A Prospective Clinical and Field Study Evaluating the Role of Salt Sensitivity Phenotyping in Guiding Antihypertensive Drug Selection and Reducing the Psychological Burden of Trial-And-Error Therapy

The objective of the prospective study was to investigate the significance of phenotypic characterization of salt sensitivity in the selection of initial antihypertensive therapy and its effect on blood pressure control among patients with stage 1 hypertension. Another aim was to assess whether a phenotype-driven strategy could reduce the psychological burden associated with trial-and-error prescribing or not. The field study was carried out as a cluster-randomized trial in three primary care centers in Tashkent and the Fergana Valley region of Uzbekistan in May to November 2025. 210 patients with recently detected stage 1 hypertension were included in the study and randomly allocated into two groups with phenotype-directed therapy (n = 112) and conventional management (n = 98). For those in the phenotype group, all participants were screened for salt sensitivity through oral salt tolerance testing prior to any interventions; their baseline and readings after administration of 200 mL of solution containing 2 g of sodium chloride were measured at 120 min, with salt sensitivity indicated by a 10 mmHg rise in systolic blood pressure. Salt sensitive patients were prescribed hydrochlorothiazide (25 mg/daily), while resistant patients were administered amlodipine (5 mg/daily). If the goal had not been met by week 4, then telmisartan 40 mg would be included. In the standard care group, one of the following monotherapies could be administered depending on the treating physician based on national guidelines: ACE inhibitor, angiotensin receptor blocker, calcium channel blocker, or thiazide diuretic. The primary objective of the study was the percentage of patients attaining their blood pressure target (<140/90 mm Hg) after week 12. In the phenotyping approach group, 53.6 percent of patients were found to have salt sensitivity phenotype. After 12 weeks, the proportion of patients having attained target blood pressure was significantly higher in the phenotyping group, that is, 78.6 percent versus 62.2 percent in the standard care group (P = 0.009). There was a significant difference in the mean systolic blood pressure decrease among the two groups (18.9 vs. 14.7 mm Hg; P = 0.001). Moreover, there was a reduced requirement for a second medication among the phenotyping group (36.4% vs. 51.6%; P=0.03), and no statistically significant difference in adverse events in both groups. The results indicate that a simple salt sensitivity phenotyping strategy can help identify patients for drug therapy and significantly increase treatment efficacy. Since this method reduces the amount of experimentation necessary to change medicines, it may also help reduce the psychological stress that patients have when first dealing with their hypertension.