Familial and phenotypic associations of the aldosterone Renin ratio.
BACKGROUND
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.


METHODS
A total of 1172 individuals from 248 Caucasian families ascertained via a hypertensive proband were evaluated.


METHODS
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.
Alvarez-Madrazo
Samantha
S
Faculty of Medicine, University of Glasgow, British Heart Foundation Glasgow Cardiovascular Research Centre, Glasgow G12 8TA, United Kingdom.
Padmanabhan
Sandosh
S
Mayosi
Bongani M
BM
Watkins
Hugh
H
Avery
Peter
P
Wallace
A Michael
AM
Fraser
Robert
R
Davies
Eleanor
E
Keavney
Bernard
B
Connell
John M
JM
D000328:Adult; D000450:Aldosterone / Q000097:blood / Q000235:genetics*; D001794:Blood Pressure / Q000502:physiology; D015992:Body Mass Index; D002940:Circadian Rhythm; D005190:Family; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012083:Renin / Q000097:blood / Q000235:genetics*; D044465:White People
D000450:Aldosterone; D012083:Renin