Impact of hypertension and renin–angiotensin system inhibitors in aortic stenosis

Abstract

Experimental studies revealed that renin-angiotensin system (RAS) could play a crucial role in the pathophysiology of aortic stenosis (AS). The objectives of this study were to examine (i) the impact of hypertension on AS progression and clinical events and (ii) the effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs). In this observational study, we retrospectively analysed clinical and Doppler echocardiographic data prospectively collected in 338 patients with AS. Patients were separated into four groups: patients without hypertension and not treated by RAS medication (Ctrl group), patients with hypertension but not treated by RAS medication (HTN group), patients treated with ACEIs, and patients treated with ARBs. AS progression rate was assessed by the annualized increase in peak aortic jet velocity. Compared with Ctrl group, patients in HTN group had faster stenosis progression (P=0·01). Patients on ARBs had slower AS progression compared with Ctrl (trend P=0·10) and HTN (P=0·002) groups, whereas patients on ACEIs had similar progression rate compared with Ctrl group (P=NS) but lower compared with HTN group (P=0·02). On multivariable analysis, compared with Ctrl group, HTN group was associated with faster AS progression rate (P=0·002), whereas ARBs with slower progression (P=0·0008). During a mean follow-up of 6·2±2·4years, HTN (hazard ratio [HR]=2·45; P=0·006) and ACEI (HR=2·30; P=0·01) groups were associated with a significant increase in all-cause mortality compared with Ctrl group, whereas ARB group (HR: 0·89; P=0·80) not. In multivariable analysis, HTN and ACEI groups remained associated with increased mortality. Hypertension is associated with significantly faster stenosis progression and higher incidence of clinical events in patients with AS. ARBs but not ACEs were found to abolish the increased risk of mortality associated with hypertension.