Dietary Sodium-Potassium Imbalance and Hypertension: Causal Pathways Involving Gut Microbiota Dysbiosis, Inflammation, and Metabolic Disorders.

Background: The urinary sodium-to-potassium (UNa/UK) ratio reflects the dietary sodium and potassium balance and may serve as a biomarker for hypertension (HTN). An imbalance in the dietary sodium-potassium ratio may contribute to systemic inflammation, alterations in gut microbiota (GM), and related metabolic disorders. This study aimed to investigate the relationship between the UNa/UK ratio, HTN, inflammation, GM, and metabolic abnormalities using cross-sectional and Mendelian randomization (MR) analyses. Methods: We included 1210 hospitalized patients (median age, 51 (43-57) years; 57.9% male) who underwent 24-hour urine electrolyte measurement. Participants were grouped by the median UNa/UK ratio (4.40) for subsequent analysis, with 605 participants in each group. Additionally, we performed two-sample MR analyses to evaluate causal relationships between the UNa/UK ratio and HTN, circulating inflammatory proteins and immune cells, GM, and plasma metabolites. Results: A cross-sectional analysis revealed significant associations between the UNa/UK ratio and HTN prevalence, inflammation scores, and metabolites. Logistic regression confirmed the UNa/UK ratio as an independent predictor of HTN (odds ratio (OR): 1.076; 95% confidence interval (CI): 1.037-1.116). Spearman correlation analysis showed a positive correlation between the UNa/UK ratio and several inflammatory scores. The MR analyses indicated a causal effect of the UNa/UK ratio on HTN (inverse-variance weighted method: OR: 1.5130, 95% CI: 1.1613-1.9712), inflammatory proteins, immune cells, GM, and plasma metabolites. Conclusions: The UNa/UK ratio was significantly associated with HTN risk, systemic inflammation, GM dysbiosis, and metabolic disorders. Integrating both cross-sectional and MR approaches, our findings highlight the UNa/UK ratio as a clinically relevant biomarker and reinforce the role of dietary sodium-potassium balance in modulating HTN through underlying mechanisms involving inflammation, GM alterations, and metabolites.