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Potential vascular mechanisms of ramipril induced increases in walking ability in patients with intermittent claudication.

Author(s): Ahimastos AA(1), Latouche C, Natoli AK, Reddy-luthmoodoo M, Golledge J, Kingwell BA.

Affiliation(s): Author information: (1)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.).

Publication date & source: 2014, Circ Res. , 114(7):1144-55

RATIONALE: 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. METHODS AND 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. CLINICAL TRIAL REGISTRATION INFORMATION URL: http://clinicaltrials.gov. Unique identifier: NCT00681226.

Page last updated: 2014-11-30

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