CURRENT THERAPEUTIC RESEARCH-CLINICAL AND EXPERIMENTAL

Background: Combination therapy with an angiotensin-converting enzyme (ACE) inhibitor and a diuretic has been shown to be highly effective in hypertension. Clinical trials have demonstrated that ACE inhibitors may improve endothelial cell dysfunction in hypertension. However, the effectiveness of the combination treatment in endothelial cell dysfunction is unknown. Objective: This study investigated the effects of a new low-dose combination, perindopril 2 mg plus indapamide 0.625 mg, on brachial artery flow-mediated vasodilation (FMD) and left ventricular diastolic function in hypertension. Methods: Patients aged 18 to 75 with newly diagnosed stage I or II hypertension were eligible. Endothelium-dependent brachial artery FMD and endothelium-independent vasodilation were assessed at baseline. Patients were treated with oral perindopril 2 mg plus indapamide 0.625-mg tablets once daily for 6 months. FMD measurements were then repeated. Percentage changes in FMD from baseline to 6 months, as well as left ventricular diastolic function parameters (isovolumic relaxation time [IVRT] and mitral diastolic E-wave deceleration time [EDT]), indicated the effectiveness of the intervention. Results: Twenty-nine Turkish patients were enrolled (17 women, 12 men; mean [SD] age, 54.5 [9.5] years [range, 38-75 years]). The mean (SD) baseline FMD was 7.00% (2.39%) (endothelial cell dysfunction) and increased significantly to 8.68% (2.78%) at 6 months (P = 0.02); FMD improved in 15 patients (51.7%). At baseline and 6 months of therapy, mean (SD) IVRT was 101.7 (12.4) ms and 95.5 (7.7) ms, respectively (P < 0.001), and EDT was 234.7 (33.9) ms and 217.9 (25.6) ms, respectively (P < 0.001). Conclusions: In this small sample of hypertensive patients, a low-dose combination ACE inhibitor and diuretic significantly improved brachial artery FMD and left ventricular diastolic function. The improvement in FMD values was independent of the stage of hypertension. These findings suggest a relationship between improvement in endothelial cell function and diastolic function. Copyright (C) 2003 Excerpta Medica, Inc