SUN-225 Primary Aldosteronism Pathophysiology and Cardiac Fat in Obesity

Abstract Disclosure: C. Tsai: None. J. Chan: None. J. Milks: None. A. Ferrebus: None. I. Hanna: None. S. Mahrokhian: None. A.J. Newman: None. S. Parisien-La Salle: None. I.R. Marques: None. K. Foote: None. R.Y. Kwong: None. M. Jerosch-Herold: None. A. Vaidya: None. J.M. Brown: None. Background: Adiposity has been linked to excess aldosterone production and mineralocorticoid receptor (MR) activation, implicating a mechanism of obesity-related cardiovascular disease. Cardiac fat, comprising epicardial and pericardial fat, is a recognized cardiovascular risk factor and has been linked to elevated aldosterone concentrations in overt primary aldosteronism (PA). We aimed to investigate the relationship between the spectrum of PA pathophysiology and cardiac fat in obese adults. Method: We here report a cross-sectional analysis of baseline data from a randomized trial of 71 participants with Stage 1-2 hypertension and obesity evaluating the impact of MR antagonist therapy on cardiac magnetic resonance imaging (MRI) endpoints. Prior to randomization, all participants were washed off of interfering medications and underwent comprehensive phenotyping of PA pathophysiology, including oral sodium suppression and saline suppression (SST) tests to assess renin-independent aldosterone production, as well as dexamethasone suppression and adrenocorticotropic hormone (ACTH) stimulation tests to assess ACTH-mediated aldosterone production. Additionally, 24-hour ambulatory blood pressure monitoring was performed. Cardiac fat was quantified from cardiac MRI studies using whole-heart short-axis cine stack imaging and was analyzed in relation to clinical parameters and aldosterone levels. Results: The mean age of participants was 55.4 years, and the mean BMI was 34.7 kg/m². Participants were divided into high and low cardiac fat groups based on the median value (217.6 ml). Participants in the high cardiac fat group exhibited significantly higher 24-hour ambulatory systolic blood pressure (122.2 vs 127.0 mmHg; P=0.022). High cardiac fat was associated with greater renin-independent aldosterone production, assessed via both post-SST aldosterone levels (12.2 vs. 8.94 ng/dL) and post-oral sodium suppression aldosterone levels (16.0 vs. 12.1 ng/dL), and with greater ACTH- dependent and ACTH-independent aldosterone production: post-ACTH aldosterone 44.0 vs. 33.0 ng/dL, post-dexamethasone aldosterone 16.8 vs. 11.8 ng/dL (global P=0.017). Repeated measures linear mixed models confirmed a significant continuous relationship of greater cardiac fat volume with greater renin-independent and ACTH-mediated aldosterone production, including after adjustment for age, sex, body mass index and 24-hour ambulatory blood pressure (global P=0.011). Conclusion: These findings demonstrate a highly prevalent spectrum of PA pathophysiology in obese hypertensive adults that is associated with greater cardiac fat, thereby implicating the role of aldosterone and MR activation with this metabolically active fat depot known to be related to adverse cardiometabolic outcomes. Presentation: Sunday, July 13, 2025