Recent studies in non-hypertensive patients have shown aldosterone renin ratio (ARR) to be heritable and associated with increased risk of blood pressure (BP) elevation. Furthermore, a raised ARR is present in 10% of hypertensive patients although the precise significance of this is unclear. The magnitude of heritability of ARR will indicate the influence of genetic determination of the phenotype. In this study, we estimated the heritabilities of the components of ARR and the ratio itself in 1429 individuals from 248 Caucasian families ascertained in a hypertensive proband, and tested their associations with a range of cardiovascular and steroid phenotypes.
Plasma aldosterone was measured by radioimmunoassay and plasma renin concentration was measured by the LIAISON Direct Renin chemiluminescent immunoassay. Aldosterone, renin and ARR were adjusted for age, sex, BMI, drug treatment and log transformed for analysis.
The heritabilities of aldosterone, renin and ARR were 28.7, 27.4 and 38.1% respectively (all P<10−9). Plasma aldosterone was associated with polymorphic variation in the CYP11B2 gene. The multivariable correlates for adjusted ARR (Model R2=0.24) were sex (β=0.38 (95% C.I. 1.321.63); P<0.0001), age (0.01 (1.001.01); 0.0002), hypertension (0.13 (1.031.24); 0.0079), BMI (−0.03 (0.960.99); <0.0001), potassium (0.26 (1.121.49); 0.0004) and beta blocker (0.65 (1.632.26); <0.0001) and ACE inhibitor use (−1.34 (0.220.31); <0.0001). Low renin (high ARR) was only associated with daytime BP; there was a J-shaped relationship between ARR and daytime BP which was primarily determined by renin. Left ventricular mass and plasma cortisol levels were also associated independently with ARR levels (all P<0.05).
ARR and its components show high heritabilities and significant associations with cardiovascular and steroid phenotypes. These relationships appear to be driven mainly by renin, indicating that subphenotyping of essential hypertension using ARR is complex and must take into account the interaction between its main components; the ARR is not simply a marker of primary aldosteronism.