Reduced arterial stiffness may contribute to angiotensin-converting enzyme inhibitor induced improvements in walking time in peripheral arterial disease patients

Abstract

Claudication is a debilitating consequence of peripheral arterial disease. Evidence is accumulating to suggest that large artery stiffness may influence peripheral perfusion and walking time through effects on peripheral hemodynamics as well as microvascular structure and function. We have previously shown that the angiotensin-converting enzyme inhibitor ramipril increased systemic arterial compliance by 64%, and increased maximum walking time by over 200% in patients with peripheral arterial disease. In the current analysis in the same patient cohort, we hypothesized that this relationship may, in part, be causal. Forty patients with peripheral arterial disease [66 +/- 4 years (mean +/- SD); n = 20 per group] were randomized to ramipril, 10 mg once daily, or placebo for 24 weeks in a double-blind study. Maximum walking time was recorded during a standard treadmill test. Indices of arterial stiffness were assessed globally by systemic arterial compliance and augmentation index and regionally via central pulse wave velocity. Ramipril increased maximum walking time by 243% and improved arterial stiffness parameters by between 17 and 64% (all P < 0.001 compared with placebo). There were moderately strong correlations between the pre/post intervention change in maximum walking time and the change in indices of arterial stiffness (systemic arterial compliance, r = 0.65, P < 0.001; central pulse wave velocity, r = -0.57, P < 0.001; augmentation index, r = -0.79, P < 0.001; time to pressure augmentation, r = 0.52, P = 0.001). The present data support the hypothesis that the beneficial effects of ramipril on maximum walking time observed in our peripheral arterial disease population are, at least partly, a consequence of reduced arterial stiffness.