Effects of the Antihypertensive Fixed-Dose Combinations on an Early Marker of Hypertensive Cardiac Damage in Subjects at Low Cardiovascular Risk

Abstract

Background: In hypertensive subjects (HTs), isolated left ventricular diastolic dysfunction (LVDD) is an early marker of cardiac damage and is associated with poor prognosis. However, few intervention trials investigated the effects of antihypertensive therapy on isolated LVDD regression. This study investigates the blood pressure (BP)-lowering efficacy and the effect on LVDD of antihypertensive drugs administered as fixed-dose combinations in untreated HTs with isolated LVDD.

Methods: A total of 168 HTs (23% of them having impaired fasting glucose (IFG)) aged 48±4.2 years were randomized to receive open-label once-daily oral treatment of beta-blocker + diuretic, angiotensin-converting enzyme inhibitor (ACEI) + diuretic, angiotensin II receptor blocker (ARB) + diuretic, ARB + calcium channel blocker (CCB), or ACEI + CCB. Clinic and 24-hour ambulatory BP values were measured before randomization and at the follow-up. Regression of LVDD was defined as normalization of both the E/A (ratio of early-to-late ventricular filling wave velocity) and E/E' (mitral velocity to early diastolic velocity of the mitral annulus) ratios. Comparisons were made between categorical variables using the χ(2) test and between continuous variables by gender using analysis of variance for repeated measures.

Results: BP reduction did not differ between groups. LVDD regression was significantly more prevalent in the ARB + CCB or ACEI + CCB groups than with other combinations; in HTs with IFG, it was most prevalent (46%) with ACEI + CCB.

Conclusions: Independently of BP reduction, the fixed-dose combinations ARB + CCB and ACEI + CCB led to regression of isolated LVDD. In those with an IFG, ACEI + CCB was most effective.

Keywords: antihypertensive drugs; blood pressure; diastolic dysfunction; fixed-dose combination; hypertension..