SOLUBLE (PRO)RENIN RECEPTOR ASSOCIATES ADVERSELY WITH LEFT VENTRICULAR STRUCTURE AND FUNCTION IN YOUNG ADULTS

Abstract

Objective: Most of the evidence on the role of (pro)renin receptor in blood pressure regulation and target organ damage emanate from animal models. Recent, though limited studies in humans confirm the contribution of soluble (pro)renin receptor (s(P)RR) to renin-angiotensin system (RAS) activation, volume retention and renal damage, with an apparent ethnic difference. This study aimed to compare levels of s(P)RR between black and white ethnicities and explore for the first time in a normotensive young bi-ethnic population the associations of s(P)RR with relative wall thickness (RWT), left ventricular mass index (LVMi), left ventricular ejection fraction (LVEF), stroke volume (SV), end-diastolic volume index (EDVI) and end-systolic volume index (ESVI). Design and method: The study population included 1175 apparently healthy young black (N = 588) and white (N = 587) participants aged 20–30 years old. We recorded ambulatory blood pressure. Echocardiography measurements were performed to determine RWT, LVMi, LVEF, SV (standardized for body height), EDVI and ESVI (both standardized for body surface area). s(P)RR was analyzed from serum, while plasma renin activity-surrogate (PRA-S) and angiotensin II were determined using the RAS™ Fingerprint. Results: s(P)RR, PRA-S, angiotensin II, SV, EDVI and ESVI were higher in the white group as compared to the black group (all P < 0.001). RWT and LVEF were higher in the black group (both P< = 0.012), while LVMi was similar between the two groups (P = 0.66). Using forward stepwise multiple regression analyses, we observed independent associations of s(P)RR with RWT (β=0.13; P = 0.009), LVEF (β=-0.12; P = 0.008), SV (β=-0.17; P < 0.001) and EDVI (β=-0.13; P = 0.006) only in white adults. The associations were independent of angiotensin II, which did not enter any of the models when included as a covariate. No associations were observed in the total or black group. Conclusions: s(P)RR associated with an increase in RWT and adversely with left ventricular function in normotensive young white adults and not in their black counterparts. These results suggest that s(P)RR has the potential to be an early marker of cardiac remodeling and dysfunction independent of hypertension and systemic renin-angiotensin activity in white populations.