ACE Inhibition to Distinguish Low-Renin Hypertension From Primary Aldosteronism

BACKGROUND: Primary aldosteronism (PA) is a distinct cause of low-renin hypertension (LRH), characterized by inappropriate aldosterone production. We investigated the distinction between LRH and PA by leveraging the physiological effects of angiotensin-converting enzyme inhibition. METHODS: We conducted a retrospective cohort study including 756 patients with LRH who underwent a captopril challenge test (CCT) for evaluation of PA. The distinction between PA and LRH was assessed using 4 CCT criteria: (1) Post-CCT plasma renin activity <1 ng/mL per hour and plasma aldosterone concentration decrease <30%; (2) Post-CCT aldosterone-to-renin ratio (ARR) >30 ng/dL per ng/mL per hour; (3) Post-CCT plasma renin activity <1 ng/mL per hour; and (4) Post-CCT plasma aldosterone concentration >11 ng/dL. Longitudinal outcomes following aldosterone-targeted therapy were assessed using the Primary Aldosteronism Surgery Outcome and Primary Aldosteronism Medical Outcome criteria. RESULTS: There was a continuous spectrum of nonsuppressible aldosterone production post-CCT. When interpreting CCT results based on both renin and aldosterone responses (criteria 1 or 2), 57.8% to 66.3% of patients were classified as having PA. In contrast, when based on aldosterone or renin responses alone (criteria 3 or 4), 82.5% to 95.1% of patients were classified as having PA. Complete or partial treatment response rates following aldosterone-targeted therapy were high, ranging from 86.5% to 91.7%, regardless of CCT interpretation. CONCLUSIONS: These findings highlight the blurred distinction between LRH and PA. Although persistently suppressed renin, or elevated aldosterone, following captopril facilitated the maximum capture of PA cases, the implementation of aldosterone-targeted therapy provided similar benefits to all patints, regardless of CCT interpretation. Empirical aldosterone-directed therapy for patients with LRH suspected of having PA may be an appropriate alternative to laborious diagnostics to confirm PA.