Cardiovascular Effects of Aldosterone

BACKGROUND: High plasma aldosterone has deleterious cardiovascular effects that are independent of blood pressure, but the role of the mineralocorticoid receptor remains unclear. Renal pseudohypoaldosteronism type 1 is a rare autosomal-dominant disease caused by NR3C2 loss-of-function mutations, which is characterized by renal salt loss and compensatory high renin and aldo secretion. We aimed to assess the cardiovascular outcomes in adults carrying NR3C2 mutations. METHODS AND RESULTS: In this case-control study, 39 NR3C2 mutation carriers were compared with sex- and age-paired noncarriers. Patients underwent cardiac and vascular ultrasound, cardiac MRI with gadolinium injection, measurement of pulse wave velocity, extracellular water, 24-hour ambulatory blood pressure, and autonomous nervous system activity. Mutation carriers showed increased aldo and renin plasma levels (4.5- and 1.6-fold, respectively; P<0.0001), together with increased salt appetite (1.8-fold; P=0.002), with normal extracellular water and blood pressure, and no autonomous nervous system activation. Cardiac and vascular parameters were not significantly different between mutation carriers and noncarriers (no left ventricular remodeling or fibrosis, normal left ventricular systolic function, and aorta stiffness). Tissue Doppler showed better diastolic left ventricular function in mutation carriers (e', P=0.001; E/e', P=0.003). Mutation carriers had significantly more frequent history of slow body weight recovery at birth, symptomatic hypotension, and miscarriage in women. CONCLUSIONS: Despite life-long increase in plasma aldosterone and renin levels, no adverse cardiovascular outcome occurred in pseudohypoaldosteronism type 1, but rather an improved diastolic left ventricular function. This suggests that the cardiovascular consequences of aldosterone excess require full mineralocorticoid receptor signaling. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov; unique identifier: NCT00646828.