A Molecular Diagnostic Approach for Hypertension Through Establishment of a Metabolite Risk Score Using a Multi-Metabolite Panel Identified via UHPLC-MS/MS.

Hypertension (HTN) is often asymptomatic and difficult to detect using blood pressure (BP) measurements unless BP is substantially elevated. Given its association with metabolic alterations and complications, this study aimed to establish a metabolite risk score (MRS) as a molecular tool to complement BP-based diagnosis. Plasma samples and clinical data from healthy individuals and HTN patients were obtained through the Korea Biobank Network, and non-targeted metabolomics was performed. Eight HTN-associated key metabolites were selected by least absolute shrinkage and selection operator (LASSO) regression. An MRS was calculated as their weighted sum in the discovery set and subsequently validated in the replication set. The MRS showed strong discriminative performance for HTN status in the replication set [area under the curve (AUC) = 0.926, 95% confidence interval (CI): 0.876-0.976] and remained significantly associated with prevalent HTN after adjustment for age and BMI [odds ratio (OR) = 1.747, 95% CI: 1.317-2.318,