Angiotensin II receptor antagonism with telmisartan increases number of endothelial progenitor cells in normotensive patients with coronary artery disease: a randomized, double-blind, placebo-controlled study

Abstract

Introduction: Circulating endothelial progenitor cells (EPCs) provide an endogenous repair mechanism of the dysfunctional endothelium and therefore can play a crucial role in the pathophysiology of coronary artery disease (CAD). Angiotensin II receptor antagonism has been shown to be able to increase EPCs in hypertension but its effect in patients with CAD is unknown. Aim of this study was to evaluate whether telmisartan, an angiotensin II receptor antagonist, can modify the number of subpopulations of EPCs and may in turn affect the endothelial function of normotensive patients with CAD.

Methods: In a prospective double-blind parallel group study, 40 normotensive patients with CAD were randomly treated with telmisartan (80 mg) or placebo for 4 weeks at time of coronary angiography. Measurements of EPCs and assessment of flow-mediated dilatation (FMD) of the brachial artery was performed before and after therapy.

Results: Absolute number of EPCs was similar at baseline in the telmisartan and placebo groups. After 4 weeks treatment, CD34+/KDR+/CD45- cells increased significantly in the telmisartan group (from 0.010+/-0.003 to 0.014+/-0.004%, P=0.0001) but not in the placebo group (from 0.009+/-0.004 to 0.009+/-0.005%, NS). Similarly, CD133+/KDR+/CD45- cells raised significantly with telmisartan (from 0.003+/-0.002 to 0.006+/-0.002%, P=0.0001) but not with placebo (from 0.004+/-0.003 to 0.003+/-0.002%, NS). Also, CD14+/CD45+ cells increased significantly with telmisartan (from 0.005+/-0.002 to 0.008+/-0.002%, P=0.0001) and were unchanged with placebo (0.006+/-0.002 vs. 0.005+/-0.003%, NS). FMD improved significantly in patients who received telmisartan (10.4+/-3.9%, P=0.0015 vs. baseline) but did not change in the placebo group (5.9+/-2.8%; P=0.32 vs. baseline; telmisartan vs. placebo, P=0.002). A significant positive correlation was found in the telmisartan group between the improvement in FMD and the increase in CD34+/KDR+/CD45- cells and CD133+/KDR+/CD45- cells (r=0.55, P<0.01, and r=0.49, P<0.05, respectively).

Conclusion: Angiotensin II receptor antagonism with telmisartan increases the number of regenerative EPCs and improves endothelial function in normotensive patients with CAD. These novel effects are interrelated and can explain, at least in part, why telmisartan has beneficial cardiovascular effects independent of its blood pressure lowering action.