Prognostic value of suppression of tumorigenesis-2 (ST2) for cardiovascular events in coronary artery disease patients with and without diabetes mellitus

Abstract Background: Suppression of tumorigenesis-2 (ST2) is implicated in myocardial overload and has long been recognized as an inflammation marker related to heart failure and acute coronary syndromes, but data on the prognostic value of ST2 in patients with coronary artery disease (CAD) remain limited. This study sought to investigate the prognostic value of ST2 in patients with established coronary artery disease and its predictive value in CAD patients with or without type 2 diabetes mellitus (T2DM).Methods: A total of 3641 consecutive patients were included in this prospective cohort study. The primary end point was major adverse cardiovascular events (MACEs). The secondary end point was all-cause death. The association between ST2 and outcomes was investigated using multivariable Cox regression.Results: During a median follow-up of 6.4 years, 775 patients had the occurrence of MACEs and 275 patients died. Kaplan-Meier survival estimates indicated that the patients with higher levels of ST2 (ST2> 19 ng/ml) had a significantly increased risk of MACEs (log-rank p＜0.001) and all-cause death (log-rank p<0.001). Multiple Cox regression models showed that higher level of ST2 was an independent predictor for MACEs developments (HR=1.36, 95% CI 1.17-1.56, p<0.001) and all-cause death (HR=2.01, 95% CI 1.56-2.59, p<0.001). The addition of ST2 to established risk factors significantly improved risk prediction of the composite outcome of MACEs and all-cause death (C-statistic, net reclassification index, and integrated discrimination improvement, all p<0.05). Subgroup analyses showed that ST2 remained a significant predictor of MACEs and all-cause death in patients with and without T2DM in multivariable models.Conclusions: A higher level of ST2 is significantly associated with long-term MACEs and all-cause death in CAD patients with and without T2DM. ST2 may provide incremental prognostic value beyond traditional risk factors.