sST2 Concentrations Research Articles

Multiple Approaches at Admission Based on Lung Ultrasound and Biomarkers Improves Risk Identification in COVID-19 Patients.

Background: Risk stratification of COVID-19 patients is fundamental to improving prognosis and selecting the right treatment. We hypothesized that a combination of lung ultrasound (LUZ-score), biomarkers (sST2), and clinical models (PANDEMYC score) could be useful to improve risk stratification. Methods: This was a prospective cohort study designed to analyze the prognostic value of lung ultrasound, sST2, and PANDEMYC score in COVID-19 patients. The primary endpoint was in-hospital death and/or admission to the intensive care unit. The total length of hospital stay, increase of oxygen flow, or escalated medical treatment during the first 72 h were secondary endpoints. Results: a total of 144 patients were included; the mean age was 57.5 ± 12.78 years. The median PANDEMYC score was 243 (52), the median LUZ-score was 21 (10), and the median sST2 was 53.1 ng/mL (30.9). Soluble ST2 showed the best predictive capacity for the primary endpoint (AUC = 0.764 (0.658–0.871); p = 0.001), towards the PANDEMYC score (AUC = 0.762 (0.655–0.870); p = 0.001) and LUZ-score (AUC = 0.749 (0.596–0.901); p = 0.002). Taken together, these three tools significantly improved the risk capacity (AUC = 0.840 (0.727–0.953); p ≤ 0.001). Conclusions: The PANDEMYC score, lung ultrasound, and sST2 concentrations upon admission for COVID-19 are independent predictors of intra-hospital death and/or the need for admission to the ICU for mechanical ventilation. The combination of these predictive tools improves the predictive power compared to each one separately. The use of decision trees, based on multivariate models, could be useful in clinical practice.

Soluble suppression of tumorigenicity 2 as outcome predictor after cardiopulmonary resuscitation: an observational prospective study

Prognostication after cardiopulmonary resuscitation (CPR) is complex. Novel biomarkers like soluble suppression of tumorigenicity 2 (sST2) may provide an objective approach. A total of 106 post-CPR patients were included in this single-center observational prospective study. Serum sST2 levels were obtained 24 h after admission. Individuals were assigned to two groups: patients below and above the overall cohort’s median sST2 concentration. Primary outcome was a combined endpoint at 6 months (death or Cerebral Performance Category > 2); secondary endpoint 30-day mortality. A uni- and multivariate logistic regression analysis were conducted. Elevated sST2-levels were associated with an increased risk for the primary outcome (OR 1.011, 95% CI 1.004–1.019, p = 0.004), yet no patients with poor neurological outcome were observed at 6 months. The optimal empirical cut-off for sST2 was 46.15 ng/ml (sensitivity 81%, specificity 53%, AUC 0.69). Levels above the median (> 53.42 ng/ml) were associated with higher odds for both endpoints (death or CPC > 2 after 6 months: 21% vs. 49%, OR 3.59, 95% CI 1.53–8.45, p = 0.003; death after 30 days: 17% vs. 43.3%, OR 3.75, 95% CI 1.52–9.21, p = 0.003). A positive correlation of serum sST2 after CPR with mortality at 30 days and 6 months after cardiac arrest could be demonstrated.

Early Measurement of Blood sST2 Is a Good Predictor of Death and Poor Outcomes in Patients Admitted for COVID-19 Infection.

Although several biomarkers have shown correlation to prognosis in COVID-19 patients, their clinical value is limited because of lack of specificity, suboptimal sensibility or poor dynamic behavior. We hypothesized that circulating soluble ST2 (sST2) could be associated to a worse outcome in COVID-19. In total, 152 patients admitted for confirmed COVID-19 were included in a prospective non-interventional, observational study. Blood samples were drawn at admission, 48–72 h later and at discharge. sST2 concentrations and routine blood laboratory were analyzed. Primary endpoints were admission at intensive care unit (ICU) and mortality. Median age was 57.5 years [Standard Deviation (SD: 12.8)], 60.4% males. 10% of patients (n = 15) were derived to ICU and/or died during admission. Median (IQR) sST2 serum concentration (ng/mL) rose to 53.1 (30.9) at admission, peaked at 48–72 h (79.5(64)) and returned to admission levels at discharge (44.9[36.7]). A concentration of sST2 above 58.9 ng/mL was identified patients progressing to ICU admission or death. Results remained significant after multivariable analysis. The area under the receiver operating characteristics curve (AUC) of sST2 for endpoints was 0.776 (p = 0.001). In patients admitted for COVID-19 infection, early measurement of sST2 was able to identify patients at risk of severe complications or death.

Association of IL1R1 Coding Variant With Plasma-Level Soluble ST2 and Risk of Aortic Dissection.

Objective: Aortic dissection (AD) is characterized by an acute onset, rapid progress, and high mortality. Levels of soluble ST2 (sST2) on presentation are elevated in patients with acute AD, which can be used to discriminate AD patients from patients with chest pain. sST2 concentrations were found to be highly heritable in the general population. The aim of this study was to investigate the associations of variations in ST2-related gene expression with sST2 concentrations and AD risk.Methods: This case-control study involving a total of 2,277 participants were conducted, including 435 AD patients and age- and sex-matched 435 controls in the discovery stage, and 464 patients and 943 controls in the validation stage. Eight ST2-related genes were selected by systematic review. Tag single-nucleotide polymorphisms (SNPs) were screened out from the Chinese population of the 1,000 Genomes Database. Twenty-one ST2-related SNPs were genotyped, and plasma sST2 concentrations were measured.Results: In the discovery stage, rs13019803 located in IL1R1 was significantly associated with AD after Bonferroni correction (p = 0.0009) and was correlated with circulating sST2 levels in patients with type A AD(AAD) [log-sST2 per C allele increased by 0.180 (95%) CI: 0.002 – 0.357] but not in type B. Combining the two stages together, rs13019803C was associated with plasma sST2 level in AAD patients [log-sST2 increased by 0.141 (95% CI: 0.055–0.227) for per C allele]. Odds ratio of rs13019803 on the risk of AAD is 1.67 (95% CI: 1.33–2.09).Conclusions: The IL1R1 SNP rs13019803C is associated with higher sST2 levels and increased risk of AAD.

The Relationship between Plasma sST2/Reg3α Levels and Acute Graft-Versus-Host Disease in Children After Allogeneic Hematopoietic Stem Cell Transplantation

To explore the relationship between plasma sST2/Reg3α levels and acute graft-versus-host disease (aGVHD) in children after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical data of 29 pediatric patients received allo-HSCT treatment in Department of Hematology and Oncology of Wuhan Children's Hospital from January 2019 to January 2020 were collected. Peripheral blood samples were collected at 14 and 28 day after allo-HSCT. The plasma concentrations of sST2 and Reg3α were detected by Luminex assay. Among 29 patients there were 15 males and 14 females with a median age of 53 (29-117) months. After allo-HSCT, 18 patients developed grade 0-I aGVHD; while 11 patients developed grade II-IV aGVHD. These included skin aGVHD in 6 cases, gastrointestinal aGVHD (GI-aGVHD) in 3 cases and gastrointestinal/skin aGVHD in 5 cases. Plasma sST2 level in II-IV aGVHD group showed significantly higher than that in 0-I aGVHD group at 28 days after allo-HSCT [101.81 (73.94-150.77) ng/ml vs 48.97 (28.82-56.69) ng/ml, P=0.021]. Also, the plasma sST2 level was significantly higher in GI-aGVHD group than that in no-aGVHD group at 28 days after allo-HSCT [118.74 (87.00-243.36) ng/ml vs 48.97 (23.55-61.40) ng/ml, P=0.004]. Plasma sST2 level ≥65.34 ng/ml at 28 days after allo-HSCT showed a sensitivity of 85.7% and a specificity of 87.5% in predicting II-IV aGVHD. And the patients with a plasma sST2 level ≥65.34 ng/ml showed a significantly higher incidence of II-IV aGVHD than those with plasma sST2 level of < 65.34 ng/ml after allo-HSCT (P=0.021). There was no significant difference in plasma Reg3α level between the patients with II-IV aGVHD and the non-aGVHD ones. The increasing plasma sST2 level after allo-HSCT in children indicates the development of II-IV aGVHD, so sST2 is promising as a biomarker for predicting II-IV aGVHD.

Prognostic value of soluble ST2 biomarker in heart failure patients with obstructive sleep apnea syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Objective. To analyze the relationships between soluble ST2 (sST2) levels, apnea/hypopnea index (AHI) and echocardiographic parameters in heart failure patients with preserved ejection fraction (HFpEF) and to evaluate prognostic values of sST2 in the development of adverse cardiac events (ASE) during the 12-month follow-up period. Methods. A total of 86 men, median age of 62.0 (41.0; 78.0) years with obstructive sleep apnea syndrome (OSAS) and HF of NYHA class I-III with baseline LVEF of 60% [52; 65]% were enrolled in the study. The severity of obstructive breathing disorders during sleep was assessed by AHI. Serum levels of NT-proBNP and sST2 were measured using ELISA at baseline. Two-dimensional transthoracic echocardiography with assessment of right ventricular (RV) function and 6-minute walk test (6MWT) were performed at baseline. Results. The values of AHI significantly correlated with body mass index (r = 0.362), left atrial volume (r = 0.570), fractional change in the area of the RV (r=-0.527), RV myocardial function index (r=-0.377), NT-proBNP (r = 0.611), 6MWT (r=-0.511), RV anterior wall thickness (r = 0,472), while the levels of sST2 significantly correlated with LV remodeling parameters: LVEF (r =-0.301), end-systolic volume (r =0.453), end-diastolic volume (r =0.396), end-systolic dimension (r = 0.373), end-diastolic dimension (r =0.288). Based on ROC-analysis, sST2 ≥29.67 ng/mL (sensitivity 63.6%, specificity 73.6%, AUC = 0.645; p &amp;lt; 0.0001) were identified as a cut-off values predicting the development of ACE. At 12 months of follow-up period all patients were divided into 2 groups according to cut-off values of sST2: group 1 (n = 29) comprised patients with sST2 ≥29.67 ng/mL, group 2 (n = 42) comprised patients with sST2 &amp;lt;29.67 ng/mL. The median baseline values of sST2 were 41.39 [33.31; 50.99] ng/mL in group 1, and 22.18 [20.64; 25.5] ng/mL in group 2. The concentrations of NT-proBNP did not differ between the groups. During the 12-month follow-up period in group 1 the rate of ACE was 29.7% cases, and 5.2% in group 2, respectively. According to Kaplan-Meier analysis, a higher sST2 levels was associated with a higher frequency of ACE during 12 months of follow-up (р&amp;lt;0.0001). Univariable and multivariable Cox regression analyses showed sST2 concentrations were significantly associated with ACE (odds ratio 2.25, 95%CI: 2.06 to 3.29, p &amp;lt; 0.001), when adding AHI and LV myocardial mass index improved reclassification of risk stratification (odds ratio 3,28, 95%CI: 3,09 to 4,49, p &amp;lt; 0.001, AUC of 0.945, percent of cases correctly classified of 90.14 %). However, NT-proBNP addition had a limited effect on risk stratification. Conclusion. Our data suggest that sST2 may be used as a diagnostic biomarker for prediction of ACE in patients with HFpEF and OSAS during the 12-month follow-up period. The combined evaluation of sST2, AHI and LV myocardial mass index values demonstrated higher diagnostic sensitivity and specificity for prediction of ACE.

Correlation Between QTc Dispersion and Soluble Growth-stimulating Gene 2 Protein on the Early Prognosis of Acute Carbon Monoxide Poisoning Heart Disease.

This study aimed to explore the correlation between QTc dispersion (QTcd) and soluble growth-stimulating gene 2 protein (sST2) after heart rate correction in patients with acute carbon monoxide poisoning heart disease. Among the 150 patients, 35 cases had severe toxic heart disease. The concentrations of sST2, cardiac troponin I, and creatine kinase-MB in the severe group began to increase from admission, 24 hours, and 2 days, respectively, and their detected values were all higher than those in the nonsevere group and the normal control group. There were statistically significant differences in sST2 and QTcd between the poisoning, nonsevere, and normal control groups before the treatment. There was a statistically significant difference between the indexes of the poisoning groups at different degrees 2 and 3 days after poisoning. Receiver operating characteristic curve analysis confirmed the sensitivity and specificity of sST2 and QTcd. The correlation analysis showed that sST2 and QTcd levels were positively correlated with the incidence of severe heart disease at admission. Generally, the combined observation of sST2 and QTcd improved the prediction sensitivity and were early predictor indexes of toxic heart disease.

Soluble ST2 and mixed venous oxygen saturation for prediction of mortality in patients with pulmonary hypertension.

BackgroundAlthough soluble suppression of tumorigenicity-2 (sST2) has been identified as a clinical biomarker for pulmonary hypertension (PH) by previous studies, the implication of sST2 combined with hemodynamic parameters in PH has not been well studied. This study aimed to evaluate the relationship between sST2 and hemodynamic parameters and to evaluate the predictive value of sST2 for mortality in patients with PH.MethodsOne hundred eighty-four incident patients with PH and 14 healthy controls were retrospectively enrolled by Shanghai Pulmonary Hospital for this retrospective study. After all patients underwent right heart catheterization, blood samples were collected and serum sST2 concentration was assessed by the Presage™ ST2 assay. Kaplan-Meier curve and Cox regression analyses were used to predict survival and the association between survival and different factors such as sST2, SvO2.ResultsDuring a follow-up of 44.9 (IQR 28.5–64.4) months, 65 patients died. The median concentration of sST2 in PH patients was 33.1 ng/mL, which is higher than that in control group (23.1 ng/mL, P=0.005). Furthermore, for PH group, the level of sST2 was higher in non-survivors than that in survivors. Cox regression analyses demonstrated that sST2 and SvO2 were independent risk factors for survival. In Kaplan-Meier curve analyses, elevated sST2 level and reduced SvO2 predicted a poor outcome for patients with PH.ConclusionsHigher sST2 was independently associated with increased mortality, as well as lower SvO2 in patients with PH. Especially, the combination of higher sST2 and lower SvO2 had the strongest predictive value of mortality in patients with PH.

Myocardial fibrosis combined with NT-proBNP improves the accuracy of survival prediction in ADHF patients

BackgroundSoluble suppression of tumorigenesis-2 (sST2), Procollagen Type III N-Terminal Peptid (PIIINP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been verified their role in predicting survival in acutely decompensated heart failure (ADHF). However, whether their combination could improve more specific and sensitive prognostic information than NT-proBNP alone remains unclear.MethodsThis was a prospective study, in which 217 ADHF patients at admission were enrolled from November 2018 and August 2019 (mean age 66.18 years ± 13.60, 63.98% male). The blood samples were collected to measure the concentrations of NT-proBNP, sST2 and PIIINP in the first 24 h of hospitalizations. All-cause mortality was registered for all patients after they were discharge over a median period of 339 days.ResultsIn univariate Cox analysis, the three biomarkers were predictive of short-term mortality of ADHF patients. After adjusted for some clinical variables including age, admission systolic blood pressure, peripheral edema on admission, history of chronic obstructive pulmonary disease, admission sodium < 135 mmol/L, admission hemoglobin, NT-proBNP, sST2 and PIIINP was significantly associated with the poor outcome (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.14–1.53, P < 0.01; HR 1.21, 95% CI 1.03–1.43, P = 0.020; HR 1.40, 95% CI 1.08–1.81, P = 0.011). After added with Log2 PIIINP, but not Log2 sST2, the area under the curves (AUC) in the model of clinical variables and Log2 NT-proBNP could increase from 0.79 to 0.85 (95% CI 0.0071–0.10, P = 0.024). Furthermore, compared with the model of clinical variables, Log2 NT-proBNP, the improvement in the prognostic model of clinical variables, Log2 NT-proBNP and Log2 PIIINP had statistical significance [net reclassification improvement (NRI) 0.31, P = 0.018; integrated discrimination improvement (IDI) 0.068, P < 0.01].ConclusionsNT-proBNP, sST2 and PIIINP are independent prognostic factors for all-cause mortality in ADHF patients. Furthermore, the combination of NT-proBNP and PIIINP may provide incremental prognostic value over NT-proBNP in the survival of ADHF patients.

Role of soluble ST2 in short-term prediction of acute heart failure in acute ST-elevation myocardial infarction

Aim. To investigate the relationship of soluble ST2 (sST2) to acute heart failure (AHF) and compare the predictive value of sST2 and brain natriuretic peptide in patients with ST-elevation myocardial infarction (STEMI).Material and methods. In 136 STEMI patients, the serum sST2 concentration was determined during the first 24 hours of hospitalization. We assessed levels of sST2, N-terminal pro-brain natriuretic peptide (NT-proBNP), incidence of Killip class II-IV AHF during hospitalization, myocardial necrosis biomarkers, parameters of complete blood count and biochemical blood tests, the incidence of cardiovascular diseases and risk factors. The predictive value of sST2 for AHF development was assessed using logistic regression. ROC analysis was performed. The areas under the ROC curve were compared for sST2 and NT-proBNP. The cut-off sST2 value was determined for predicting AHF.Results. The mean sST2 level was 43,4 (33,6-73,9) ng/ml. During the followup period, AHF was diagnosed in 54 people (39,7%). The prevalence of AHF in the 1st, 2nd and 3rd tertiles of sST2 was 15,6%, 33,3% and 69,7%, respectively. The NT-proBNP levels were 319 (128-1072) pg/ml, 430 (147-1140) pg/ml and 1317 (533-2386) pg/ml. The predictive value of 3rd sST2 tertile was retained adjusted for age, sex, NT-proBNP, troponin T, creatine phosphokinase-MB, high-sensitivity C-reactive protein, hemoglobin, blood glucose, left ventricular ejection fraction. The areas under the ROC curves for sST2 and NT-proBNP were comparable (0,828 and 0,733, respectively; p=0,056). The cut-off sST2 value was 64 ng/ml, above which the odds ratio of AHF was 11,1 (95% confidence interval, 4,7-26,1.Conclusion. An increase in blood sST2 is associated with an increase in AHF (Killip II-IV) prevalence in hospitalized patients with acute STEMI. Soluble ST2 has an independent predictive value for AHF in STEMI, comparable in strength and predictive model quality to NT-proBNP. The cut-off sST2 value for AHF (&gt;64 ng/ ml) was calculated, which provides an optimal balance of sensitivity, specificity and accuracy of the prognostic model. These data support the potential value of sST2 as a biomarker of AHF in STEMI.

Association Between Angiotensin Receptor-Neprilysin Inhibition, Cardiovascular Biomarkers, and Cardiac Remodeling in Heart Failure With Reduced Ejection Fraction.

Sacubitril/valsartan (S/V) treatment is associated with reverse cardiac remodeling and reductions in biomarkers reflecting ventricular wall stress and myocardial injury, such as NT-proBNP (N-terminal pro-B-type natriuretic peptide), hs-cTnT (high-sensitivity cardiac troponin T), and soluble suppressor of tumorigenicity 2 (sST2). How longitudinal changes in these biomarkers analyzed collectively are associated with cardiac remodeling in patients with heart failure with reduced ejection fraction treated with S/V is uncertain. In a prospective study of S/V in patients with heart failure with reduced ejection fraction, this prespecified exploratory analysis included patients with serially collected biomarkers and echocardiographic measures of cardiac remodeling through 12 months of treatment. A multivariate latent growth curve model assessed associations between simultaneous changes in biomarkers and left ventricular ejection fraction and left atrial volume index. Seven hundred fifteen out of 794 total study participants were included (mean age 65 years, 73% male). Mean baseline left ventricular ejection fraction and left atrial volume index were 29% and 40 mL/m2, respectively. Adjusted geometric mean baseline concentrations for biomarkers included NT-proBNP of 649 pg/mL, hs-cTnT of 15.9 ng/L, and sST2 of 24.7 ng/mL. Following initiation of S/V, circulating concentrations of NT-proBNP, hs-cTnT, and sST2 significantly decreased within 30 days and remained significantly different than baseline at all subsequent timepoints. From baseline to month 12, decreases in adjusted biomarker concentrations averaged -27.9% (95% CI, -35.1% to -20.7%; P<0.001) for NT-proBNP; -6.7% (95% CI, -8.8% to -4.7%; P<0.001) for hs-cTnT; and -1.6% (95% CI, -2.9% to -0.4%; P<0.001) for sST2. NT-proBNP concentrations were predictive of later changes in hs-cTnT. The magnitude of reductions in NT-proBNP and hs-cTnT concentrations associated with improvements in left ventricular ejection fraction and left atrial volume index. There was no association between changes in sST2 and changes in other measures. Following initiation of S/V, NT-proBNP, hs-cTnT, and sST2 concentrations decreased significantly. Longitudinal changes in NT-proBNP and hs-cTnT together associated with left atrial and left ventricular reverse remodeling. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02887183.

Heart failure patients with implantable cardioverter-defibrillator: molecular predictors for risk assessment of adverse events

Abstract Funding Acknowledgements Type of funding sources: None. Objective. The objectives of the study were to evaluate a multimarker strategy including galectin-3, soluble ST2 (sST2) and NT-proBNP for risk stratification of adverse cardiovascular events (ACE) and death in heart failure (HF) patients with implantable cardioverter-defibrillator (ICD) during the 12-month follow-up period. Methods. A total of 57 patients (41 men, median age of 65 [59; 68] years) of New York Heart Association (NYHA) class II-IV and baseline LVEF of 34% [26; 44]% were enrolled in the study. 71% of patients had prior myocardial infarction and 86% received prior myocardial revascularization (coronary artery bypass graft/stent). Serum levels of sST2, NT-proBNP and galectin-3 were measured using an enzyme immunoassay at baseline. All patients received implantation of cardioverter-defibrillator. Results. After the 12-month follow-up period, all patients were divided into 2 groups: group A (n = 17) comprised patients with ASE, group B (n = 40) comprised those without it. During 12-month follow-up period 15.8% of patients (n = 9) died. The median values of sST2 in group A were higher (p = 0.001) by 51% than in group B (24.42 [22.46; 31.4] and 49.94 [37.4; 58.54] ng/mL, respectively). The median values of galectin-3 in group A (p = 0.002) were 14.7 [9.95; 24.3] ng/L and 9.2 [7.2; 14.7] ng/L in group B. The median values of NT-proBNP were also higher (p = 0.021) by 22% in patients with ASE. Odds ratio for hyperexpression of sST2 was 3.06 (95% CI 2.89-3.17; p &amp;lt;0.0001), 3.79 for galectin-3 (95% CI 2.67-4.11; p &amp;lt; 0.001), and 1.27 for NT-proBNP (95% CI 0.89-2.21; p = 0.036). Reclassification did not significantly benefit after NT-proBNP addition into the full model; some indices even worsened with all 3 biomarkers. Based on ROC-analysis, baseline sST2 concentration of 34.43 ng/mL (sensitivity of 86.7%, specificity of 71.9%, and AUC of 0.78; p &amp;lt; 0.0001) and baseline galectin-3 concentration of 11.6 ng/L (sensitivity of 67.5%, specificity of 70.6%, and AUC of 0.72; p = 0.0014) were identified as a cut-off values predicting adverse cardiac events. The combined evaluation of both biomarkers increased the predictive value of the analysis (sensitivity of 90.1%, specificity of 79.1%, and AUС of 0.84; p &amp;lt; 0.0001). Conclusion. Our data suggest that ST2 and galectin-3 may be used as diagnostic biomarkers in HF patients with ICD. The combined use of sST2 and galectin-3 demonstrated higher diagnostic sensitivity and specificity for prediction of adverse outcomes. However, NT-proBNP in addition to ST2 and galectin-3 biomarkers had a limited effect on risk stratification.

Alarmins (IL-33, sST2, HMGB1, and S100B) as potential biomarkers for schizophrenia

There is growing evidence that immune/inflammatory processes are related to the etiology of schizophrenia. Danger-/damage-associated molecular patterns (DAMPs), also called alarmins, are recognized as inflammatory mediators that play an important role in the development of many infection-induced or sterile inflammatory diseases. The importance of DAMPs particles in various mental disorders is still not clear. Therefore, this study aimed to evaluate serum levels of the most promising alarmins (IL-33, sST2, HMGB1, and S100B), as potent schizophrenia biomarkers. Sixty-eight adult patients with chronic schizophrenia and twenty-nine healthy volunteers were included in this prospective study. Enzyme-linked immunosorbent assay (ELISA) was used to assess the serum concentration of IL-33, sST2, HMGB1, and S100B. We documented that the serum levels of IL-33 (p = 0.006), sST2 (p = 0.02), HMGB1 (p = 0.01), and S100B (p = 0.04) are significantly higher in patients with schizophrenia than in healthy subjects. In male, but not in female, patients with schizophrenia, we found a significant difference in the serum IL-33, sST2, and HMGB1 concentrations as compared to the healthy men. In both male and female patients with schizophrenia, there was no significant difference in the serum concentrations of S100B in comparison to control subjects. In patients with schizophrenia, no significant correlations were noticed neither between any studied alarmins and PANSS scores nor between CDSS scores. Given that all investigated alarmins participate in the course of the neuroinflammatory process, they might be considered as biomarkers of neuroinflammatory process underlying schizophrenia. Based on our observations, it seems that the most useful biological indicator of schizophrenia would be IL-33.

Long-Term and Short-Term Prognostic Value of Circulating Soluble Suppression of Tumorigenicity-2 Concentration in Chronic Heart Failure: A Systematic Review and Meta-Analysis

Introduction: Soluble suppression of tumorigenicity-2 (sST2) has been considered as a prognostic factor of cardiovascular disease. However, the prognostic value of sST2 concentration in chronic heart failure remains to be summarized. Methods: We searched PubMed, Embase, and Web of Science for eligible studies up to January 1, 2020. Data extracted from articles and provided by authors were used in agreement with the PRISMA statement. The endpoints were all-cause mortality (ACM), cardiovascular mortality (CVM)/heart failure-related hospitalization (HFH), and all-cause mortality (ACM)/heart failure-related readmission (HFR). Results: A total of 11 studies with 5,121 participants were included in this analysis. Higher concentration of sST2 predicted the incidence of long-term ACM (hazard ratio [HR]: 1.03, 95% confidence interval [CI]: 1.02–1.04), long-term ACM/HFR (HR: 1.42, CI: 1.27–1.59), and long-term CVM/HFH (HR: 2.25, CI: 1.82–2.79), regardless of short-term ACM/HFR (HR: 2.31, CI: 0.71–7.49). Conclusion: Higher sST2 concentration at baseline is associated with increasing risk of long-term ACM, ACM/HFR, and CVM/HFH and can be a tool for the prognosis of chronic heart failure.

Admission biomarkers among patients with acute myocardial-infarction related cardiogenic shock with or without out-of-hospital cardiac arrest

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Lundbeck Foundation OnBehalf Critical Cardiac Care Research Group Background Approximately half of all patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) present with out-of-hospital cardiac arrest (OHCA). Cardiogenic shock due to OHCA is caused by abrupt cessation of circulation, whereas AMICS without OHCA is due to cardiac failure with low cardiac output. Thus, there may also be differences between the two conditions in terms of blood borne biomarkers. Purpose To explore the potential differences in the admission plasma concentrations of biomarkers reflecting tissue perfusion (lactate), neuroendocrine response (mid-regional proadrenomedullin [MRproADM], Copeptin, pro-atrial natriuretic peptide [proANP]), endothelial damage (Syndecan-1, soluble thrombomodulin [sTM]), inflammation (soluble suppression of tumorigenicity 2 [sST2]) and kidney injury (neutrophil gelatinase-associated lipocalin [NGAL]), in patients with AMICS presenting with or without OHCA. Method Consecutive patients admitted for acute coronary angiography due to suspected ST-elevation myocardial infarction (STEMI) were enrolled during a 1-year period. A total of 2,713 patients were screened. In the present study 86 patients with confirmed STEMI and CS at admission were included. Results Patients with OHCA (had significantly higher median admission concentrations of Lactate (6,9 mmol/L vs. 3.4 mmol/L p &amp;lt;0.001), NGAL (220 ng/ml vs 150 ng/ml p = 0.046), sTM (10 ng/ml vs. 8.0 ng/ml p = 0.026) and Syndecan-1 (160 ng/ml vs. 120 ng/ml p= 0.015) and significantly lower concentrations of MR-proADM (0.85 nmol/L vs. 1.6 nmol/L p &amp;lt;0.001) and sST2 (39 ng/ml vs. 62 ng/ml p &amp;lt; 0.001). After adjusting for age, sex, and time from symptom onset to coronary angiography, lactate (p = 0.008), NGAL (p = 0.03) and sTM (p = 0.011) were still significantly higher in patients presenting with OHCA while sST2 was still significantly lower (p = 0.029). There was very little difference in 30-day mortality between the OHCA and non-OHCA groups (OHCA 37% vs. non-OHCA 38%). Conclusion Patients with STEMI and CS at admission with or without concomitant OHCA had similar 30-day mortality but differed in terms of Lactate, NGAL, sTM and sST2 levels at the time of admission to catheterization laboratory. These findings propose that non-OHCA and OHCA patients with CS could be considered as two individual clinical entities. Abstract Figure. Level of biomarkers OHCA vs. non-OHCA

Lack of prognostic significance for major adverse cardiac events of soluble suppression of tumorigenicity 2 levels in patients with ST-segment elevation myocardial infarction.

Elevation of soluble suppression of tumorigenicity 2 (sST2) is associated with cardiac fibrosis and hypertrophy. Under investigation herein, was whether sST2 level is associated with major adverse cardiac events (MACE) and left ventricular (LV) remodeling after primary percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI). In total, this study included 184 patients who underwent successful primary PCI. A subsequent guideline-based medical follow-up was included (61.4 ± 11.8 years old, 85% male, 21% with Killip class ≥ I). sST2 concentration correlations with echocardiographic, angiographic, laboratory parameters, and clinical outcomes in STEMI patients were evaluated. The median sST2 level was 60.3 ng/mL; 6 (3.2%) deaths occurred within 1 year. The sST2 level correlated with LV ejection fraction (LVEF) changes from baseline to 6 months (r= -0.273; p = 0.006) after adjustment for echocardiographic parameters including wall motions score index (WMSI). Recovery of LVEF at 6 months was highest in the tertile 1 group (Δ6 months - baseline LVEF; tertile 1, p = 0.001; tertile 2, p = 0.319; tertile 3, p = 0.205). The decrease in WMSI at 6 months was greater in the tertiles 1 and 2 groups than in the tertile 3 group (Δ6 months - baseline WMSI; tertile 1, p = 0.001; tertile 2, p = 0.013; tertile 3, p = 0.055). There was no association between sST2 levels and short-term (log rank p = 0.598) and long-term (p = 0.596) MACE. sST2 concentration have predictive value for LV remodeling on echocardiography in patients with STEMI who underwent primary PCI. However, sST2 concentration was not associated with short-term and long-term MACE.

Soluble sST2 biomarker analysis for fibrosis development in atrial fibrillation. A case control study.

Objectives. Atrial fibrillation (AF) is a clinically relevant supra-ventricular arrhythmia which represents an independent risk factor for development of heart failure and ischemic stroke. The present study aims at the investigation of the possible clinical role of the soluble sST2 biomarker to evaluate the fibrosis in a group of patients with first diagnosed or permanent AF. The possible association with the left atrium size is also studied. Materials and Methods. The serum concentrations of the biomarker have been measured in a group of 58 patients (mean age 83.6 ± 6.0 years) and 40 individuals, assumed healthy and without AF, constituted the control group. The analysis is carried out by means of a high-sensitivity enzyme-linked immunosorbent assay. Results. The mean concentration of sST2 is 26.1 (22.7-30.5) ng/mL in the AF group, while in the control is 17.3 (15.7-18.9) ng/mL. Remarkable differences have been obtained for the two subsets with first diagnosed (23 (21.2-24) ng/mL) and permanent AF (30.5 (28.6-32) ng/mL). The analysis has been completed with a trans thoracic echocardiographic exam to evaluate the left atrium size and the left ventricular ejection fraction. Conclusions. The sST2 serum concentrations are found to be higher in the permanent AF with respect to the cases where the AF is of new onset or follow a paroxysmal pattern. The results support the adoption of the marker to evaluate the degree of fibrosis related to the left atrium of fibrillating patients. A positive association has been proved between the left atrium size and the sST2 concentrations.

Soluble ST2 is increased in systemic lupus erythematous and is a potential marker of lupus nephritis.

To investigate the role of the interleukin IL-33/ST2 axis in systemic lupus erythematosus (SLE). Serum concentrations of IL-33 and sST2 were measured by sandwich ELISA in SLE patients (n=111) compared to sex- and age-matched healthy controls (n=36). The serum concentrations of IL-33 and sST2 were correlated with various clinical and biological parameters. The expressions of IL-33 and ST2L were investigated in kidney sections by immunohistochemistry in lupus nephritis patients (n=23) and controls (n=10). Serum levels of IL-33 were significantly higher in SLE patients (11.64±3.141 pg/mL) than in controls (1.043±0.8526 pg/mL) (p<0.0001). Similarly, the serum concentrations of sST2 were significantly higher in SLE patients (34.013±2.043 pg/mL) than in controls (25.278±2.258 pg/mL) (p=0.046). sST2, but not IL-33, correlated significantly with disease activity index (SLEDAI). In addition, serum levels of sST2 were significantly higher in patients with lupus nephritis (45.438±5.661 pg/mL) that in SLE patients without renal involvement (30.691±1.941 pg/mL) (p=0.016). The immunoreactivity of IL-33 in renal biopsies of patients with lupus nephritis was not increased compared to controls, while the glomerular expression of ST2L was significantly higher in nephritis patients compared to controls. Although IL-33 and sST2 levels are both increased in SLE, sST2 represents a surrogate marker of disease activity and complications of nephritis.

Soluble ST2 levels for predicting the presence and severity of metabolic syndrome.

To explore the relationship between soluble ST2 (sST2) and metabolic syndrome (MetS) and determine whether sST2 levels can predict the presence and severity of MetS. We evaluated 550 consecutive subjects (58.91 ± 9.69 years, 50% male) with or without MetS from the Department of Vascular & Cardiology, Shanghai Jiao Tong University-Affiliated Ruijin Hospital. Serum sST2 concentrations were measured. The participants were divided into three groups according to the sST2 tertiles. Univariate and multivariable logistic regression models were used to evaluate the association between serum sST2 concentrations and the presence of MetS. Serum sST2 concentrations were significantly higher in the MetS group than in those in the no MetS group (14.80 ± 7.01 vs 11.58 ± 6.41 ng/mL, P < 0.01). Subjects with more MetS components showed higher levels of sST2. sST2 was associated with the occurrence of MetS after multivariable adjustment as a continuous log-transformed variable (per 1 SD, odds ratio (OR): 1.42, 95% CI: 1.13–1.80, P < 0.01). Subgroup analysis showed that individuals with MetS have significantly higher levels of sST2 than those without MetS regardless of sex and age. High serum sST2 levels were significantly and independently associated with the presence and severity of MetS. Thus, sST2 levels may be a novel biomarker and clinical predictor of MetS.

Association of Soluble Suppression of Tumorigenicity with No-Reflow Phenomenon and Long-Term Prognosis in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome after Percutaneous Coronary Intervention.

Aims: Soluble suppression of tumorigenicity 2 (sST2) was validated to independently predict prognosis for heart failure (HF) and ST-segment elevation myocardial infarction (STEMI). In this study, we aimed to evaluate the relation between sST2 and coronary artery stenosis, and no-reflow phenomenon and one-year prognosis in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Methods: This prospective study consecutively enrolled 205 patients who were diagnosed with NSTE-ACS and underwent percutaneous coronary intervention (PCI). sST2 was measured for all patients during admission. Patients were divided into two groups based on the optimal cutoff value: sST2 ＞34.2 ng/ml and sST2 ≤ 34.2 ng/ml groups. Results: Patients in the sST2 ＞34.2 ng/ml group was associated with higher Gensini scores and multivessel disease. sST2 had weak predictive value for no-reflow phenomenon (area under the curve [AUC], 0.662; 95% confidence interval [CI], 0.53–0.79; P =0.015) with 66.7% sensitivity and 65.2% specificity, and it also had independent predictive value of no-reflow phenomenon after adjusting for confounding factors (odds ratio [OR], 3.802; 95% CI, 1.03–14.11; P =0.046). sST2 ＞34.2 ng/ml had a commendable predictive value for the one-year prognosis (AUC, 0.84; 95% CI, 0.75–0.93; P ＜0.001) with 72% sensitivity and 84% specificity, and it independently predicted one-year major cardiovascular and cerebrovascular events (MACCE) (hazard ratio [HR], 10.22; 95% CI, 4.05–25.7; P ＜0.001). Conclusion: The sST2 concentration on admission is correlated with the degree of coronary artery stenosis. sST2 can predict both no-reflow and MACCE in patients with NSTE-ACS after PCI and was an independent predictor of MACCE and no-reflow phenomenon.