Abstract
BACKGROUND: Obesity-related aldosteronism may increase risk for adverse cardiometabolic outcomes. We investigated the association between dysregulated aldosterone production and cardiac structure, function, and adiposity under controlled physiological conditions in obese hypertensive adults. METHODS: Community-dwelling participants with overweight or obesity and stage 1-2 hypertension were prospectively enrolled to undergo comprehensive phenotyping of aldosterone production, along with cardiac and abdominal MRI. Aldosterone production was assessed via four controlled physiological maneuvers designed to assess both renin-independent aldosterone production: seated saline suppression testing (SST) and oral sodium loading (OSLT), and ACTH-modifiable aldosterone production: overnight dexamethasone suppression (DST), and adrenocorticotropic hormone (ACTH) stimulation. Cardiac structure and function, cardiac fat volume, hepatic fat content, and visceral-to-subcutaneous fat ratio were assessed by MRI. RESULTS: 72 participants were enrolled, with a mean age of 55.2±9.5 years, a mean BMI of 37.8±5.3 kg/m², and of whom 68.1% were women. After SST, a continuum of non-suppressible and dysregulated aldosterone production was observed, with 29.2% of participants meeting criteria for overt primary aldosteronism. Greater post-SST aldosterone levels were independently associated with greater left ventricular mass index (p<0.001), left ventricular global longitudinal strain (p=0.038), cardiac fat volume (p=0.023), and visceral-to-subcutaneous fat ratio (p=0.003). These associations between dysregulated aldosterone production and cardiac remodeling and adipose-tissue parameters were consistently replicated under conditions of oral sodium loading and dexamethasone suppression and ACTH-stimulation. CONCLUSIONS: In obese adults with hypertension, dysregulated aldosterone production and overt primary aldosteronism are prevalent and independently associated with adverse cardiac remodeling and increased cardiometabolic adipose tissue volume. These findings highlight a potential pathophysiologic link between aldosterone excess and obesity-related cardiometabolic disease that should be investigated in interventional studies.