Associations of Metabolites Related Salt Sensitivity of Blood Pressure and Essential Hypertension in Chinese Population: The EpiSS Study.

BACKGROUND

Salt sensitivity of blood pressure (SSBP) is an important risk factor for essential hypertension and cardiovascular diseases, and its metabolic mechanisms remain poorly understood. This study aimed to identify SSBP-associated metabolic biomarkers and investigate their potential mediating role in the SSBP-hypertension pathophysiology.

METHODS

Based on the Systematic Epidemiological Study of Salt Sensitivity (EpiSS) conducted in 2014-2016, we performed a case-control study involving 54 matched pairs of participants classified as salt-sensitive or salt-resistant with targeted metabolomics detected. Multivariable logistic regression analyses were conducted to assess the metabolites associations with SSBP and hypertension. The diagnostic performance of the model was evaluated using the receiver operating characteristic curve (ROC) analysis yielded an area under the curve (AUC) value, sensitivity, and specificity. Furthermore, the potential mediating effects of targeted metabolites on the relationship between SSBP and essential hypertension were explored.

RESULTS

Three metabolites demonstrated significant SSBP associations: L-Glutamine (OR = 0.998; 95% CI: 0.997, 0.999), PC (16:1/14:0) (OR = 1.039; 95% CI: 1.003, 1.077), and ChE (22:4) (OR = 1.115; 95% CI: 1.002, 1.240). Among them, L-Glutamine demonstrated the highest diagnostic efficiency for SSBP (AUC = 0.766; 95% CI: 0.677, 0.855). The combined model of the three metabolites slightly improved diagnostic efficiency (AUC = 0.788; 95% CI: 0.703, 0.874). L-Glutamine and Cer (d18:0/24:1) were identified as potential protective factors against essential hypertension (p < 0.05). Mediation analyses further indicated that L-Glutamine partially mediated the relationship between SSBP and essential hypertension, demonstrating a suppressive effect.

CONCLUSIONS

This study identified L-Glutamine as both a diagnostic biomarker for SSBP and a metabolic modulator attenuating hypertension risk, providing insights for early SSBP screening and the pathways governing SSBP progression to overt hypertension.