Renin, aldosterone, the aldosterone-to-renin ratio, and incident hypertension among normotensive subjects from the general population

Abstract

Aims To investigate the predictive ability of direct plasma renin and aldosterone concentrations as well as their ratio (aldosterone-to-renin (ARR)) for incident hypertension in the general population. Methods and Results Concentration of renin and aldosterone were measured by a chemiluminescence immunoassay (CLIA) using the fully-automated LIAISON® platform (DiaSorin) among 5,362 participants of the population-based Gutenberg Health Study, who were normotensive and had no clinically-overt CVD at baseline. During a follow-up period of five years, 18.6% (n = 996) developed a new-onset hypertension. Comparing extreme quartiles of biomarker distribution, the relative risk (RR) for incident arterial hypertension was found to be 1.58 (95% confidence interval (CI) 1.25-2.00; p = 0.00015; Q1 vs Q4ref) for renin; 1.29 (95% CI 1.05-1.59, p = 0.018; Q4 vs Q1ref) for aldosterone and 1.70 (95%CI 1.33-2.12; p < 0.0001; Q4 vs Q1ref) for ARR after multivariable adjustment in men. In females, only high ARR was independently predictive for incident hypertension over five years (RR 1.29 (95% CI 1.04-1.62); p = 0.024). Even in the subgroup of individuals having biomarker concentrations within the reference range, high ARR was predictive for new-onset hypertension in men (RR 1.44 (95%CI 1.13-1.83); p = 0.003). Finally, synergistic effects of co-prevalent obesity and ARR on incident hypertension were also demonstrated, resulting in markedly higher risk estimates as seen for biomarker alone (RR of 2.70 (95% 2.05-3.6) for Q4 of ARR and having BMI ≥ 30 kg/m2 vs low ARR (Q1ref) and normal weight; p < 0.0001). Conclusion Among normotensives from the general population ARR possesses a stronger predictive value for incident hypertension than renin or aldosterone alone. The prediction of arterial hypertension by ARR was even stronger in obese subjects. Translational Perspective These findings may help in a better understanding of importance of aldosterone-renin imbalance for the development of new-onset hypertension among normotensive subject and identify individuals at greatest risk, who probably required more intensive preventive measures.

Aldosterone and renin concentrations and blood pressure in young Indigenous and non‐Indigenous adults in the Northern Territory: a cross‐sectional study

“…However, the Raine Study found that higher ARR at 17 years of age was associated with higher blood pressure at 27 years of age 20 . Moreover, given evidence for increased risk of incident hypertension in people with low renin and high aldosterone levels, 7,26 the relationship between ARR and blood pressure may evolve over time.…”

“…The prevalence of positive screening test results depends on its definition; the threshold we applied (70 pmol/mU) is typical for Australian practice, 13 and no minimum plasma aldosterone concentration was required; this relatively high threshold yields a conservative estimate of the number of participants with possible primary aldosteronism 30 . Finally, primary aldosteronism screening was not conducted according to the international Endocrine Society recommendations, 31 (ie, we screened all participants, not just those with higher blood pressure or resistant hypertension) as abnormal aldosterone regulation has been identified in some people without hypertension, 7,26,32 suggesting that its production can begin to rise prior to the onset of hypertension 6 …”

Novel biomarkers and emerging tools to identify causal molecular pathways in hypertension and associated cardiovascular diseases

“…The potential of RAAS proteins as biomarkers predicting new-onset of HT was long limited and not consistent between studies mainly due to the analytical challenges in protein measurement methods [29]. However, a recent study revealed that aldosterone-to-renin ratio obtained by simultaneous measurement of both analytes using fully automated chemiluminescence immunoassay (CLIA), possesses a relatively stronger predictive potential for incidental HT, compared to individual aldosterone or renin levels [30]. This novel analytical method may be used in the future in large-scale biobanks allowing testing causal relationships between RAAS proteins and BP traits.…”