RENIN, ALDOSTERONE, THE ALDOSTERONE-TO-RENIN RATIO AND INCIDENT ARTERIAL HYPERTENSION AMONG NORMOTENSIVE SUBJECTS FROM THE POPULATION

Abstract

Objective: To investigate the predictive value of directly-measured plasma renin concentration (PRC), aldosterone (PAC) and the aldosterone-to-renin ratio (ARR) for incident arterial hypertension in the population. Design and method: From the sample of 15,010 participants of the population-based Gutenberg Health Study, only normotensive subjects at baseline (n = 5,362) were included in the present analysis. Concentrations of renin and aldosterone were determined by a competitive chemiluminescence immunoassay (CLIA) using the fully-automated LIAISON® platform (DiaSorin). Extreme quartiles (Q) of biomarker concentrations were compared by means of regression analysis, adjusted for traditional CVRF, renal function and hormonal status (in women only). Results: During a follow-up period of five years, new-onset hypertension developed in 996 participants (18.6%). Among men, the relative risk (RR) for incident arterial hypertension was found to be 1.49 (95% confidence interval (CI) 1.19–1.86; p = 0.00054; Q1 vs Q4ref) for renin; 1.26 (95%CI 1.02–1.56, p = 0.029; Q4 vs Q1ref) for aldosterone and 1.70 (95%CI 1.33–2.12; p < 0.0001; Q4 vs Q1ref) for ARR in a fully adjusted model. In females, only high ARR was an independent predictor of incident arterial hypertension (RR 1.29 (95% CI 1.04–1.62); p = 0.024). In the subgroup of individuals with concentrations within the reference range, only ARR (Q4 vs Q1ref) was predictive for the new-onset hypertension in men (RR 1.44 (95%CI 1.13–1.83) p = 0.003). Synergistic effects of co-prevalent obesity and biomarker concentrations on incident hypertension were also demonstrated, resulting in a markedly higher risk estimates (e.g. men in Q4 of ARR and having BMI >= 30 kg/m2 had compared to subjects with normal weight and low ARR (Q1ref), a RR of 2.92 (95% 1.90–4.49); p < 0.0001)). Conclusions: Among normotensives from the general population ARR possesses a stronger predictive value for the development of new-onset hypertension than renin or aldosterone alone. The prediction of the development of arterial hypertension by ARR was even stronger in obese subjects.