Familial and phenotypic associations of the aldosterone renin ratio

Alvarez-Madrazo, S., Padmanabhan, S. , Mayosi, B. M., Watkins, H., Avery, P., Wallace, A. M., Fraser, R., Davies, E. , Connell, J. M. and Keavney, B. (2009) Familial and phenotypic associations of the aldosterone renin ratio. Journal of Clinical Endocrinology and Metabolism, 94(11), pp. 4324-4333. (doi:10.1210/jc.2009-1406)

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Publisher's URL: http://dx.doi.org/10.1210/jc.2009-1406

Abstract

<p>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.</p> <p>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.</p> <p>Design and Setting: A total of 1172 individuals from 248 Caucasian families ascertained via a hypertensive proband were evaluated.</p> <p>Main Outcome Measure: Plasma aldosterone was measured by RIA, and plasma renin concentration was measured by the LIAISON Direct Renin chemiluminescent immunoassay.</p> <p>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 (β = −0.07; P = 0.04).</p> 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Wallace, Ms Alison and Davies, Professor Eleanor and Padmanabhan, Professor Sandosh and Alvarez-Madrazo, Dr Samantha and Fraser, Prof Robert and Keavney, Prof Bernard
Authors: Alvarez-Madrazo, S., Padmanabhan, S., Mayosi, B. M., Watkins, H., Avery, P., Wallace, A. M., Fraser, R., Davies, E., Connell, J. M., and Keavney, B.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of Clinical Endocrinology and Metabolism
Publisher:The Endocrine Society
ISSN:0021-972X
ISSN (Online):1945-7197
Published Online:09 October 2009
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
392521Regulation of aldosterone and cortisol synthesis in hypertension and cardiovascular diseaseEleanor DaviesMedical Research Council (MRC)G0400874Institute of Cardiovascular and Medical Sciences
392522Regulation of aldosterone and cortisol synthesis in hypertension and cardiovascular diseaseEleanor DaviesMedical Research Council (MRC)G0400874Institute of Cardiovascular and Medical Sciences