Precision medicine for resistant hypertension: integrating molecular phenotyping, gut microbiome, device therapy and digital care

Resistant hypertension confers substantial cardiovascular and renal risk. However, apparent treatment resistance often arises from reversible problems rather than a discrete biological disease. Precision management starts with confirming true resistant hypertension through standardized office measurement, out-of-office evaluation, validation of treatment adequacy and medication exposure, adherence assessment, and screening for secondary causes. Mechanism-driven phenotyping further identifies treatable pathogenic drivers. Primary aldosteronism, characterized by autonomous aldosterone excess, renin suppression, and sodium retention, serves as the best-defined prototype. Other contributors, including chronic kidney disease, obstructive sleep apnea, sympathetic overactivity, vascular and immune-metabolic dysfunction, and gut microbiome–metabolite pathways, remain at different stages of clinical translation. Phenotypic characterization guides optimized diuretic and mineralocorticoid receptor antagonist regimens, selected targeted agents, appropriate device therapies, continuous safety monitoring and long-term care. Digital monitoring, team-based care, registries and learning health systems support adherence optimization, treatment titration, safety surveillance and equitable care access. The overarching aim is to progress from simplistic diagnostic labels to validated clinical phenotyping, personalized treatment matching, and sustained blood pressure control.