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Familial and Phenotypic Associations of the Aldosterone Renin Ratio

Lookup NU author(s): Dr Peter Avery, Professor Bernard Keavney


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Context: The aldosterone to renin ratio (ARR) is a marker of aldosterone excess, widely used to screen for primary aldosteronism (PA). The significance of a raised ARR in normotensive and hypertensive subjects and the phenotypic and familial factors affecting it are unclear. Objective: We estimated the distribution and heritability of the ARR and tested for associations between ARR and blood pressure (BP) with 11 polymorphisms at the CYP11B1/CYP11B2 locus. Design and Setting: A total of 1172 individuals from 248 Caucasian families ascertained via a hypertensive proband were evaluated. Main Outcome Measure: Plasma aldosterone was measured by RIA, and plasma renin concentration was measured by the LIAISON Direct Renin chemiluminescent immunoassay. Results: Unadjusted and adjusted ARR were continuously distributed in normotensives and hypertensives, with no evidence of a cutoff that would identify a separate population with PA. Median ARR was 4.19 ng/liter per mIU/liter (range, 0.04-253.16). ARR levels were higher in females and associated with age, body mass index, and potassium. Antihypertensive agents had significant predictable effects on the ARR. Renin was negatively associated, and ARR was positively associated with ambulatory BP readings (P < 0.001) in subjects not taking antihypertensives. The heritability of the ARR was 38.1% (P < 10(-8)). Plasma aldosterone, but not ARR, was influenced by the intron 2 conversion variation in the CYP11B2 gene (beta = -0.07; P = 0.04). Conclusions: The ARR is continuously distributed, is influenced by genetic and environmental factors, and is not a marker of a distinct pathological abnormality but possibly reflects the long-term influence of aldosterone on cardiovascular homeostasis. (J Clin Endocrinol Metab 94: 4324-4333, 2009)

Publication metadata

Author(s): Alvarez-Madrazo S, Padmanabhan S, Mayosi BM, Watkins H, Avery P, Wallace AM, Fraser R, Davies E, Keavney B, Connell JM

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Endocrinology & Metabolism

Year: 2009

Volume: 94

Issue: 11

Pages: 4324-4333

ISSN (print): 0021-972X

ISSN (electronic): 1945-7197

Publisher: The Endocrine Society


DOI: 10.1210/jc.2009-1406


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Funder referenceFunder name
National Research Foundation
Lily and Ernst Hausman Trust
Medical Research Council
CONACYT187101Mexican National Council for Science and Technology
FS/05/095/19937British Heart Foundation
G0400874Medical Research Council