sST2 Levels Research Articles

Association of biomarkers of cardiac remodeling, myocardial fibrosis and inflammation with parameters of heart function and structure in patients with arterial hypertension.

Early evaluation of cardiac remodeling may be useful in predicting heart failure in patients with arterial hypertension. The identification of biomarkers as useful clinical tools in this regard is ongoing. The aim of this study was to evaluate the association of selected cardiac biomarkers levels with parameters of cardiac structure and function in patients with arterial hypertension. Included in the study were patients with arterial hypertension with normal left ventricular ejection fraction (LV EF) and absence of signs of heart failure. The levels of selected biomarkers: NT-proBNP, sST2, Galectin-3, GDF-15, Cystatin C, TIMP-1 and ceruloplasmin were measured and assessed together with other biochemical and echocardiographic parameters. A total of 92 patients (61% men) mean age 61.5 years were included. Mean LV EF was 64.7% and mean LV mass index was 91.7 g/m2. NT-proBNP level correlated significantly with the parameters of LV diastolic function: velocity of E wave (r=0.377, P<0.002), and with E/A ratio, (r=0.455, P<0.0001), with E lat (r=-0.354, P=0.006), E/E' ratio, r=0.393, P<0.002, with ePAP (r=0.390, P=0.014), and with age (r=0.384, P<0.0001). Statistically significant correlations for GDF-15 were as follows: with age (r=0.426, P<0.0001) and left atrial diameter (LA) (r=0.401, P<0.0001), for Cystatin C there are statistically significant correlation with age (r=0.288, P=0.006) and LA (r=0.329, P=0.004). Only sST2 level correlated significantly with parameters of cardiac structure: with LV mass (r=0.290, P<0.01) and LV mass index (r=0.307, P=0.012) and with posterior wall thickness PW (r=0.380, P<0.001). No other observed variables including Galectin-3 and TIMP-1, correlated significantly with age or echocardiographic variables. In a comparison of patients with and without left ventricular hypertrophy, statistically significant differences were found only in LA (P<0.0001) and sST2 (P=0.004). In a multivariate logistic regression, sST2 and TIMP were independent predictors of left ventricular hypertrophy. NT-proBNP level as a biomarker of cardiac remodeling correlated with parameters of LV diastolic function in patients with arterial hypertension. Soluble ST2 correlated with parameters of cardiac structure. Biomarkers sST2 and TIMP-1 were associated with left ventricular hypertrophy.

Relationship between sST2 and NT-proBNP levels and postoperative atrial fibrillation in patients having non-cardiac surgery.

We explored the link between sST2 and NT-proBNP levels and postoperative atrial fibrillation (POAF) incidence in non-cardiac surgery patients in this study. The research involved 302 participants over 40 years old who underwent medium and/or high-risk non-cardiac surgeries. These patients were divided into two groups: those who developed POAF and those who did not. The study cohort consisted of a total of 302 patients, with 14 (4.6%) experiencing POAF. POAF was more common in patients with previous heart failure, a high Left Atrial Volume Index (LAVI), and elevated ASA and RCRI scores (all P<0.05). LAVI, sST2, NT-proBNP, and RCRI scores were found to be independent predictors of POAF in patients undergoing non-cardiac surgeries (all P<0.05). The area under the curve (AUC) for sST2 and NT-proBNP in predicting POAF was 0.707 (95% CI 0.544-0.869; P=0.009) and 0.727 (95% CI 0.598-0.857; P=0.004), respectively. Combined elevation of sST2 and NT-proBNP increased the likelihood of developing POAF by approximately 8.5 times (OR: 8.65, CI 95% 1.06-35.3, P=0.044). sST2 and NT-proBNP are valuable predictors of POAF in patients undergoing non-cardiac surgery. Identifying these predictors can help in recognizing high-risk patient groups for POAF.

The mortality implications of increasing and decreasing sST2 levels during acute decompensated heart failure

Abstract Introduction Soluble Suppressor of Tumorigenicity (sST2), a marker of cardiac remodelling and fibrosis, has demonstrated promises in prognostication of heart failure (HF) and therefore recommended as an additional test for risk stratification of HF in the 2017 ACC/AHA/HFSA guidance. It is well investigated as single measurements in acute and ambulatory settings. Data regarding sST2 level changes during acute decompensated heart failure (ADHF) and its potential in providing additional prognostic information is however sparse. We therefore sought to evaluate changes in sST2 and its prognostic implications in hospitalized patients during ADHF. Methods Between December 2019 and February 2022, consecutive patients with ADHF and reduced ejection fraction (EF&amp;lt;50%) presenting to our University Hospital were recruited as part of the Investigating the soluble ST2 biomarker in addition to Natriuretic peptides in managing patients with Heart Failure and a Reduced Ejection Fraction (INST2ANT-HF) study (REC Reference: 19/EE/0269). Serum samples were taken at clinician determined decompensation and recompensation in all participants, who were then followed up for one year post discharge. The study primary end point was all-cause mortality at one year. A 2x2 contingency table was constructed to display the relationship between the frequency of unchanged/increased or decreased sST2 levels at recompensation and the frequency of mortality at one year (Table 1). A Kaplan-Meier curve was plotted to display the survival probability of the two groups during one-year follow up (Figure 1), and log-rank test applied to evaluate for significant difference in the survival distributions. Results In 169 patients with paired sST2 samples, median age (IQR) was 72 (62-80.8), 39 (23.2%) were female and 160 (95.2%) were ethnically white. 158 (94.1%) presented with NYHA class II-IV and the median (IQR) EF was 26% (17.5-32.5). Median (IQR) length of stay in hospital was 8 days (5-13). Median (IQR) sST2 level at decompensation and recompensation were 60ng/ml (40-93.3) and 39.5ng/ml (24-64.8) respectively. At clinician determined recompensation, sST2 level decreased in 136 (81%) patients while 32 (19%) had unchanged/increased sST2 levels. One-year mortality was 37.5% in patients with unchanged or increasing sST2 levels during ADHF, compared to 16.2% in those with decreased sST2 levels. The mean (SE) survival time was 332 (7) days for patients with unchanged/increasing sST2, and 274 (22.5) days for patients with decreasing sST2 at HF recompensation (p=0.003). Conclusion Our data demonstrates that there was a downward trend in sST2 in most patients during recovery from an ADHF episode. Importantly, a static or increasing sST2 level from HF decompensation to recompensation was associated with a significantly higher risk of mortality at one year. Further research may ascertain if the mortality risk is also dependent on the percentage changes in sST2 concentrations.Table 1:2x2 contingency tableFigure 1:Kaplan-Meier curve

Association of soluble ST2 with heart failure and other comorbidities in patients with severe coronary heart disease

Abstract Background Circulating levels of soluble suppression of tumorigenicity-2 (sST2) reflect vascular congestion, inflammation, and fibrosis. sST2 has been proposed as a useful biomarker to predict the mortality and hospitalization due to heart failure. However, there is limited evidence regarding the relationship between sST2 and heart failure, as well as other comorbidities, in severe coronary heart disease (CAD). Purpose This study aims to measure the circulating levels of soluble ST2 (sST2) in a large population of patients with severe CAD to determine its association with heart failure, cardiac function, inflammation, and other important comorbidities. Methods This subanalysis is part of the ongoing perspective observational study. Available serum samples from 520 patients undergoing elective coronary artery bypass grafting (CABG) were analysed for sST2 levels. The inclusion criteria were written informed consent and age between 18-85 years. Exclusion criteria for this analysis were severe valvular disease, severe chronic obstructive pulmonary disease, oxygen therapy, nocturnal positive airway pressure support or mechanical ventilation, and the need for catecholamines or circulatory assist devices. The circulating levels of human sST2 were measured from frozen serum (-80°C) using commercially available ELISA kits. The plasma was diluted 100 times to detect sST2 levels (assay range of 31.2 - 2,000 pg/mL). Two measurements were taken to account as means for intra-assay variabilities. Logarithmic transformation was used to convert non-normal distributed data. Student t' test and linear regression were applied to categorical or continuous variables as appropriate. Results sST2 levels (median 20.4 ng/ml, [IQR 15.5 – 28.8]) significantly predict worse left ventricular ejection fraction (β = -0.164, p = 0.006), and significantly correlate with levels of NT-proBNP (β = 3.263, p &amp;lt; 0.001), hs-Troponin T (β = 3.391, p &amp;lt; 0.001), high-sensitivity C-reactive protein (β = 2.472, p = 0.014) and heart failure (p= 0.002). Interestingly, common comorbidities such as chronic kidney disease (estimated glomerular filtration rate &amp;lt; 60 mL/min/1.73 m2, p = 0.004), diabetes mellitus (p = 0.001) and higher levels of glycated haemoglobin (HbA1c, β = 3.615, p &amp;lt; 0.001) showed also a significant association with sST2 levels. No significant association of sST2 was observed with arterial hypertension (p = 0.190), atrial fibrillation (p = 0.289), obesity (BMI ≥ 30 kg/m2, p = 0.302), sleep apnoea (apnoea-hypopnoea index ≥ 15/h, p = 0.068), peripheral artery disease (p = 0.823), or previous stroke (p = 0.861). Conclusion(s) Circulating levels of sST2 significantly correlate with heart failure, NT-proBNP, hs-TnT, and hs-CRP in patients with severe CAD. Additionally, sST2 levels were found to be elevated in patients with diabetes mellitus and chronic kidney disease.

Blood biomarkers to detect functional impairment in adult patients with repaired Tetralogy of Fallot

Abstract Background The relationship between plasma brain natriuretic peptide (NT-proBNP) and soluble suppression of tumorigenicity-2 (sST2) with structural adaptions and exercise capacity remains incompletely described in patients with repaired Tetralogy of Fallot (rTOF). Methods Peripheral venous blood samples were drawn for 99 patients with repaired TOF, 59 patients with severe pulmonary regurgitation (PR) and 40 patients with no or mild PR. NT-proBNP was measured using enzyme-linked immunosorbent assays (Roche Diagnostics, Indianapolis, IN). Soluble ST2 levels were assessed on Aspect-plus ST2 quantitative rapid test. Results The mean value of NT-proBNP was 160±137 pg/ml, and sST2 was 29±13, ng/ml in the entire population. Mean NT-proBNP was significantly higher in patients with severe PR (169±150 vs145±118, pg/ml, p&amp;lt;0.001), while similar sST2 levels were observed in both groups (29±14 vs30±12, ng/ml, p&amp;gt;0.05). NT-proBNP and sST2 levels were higher in patients with transannular patch when compared to other RVOT intervention. Both biomarkers were significantly associated with exercise capacity, but NT-proBNP (r=-.60, p&amp;lt;0.001) was stronger. The optimal cut-off of 90pg/ml for NT-proBNP had a sensitivity of 74% and specificity of 63% for detection of impaired exercise capacity. Conclusions Serum levels of sST2 and NT-proBNP are elevated in patients with repaired TOF, with higher values observed in those with severe PR, but also in patients undergoing transannular patch. Incorporating both markers in these patients increased the ability to detect impairment in exercise capacity.

Pulmonary Congestion and Anemia in Hemodialysis: The Potential Link to Inflammation

Pulmonary congestion (PC) is common in hemodialysis (HD) patients. We explored the association of anemia and pulmonary congestion in HD patients. A prospective pilot observational study included 18 patients on maintenance HD. Individual B-lines scores (BLS; 8-sites method) were obtained by lung ultrasound, before and after the first two consecutive HD sessions of the week (HD1-HD2), with different inter-dialytic intervals (68 vs. 44 h). Bioimpedance spectroscopy body composition (BIS) was performed before each HD session. Hemoglobin (Hb) levels, in addition to circulating markers of chronic inflammation (soluble urokinase Plasminogen Activator Receptor [suPAR], soluble Suppression of Tumorigenicity 2 [sST2]) were obtained. Mean (±SD) BLS values were quite elevated at all time points: Pre-HD1 (16 ± 5.53), post-HD1 (15.3 ± 6.63), pre-HD2 (16.3 ± 5.26) and post-HD2 (13.6 ± 5.83), respectively. No direct significant correlation was found between inflammation markers levels and BLS. However, mean levels (±SD, ng/mL) of suPAR pre-HD1 (7.88 ± 3.07) and pre-HD2 (7.78 ± 3.02) remained significantly above the normal range (&lt;4 ng/mL), and sST2 levels reached 2-fold the upper normal value in most patients (27.4 ± 17.8). Pulmonary congestion reflected by BLS was negatively correlated to Hb levels pre-HD1 (R² = 0.439, p = 0.003), and pre-HD2 (R² = 0.301, p = 0.018). In addition, Hb levels were negatively correlated to global volume status estimated by BIS (R² = 0.351, p = 0.009). Hemoglobin levels were negatively correlated to pulmonary congestion and to the global volume status evaluated by BIS. Chronic inflammation markers were increased in HD patients, suggesting a complex volume- and non-volume-dependent pathophysiology of pulmonary congestion in HD patients.

Circulating soluble suppression of tumorigenicity-2 and the recurrence of atrial fibrillation after catheter ablation: A meta-analysis.

Soluble suppression of tumorigenicity-2 (sST-2), a marker of myocardial fibrosis and remodeling, has been related to the development of atrial fibrillation (AF). The aim of this meta-analysis was to evaluate the relationship between baseline serum sST-2 levels and the risk of AF recurrence after ablation. Relevant observational studies were retrieved from PubMed, Web of Science, Embase, Wanfang and China National Knowledge Infrastructure (CNKI). A random-effects model was used to combine the data, accounting for between-study heterogeneity. Fourteen prospective cohorts were included. Pooled results showed higher sST-2 levels before ablation in patients with AF recurrence compared to those without AF recurrence (standardized mean difference = 1.15, 95% confidence interval [CI] = 0.67 to 1.63, P < 0.001; I2 = 92%). Meta-regression analysis suggested that the proportion of patients with paroxysmal AF (PaAF) was positively related to the difference in serum sST-2 levels between patients with and without AF recurrence (coefficient = 0.033, P < 0.001). Subgroup analysis showed a more remarkable difference in serum sST-2 levels between patients with and without AF recurrence in studies where PaAF was ≥ 60% compared to those where it was < 60% (P = 0.007). Further analyses showed that high sST-2 levels before ablation were associated with an increased risk of AF recurrence (odds ratio [OR] per 1 ng/mL increment of sST-2 =1.05, OR for high versus low sST-2 = 1.73, both P values < 0.05). In conclusion, high sST-2 baseline levels may be associated with an increased risk of AF recurrence after catheter ablation.

An elevated level of soluble suppression of tumorigenicity 2, but not galectin-3, is associated with the presence of coronary artery disease in hypertensive patients.

We investigated whether there were associations between coronary artery disease (CAD) and soluble suppression of tumorigenicity (sST2) and galectin-3 levels at the time of coronary artery computed tomography angiography (CCTA) for CAD screening. The subjects consisted of 429 patients who underwent CCTA examination. CAD was diagnosed when there was 50% or more stenosis in the coronary artery. Patient backgrounds were collected and plasma levels of sST2 and galectin-3 were measured. The presence or absence of CAD and factors that contributed to CAD were analyzed for all patients and for those with or without hypertension (HTN). The CAD group had significantly higher sST2 levels than the non-CAD group, whereas there was no significant difference in galectin-3 levels. The number of patients in the non-HTN and HTN groups was 174 and 255, respectively. In the HTN group, the CAD group was significantly older than the non-CAD group and had higher sST2 levels. Multivariate analysis showed that the factors that contributed to CAD in the HTN group were age and sST2 levels. On the other hand, in the non-HTN group, the CAD group was significantly older than the non-CAD group, and had a higher proportion of males and higher sST2 levels, while the contributing factors for the CAD group were age and male gender, but not sST2. In conclusion, a higher level of sST2, but not galectin-3, was a contributing factor for CAD in HTN patients. However, in non-HTN patients, a high level of sST2 was not a contributing factor for CAD.

. The significance of serum sST2 and cfDNA in children with severe pneumonia complicated by myocardial damage

Objective: The paper aimed to explore the significance of serum sST2 and cfDNA to prevent atrial inflammation in children with severe pneumonia complicated by myocardial damage. Methods: 120 children with severe pneumonia complicated by myocardial damage who were treated in the Children's Department of the author's hospital from April 2021 to December 2023 were recruited as research subjects. The children were randomly divided into two groups, one group of 60 children received personalized care intervention based on serum sST2 and cfDNA (personalized care group), and the other group of 60 children received routine care (routine care group). The clinical data of the two groups of patients were compared. The changes in serum sST2 and cfDNA levels of patients were compared before and after care. ELISA kits were used to test atrial inflammation marker levels before and after patient care. The patient's cardiac function was assessed through cardiac ultrasound. the nursing intervention effects of the two groups was compared. The patient satisfaction with nursing care was compared between the two groups. Results: There was no distinction in the general record of the two groups (P&gt;0.05). Before care, there was no distinction in serum sST2 and cfDNA levels between the two groups (P&gt;0.05). After care, the serum sST2 and cfDNA levels in the personalized care group were lower than those in the routine care group (P&lt;0.05). There was no difference in CRP, cTn, 1L-6 and TNF-α between the two groups before nursing (P&gt;0.05). After nursing, the levels of CRP, cTn, 1L-6 and TNF-α in personalized nursing were lower than those in the conventional nursing group (P&lt;0.05). Parameters such as EF and E/A in the personalized care group were higher than those in the routine care group (P&lt;0.05). The LVEDd and LVESd in the personalized care group were smaller than routine care group (P&lt;0.05). The improvement rate of cardiac function, remission rate of atrial inflammation and 6-month re-hospitalization rate in the personalized care group were lower than conventional care group (P&lt;0.05). The very satisfied rate in the personalized care group was higher than routine care group (P&lt;0.05), and the dissatisfaction rate in the personalized care group was lower than routine care group (P&lt;0.05). Conclusion: Personalized nursing intervention based on serum sST2 and cfDNA can significantly improve the cardiac function of children with severe pneumonia complicated by myocardial damage, reduce the levels of atrial inflammation markers, and advance the satisfaction of children and their families. These findings underscore the importance of applying serum sST2 and cfDNA monitoring in clinical care and the significant benefits of personalized care in preventing atrial inflammation, improving heart health, and improving patient quality of life.

Assessment of combined serum sST2 and AFP levels in the diagnosis of hepatocellular carcinoma

Background Hepatocellular carcinoma (HCC) is a common malignant tumor with high morbidity and mortality. Alpha-fetoprotein (AFP) is the most widely used diagnostic serum biomarker, but it still has limited accuracy in detecting HCC, suggesting the necessity of seeking more ideal biomarkers with high sensitivity and specificity. Soluble growth stimulation gene 2 (sST2) form of growth stimulating expression gene 2 (ST2), is expressed in various organs and can bind competitively to interleukin 33 (IL-33). Whether sST2 can serve as a serum biomarker for HCC is largely unknown. Objective To investigate the value of sST2 as a serum diagnostic marker for HCC. Methods This study included 93 newly diagnosed HCC patients (HCC group), 90 chronic hepatitis B patients (CHB group), and 90 healthy individuals (HCs group). Spearman correlation analysis was used to explore the relationships between sST2 and the experimental indicators in HCC group. The receiver operating characteristic (ROC) curve evaluated the efficacy of sST2 alone or in combination with AFP in the diagnosis of HCC. Result The median level of sST2 was significantly higher in HCC group (24.00 [15.20-49.90] ng/mL) compared to CHB group (19.55 [15.23-24.95] ng/mL) and HCs group (7.65 [5.20-10.53] ng/mL). No significant correlations were found between sST2 and other clinical indicators in HCC group. The Area Under Curve (AUC) of ROC curve to distinguish HCC patients from healthy controls and CHB group was 0.861 (sensitivity 82.80%, specificity 72.10%) and 0.709 (sensitivity 80.60%, specificity 52.50%), respectively. When combined with AFP, the AUC increased to 0.963 (sensitivity 82.90%, specificity 94.20%), and 0.895 (sensitivity 72.0%, specificity 100%), respectively. Conclusions The serum level of sST2 increased in HCC and its diagnostic performance is comparable to that of AFP, supporting its potential as a promising biomarker for detection of HCC. The combined use of sST2 and AFP enhances diagnostic efficacy for HCC.

A-015 Changes of sST2 and NT-proBNP levels predict early cardiovascular toxicity in breast cancer patients treated with anthracycline-containing chemotherapy

Abstract Background Cardiovascular biomarkers play a crucial role in monitoring the risk for cancer therapy-related cardiovascular toxicity, but their changes and values at the early stage of chemotherapy are still inadequate, especially for some new biomarkers.The purpose of this study was to examine changes in cardiovascular biomarkers and evaluate the prognostic values for cardiovascular toxicity in patients with breast cancer treated with anthracycline-containing chemotherapy. Methods In a prospective cohort of 73 patients treated with anthracycline-containing chemotherapy, soluble ST2 (sST2), high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), Myoglobin (Myo), Creatine kinase isoenzyme MB (CK-MB) and heart-fatty acid binding protein (H-FABP) were measured at baseline, during every chemotherapy cycle (C1-C6, about every month).Cardiovascular toxicity was defined as cancer therapy-related arrhythmias, which was differentiated into bradycardia,tachycardia or atrial fibrillation. According to whether arrhythmia occurred, patients were divided into two groups (healthy group and arrhythmias group), and the basic clinical characteristics were collected and compared among the two groups. Logistic regression analyses and receiver operating characteristic (ROC) curves were conducted to investigate the relationship between the changes in biomarkers and anthracycline-induced cardiotoxicity. Results sST2 levels increased significantly from baseline to C1 (P&amp;lt;0.01). NT-proBNP decreased from baseline to C1, C5 (P&amp;lt; 0.01). Logistic regression analysis showed a greater risk of cardiovascular toxicity was associated with greater interval increase in sST2 from baseline to C1(ΔsST2) (OR:1.27; 95% CI:1.03 to1.56; P= 0.024) and interval decline in NT-proBNP from baseline to C1(ΔNT-proBNP) was associated with cardiovascular toxicity (OR: 0.83; 95% CI: 0.70 to 0.98; P= 0.029). ROC curves showed that ΔsST2, ΔNT-proBNP and ΔsST2+ΔNT-proBNP had good predictive value for cardiovascular toxicity (areas under the curves were 0.631, 0.633, and 0.735, respectively, P&amp;lt;0.05). Conclusions Early changes in sST2 and NT-proBNP levels offer additive information in early cardiovascular toxicity risk prediction in patients with breast cancer who receive anthracycline-containing chemotherapy.

Colchicine effect on biomarkers of cardiac remodelling and atherosclerosis in ST-elevation myocardial infarction: A randomized controlled trial.

Owing to its underlying inflammatory nature, atherosclerotic cardiovascular disease remains the leading global cause of mortality, particularly post-ST-elevation myocardial infarction (STEMI), a condition with significant risk for further cardiovascular events and mortality. This study aimed to investigate colchicine's effect on inflammation, cardiac remodelling and atherosclerotic risk in STEMI patients. We conducted a randomized controlled study on 88 STEMI patients undergoing percutaneous coronary intervention. Eligible patients were randomly assigned to 1 of 2 groups. The control group received the guideline-directed medical therapy for STEMI, and the test group received guideline-directed medical therapy and 0.5mg colchicine twice daily for 3months. The soluble suppressor of tumorigenicity (sST2), interleukin-1β, lipid profile parameters, triglyceride (TG)/high-density lipoprotein (HDL-C) ratio levels and left ventricular ejection fraction were evaluated for patients at baseline and the end of the 3months. No significant effects were reported for colchicine on sST2, interleukin-1β levels or left ventricular ejection fraction. Colchicine significantly lowered TG levels vs. controls, 134 (46-353) vs. 176 (72-825) respectively, P= .02, as well as TG/HDL-C ratio levels, 4.16 (2.75-5.24) vs. 5.11 (3.51-8.33),` respectively, P= .024. sST2 levels of the studied cohort were positively correlated with their TG/HDL-C ratio levels (R= .459, P< .001) at the end of follow-up. Our study highlights a promising impact of colchicine on atherosclerosis and cardiac remodelling factors in STEMI patients. Colchicine significantly reduced TG levels and TG/HDL-C ratio and was safe and well tolerated. Larger long-term studies powered to assess clinical outcomes of remodelling are necessary to confirm its beneficial effects in STEMI. NCT06054100.

The Value of REG3α, sST2, and TNFR1 in Risk Stratification and Prognostic Evaluation of Acute Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation in Children

To explore the value of REG3α, sST2 and TNFR1 in peripheral blood for risk stratification and prognostic evaluation of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. From January 2020 to March 2022, 70 children with aGVHD after allo-HSCT in the First Affiliated Hospital of Zhengzhou University were selected as the research objects, of which 50 cases were mild aGVHD (grade I-II) and 20 cases were severe aGVHD (grade III-IV). 30 healthy children who underwent physical examinations in our hospital during the same period were selected as the control group. Luminex platform was used to detect the protein expression levels of REG3α, sST2 and TNFR1 during aGVHD occurrence, and the differences between the three groups were analyzed by one-way ANOVA. According to the outcome of aGVHD treatment within 28 days, the patients were divided into a good prognosis group of 58 cases and a poor prognosis group of 12 cases. The ROC curve was used to analyze the value of REG3α, sST2 and TNFR1 in predicting the prognosis of children with aGVHD. The peripheral blood levels of REG3α, sST2 and TNFR1 in the mild aGVHD and severe aGVHD groups were significantly higher than those in the control group (P <0.05), and those in the severe aGVHD group were significantly higher than those in the mild aGVHD group (P <0.05). Compared with the good prognosis group, the peripheral blood levels of REG3α, sST2 and TNFR1 in the poor prognosis group were significantly higher ( t =9.27,3.33,2.97; P <0.01). ROC curve analysis showed that the area under the curve (AUC), sensitivity and specificity of the combined detection of REG3α, sST2 and TNFR1 in predicting the prognosis of children with aGVHD were higher than those of the above indicators detected alone or in pairs. The expression levels of REG3α, sST2 and TNFR1 were related to the severity of aGVHD. The combination of REG3α, sST2 and TNFR1 has a high clinical value in predicting the prognosis of children with aGVHD, which is expected to provide a reliable reference for clinical evaluation of the prognosis of children with aGVHD.

Examining the Long-Term Prognostic Significance of Serum sST2: Influence of Myocardial Infarction History and Subgroup Level Standardization.

In this study, the predictive value of soluble growth stimulation expressed gene 2 protein (sST2) for long-term clinical outcomes in patients with acute heart failure (AHF) is assessed. In addition, the influence of a history of myocardial infarction on the levels of sST2 in patients with HF, as well as its impact on outcome events, is explored. We also aim to establish a specific standard for sST2 levels in this subgroup. We conducted an ambispective cohort study involving hospitalized patients with AHF, measuring their sST2 levels and following their progress over three years. The primary endpoint was major adverse cardiovascular events (MACEs), encompassing heart failure readmission and all-cause mortality over three years. Cox regression analysis was used to evaluate the prognostic significance of sST2 levels, along with a subgroup analysis using propensity score matching (PSM) to adjust for confounding variables. Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal sST2 threshold using Youden's J statistics, and a sensitivity analysis included Kaplan-Meier survival curves. The study included 149 patients with a median age of 68 years, of whom 57% were male. Both univariate and multivariate Cox regression analyses confirmed sST2 as an independent predictor of MACEs. Post-PSM analysis, 124 samples were grouped by MI history ROC curve analysis revealed an area under the curve of 0.726 for predicting MACEs in patients with MI, demonstrating a significant predictive value for sST2 levels above 34 ng/mL, which correlated with increased readmission and mortality rates. In contrast, sST2 levels in patients without MI history showed no significant predictive relevance. sST2has significant long-term predictive value for clinical outcomes in patients with AHF, particularly for those with a prior MI history, indicating a need for heightened clinical attention and thorough follow-up to mitigate long-term adverse cardiovascular outcomes.

Comparative Study Between the Effects of High Doses of Rosuvastatin and Atorvastatin on Ventricular Remodeling in Patients with ST-Segment Elevation Myocardial Infarction.

Most studies reported that treating ST-Elevation Myocardial Infarction (STEMI) patients with high doses of rosuvastatin or atorvastatin could improve left ventricular remodeling and cardiac function. The current study compared the impact of high doses of rosuvastatin and atorvastatin on hypertrophy, fibrosis markers, serum inflammatory markers, and left ventricular function in STEMI patients after primary percutaneous coronary intervention (PCI). After primary PCI, eighty STEMI patients were randomized to receive either 20 mg of rosuvastatin (n = 40) or 40 mg of atorvastatin (n = 40) once daily for 3 months. Soluble Suppression of Tumorigenicity-2 (sST2), Matrix Metalloproteinase-9 (MMP9), C-Reactive Protein (CRP), lipid parameters, liver enzymes, and echocardiographic parameters were assessed for the two groups at baseline and after 3 months. After 3 months of treatment, a statistically significant reduction was observed in the rosuvastatin group regarding the levels of CRP (16 ± 6 vs. 20 ± 10 mg/L, P = 0.024) and MMP9 (104 ± 33 vs. 130 ± 42 ng/L, P = 0.003) compared with the atorvastatin group. The median percentage decrease in sST2 level in the rosuvastatin group was higher (6.1%) than in the atorvastatin group (2.3%) after 3 months of treatment. Also, in the rosuvastatin group, LVEF was significantly increased (48.5 ± 9 vs. 43.5 ± 11%, P = 0.029), while LVEDV and LVESV were significantly decreased compared to those of the atorvastatin group (101 [81/135] vs. 134 [100/150] ml, P = 0.041) (53 [37/75] vs. 73 [52/92] ml, P = 0.033), respectively. High-intensity rosuvastatin was superior to high-intensity atorvastatin in reducing the inflammatory response and myocardial fibrosis, thus improving ventricular remodeling and cardiac function better in STEMI patients. This randomized controlled trial was registered on October 11, 2022, on ClinicalTrials.gov under registration number: NCT05895123 "retrospectively registered".

Зміни концентрації sST2, активності мієлопероксидази та iндуцибельної NO-синтази в сироватці крові та лімфоцитах як показник важкості перебігу захворювання у пацієнтів з артеріальною гіпертензією та на тлі коронавірусної хвороби

The prevalence of COVID-19 and its polymorphic clinical manifestations are attributed to a systemic inflammatory response, which also plays a key role in the development of arterial hypertension (AH). The prognosis and effectiveness of treatment in patients with AH and COVID-19 should be assessed based on the levels of inflammatory biomarkers sST2, myeloperoxidase, and iNOS. The aim of the work was to analyze the prognostic value sST2, myeloperoxidase and iNOS levels in the blood serum of patients with arterial hypertension (AH) and COVID-19. Methods. 2 groups of patients were examined: group 1- 36 patients with AH and hypertensive crisis. Group 2 – 35 patients with AH and polysegmental pneumonia on the background of COVID-19. The control group – 16 practically healthy individuals. All patients underwent anthropometry, determination of biochemical blood tests, echocardiography, level of sST2, and activity of iNOS and MPO using ELISA in blood serum and lymphocytes. Results. A 2.4-fold increase in sST2 content in blood serum was noted in AH and 2.9-fold in the background of COVID-19. The level of myeloperoxidase in blood serum increased 2.5 times in hypertension and 3.4 times in coronavirus disease. In lymphocytes, iNOS activity increased 3.25 times in hypertension and 4.3 times in COVID-19. sST2 level has a significant correlation with the size of the left atrium, left ventricle, and ejection fraction in patients with AH. A positive correlation with age was noted in the group of patients with AH and COVID-19. Conclusions. Levels of sST2, iNOS and myeloperoxidase are important markers of the severity of cardiovascular pathology, as well as in COVID-19 patients. In patients with arterial hypertension and in combination with COVID-19, a significant increase in the concentration of sST2, myeloperoxidase and iNOS was observed compared to practically healthy individuals. A significant elevation in myeloperoxidase levels has been noted in patients with AH without coronavirus disease, indicating the utility of its use as a highly sensitive marker for low-intensity inflammation, particularly in arterial hypertension. This makes this marker more promising for use than C-reactive protein.

Temporal trajectory and left ventricular ejection fraction association of eight circulating biomarkers in first acute myocardial infarction patients: a 12-month prospective cohort study.

Our study aimed to explore the temporal trajectory of eight circulating biomarkers, measured serially over 12 months, in a prospective observational cohort of patients with acute myocardial infarction (AMI) and to investigate the association between these biomarkers and left ventricular ejection fraction (LVEF) during follow-up assessments. We enrolled 155 patients admitted for a first AMI requiring percutaneous coronary intervention (PCI). Baseline characteristics, laboratory test results, and cardiac ultrasound examinations were collected at pre-PCI (H0), immediately post-PCI (H24), at discharge (D3), and at 6 months (M6) and 12 months (M12) post-PCI. Blood samples were analysed for established and emerging biomarkers described in left ventricular dysfunction: soluble suppression of tumorigenicity 2 (sST2), interleukin-6 (IL-6), osteopontin, angiopoietin-2, insulin-like growth factor-binding protein 2 (IGFBP-2), growth differentiation factor 15 (GDF-15), hepcidin, and galectin-3. Values at H24, D3, M6, and M12 were compared with value at H0. Three kinetic profiles were identified, with six biomarkers peaking during the acute MI phase. Crude relationships between clinical variables and the peak values (highest observed between H0 and D3) of each biomarker were studied. Peak levels of sST2, IL-6, osteopontin, and angiopoietin-2 demonstrated significant correlations with both baseline and follow-up LVEF values. The assessment of the temporal trajectories of these biomarkers and their associations with LVEF suggests that sST2, IL-6, osteopontin, and angiopoietin-2 hold significant promise as companion biomarkers. These biomarkers may improve the identification of patients at risk for developing impaired LVEF following AMI, thereby enabling more targeted and effective management strategies.

The soluble ST2 level predicts risk of atrial fibrillation recurrences in long-term period after radiofrequency ablation

Background and objectives:The hypothesis of the study was the assumption that the serum levels of soluble ST2 (sST2) and growth differentiation factor (GDF-15) can be predictors of atrial fibrillation (AF) recurrence in long-term period after primary radiofrequency catheter ablation (RFA).MethodsOf the 165 patients included in the prospective follow-up, the final analysis included 131 patients whose follow-up duration reached 18 months after the end of the blanking period (3 months after RFA). The median age of patients was 59.0 (50.0; 64.0) years, and 80 (61%) were men. Paroxysmal AF was present in 103 (79%) and persistent AF in 28 (21%) patients. All patients underwent transthoracic and transesophageal echocardiography, and electroanatomic mapping was used to assess the area of low-voltage zones (LVZ). sST2 and GDF-15 levels were determined by ELISA using GDF-15/MIC-1 analytical kits (BioVender, Czech Republic) and Presage ST2 (Critical Diagnostics, USA) before RFA. After RFA, patients had regular follow-up visits at 3-6-9-12-18 months with 12-lead ECG or Holter ECG monitoring and with clinical evaluation. The primary endpoint was the occurrence of the first symptomatic AF recurrence (AFr) lasting > 30 s, recorded on an ECG or during daily ECG monitoring, after a blanking period.ResultsAt the 18-month follow-up, 47 patients (35.9%) had AFr. The groups with and without AFr didn`t differ in the LVZ area. The medians of NT-proBNP, GDF-15 and sST2 also didn`t differ significantly between the groups, but in patients with AFr, the proportion of those with sST2 ≥ 36 ng/ml (the border of the lower and middle terziles) was higher (p = 0.03). According to the one-factor Cox regression analysis, AFr were associated with four factors: AF history ≥ 1 year, early AFr (during the blanking period), left atrial appendage flow velocity (LAAFV) < 54 cm/sec and sST2 ≥ 36 ng/ml. In the multivariate Cox analysis two independent predictors of AFr were obtained: sST2 ≥ 36 ng/ml (HR = 3.8; 95% CI 1.5–9.8, p = 0.006) and LAAFV < 54 сm/sec (HR = 1.96; 95% CI 1.01–3.82, p = 0.048).ConclusionsSerum sST2 level with a cut-off value of 36 ng/ml or more can be used as a predictor of AF recurrence in the long-term period after primary RFA.

Predictors of left ventricular dilation and left ventricular aneurysm development in patients with ST-segment elevation myocardial infarction

Aim. To establish predictors of left ventricular (LV) dilatation and post-infarction left ventricular aneurysm (LVA) development in patients with ST-segment elevation myocardial infarction (STEMI) and/or with Q wave.Material and methods. This registry study included patients admitted with STEMI and/or with Q wave in the first 24 hours from the disease onset in the period from November 1, 2022 to March 31, 2023. The study included 138 patients. The mean age of the patients was 62±11 years. Treatment and examination were carried out in accordance with the current Russian clinical guidelines (2020) on STEMI. The levels of stimulating growth factor expressed by genome 2 (sST2), proprotein convertase subtilisin-kexin type 9, N-terminal pro-brain natriuretic peptide and high-sensitivity C-reactive protein were determined in patients by enzyme immunoassay on the first day of the disease. The patients were divided into two following groups: group 1 — patients with LV dilatation/LVA, n=25 (18,1%), group 2 — patients without LV geometry disorders, n=113 (81,9%). Univariate and multivariate regression analyzes were performed to determine independent predictors of LV dilation/postinfarction LVA.Results. This study showed that with an increase in sST2 levels by 1 ng/L, the probability of LV dilation/LVA formation increase by 1,53 times. Anterior location of myocardial infarction increases the probability of LV dilation/LVA formation by 63,55 times. An increase in eGFR on day 2 of hospitalization by 1 ml/min/1,73 m2 reduces the probability of LV dilatation/LVA formation by 1,07 times.Conclusion. The study showed that anterior location of myocardial infarction and increased sST2 levels increase the probability of LV dilation/LVA formation.

Population pharmacokinetic/target engagement modelling of tozorakimab in healthy volunteers and patients with chronic obstructive pulmonary disease.

This study describes the pharmacokinetic (PK)/target engagement (TE) relationship of tozorakimab, an anti-interleukin (IL)-33 antibody, by building a mechanistic population PK/TE model using phase 1 biomarker data. The analysis included tozorakimab PK and TE in serum assessed in 60 tozorakimab-treated participants, including healthy adults and patients with mild chronic obstructive pulmonary disease. Scenarios evaluated three dose frequencies (once every 2, 4 or 6weeks) administered subcutaneously at seven doses of tozorakimab (30, 60, 90, 120, 150, 300 or 600 mg). For each dose, simulations were performed with 5000 virtual individuals to predict systemic TE. Inhibition of IL-33/soluble ST2 (sST2) complex levels at trough PK at steady state was assessed in each dosing scenario. The PK/TE modelling analyses were performed using a nonlinear mixed-effect modelling approach. The final two-compartment PK model with tozorakimab binding IL-33 in the central compartment adequately described the systemic PK and TE of tozorakimab at population and individual levels. The mean PK parameter estimates of absorption rate, central volume of distribution and clearance were 0.48 (90% confidence interval [CI]: 0.40-0.59, 1/day), 12.64 (90% CI: 8.60-18.62, L) and 0.87 (90% CI: 0.65-1.16, L/day), respectively. Consistent with the observed value, tozorakimab bioavailability was 45%. For all three dose frequencies, predicted inhibition of systemic IL-33/sST2 levels was more than 95% at doses greater than 90 mg. The PK/TE model reliably quantified the relationship between PK and systemic TE of tozorakimab, with potential utility for predicting clinical dose-response relationships and supporting clinical dose selection.