Abstract
BackgroundSoluble suppression of tumorigenesis-2 (sST2) is implicated in myocardial overload and has long been recognized as an inflammatory marker related to heart failure and acute coronary syndrome, but data on the prognostic value of sST2 in patients with coronary artery disease (CAD) remain limited. This study sought to investigate the prognostic value of sST2 in patients with established CAD and its predictive value in CAD patients with and without type 2 diabetes mellitus (T2DM).MethodsA 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 sST2 and outcomes was investigated using multivariable Cox regression.ResultsDuring a median follow-up of 6.4 years, MACEs occurred in 775 patients, and 275 patients died. Multiple Cox regression models showed that a higher level of sST2 was an independent predictor of MACEs development (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 sST2 to established risk factors significantly improved risk prediction of the composite outcome of MACEs and all-cause death (C-index, net reclassification index, and integrated discrimination improvement, all p < 0.05). In subgroup analysis depending on diabetes status, the diabetes group had a significantly higher level of sST2, which remained a significant predictor of MACEs and all-cause death in patients with and without T2DM in multivariable models. The area under the curve (AUC) of CAD patients with diabetes mellitus was significantly higher than that of those without T2DM. For MACEs, the AUC was 0.737 (patients with T2DM) vs 0.620 (patients without T2DM). For all-cause death, the AUC was 0.923 (patients with T2DM) vs 0.789 (patients without T2DM).ConclusionsA higher level of sST2 is significantly associated with long-term MACEs and all-cause death in CAD patients with and without T2DM. sST2 has strong predictive value for cardiovascular adverse events in CAD patients with T2DM, and these results provide new evidence for the role of sST2.
Highlights
Soluble suppression of tumorigenesis-2 is implicated in myocardial overload and has long been recognized as an inflammatory marker related to heart failure and acute coronary syndrome, but data on the prognostic value of sST2 in patients with coronary artery disease (CAD) remain limited
IL-33 promotes the production of inflammatory cytokines and Th2 immune responses by signaling through a heterodimer receptor complex composed of ST2L and IL-1 receptor attachment proteins; sST2 is known to bind to IL-33, and it acts as a “decoy” receptor for IL-33 to inhibit IL-33/ST2L signaling [5, 6]
After adjusting for the established factors included in Model 1 and using the lower level of sST2 as a reference, we found that patients with an sST2 level ≥ 19 ng/ mL had a significantly higher risk of experiencing a primary outcome (HR = 1.36, 95% confidence intervals (CIs) 1.17–1.56, p < 0.001) (Table 3)
Summary
Soluble suppression of tumorigenesis-2 (sST2) is implicated in myocardial overload and has long been recognized as an inflammatory marker related to heart failure and acute coronary syndrome, but data on the prognostic value of sST2 in patients with coronary artery disease (CAD) remain limited. Soluble sST2 has been shown to be a powerful independent prognosticator in patients with acute coronary syndrome (ACS) [10, 11], as well as heart failure (HF) [12,13,14]. It remains unclear whether sST2 is predictive of MACEs and all-cause death in long-term follow-up of CAD [13, 15,16,17,18]. We performed a large-scale, prospective study to evaluate the prognostic value of sST2 for MACEs and all-cause mortality in patients with established CAD with and without T2DM over long-term follow-up
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