Abstract 2767: Ramipril Reduces Large Artery Stiffness and Improves Walking Ability in Patients With Peripheral Arterial Disease: A Causal Relationship?
Introduction: A Framingham sub-study has shown that large artery stiffening impairs peripheral microvascular vascular reactivity, most likely through elevation in pulse pressure which impairs endothelial function. We have shown that the ACE inhibitor ramipril reduced arterial stiffness and increased maximum walking time by over 200% in patients with peripheral arterial disease (PAD). We hypothesised that this relationship may, in part, be causal.
Methods: Forty PAD patients (66±4 years (mean±SD); n=20 per group) were randomised to ramipril, 10 mg once daily or placebo for 24 weeks in a randomised, double blind study. Maximum walking time was recorded during a standard treadmill test. Indices of arterial stiffness were assessed globally via systemic arterial compliance (SAC) and augmentation index (carotid tonometry and Doppler velocimetry), and regionally via carotid-femoral pulse wave velocity (PWVc).
Results: Ramipril increased maximum walking time (453±47s, mean±SEM), and reduced arterial stiffness as assessed by SAC (0.10±0.02 mL/mmHg), PWVc (-1.7±0.2 m/s) and AI (-4.1±0.3%, all <0.01 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 (SAC, r=0.65, p<0.001; PWVc, r=-0.57, p<0.001; AI, r=0.79, p<0.001, time to pressure augmentation, r=0.52, p=0.001).
Conclusion: These relationships are likely to be partly accountable by independent effects of ramipril on both the large and small arteries. Our findings are also consistent with the hypothesis that arterial stiffness impacts on peripheral blood flow via effects on pulse pressure and peripheral microvascular reactivity.