The Role of Antigen Carbohydrate 125 in Modulating Soluble ST2. Prognostic-Related Effects in Acute Heart Failure

Background: Acute heart failure (AHF) is a complex syndrome associated with high mortality and hospital readmissions, characterized by volume overload and inflammation. Soluble ST2 (sST2) and antigen carbohydrate 125 (CA125) are emerging biomarkers that reflect these processes and may interact to influence long-term outcomes in AHF patients. This study aims to examine the prognostic relationship between sST2 and CA125 in predicting mortality and heart failure (HF)-related hospitalizations in patients with decompensated heart failure. Methods: In a cohort of 635 patients with AHF, we investigated whether the prognostic value of sST2 varies according to CA125 levels (≤35 vs. >35 U/ ml). The endpoints were: a) time to all-cause death, and b) the combined of time to death or new HF-admission. Results: This substudy of the EAHFE registry shows that the association between sST2 and long-term adverse outcomes (mortality and HF-hospitalizations) in patients with AHF was differentially influenced by CA125 concentrations (p-value for interactions= 0.031 and 0.029, respectively). Higher sST2 was associated with the risk of death and the composite of death/HF readmission when CA125 was >35 U/mL [HR=1.02 (CI 95%: 1.01-1.04), p=0.006 and 1.02 (CI 95%: 1.01-1.03), p=0.013 per increase in 10 ng/mL, respectively], but not when CA125 was ≤35 U/mL. Conclusions: This study highlights the prognostic interaction between sST2 and CA125 in AHF. Elevated sST2 predicts poor outcomes mainly in patients with high CA125 levels (>35 U/mL), suggesting CA125's role in modulating inflammatory activity in HF. Further research is needed.