PLASMA ENDOTHELIN-1 IS ASSOCIATED WITH AORTIC STIFFNESS IN ESSENTIAL HYPERTENSION

Abstract

Background: Experimental studies documented that endothelin-1 (ET-1) contributes to arterial stiffness and recently, in patients with chronic kidney diseases, it has been observed that selective endothelin-A receptor antagonism reduces arterial stiffness, in part independently of blood pressure lowering. Little is known about the relationships between ET-1 plasma levels and aortic distensibility in subjects with essential hypertension. Objective: The aim of our study was to analyse the relationships between plasma concentrations of ET-1 and carotid-femoral pulse wave velocity (c-f PWV), as an index of aortic stiffness, in a group of hypertensive patients without overt renal insufficiency [estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 ]. Methods: We enrolled 216 pharmacologically untreated hypertensive patients (mean age 46 ± 10 years, males 62%). In all the subjects routine biochemical parameters and ET-1 plasma values, measured by a solid-phase specific sandwich enzyme-linked immunosorbent assay (Amersham kits), were obtained. Moreover, ambulatory blood pressure monitoring and measurement of c-f PWV, by a computerized automatic method (Complior), were performed. Results: The patients (n = 41) with elevated values of c-f PWV (> 12 m/sec) showed significantly higher ET-1 plasma levels than those of subjects with PWV < 12 m/sec (3.43 ± 0.43 vs 3.18 ± 0.42 pg/ml; p = 0.001 and p = 0.01, before and after adjustment for age and mean arterial pressure). A statistical significant correlation was found between ET-1 and c-f PWV in the whole study population (r = 0.29; p < 0.001). This association held even after adjustment for age, gender, mean arterial pressure, smoking, total cholesterol, glicaemia, waist circumference, HLD cholesterol, triglycerides and eGFR (beta = 0.17; p = 0.01). The correlation between ET-1 and aortic stiffness was equally significant in both sexes and stronger in diabetic patients (n = 17; r = 0.60) when compared to non diabetic subjects (r = 0.26). Conclusions: Our results seem to suggest that in hypertensive men and women, and especially in those with diabetes, an independent relationship exists between ET-1 plasma levels and aortic stiffness.