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Familial and Phenotypic Associations of the Aldosterone Renin Ratio

British Heart Foundation Glasgow Cardiovascular Research Centre (S.A.-M., S.P., R.F., E.D., J.M.C.), Faculty of Medicine, University of Glasgow, Glasgow G12 8TA, United Kingdom; Department of Medicine (B.M.M.), Groote Schuur Hospital and University of Cape Town, Cape Town 7701, South Africa; Department of Cardiovascular Medicine (B.M.M., H.W.), University of Oxford, Oxford OX3 9DU, United Kingdom; School of Mathematics and Statistics (P.A.), Newcastle University, Newcastle upon Tyne, NE1 7RU, United Kingdom; Department of Clinical Biochemistry (A.M.W.), Glasgow Royal Infirmary, Glasgow G4 0SF, United Kingdom; and Department of Cardiovascular Sciences (B.K.), Newcastle University, Newcastle upon Tyne, NE1 3BZ, United Kingdom

Address all correspondence and requests for reprints to: Professor Bernard Keavney, Department of Cardiovascular Sciences, University of Newcastle, Newcastle upon Tyne NE1 3BZ, United Kingdom. E-mail: b.d.keavney{at}ncl.ac.uk.

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 (β = –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.