Subclinical primary aldosteronism: toward a conceptual framework linking primary aldosteronism and low-renin...

Primary aldosteronism (PA) has traditionally been considered a rare cause of secondary hypertension, but growing evidence supports a broader continuum of renin-independent aldosterone production extending into normotensive and mildly hypertensive populations. Subclinical primary aldosteronism (SPA) has emerged as a conceptual framework describing this milder phenotype. However, a universally accepted definition of SPA remains lacking, and consensus diagnostic criteria have yet to be established. This review synthesizes current evidence regarding SPA, including its epidemiology, pathophysiology, clinical implications, diagnostic challenges, and potential therapeutic strategies. Low-renin phenotypes are observed in a substantial proportion of individuals, although the true prevalence of SPA remains uncertain due to the lack of consensus diagnostic criteria. Observational studies have associated SPA with adverse cardiovascular and renal outcomes, including arterial stiffness, adverse cardiac remodeling, major adverse cardiovascular events, albuminuria, and chronic kidney disease progression, with effects not fully explained by blood pressure elevation alone. Conventional screening strategies based on the aldosterone-to-renin ratio have limitations in detecting this subclinical spectrum. Mineralocorticoid receptor antagonists and aldosterone synthase inhibitors represent hypothesis-generating therapeutic strategies, although prospective interventional evidence in SPA populations is lacking. At present, SPA should be regarded as an emerging risk-associated biochemical phenotype rather than an established disease category, pending prospective validation. Future studies are needed to determine whether consensus diagnostic criteria can be established and to validate clinically applicable screening strategies for this emerging endocrine phenotype.