Angiopoietin-2 Surpasses Soluble Thrombomodulin and Syndecan-1 in Characterizing Septic Shock and Predicting Mortality--A Prospective Observational Study.

BACKGROUND: The angiopoietin/Tie pathway, essential for endothelial homeostasis, plays a key role in sepsis-induced endothelial dysfunction. This study evaluated angiopoietin-2 (Ang-2) as a biomarker for assessing disease severity in adult sepsis patients, comparing it with syndecan-1 and soluble thrombomodulin (sTM). METHODS: Based on predefined criteria, we recruited sepsis patients admitted to the Department of Critical Care Medicine in the First Affiliated Hospital of China Medical University from April 2024 to May 2025. These patients were stratified into sepsis without shock and septic shock groups according to their clinical presentation at ICU admission. Peripheral blood samples were collected at enrollment for endothelial biomarker quantification. Multivariate logistic regression was performed to assess the independent association of these biomarkers with septic shock; intergroup comparisons and correlation analyses were conducted to evaluate their associations with organ dysfunction; and receiver operating characteristic curves were constructed to evaluate their predictive performance for short-term mortality. RESULTS: This study enrolled 233 sepsis patients. Ang-2, syndecan-1, and sTM levels were significantly higher in patients with septic shock compared to those without shock. Multivariate analysis identified Ang-2 as an independent risk factor for septic shock. All three endothelial biomarkers were markedly higher in patients with more severe organ dysfunction (SOFA-1 score>5) compared to those with lower scores (SOFA-1≤5) (all P<0.001), with Ang-2 demonstrating the strongest positive correlation with SOFA-1 scores (ρ=0.403, P<0.01). Furthermore, in predicting short-term mortality, including both ICU and 28-day mortality, Ang-2 exhibited the highest prognostic performance (AUC=0.748), and its predictive accuracy was further enhanced when combined with interleukin-6 (IL-6) and tissue plasminogen activator inhibitor complex (t-PAI-C). CONCLUSION: Ang-2 serves as a superior biomarker compared to sTM and syndecan-1 for characterizing septic shock, evaluating organ dysfunction severity and predicting short-term mortality.