BACKGROUND: Isthmin-1 (ISM1) plays an important role in maintaining glucose homeostasis and lipid metabolism. However, the relationship between circulating ISM1 and hypertension remains unclear. This study was aimed to investigate the association between serum ISM1 levels and blood pressure and evaluate value of circulating ISM1 for predicting abnormal Na METHODS: Four hundred sixty-eight individuals newly diagnosed with primary hypertension and 582 healthy individuals were initially screened. 84 participants were eligible for this case-control study. Serum ISM1 levels were assessed using ELISA. Spearman correlation analysis and partial correlation analysis were conducted to confirm the correlation. Multiple linear regression analysis was used to assess the independent association of serum ISM1 concentration with blood pressure. The receiver operating characteristic (ROC) curve was employed to evaluate the sensitivity of ISM1 in predicting abnormal Na RESULTS: The serum ISM1 levels of hypertensive individuals were higher than that of healthy individuals. ISM1 levels were positively associated with systolic blood pressure (SBP), diastolic blood pressure (DBP) and brachial-ankle pulse wave velocity, but negatively associated with nocturnal urine Na CONCLUSIONS: Serum ISM1 levels were positively associated with SBP and DBP. ISM1 may serve as a potential biomarker of abnormal urine Na TRIAL REGISTRATION: Registered on chictr.org.cn 18/04/2024 (Registration number: ChiCTR2400083204).