Prognostic value of soluble suppression of tumorigenesis-2 (sST2) for cardiovascular events in coronary artery disease patients with and without diabetes mellitus

Abstract

Background 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. 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). 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 sST2 and outcomes was investigated using multivariable Cox regression. Results During 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). Conclusions A 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.

Prognostic value of soluble ST2, high-sensitivity cardiac troponin, and NT-proBNP in type 2 diabetes: a 15-year retrospective study

“…A short-term (180 days) follow-up study on patients with T2DM and HD showed that sST2 levels > 54 ng/mL were associated with a higher risk of death and rehospitalization for cardiovascular causes [ 43 ]. Another study showed that plasma sST2 levels ≥ 19 ng/mL significantly predicted the development of MACEs and other CV endpoints in patients with CAD after adjusting for age, sex, and presence of T2DM [ 19 ].…”

“…By acting as a circulating decoy for interleukin-33 (IL-33), it prevents the cardioprotective effects of the ST2/IL-33 signaling, thus promoting maladaptive myocardial hypertrophy and cardiomyocyte apoptosis [ 18 ]. While a number of observational studies have investigated sST2 levels in T2DM [ 19 , 20 ], data on its prognostic role is limited to short follow-up periods, and its incremental value over the established cardiac biomarkers—BNP and cTn–has not been extensively assessed.…”

The Prognostic Role of ST2L and sST2 in Patients Who Underwent Carotid Plaque Endarterectomy: A Five-Year Follow-Up Study

“…Kim et al [ 20 ] observed that patients with stable coronary artery diseases (CAD) and higher plasma levels in sST2 showed a 13.7-fold increase in major cardiovascular events (MACE)—namely, cardiac death, non-fatal myocardial infarction, coronary revascularization (90 days after ICA), and ischemic stroke. The risk for death in CAD patients with increased plasma concentration of sST2 was twofold higher as compared with those in the lowest percentiles [ 21 , 22 ]. Indeed, a meta-analysis from Liu et al [ 12 ] indicated that elevated baseline sST2 levels promote a 74% increase in the long-term risk of MACE in patients with the acute coronary syndrome (ACS), thus considering a possible implication of sST2 in vulnerable plaques.…”

Diagnostic and prognostic value of serum soluble suppression of tumorigenicity-2 in heart failure with preserved ejection fraction: A systematic review and meta-analysis

“…Serum sST2 is unaffected by potential confounding variables, including age, sex, body mass index, and comorbidities such as renal disease and diabetes ( 41 ), making it a promising biomarker. Relevant clinical investigations have confirmed that serum sST2 can be utilized as an additional parameter for the diagnosis and prognosis of cardiovascular illnesses such as coronary heart disease ( 42 , 43 ), aortic dissection ( 44 , 45 ), and HF ( 46 , 47 ).…”