Subclinical Primary Aldosteronism Is Characterized by Maladaptive Natriuretic Peptide and Adrenal Hormonal Physiology

Abstract Context A continuum of non-suppressible aldosterone production has been demonstrated in normotensive individuals, termed subclinical primary aldosteronism (PA), and is consistently associated with increased risk for developing hypertension and cardiovascular disease. The hormonal mechanisms accounting for subclinical PA are not well understood. Methods To quantify the magnitude of subclinical PA, prospectively recruited normotensive participants (n = 75) had their maximally suppressed plasma aldosterone assessed after maintaining supine posture following an oral sodium loading protocol. To investigate the endocrine mechanisms involved with this continuum, multiple maneuvers were conducted to evaluate: (i) natriuretic peptide physiology (N-terminal pro B-type natriuretic peptide [NT-proBNP] suppression and stimulation using dietary sodium modulation); (ii) angiotensin II (AngII)-dependent aldosterone production (via dietary sodium restriction and via infusion of exogenous AngII); (iii) AngII-independent aldosterone production (via saline suppression test [SST]); and (iv) ACTH-mediated aldosterone production (via dexamethasone suppression test and ACTH-stimulation test). Results Greater magnitude of subclinical PA was associated with lower basal NT-proBNP (P-trend < .01) and blunted stimulation of NT-proBNP following sodium loading (P-trend = .023). The magnitude of subclinical PA was also associated with greater AngII-dependent (P-trend < .001) and AngII-independent (P-trend < .001) aldosterone production and paralleled the severity of ACTH-mediated aldosterone production (P-trends < .001). Following SST, 24.2% of participants had a post-saline aldosterone greater than 10 ng/dL and 72.7% had a post-saline aldosterone greater than 6 ng/dL, confirming that the continuum of subclinical PA included overt PA pathophysiology within these normotensive participants. Conclusion These findings demonstrate that the pathophysiologic continuum of subclinical PA in normotensive people is characterized by natriuretic peptide insufficiency and heightened aldosterone responses to both AngII and ACTH. These early maladaptive hormonal changes provide mechanistic explanations for the role of subclinical PA in the pathogenesis of hypertension.