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

Author:

Arnold Natalie123,Hermanns Iris M14ORCID,Schulz Andreas1,Hahad Omar45ORCID,Schmitt Volker H45ORCID,Panova-Noeva Marina146,Prochaska Jürgen H1456,Binder Harald78ORCID,Pfeiffer Norbert9,Beutel Manfred10ORCID,Lackner Karl J411,Münzel Thomas45ORCID,Wild Philipp S1456

Affiliation:

1. Preventive Cardiology and Preventive Medicine, Department of Cardiology I, University Medical Center of the Johannes Gutenberg-University Mainz , Mainz , Germany

2. Department of Cardiology, University Heart and Vascular Center Hamburg , Hamburg , Germany

3. German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck , Hamburg , Germany

4. German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main , Mainz , Germany

5. Department of Cardiology—Cardiology I, University Medical Center of the Johannes Gutenberg-University Mainz , Langenbeckstraße 1, 55131 Mainz , Germany

6. Center for Thrombosis and Hemostasis, University Medical Center of the Johannes-Gutenberg University Mainz , Mainz , Germany

7. Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg-University Mainz , Mainz , Germany

8. Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg , Freiburg , Germany

9. Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz , Mainz , Germany

10. Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz , Mainz , Germany

11. Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg-University Mainz , Mainz , Germany

Abstract

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 using the fully automated LIAISON® platform (DiaSorin) among 5362 participants of the population-based Gutenberg Health Study, who were normotensive and had no clinically overt cardiovascular disease at baseline. During a follow-up period of 5 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 5 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% CI 2.05–3.6) for Q4 of ARR and having body mass index ≥ 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.

Funder

Stiftung Rheinland Pfalz für Innovation

Initiative Health Economy Rhineland-Palatinate by the Ministry of Health and the Ministry of Economics, Rhineland-Palatinate

Federal Ministry of Education and Research, Germany

P.S.W. and T.M. are PI’s of the DZHK (German Center for Cardiovascular Research), Partner Site Rhine-Main, Mainz, Germany

Publisher

Oxford University Press (OUP)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

Reference26 articles.

1. Hypertension: renin–angiotensin–aldosterone system alterations;Te Riet;Circ Res,2015

2. Serum aldosterone and the incidence of hypertension in nonhypertensive persons;Vasan;N Engl J Med,2004

3. High plasma aldosterone and low renin predict blood pressure increase and hypertension in middle-aged Caucasian populations;Meneton;J Hum Hypertens,2008

4. Clinical and genetic correlates of aldosterone-to-renin ratio and relations to blood pressure in a community sample;Newton-Cheh;Hypertension,2007

5. The spectrum of subclinical primary aldosteronism and incident hypertension: a cohort study;Brown;Ann Intern Med,2017

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