Serum sST2 Levels Research Articles

Prognostic value of serum soluble ST2 in stable coronary artery disease: a prospective observational study

The role of ST2 in stable coronary artery disease (CAD) has not yet been well defined. This study was performed to investigate baseline serum soluble ST2 (sST2) level can predict clinical outcomes in patients with stable CAD. A total of 388 consecutive patients with suspected CAD (65 years and 63.7% male) in stable condition referred for elective invasive coronary angiography (ICA) was prospectively recruited. Major adverse cardiovascular event (MACE), including cardiac death, non-fatal myocardial infarction, coronary revascularization (90 days after ICA), and ischemic stroke during clinical follow-up was assessed. Most of the patients (88.0%) had significant CAD (stenosis ≥ 50%). During median follow-up of 834 days, there was 29 case of MACE (7.5%). The serum sST2 level was significantly higher in patients with MACE than those without (47.3 versus 30.6 ng/ml, P < 0.001). In multiple Cox regression model, higher sST2 level (≥ 26.8 ng/ml) was an independent predictor of MACE even after controlling potential confounders (hazard ratio, 13.7; 95% confidence interval 1.80–104.60; P = 0.011). The elevated level of baseline sST2 is associated with an increased risk of adverse clinical events in stable CAD patients. Studies with larger sample size are needed to confirm our findings.

Increased Serum Levels of soluble ST2 as a Predictor of Disease Progression in Systemic Sclerosis

Objective Interleukin-33 (IL-33) has been investigated as a mediator in the pathogenesis of fibrosis in lung, liver, and heart. There is accumulating evidence for the involvement of the IL-33/IL-33 receptor ST2L signalling pathway in systemic sclerosis (SSc). Little is known about the role of serum sST2 in SSc, which is the subject of the present investigation. Method Serum levels of sST2 were measured in 49 patients with SSc, recruited prospectively between November 2017 and March 2019. Patients were divided into those with progressive and those with stable disease. Receiver operating characteristics (ROC) curve analysis was applied to study sST2 as a marker for identifying patients with progressive disease. We used multivariate logistic regression analysis to evaluate the predictive value of sST2 for progressive disease after adjustment for potential confounding factors. Results Serum sST2 levels in patients with progressive disease were significantly elevated compared with patients with stable disease (mean ± sem: 50.4 ± 4.7 ng/mL vs 29.2 ± 2.97 ng/mL, p < 0.001). ROC curve analysis identified an sST2 cut-off value of 37.8 ng/mL as optimal for discriminating patients with progressive disease from those with stable disease (sensitivity 80.0%, specificity 79.3%, area under the curve 0.80). After controlling for potential confounding factors (age, gender, C-reactive protein, pro-brain natriuretic peptide, and sum of internal medicine comorbidities), sST2 remained predictive of progressive disease (odds ratio 1.070, 95% confidence interval 1.017–1.126, p < 0.009). Conclusion In the present study, sST2 serum levels were predictive of disease progression in patients with SSc.

The Clinical Significance of Serum IL-33 and sST2 Alterations in the Post-Stroke Depression

IntroductionThis study was to test whether the serum levels of IL-33 and sST2 are correlated with the development of depression after acute ischemic stroke.MethodsPatients diagnosed with acute ischemic stroke were selected. This study took the 24-item Hamilton Depression Rating Scale (HAMD) (score ≥20) as the diagnostic criteria for depression. On the 21st day after admission, patients who met the depression diagnostic criteria were included in the depression group, and patients who failed to meet the diagnostic criteria were included in the non-depression group. The serum levels of IL-33, sST2 and hsCRP were measured by enzyme-linked immunosorbent assay (ELISA).ResultsOn 1st day after stroke, compared with the non-depression group, there was no significant difference in the serum IL-33, sST2 and hsCRP levels in the depression group; on 21st day after stroke, compared with the non-depression group, the serum IL-33 and hsCRP levels were significantly increased, while the sST2 level was significantly decreased in the depression group. Correlation analysis showed that IL-33 was positively correlated with the depression quantitative score and hsCRP, while sST2 was negatively correlated with the depression quantitative score and hsCRP. Regression analysis showed that IL-33 and sST2 were independent risk factors for the depression after acute ischemic stroke.DiscussionThe abnormal alterations of serum IL-33 and sST2 levels in the stroke patients may serve as one of the risk factors for the occurrence and exacerbation of the depression, and its mechanism may be related to the promotion of inflammatory factor production in vivo.

Serum Soluble ST2 Correlated with Symptom Severity and Clinical Response of Sublingual Immunotherapy for House Dust Mite-Induced Allergic Rhinitis Patients.

Background Suppressor of tumorigenicity 2 (ST2) is a key biomarker in inflammation and cardiovascular diseases, but limited data is available on its role in allergic rhinitis (AR). Objective The aim of this study is to explore the role of serum soluble ST2 (sST2) in evaluating disease severity and predicting the efficacy of sublingual immunotherapy (SLIT) in house dust mite- (HDM-) induced AR patients. Methods Eighty healthy controls (HC group) and 160 HDM-induced AR patients, including 40 mild patients (MAR group) and 120 moderate-severe patients (MSAR group), were recruited in this study. Serum was collected from all participants and levels of sST2 were determined by ELISA and the relationship between sST2 levels and disease severity was assessed. In the MSAR group, 109 patients received 3 years of SLIT, and the relationship between serum levels of sST2 and efficacy of SLIT was exampled. Results Serum sST2 levels were increased in HDM-induced AR patients compared to the HC group (P < 0.001), and the concentrations were higher in the MSAR group than in the MAR group and HC group (all P < 0.05). Moreover, sST2 levels positively correlated with the total nasal symptom score (TNSS), visual analogue scale (VAS), and specific IgE levels (P < 0.05). Seventy-eight MSAR patients accomplished SLIT, and they were divided into an effective group (n = 40) and an ineffective group (n = 38). The serum sST2 levels in the effective group were lower than those in the ineffective group (P < 0.001). In addition, patients in the effective group levels exhibited significantly lower sST2 levels post-SLIT than pre-SLIT (P < 0.001), but no statistic difference was observed in the ineffective group (P > 0.05). Receiver operating characteristic (ROC) curve showed promising accuracy for predicting clinical efficacy of SLIT in AR patients (area under the curve = 0.839, P < 0.001). Conclusion Serum sST2 is a potential biomarker for assessing disease severity and may serve as a sensitive biomarker for predicting the therapeutic response of SLIT in HDM-induced AR patients.

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.

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.

Концентрація розчинного ST2 у плазмі крові та дисфункція серця в пацієнтів з есенціальною гіпертензією

Мета роботи – оцінити роль розчинного ST2 (sST2) як можливого біомаркера ремоделювання та дисфункції серця у хворих з есенціальною гіпертензією (ЕГ) різної тяжкості.Матеріали і методи. Обстежено 150 чоловіків з підтвердженою ЕГ різної тяжкості та 70 чоловіків без серцево-судинних захворювань, репрезентативних за віком, які становили контрольну групу. Критерії залучення в дослідження: вік 40–60 років, чоловіча стать, верифікований діагноз ЕГ. Рівень sST2 у плазмі крові визначали методом імуноферментного аналізу. Результати та обговорення. Встановлено, що концентрація пептиду в плазмі крові в чоловіків без серцево-судинних захворювань статистично значуще не корелює з віком та особливостями конституції, функцією нирок, станом системної та внутрішньосерцевої гемодинаміки, морфометричними показниками серця. У пацієнтів з ЕГ середній рівень sST2 у плазмі крові статистично значуще вищий, ніж у осіб контрольної групи. Виявлено, що до статистично значущого зростання концентрації пептиду в плазмі крові у хворих з ЕГ призводить формування гіпертрофії лівого шлуночка (ЛШ), незалежно від її типу, та діастолічної дисфункції серця. Також у пацієнтів з ЕГ і фракцією викиду (ФВ) ЛШ менше 40 % концентрація пептиду статистично значуще більша, ніж у хворих зі збереженою ФВ ЛШ.Висновки. Таким чином, у чоловіків з ЕГ різної тяжкості рівень sST2 у плазмі крові статистично значуще вищий, ніж у осіб без серцево-судинних захворювань. В обох випадках концентрація пептиду в плазмі крові не пов’язана з віком та особливостями конституції. У пацієнтів з неускладненою ЕГ статистично значуще вищі рівні sST2 асоціюються з розвитком гіпертрофії ЛШ, незалежно від її типу, та з порушенням діастолічної функції серця. У разі розвитку серцевої недостатності на тлі ЕГ рівень sST2 у плазмі крові також статистично значуще вищий, особливо при формуванні систолічної дисфункції серця з ФВ ЛШ &lt; 40 %.

Relationship between Soluble ST2 and Left Ventricular Geometry in Maintenance Hemodialysis Patients

Introduction: Left ventricular hypertrophy (LVH) is a highly prevalent presentation of cardiac structural abnormality and a strong predictor of adverse outcomes in maintenance hemodialysis (MHD) patients. Different left ventricular geometry may provide additional clinical information. Soluble ST2 is a novel cardiac prognostic biomarker in MHD patients and is closely related to cardiac remodeling. Objective: This study sought to evaluate the association of sST2 and left ventricular structure in a cohort of MHD patients. Methods: Two hundred eighty-seven patients were enrolled. Left ventricular structure was assessed via transthoracic echocardiography. Left ventricular geometric patterns were defined according to left ventricular mass index and relative wall thickness (RWT). Serum sST2 levels were measured. Results: Prevalence of LVH was 44.9% in the study population. In univariate analysis, sST2 levels were correlated with interventricular septal wall thickness, posterior wall thickness, and RWT. After multivariate adjustment, sST2 was independently correlated with only RWT (p = 0.028). Comparing sST2 concentrations across different LV geometric patterns, we found sST2 levels were significantly increased in patients with concentric cardiac remodeling and concentric LVH. Conclusions: The present study found that sST2 were significantly increased in patients with concentric remodeling and concentric LVH. ST2/interleukin (IL)-33 signaling might participate in the process of cardiac remodeling via its pro-fibrotic action. Future studies on the mechanism of ST2/IL-33 pathway are needed.

SST2 is a promising biomarker in hypertensive patients undergoing renal denervation

Abstract Introduction Therapy resistant arterial hypertension (raHTN) is a major clinical burden. While therapeutic alternatives are still missing, novel interventional procedures like renal denervation (RD) are still evolving. Indeed, despite discoursing results of the Simplicity HTN-3 trial, new promising results resulted in a revival of this procedure. Therefore, predictors for the success of future interventions would be of great clinical benefit. The novel biomarker sST2 shows promising results for risk stratification of cardiovascular patient. While, sST2 belongs to the IL-1 receptor family, it has an influence on immunologic processes with consequent cardioprotective effects including prevention of myocardial hypertrophy and fibrosis indicating predictive potential in hypertensive heart disease. Nevertheless, clinical implementation of this promising biomarker was not investigated in patients with raHTN undergoing RD. Purpose To investigate a potential clinical relevance of sST2 in patients with raHTN undergoing RD. Methods We evaluated 58 patients with raHTN (age: 63±11 years, systolic blood pressure at baseline: 178±24mmHg) undergoing bilateral RD. If available, serum levels of sST2 were analyzed at baseline as well as at follow-up at one and/or three month. Results While RD was able to decrease blood pressure levels after one month (systolic blood pressure at one month: 158±21mmHg, p&amp;lt;0.01), on echocardiography a reduction of left ventricular mass (LVM) was observed at one month with a further significant reduction at three month (LVM at baseline: 233±68g, LVM at one month: 218±59g and LVM at three month: 181±59, p&amp;lt;0.01). This observation was accompanied by a significant decrease of sST2 levels at three month (sST2 baseline: 6322±3578pg/ml vs. sST2 three month: 4704±1586pg/ml, p=0.02). Furthermore, baseline sST2 was positively correlated with systolic blood pressure at one month, measured either at office (r=0.57, p&amp;lt;0.01) or invasively in the aorta (r=0.49, p=0.03) indicating a potential predictive value of this biomarker. Conclusion In patients with raHTN, RD is associated with a significant decrease of sST2 levels, indicating sST2 to be involved in remodeling processes after RD. Furthermore, sST2 levels at baseline might be a potential predictor of intervention success of RD. Further, studies need to investigate the association of sST2 levels and RD. Funding Acknowledgement Type of funding source: None

Circulating sST2 and catestatin levels in patients with acute worsening of heart failure: a report from the CATSTAT-HF study.

AimsSoluble suppression of tumourigenicity 2 (sST2) and catestatin (CST) reflect myocardial fibrosis and sympathetic overactivity during the acute worsening of heart failure (AWHF). We aimed to determine serum levels and associations of sST2 and CST with in‐hospital death as well as the association between sST2 and CST among AWHF patients.Methods and resultsA total of 96 AWHF patients were consecutively enrolled, while levels of sST2 and CST were determined and compared between non‐survivors and survivors. Predictive values of sST2 and CST for in‐hospital death were determined by the penalized multivariable Firth logistic regression. The diagnostic ability of sST2 and CST for in‐hospital death was assessed by the receiver operating characteristic analysis and examined with respect to the N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), high‐sensitivity cardiac troponin I, and C‐reactive protein. The in‐hospital death rate was 6.25%. Serum sST2 and CST levels were significantly higher among non‐survivors than survivors [146.6 (inter‐quartile range, IQR 65.9–156.2) vs. 35.3 (IQR 20.6–64.4) ng/mL, P < 0.001, and 19.8 (IQR 9.9–28.0) vs. 5.6 (IQR 3.4–9.8) ng/mL, P < 0.001, respectively]. Both sST2 and CST were independent predictors of in‐hospital death [Firth coefficient (FC) 6.00, 95% confidence interval (CI), 1.48–15.20, P = 0.005, and FC 6.58, 95% CI 1.66–21.78, P = 0.003, respectively], while NT‐proBNP was not a significant predictor (FC 1.57, 95% CI 0.51–3.99, P = 0.142). In classifying non‐survivors from survivors, sST2 provided area under the curve (AUC) of 0.917 (95% CI 0.819–1.000, P < 0.001) followed by CST (AUC 0.905, 95% CI 0.792–1.000, P < 0.001), while NT‐proBNP yielded AUC of 0.735 (95% CI 0.516–0.954, P = 0.036). High‐sensitivity cardiac troponin I and C‐reactive protein were not found as significant classifiers of in‐hospital death (AUC 0.719, 95% CI 0.509–0.930, P = 0.075, and AUC 0.682, 95% CI 0.541–0.822, P = 0.164, respectively). Among survivors, those with sST2 serum levels ≥35 ng/mL had significantly higher CST levels, compared with those with sST2 < 35 ng/mL (9.05 ± 5.17 vs. 5.06 ± 2.76 ng/mL, P < 0.001). Serum sST2 levels positively and independently correlated with CST levels in the whole patient cohort (β = 0.437, P < 0.001).ConclusionsElevated sST2 and CST levels, reflecting two distinct pathophysiological pathways in heart failure, might indicate impending clinical deterioration among AWHF patients during hospitalization and facilitate prognosis beyond traditional biomarkers regarding the risk of in‐hospital death (CATSTAT‐HF ClinicalTrials.gov Number NCT03389386).

Serum soluble ST2 is a potential long-term prognostic biomarker for transient ischaemic attack and ischaemic stroke.

Soluble ST2 (sST2) is a promising biomarker in inflammation, atherosclerosis and cardiovascular diseases. We investigated the association between serum sST2 and poor outcome in patients with transient ischaemic attack (TIA)/ischaemic stroke. Patients within 24h after onset and with measured serum sST2 were prospectively enrolled in this study. Poor outcome was a combination of a new stroke event (ischaemic or haemorrhagic) and all-cause death within 90days and 1year. The associations of serum sST2 with poor outcome were analysed by Cox proportional hazards. Among the 430 patients included, the median (interquartile range) sST2 was 17.72 (9.31-28.84)ng/mL. A total of 19 (4.4%) and 38 (8.8%) patients experienced poor outcome within 90days and 1year, respectively. Compared with the lowest sST2 tertile, hazard ratios (HRs) [95% confidence intervals (CI)] for the highest tertile were 5.14 (1.43-18.51) for poor outcome within 90days and 3.00 (1.29-6.97) at 1year after multivariate adjustments. Adding sST2 to a prediction model significantly improved risk stratification of poor outcome in TIA/ischaemic stroke, as observed by the continuous net reclassification improvement of 60.98% (95% CI, 15.37-106.6%, P=0.009) and integrated discrimination improvement of 2.63% (95% CI, 0.08-5.18%, P=0.043) at 90days and the continuous net reclassification improvement of 41.68% (95% CI, 8.74-74.61%, P=0.013) at 1year. Increased serum sST2 levels in TIA/ischaemic stroke were associated with increased risks of poor outcome within 90days and 1year, suggesting that serum sST2 may be a potential long-term prognostic biomarker for TIA/ischaemic stroke.

High Expression of Interleukin-33/ST2 Predicts the Progression and Poor Prognosis in Chronic Hepatitis B Patients with Hepatic Flare

BackgroundInterleukin-33 (IL-33), along with its receptor suppression of tumorigenicity 2 (ST2), is capable of regulating immune responses. Immunologically mediated events play a critical role in the acute phase of chronic hepatitis B (CHB) infection. The present study primarily aimed to determine whether the IL-33/ST2 axis could be used as a reliable biomarker to predict disease progression and prognosis. MethodsThe study included 130 cases of CHB, with 48 cases in stable condition, 50 cases of progression to hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), and 32 cases of progression to HBV related pre-ACLF. The demographic data and laboratory test results were recorded and compared among the groups. The blood samples for the measurement of serum IL-33 and soluble ST2 (sST2) levels were collected at admission and evaluated twice using the ELISA method. ResultsThe patients in which the disease progressed to HBV-ACLF had the highest serum IL-33 and sST2 levels among the three groups (p<0.001). The correlation analysis showed that the serum IL-33 levels were associated with the levels of ALT (r = 0.367, p<0.001), AST (r = 0.456, p<0.001) and the MELD score (r = 0.377, p = 0.001). The area under the curve (AUC) of IL-33 and sST2 levels for differentiation of disease progression were 0.861 (95% CI: 0.787–0.934, p<0.001) and 0.788 (95% CI: 0.692–0.884, p<0.001), respectively. The serum IL-33 levels combined with the MELD score had the highest 90-day mortality prediction efficiency, with an AUC of 0.918 (95% CI: 0.859–0.977, p<0.001), a sensitivity of 92.3%, and a specificity of 88.7%. ConclusionsThe IL-33/sST2 axis could be used to evaluate the progression and mortality in CHB patients with hepatic flare. The combinatorial use of multiple indicators could achieve the highest diagnostic and predictive accuracy.

Soluble ST2 (sST2) as potential marker for hepatic cystic echinococcosis activity

Objectivesthis study aims to identify the potential marker for hepatic cystic echinococcosis (CE) activity. Methodstotally 97 CE patients and 47 health control (HC) subjects were included. Based on the ultrasound (US) images, CE patients were further categorized as active CE (ACE; 52 cases) and inactive CE (IACE; 45 cases). The sST2 and IL (interleukin)-33 levels were measured by enzyme-linked immunosorbent assay. Univariate, multivariate and subgroup analysis were performed. The relationship between sST2 and CE activity was analyzed by the smooth curve fitting. The receiver operating characteristic (ROC) curve analysis was also performed. Resultsthe serum sST2 level in the CE patients was significantly higher than the HC subjects. Moreover, there was significant difference in the serum sST2 level between the ACE and IACE group. However, no significant difference was observed in the IL-33 level between the ACE and IACE groups. Univariate analysis showed that CE activity was significantly correlated with the sST2 level when the sST2 was greater than 1496.6 pg/mL. Multivariable analysis after adjustment for potential confounding factors, and subgroup analysis showed that sST2 had independent effect on CE activity. ROC curve showed that sST2 could differentially diagnose CE activity at the cut-off value of 1246.550 pg/mL with an AUC of 0.770. Conclusionthe sST2 could be used as a biomarker for hepatic CE activity. High levels of sST2 suggest that the hepatic CE is more likely to be active. Our findings have important guiding significance for the diagnosis of CE activity and the choice of treatment methods.

Positive association between heart dosimetry parameters and a novel cardiac biomarker, solubleST-2, in thoracic cancer chest radiation.

BackgroundEarly screening and diagnosis of radiation‐induced heart disease (RIHD) is difficult in patients with chest radiation exposure. sST‐2 is involved in myocardial stress or injury. We evaluated the relationship between heart dose parameters and sST‐2 changes in chest malignant tumor patients who received chest radiation.MethodsWe prospectively collected thoracic malignancy cancer patients who had received chest radiotherapy. Heart dosimetry parameters were extracted from the treatment planning system. sST‐2 was measured at baseline, the middle stage, and after radiotherapy (recorded as pre‐ST‐2, mid‐ST‐2, and post‐ST‐2). sST‐2 change rate was calculated. Scatter plots showed the relationship between cardiac dose parameters and ST‐2 change rate. Multiple regression was used to analyze the relationship between cardiac dose parameters and ST‐2 change rate.ResultsTotally, 60 patients were enrolled. The mean V5, V10, V20, V30, V40, and MHD was 60.93 ± 27.79%, 51.43 ± 25.44%, 39.17 ± 21.75%, 28.07 ± 17.15%,18.66 ± 12.18%, and 18.60 ± 8.63 Gy, respectively. The median M‐LAD was 11.31 (IQR 3.33‐18.76) Gy. The mean pre‐ST‐2, mid‐ST‐2, and post‐ST‐2 was 5.1 ± 3.8, 6.4 ± 3.9, and 7.6 ± 4.4, respectively. sST‐2 was elevated with thoracic irradiation (P < .001). Multivariate linear regression analyses showed that V5, V10, V20, and MHD were independently and positively associated with ST‐2 change rate (β = .04, .04, .04, and .10, respectively, all P < .05).ConclusionSerum sST‐2 levels were elevated over time during radiotherapy. V5, V10, V20 and MHD were independently and positively associated with the elevated ST‐2 change rate.

Serum Soluble ST2 as a Novel Biomarker Reflecting Inflammatory Status and Disease Severity in Patients with COVID-19

Background: The COVID-19 pandemic, caused by a novel coronavirus (SARS-CoV-2), currently impacts over 100 countries. Soluble ST2 (sST2) is secreted and detectable in human serum, which acts as a decoy receptor for interleukin (IL)-33 to prevent IL-33-mediated T cell immune responses. Serum sST2 has been found to be a novel biomarker in several viral infectious diseases. Here, we studies the role of sST2 in COVID-19 and its relationship with inflammatory status and disease severity. Methods: A total of 80 subjects diagnosed as COVID-19 were recruited in this study, including 36 mild, 41 severe and 3 asymptomatic cases. On admission the levels of C-reactive protein (CRP), serum amyloid protein (SAA), IL-6 and procalcitonin (PCT) were collected, and T lymphocyte subsets were tested by flow cytometry. Serum levels of sST2 and IL-33 were measured using enzyme-linked immunosorbent assay. Findings: Serum sST2 levels were significantly increased in patients with COVID-19. Line regression analysis indicated that there was a positive correlation between serum sST2 and CRP level in COVID-19 patients. Conversely, serum sST2 levels negatively correlated with CD4+ and CD8 + T lymphocyte counts. Moreover, dynamic changes of serum sST2 persisted at a high level in severe cases. No obvious difference in the levels of serum IL-33 was observed between the control subjects and COVID-19 patients. Interpretation: Surveillance of serum sST2 is helpful in the early screening of inflammatory status and critical illness of COVID-19. High sST2 level combined with the decreased T lymphocytes may reflect the dysregulated T cell immune response and infection severity. Funding Statement: This study was supported by the National Natural Science Foundation of China (No. 81501033). Declaration of Interests: All authors have not any financial conflict of interest. Ethics Approval Statement: The study was approved by the ethics committee of Zhongnan Hospital of Wuhan University (No. 2019125). Written informed consent was obtained from patients.

The Correlation between sST2 and Atrial Fibrillation and Its Clinical Significance

Objective: To explore the level of soluble growth-stimulated expression gene 2 (sST2) in patients with atrial fibrillation (AF) and its relationship with atrial remodeling. Methods: From December 2018 to July 2019, 86 patients were enrolled in the cardiovascular department of Jingzhou Central Hospital in Hubei Province. AF group was 60 patients with AF diagnosed according to the diagnostic criteria of electrophysiology and pacing branch of Chinese Medical Association, while the control group was 26 normal ECG patients with sinus rhythm examined by ECG and/or DCG. Clinical data, NT proBNP and birth rate of all patients were collected chemical indicators. All the patients in the groups were examined by ECG and color Doppler echocardiography. The serum level of ST2 was detected by enzyme-linked immunosorbent assay (ELISA), and the indexes related to atrial remodeling in echocardiography, left atrial diameter (LAD), were collected, compared and analyzed. Results: Serum sST2 levels and LAD and RAD values in the AF group were higher than those in the control group (P < 0.05 or P < 0.01). Serum sST2 levels were higher in the AF group than in the paroxysmal atrial fibrillation group (P = 0.031). 1) The sST2 level was positively correlated with LAD and RAD measured by cardiac ultrasound (r = 0.388, P = 0.029). Conclusion: Serum sST2 levels have early recognition value in patients with high-risk atrial fibrillation, which contributes to the stratification of risk of atrial fibrillation and the prediction of disease activity. Elevated serum sST2 levels may be associated with atrial remodeling. sST2 may be an objective biomarker that predicts the risk of emergency admission in patients with atrial fibrillation. Elevated sST2 levels may be associated with atrial fibrillation progression.

Взаимосвязь тяжести поражения коронарных артерий и экспрессии ST2 у больных с сердечной недостаточностью

Aim: to study the association between ST2 (sST2) and severity of coronary artery lesion in patients with chronic heart failure (CHF), and to analyze changes in sST2 levels and left ventricle (LV) remodeling indicators depending on complete or incomplete myocardial revascularization (MR) after the 12-month follow-up period.Patients and Methods: a total of 118 patients (16.1% women, mean age of 62.5 [57; 68] years) with stable coronary heart disease (CHD) with LV ejection fraction 60% [46; 64] and CHF of NYHA functional class I–III were enrolled in the study. All patients underwent MR. Depending on the completeness of the performed MR, all patients were retrospectively divided into 2 groups: group 1 (n=75) consisted of patients with complete MR, group 2 (n=43) — with incomplete MR. Serum levels of sST2 were measured using an enzyme immunoassay before MR and after the 12-month follow-up period.Results: the sST2 level in patients with single vessel coronary artery disease was 29.92 [22.43; 32.68] ng/ml and was 21% lower (p=0.002) than in patients with two or more coronary arteries (CA) — 37.87 [37.87; 51.82] ng/ml. During 12-month follow-up, the incidence of adverse cardiovascular events (CVE) in group 1 was 18.7%, in group 2–46.5% (p=0.001). After 12-month follow-up, the level of sST2 in group 1 decreased by 33.6% (p=0.0001) (from 30.51 [26.38; 37.06] to 20.27 [16.56; 27.11] ng/ml), while in group 2 there was only a tendency to decrease in the level of this biomarker, which was 6.9%. In group 2, after 12-month follow-up, there was a tendency to increase in the LV EF, which increased by only 2.4%, as well as a tendency to increase in the end-systolic dimension (ESD), which increased by 5.4%. In the group of patients with complete MR, the increase in the LV EF was significant (p=0.001) — by 13.6% (from 54.0 [42.0; 63.0] to 62.5 [49.0; 64.0]%), and the ESD decreased by 3%, the final ESV — by 4.6%.Conclusion: the sST2 level can be used as a diagnostic marker for assessing the severity of atherosclerotic CA lesion in patients with CHF. Performing complete MR in patients with stable CHD with CHF has a predominance over incomplete MR, leading to reversed LV remodeling, a decrease in sST2 levels and, as a result, the incidence of adverse CVE during the 12-month follow-up. KEYWORDS: coronary atherosclerosis, soluble ST2, myocardial revascularization, heart failure, prognosis, left ventricular remodeling.FOR CITATION: Grakova E.V., Kopieva K.V., Teplyakov A.T., Soldatenko M.V. Association between the severity of coronary artery disease and ST expression in patients with heart failure. Russian Medical Inquiry. 2020;4(7):399–405. DOI: 10.32364/2587-6821-2020-4-7-399-405.

Superior prognostic value of soluble suppression of tumorigenicity 2 for the short-term mortality of maintenance hemodialysis patients compared with NT-proBNP: a prospective cohort study

Background Both soluble suppression of tumorigenicity 2 (sST2) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are promising biomarkers associated with the adverse clinical outcomes of dialysis patients. Our research aims at exploring and comparing the roles of sST2 and NT-proBNP in predicting the short-term and long-term mortality of maintenance hemodialysis (MHD) patients. Methods A prospective cohort study was performed. Patients undergoing hemodialysis in July 2014 were enrolled from the Blood Purification Center of Ruijin Hospital. MHD patients were followed up for 3 years. The primary outcome was all-cause mortality at the 1-year and 3-year follow-up, while the secondary outcome was cardiovascular mortality. Serum sST2 level was detected by quantified ELISA kits. Clinical data were analyzed by SPSS 23.0 version. Results 205 patients were recruited. The median sST2 level was 15.99 (11.60, 20.49) ng/ml. After 3 years of follow-up, both all-cause and cardiovascular mortality in 1 year and all-cause and cardiovascular mortality in 3 years increased significantly with serum sST2. For short-term mortality, no significant difference was observed in patients with increasing NT-proBNP levels. Cox regression analysis indicated that only sST2 was independent in predicting the risk of short-term outcomes. For long-term mortality, both sST2 and NT-proBNP were independent risk factors, while a higher hazard ratio was observed for NT-proBNP. Conclusions Serum sST2 is a novel biomarker associated with adverse clinical outcomes in MHD patients. It was significant for both all-cause and cardiovascular mortality in MHD patients and may provide better prognostic value in short-term prognosis than the classic biomarker NT-proBNP.

Dynamic changes of soluble ST2 levels predicted fatality and were involved in coagulopathy in dengue fever in the elderly.

BackgroundSevere dengue virus (DENV) infection involves plasma leakage and vascular collapse, and leads to significant morbidity and death. Serum soluble ST2 (sST2 [interleukin (IL)-1 receptor like-1 protein: IL-1-RL-1]) levels are high in pediatric cases of DENV infection, and the disease progresses. However, the correlation between serum sST2 levels and the outcomes of DENV infection in the elderly (≥65 years) is unclear. We thus explored the mechanisms of serial sST2 level changes involved in the coagulopathy and bloodstream infections of elderly patients in Taiwan’s 2015 DENV outbreak.MethodsThis retrospective study was done in a tertiary medical center in southern Taiwan during the outbreak. All DENV-infected patients who, between July 1, 2015, and December 31, 2015, provided a written informed consent for at least two blood sample analyses were enrolled and reviewed. The serum levels of sST2 were quantified. ΔsST2 is defined as the “changes of sST2 levels in serially paired samples”. Receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) analyses were used to evaluate the prognostic ability of ΔsST2.ResultsForty-three patients with DENV infection were enrolled. Mean patient age was 75.0 ± 12.2 years and the case fatality rate was 44.2% (19/43). Significantly more non-survivors than survivors had increased ST2 level (78.9% vs. 12.5%, p < 0.001). The AUC value for serum ΔsST2 level was 0.857 for predicting DENV fatality. Moreover, patients given frozen fresh plasma (FFP) transfusions were significantly (p = 0.025) more likely to have higher serum ST2 level changes than were those who had not. DENV-infected patients with early bloodstream infections (BSIs) seemed to have higher ST2 levels than those who did not have BSIs.ConclusionsSerum ST2 levels increased in the elderly (≥ 65 years of age) with DENV infection. The changes in serum sST2 levels might be a critical indicator of DENV infection severity for the elderly; sST2 is an important modulator of coagulopathy in severe DENV infections.