebrand factor, all the above changes correlated significantly with the change in maximum walking time (P=0.02-0.001) in the group treated with ramipril.
  
  
  CONCLUSIONS
  Ramipril is associated with an increase in the biomarkers of angiogenesis/arteriogenesis and reduction in the markers of thrombosis, inflammation, and leukocyte adhesion. This study informs strategies to improve mobility in patients with intermittent claudication.
  http://clinicaltrials.gov. Unique identifier: NCT00681226.
authors.affiliation: From Baker IDI Heart and Diabetes Institute and Department of Cardiovascular Medicine, Alfred Hospital, Melbourne, Australia (A.A.A., C.L., A.K.N., M.R., B.A.K.); Queensland Research Centre for Peripheral Vascular Disease, James Cook University, Townsville, Queensland, Australia (J.G.); and Department of Vascular and Endovascular Surgery, Townsville Hospital, Queensland, Australia (J.G.).
authors.forename: Anna A
authors.initials: AA
authors.lastname: Ahimastos
authors.forename: Celine
authors.initials: C
authors.lastname: Latouche
authors.forename: Alaina K
authors.initials: AK
authors.lastname: Natoli
authors.forename: Medini
authors.initials: M
authors.lastname: Reddy-luthmoodoo
authors.forename: Jonathan
authors.initials: J
authors.lastname: Golledge
authors.forename: Bronwyn A
authors.initials: BA
authors.lastname: Kingwell
mesh_terms: D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000990:Antithrombin III; D002097:C-Reactive Protein / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D006801:Humans; D007383:Intermittent Claudication / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000097:blood; D010447:Peptide Hydrolases / Q000097:blood; D017257:Ramipril / Q000008:administration & dosage / Q000627:therapeutic use*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D016138:Walking; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C046193:antithrombin III-protease complex; D014841:von Willebrand Factor; D016222:Fibroblast Growth Factor 2; D053495:Osteopontin; D000990:Antithrombin III; D002097:C-Reactive Protein; D010447:Peptide Hydrolases; D017257:Ramipril
keywords: biological markers; inflammation; peripheral arterial disease; thrombosis