sST2 Concentrations Research Articles

Clinical and prognostic relevance of sST2 in adults with dengue-associated cardiac impairment and severe dengue.

Dengue can be complicated by severe outcomes including cardiac impairment, and the lack of reliable prognostic biomarkers poses a challenge in managing febrile dengue patients. Here, we investigated the functionality of soluble suppressor of tumorigenicity (sST2) as a predictive marker of severe dengue and its association in dengue-associated cardiac impairment. Plasma samples, aged >16 years, collected from 36 dengue fever, 43 dengue with warning signs, 11 severe dengue (collected at febrile, critical and recovery phases) and 30 controls were assayed for plasma levels of sST2, troponin T and N-terminal (NT)-pro hormone brain natriuretic peptide (NT-proBNP) by ELISA. Cardiac parameters: stroke index (SI), cardiac index (CI) and Granov-Goor Index (GGI) were measured with a bioimpedance device during the different phases for dengue subjects and once for the controls. In the febrile, critical and early recovery phases, sST2 levels were significantly elevated in dengue participants and sST2 levels increased with increasing disease severity (P < 0.01 for all). sST2 concentrations were negatively correlated with SI (r = -0.48; P < 0.001, r = -0.55; P < 0.001), CI (r = -0.26; P = 0.02, r = -0.6: P < 0.001) and GGI (r = -0.44; P < 0.001, r = -0.57; P < 0.001) in the critical and early recovery phases. In contrast, sST2 levels in the febrile and critical phases, were positive correlated to troponin T (r = 0.44, P < 0.001; r = 0.22, P = 0.03, respectively) and NT-proBNP (r = 0.21, P = 0.03; r = 0.35, P < 0.001). ROC analysis demonstrated sST2 as a good biomarker of severe dengue in the critical phase, AUROC 0.79, P < 0.001. sST2 levels were elevated in patients with dengue especially in cases of severe dengue. Furthermore, increased sST2 levels were associated with cardiac indicators suggesting lower cardiac performance. While further research is needed to demonstrate its clinical utility, sST2 may be a useful prognostic biomarker of severe dengue.

The correlation between maternal serum sST2, IL‐33 and NT‐proBNP concentrations and occurrence of pre‐eclampsia in twin pregnancies: A longitudinal study

The primary objective of this study was to determine the longitudinal profile of serum sST2 (soluble suppression of tumorigenicity 2), IL-33 (interleukin-33) and NT-proBNP (N-terminal pro-brain natriuretic peptide) concentrations in twin pregnancies with pre-eclampsia (PE) and those normotensive twins. The secondary objective was to test whether the change of serum sST2,IL-33 and NT-proBNP is related to PE in twin pregnancies. This is a longitudinal nested case-control study and all 156 dichorionic (DC) pregnancies were from a prospective cohort of twin pregnancies who received antenatal care and gave two live births at Peking University Third Hospital between October 2017 and September 2020. Four to five milliliters of peripheral blood of each pregnant woman were collected during the following three intervals: (1) 6-11+6 weeks; (2) 24-27+6 weeks; (3) 28-31+6 weeks. We found that sST2 and NT-proBNP levels increased as pregnancy progressed in normotensive twin pregnancies and further increased in PE group, while no differences were found in IL-33 levels throughout pregnancy. Then the correlation of biomarker levels with the occurrence of PE was assessed. Our results indicated that combining maternal serum sST2 and NT-proBNP levels yielded the highest predictive value on the occurrence of PE significantly higher than the predictive value of any markers alone. Interestingly, the predictive value of second trimester (AUC=0.876, 95%CI 0.824-0.928, LR-0.338, LR+7.67, p<0.001)was higher than that of early-third trimester (AUC=0.832, 95%CI 0.769-0.896, LR-0.29, LR+3.845, p<0.001). Serum sST2 and NT-proBNP concentrations during second and early-third trimester were associated with the occurrence of PE in twin pregnancies.

Soluble ST2 as a Potential Biomarker for Abdominal Aortic Aneurysms-A Single-Center Retrospective Cohort Study.

The maximal aortic diameter is the only clinically applied predictor of abdominal aortic aneurysm (AAA) progression and indicator for surgical repair. Circulating biomarkers resulting from AAA pathogenesis are attractive candidates for the diagnosis and prognosis of aneurysmal disease. Due to the reported role of interleukin 33 in AAA development, we investigated the corresponding circulating receptor molecules of soluble suppression of tumorigenesis 2 (sST2) in AAA patients regarding their marker potential in diagnosis and prognosis. We conducted a single-center retrospective cohort study in a diagnostic setting, measuring the circulating serum sST2 protein levels of 47 AAA patients under surveillance, matched with 25 peripheral artery disease (PAD) patients and 25 healthy controls. In a prognostic setting, we analyzed the longitudinal monitoring data of 50 monitored AAA patients. Slow versus fast AAA progression was defined as a <2 or ≥2 mm increase in AAA diameter over 6 months and a <4 or ≥4 mm increase over 12 months. Additionally, the association of circulating serum sST2 and AAA growth was investigated using a specifically tailored log-linear mixed model. Serum sST2 concentrations were significantly increased in AAA patients compared with healthy individuals: the median of AAA patient cohort was 112.72 ng/mL (p = 0.025) and that of AAA patient cohort 2 was 14.32 ng/mL (p = 0.039) versus healthy controls (8.82 ng/mL). Likewise, PAD patients showed significantly elevated sST2 protein levels compared with healthy controls (the median was 12.10 ng/mL; p = 0.048) but similar concentrations to AAA patients. Additionally, sST2 protein levels were found to be unsuited to identifying fast AAA progression over short-term periods of 6 or 12 months, which was confirmed by a log-linear mixed model. In conclusion, the significantly elevated protein levels of sST2 detected in patients with vascular disease may be useful in the early diagnosis of AAA but cannot distinguish between AAA and PAD or predict AAA progression.

Soluble ST2 in serum predicts the prognosis of idiopathic pulmonary fibrosis: a retrospective study.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a heterogeneous and progressive fibrosing interstitial lung disease with a poor prognosis. However, there are currently no effective biomarker that can reliably predict the prognosis for IPF in clinic. The serum level of soluble suppression of tumorigenicity-2 (sST2), which is involved in the immune response, has proven to be a prognostic predictor for various diseases. Previous studies have confirmed that the immune dysfunction plays an important role in the pathogenesis of IPF and the serum sST2 concentrations in patients with IPF are elevated. However, the relationship between sST2 and the prognosis of IPF remains unknown.MethodsA total of 83 patients with IPF and 20 healthy controls from 2016 to 2021 were enrolled and demographic variables, indices of lung function testing as well as the biomarkers including the sST2 were obtained at baseline. During follow-up, the primary endpoint was defined as all-cause death and clinical deterioration. Cox hazard models and Kaplan-Meier method were used to assess the prognostic value of various indices including sST2.ResultsMean duration of follow-up was 29 months, during which 49 patients had an event, and of them, 35 patients died. The sST2 level was higher in the IPF patients compared with the healthy controls. Although the sST2 level did not directly predict all-cause death in the present study, it was proved to be an independent predictor of event-free survival. Multivariate forward stepwise model which was adjusted by age, sex, and body surface area (BSA) showed that the overexpression of sST2 increased the hazard ratio [1.005, 95% confidence interval (CI): 1.001–1.010]. A higher sST2 serum level heralded more deterioration and the poor outcomes. Moreover, the effect of sST2 on the prognosis of IPF may not necessarily involve the development of IPF-related pulmonary hypertension (PH).ConclusionsIn our study, the sST2 serum level was significantly elevated and a higher serum level of sST2 predicted more deterioration and poor outcomes in patients with IPF. Thus, sST2 can serve as a valuable prognostic biomarker for the outcome of IPF. However, further multicenter clinical trials of larger sample size are needed in the future.

Elevated Plasma Soluble ST2 Levels are Associated With Neuronal Injury and Neurocognitive Impairment in Children With Cerebral Malaria.

Background:Murine experimental cerebral malaria studies suggest both protective and deleterious central nervous system effects from alterations in the interleukin-33 (IL-33)/ST2 pathway.Methods:We assessed whether soluble ST2 (sST2) was associated with neuronal injury or cognitive impairment in a cohort of Ugandan children with cerebral malaria (CM, n=224) or severe malarial anemia (SMA, n=193).Results:Plasma concentrations of sST2 were higher in children with CM than in children with SMA or in asymptomatic community children. Cerebrospinal fluid (CSF) sST2 levels were elevated in children with CM compared with North American children. Elevated plasma and CSF ST2 levels in children with CM correlated with increased endothelial activation and increased plasma and CSF levels of tau, a marker of neuronal injury. In children with CM who were ≥5 years of age at the time of their malaria episode, but not in children <5 years of age, elevated risk factor-adjusted plasma levels of sST2 were associated with worse scores for overall cognitive ability and attention over a 2-year follow-up.Conclusions:The study findings suggest that sST2 may contribute to neuronal injury and long-term neurocognitive impairment in older children with CM.

How Do Cardiovascular Biomarkers Behave in Patients with Severe Aortic Valve Stenosis with and without Echocardiographically Proven Pulmonary Hypertension?—A Retrospective Study of Biomarker Trends before and after Transcatheter Aortic Valve Replacement

Background: Since right heart catheterization is rarely performed in patients with severe aortic valve stenosis (AS), echocardiography is currently the tool of choice to determine the presence or absence of pulmonary hypertension (PH). The systolic pulmonary artery pressure (sPAP) has established itself as a reliable measurement value for this purpose. The aim of our study was to evaluate the behavior of plasma-level concentrations of novel cardiovascular biomarkers (sST2, GDF-15, H-FABP, IGF-BP2, and suPAR) in patients with severe AS and an sPAP &lt; 40 mmHg in comparison to patients with an sPAP ≥ 40 mmHg before transcatheter aortic valve replacement (TAVR) and after TAVR (24 h, 96 h, 3 months, and 12 months). Methods: We retrospectively separated 85 patients with echocardiographic evidence of severe AS before TAVR procedure into two groups based on sPAP level. An sPAP of 40 mmHg was considered the cut-off value, with the absence of PH defined by an sPAP &lt; 40 mmH (n = 32) and the presence of PH defined by an sPAP ≥ 40 mmHg (n = 53). Blood samples were drawn from each patient one day before TAVR and 24 h, 96 h, 3 months, and 12 months after TAVR. Plasma concentrations of the cardiovascular biomarkers sST2, GDF-15, H-FABP, IGF-BP2, and suPAR were determined and analyzed with univariate and multivariate binary logistic regression and AUROC curves. Results: Patients with severe AS and an sPAP ≥ 40 mmHg had significantly higher plasma concentrations of H-FABP (baseline: p = 0.022; 24 h: p = 0.012; 96 h: p = 0.037; 3 months: p = 0.006; 12 months: p = 0.030) and IGF-BP2 (baseline: p = 0.029; 24 h: p = 0.012; 96 h: p = 0.001; 3 months: p = 0.015; 12 months: p = 0.022) before and continuously up to 12 months after TAVR than did patients with an sPAP &lt; 40 mmHg sST2, with the exception of the 12-month follow-up. We also consistently found significantly higher plasma concentrations in the sPAP ≥ 40 mmHg group (baseline: p = 0.007; 24 h: p = 0.006; 96 h: p = 0.014; 3 months: p ≤ 0.001; 12 months: p = 0.092), whereas suPAR had significantly elevated values at baseline and after 24 h in patients with echocardiographic evidence of PH and significantly decreased values after 3 months (baseline: p = 0.003; 24 h p = 0.041; 96 h: p = 0.127; 3 months: p = 0.006; 12 months: p = 0.477). Plasma concentrations of GDF-15 were only significantly different after 24 h (baseline: p = 0.075; 24 h: p = 0.016; 96 h: p = 0.101; 3 months: p = 0.244; 12 months: p = 0.090). In a multivariate binary logistic regression, atrial fibrillation, tricuspid annular plane systolic excursion (TAPSE), and sST2 at baseline were found to have a significant p-value &lt; 0.050. Conclusion: In this descriptive study, sST2, H-FABP, and IGF-BP2 emerged as the cardiovascular biomarkers with the greatest potential with respect to echocardiographically PH detection in long-term follow-up after TAVR, as patients with an sPAP ≥ 40 mmHg had significantly continuously higher plasma biomarker concentrations than the corresponding cohort did, with an sPAP &lt; 40 mmHg.

ASSOCIATION OF ST2, GALECTIN-3, N-TERMINAL PRO-BRAIN NATRIURETIC PEPTIDE, PENTRAXIN WITH MYOCARDIAL DYSFUNCTION DETECTED BY SPECKLE-TRACKING ECHOCARDIOGRAPHY IN PATIENTS WITH RHEUMATOID ARTHRITIS PRIOR TO BIOLOGICAL THERAPY

TYPE: Late Breaking Abstract TOPIC: Cardiovascular Disease PURPOSE: to determine the frequency of lower global longitudinal epicardial strain of left ventrical (GLESLV), NT-proBNP, pentraxin, galectin-3, sST2 levels in patients (pts) with RA prior to therapy with bDMARDs. METHODS: 41 pts with RA were included: 63% of women, 56[37;66] years, disease duration 24[8;96] months; DAS28 6,01[5.3;6.3] without CVD and prior administration of bDMARDs. All pts underwent echocardiography with speckle tracking assessment of GLESLV. 44% RA pts received methotrexate, 35%-leflunomide. We measured plasma concentrations of sST2, galectin-3, NT-proBNP, pentraxin. The control group consisted of 10 healthy subjects, which were matched by sex and age. RESULTS: In RA pts speckle tracking method detected GLESLV(–16.5 [-14.6;-18.5]%), compared to control group (–21.58 [-22.1;-20.4]%, p=0.0001). 27 (67%) RA pts showed a decrease GLESLV. RA pts had higher NT-proBNP (114.8 [45.1;277.5] vs 52[40.5;69.1] pg/ml, p<0.05), lower sST2 (10.6 [9.2;13.1] vs 13.5 [11.0;19.7] ng/ml, p<0.04) compared to control group. RA pts were divided into 2 groups: group 1-with low GLESLV, group 2 -with preserved GLESLV. In group 1, ST2 were higher than in group 2 (18.3 [13.7; 60.9] vs 13.2 [10.6; 17.0] ng/ml, p<0.05) (Tabl.1). There were negative correlations between GLESLV and age (r=-0,9, p<0,02), E LV (r=-0,5, p<0,04), sST2 (r=-0,5, p<0,02). Galectin-3 correlate with LA volume (r=0,4, p<0,04), e’(r=0,6, p<0,008); ST2 correlate with ESR (r=0,6, p<0,04), CRP (r=0,5, p<0,002). Tabl.1 Biomarker levels in groups CONCLUSIONS: Conclusion: In RA pts frequently were detected lower GLES, higher NT-proBNP and lower sST2 levels. In RA pts sST2 is better associated with inflammatory activity and myocardial dysfunction. CLINICAL IMPLICATIONS: CT2 and GLESLV contribute to early diagnosis of myocardial dysfunction in RA patients. DISCLOSURE: No significant relationships. KEYWORD: myocardial dysfunction

Diagnostic Significance of the Level of Soluble Stimulating Growth Factor in Patients with Spondyloarthritis as an Early Marker of Cardiovascular Pathology

Aim to determine the clinical and laboratory relationships of the level of soluble stimulating growth factor expressed by genome 2 (sST2) with indicators characterizing the development of cardiovascular pathology in patients with spondyloarthritis (SPA). Materials and methods . A total of 46 patients aged 39.2 ± 10.2 years with SpA (including 40 (87 %) with ankylosing spondylitis, 6 (13 %) with psoriatic arthritis) were examined. There were 36 (78.3 %) males, 10 (21.7 %) females among the enrolled patients. 27 (84.4 %) of 32 examined patients had HLA-B27. To assess the disease activity the BASDAI and ASDAS scores were used, the erythrocyte sedimentation rate and C-reactive protein values were measured; the levels of tumor necrosis factor-alpha (TNF-alpha), N-terminal fragment of brain natriuretic peptide (NT-proBNP), interleukin-6 (IL-6), sST2 in blood serum were evaluated. Traditional cardiovascular risk factors, aortic pulse wave velocity (PWVAo), the results of standard electrocardiography, transthoracic echocardiography, carotid duplex ultrasonography were assessed. Results . The mean sST2 level was 33.34±11.2 ng/ml, an sST2 concentration above the threshold value was found in 19 (41.3 %) patients. No significant relationships between serum sST2 level and disease activity indicators, echocardiographic parameters, rhythm and/or conduction disturbances on electrocardiograms were found. A higher PWVAo was noted in patients with sST2 level above the average (p=0.036); the level of NT-proBNP was more often increased in patients with high levels of sST2 (p=0.085). Higher sST2 concentrations were found in patients treated with biological disease-modifying antirheumatic drugs due to the high disease activity (р=0.039). Conclusion . An increase in sST2 levels was found in 41.3 % of patients with SpA. An increase in serum sST2 concentration is associated with an elevated PWVAo and an increase in the level of NT-proBNP, which may indicate incipient cardiac remodeling, cardiac fibrosis, and the initial stages of the development of heart failure. The new data obtained indicate the advisability of planning and performing larger prospective studies of patients with SpA for the early detection of preclinical signs of damage to the cardiovascular system, cardiac remodeling, and assessment of the effectiveness of therapy.

Predictive Values of Serum IL-33 and sST2 in Endotypes and Postoperative Recurrence of Chronic Rhinosinusitis with Nasal Polyps.

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disease with high heterogeneity and postoperative recidivation. The IL-33/ST2 axis is known to be involved in Th2 immune responses. This study is aimed at exploring levels of serum IL-33 and soluble ST2 (sST2) in CRSwNP patients and their potential for predicting CRSwNP endotypes and postoperative recurrence. Methods The present study recruited 149 CRSwNP patients, 80 of whom were noneosinophilic (neCRSwNP) and 69 eosinophilic (eCRSwNP), as well as 60 healthy controls (HCs). Serum samples were collected from all participants, and sST2 and IL-33 concentrations were measured using ELISA. Multivariate analysis, receiver operating characteristic (ROC) curves, and Kaplan-Meier curves were used to evaluate the value of serum sST2 and IL-33 levels in distinguishing CRSwNP endotypes and predicting postoperative recurrence. Results The levels of serum sST2 and IL-33 in CRSwNP patients were significantly higher than those in HCs, especially in the eCRSwNP group. Increased sST2 and IL-33 levels were associated with eosinophil counts and percentages in both tissue and blood. Multivariate regression and ROC curve analysis showed that serum sST2 and IL-33 exhibited potential for distinguishing CRSwNP endotypes, and the combination of serum IL-33 and sST2 showed even more predictive power. Finally, 124 CRSwNP patients completed the entire 3-year follow-up. Multivariate analysis and Kaplan-Meier curves showed that serum sST2 and IL-33 levels were associated with recurrence; serum sST2 and IL-33 each exhibited potential for predicting postoperative recurrence, and combining serum sST2 and IL-33 exhibited better accuracy and practicability. Conclusion Our results suggested that serum sST2 and IL-33 levels were upregulated in CRSwNP patients and related to the degree of mucosal eosinophil infiltration and postoperative recurrence. Serum sST2 and IL-33 might serve as objective biomarkers for distinguishing phenotypes and predicting recurrence in CRSwNP, and their combined use outperformed either marker alone.

Soluble suppression of tumorigenesis-2 is a strong predictor of all-cause, cardiovascular and infection-related mortality risk in haemodialysis patients with diabetes mellitus

ABSTRACTBackgroundSoluble suppression of tumorigenesis-2 (sST2) is a strong prognostic biomarker of cardiovascular (CV) disease. End-stage kidney disease (ESKD) patients are at high risk of CV events and infections. Herein we investigated the utility of sST2 to predict all-cause and cause-specific mortality in haemodialysis (HD) patients with diabetes mellitus.MethodssST2 concentrations were measured in plasma samples of 1196 participants of the German Diabetes and Dialysis (4D) study who had type 2 diabetes mellitus and received maintenance HD for ESKD. Hazard ratios (HRs) for prespecified, adjudicated endpoints were determined according to sST2 levels at baseline by multivariate Cox proportional hazards analysis.ResultsParticipants (mean age 66 years, 54% male) had a median sST2 concentration of 25 ng/mL and were followed up for 4 years. After adjustment for possible confounders, participants with sST2 concentrations in the highest (>32.6 ng/mL) compared with the lowest (<20.1 ng/mL) quartile exhibited a 2-fold higher all-cause mortality risk {[HR 2.06 95% confidence interval (CI) 1.61–2.61]; P < .001}. High sST concentrations (fourth versus first quartile) were strongly associated with the risk of cardiac death [HR 2.29 (95% CI 1.55–3.39); P < .001]. Analysis of individual components of cardiac causes of death showed an increased risk of sudden death [HR 2.24 (95% CI 1.33–3.77); P < .001], death due to myocardial infarction [HR 2.12 (95% CI 0.9–5.0); P = .087] and heart failure [HR 3.34 (95% CI 1.15–9.75); P = .027] in participants with sST2 levels in the highest compared with the lowest quartile. Likewise, participants with the highest sST2 levels had an increased risk of fatal stroke [HR 1.92 (95% CI 1.17–3.14); P = .009] and fatal infections [HR 2.01 (95% CI 1.2–3.37); P = .008]. In contrast to fatal CV events, sST2 was not associated with the risk of non-fatal myocardial infarction [HR 0.68 (95% CI 0.41–1.12); P = .132] or non-fatal stroke [HR 1.28 (95% CI 0.64–2.53); P = .485].ConclusionsIn HD patients with diabetes mellitus, high concentrations of sST2 were strongly and independently associated with an increased risk of all-cause mortality, CV mortality and death due to infection but not non-fatal CV events.

Circulating levels and prognostic cut-offs of sST2, hs-cTnT, and NT-proBNP in women vs. men with chronic heart failure.

AimsTo define plasma concentrations, determinants, and optimal prognostic cut‐offs of soluble suppression of tumorigenesis‐2 (sST2), high‐sensitivity cardiac troponin T (hs‐cTnT), and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) in women and men with chronic heart failure (HF).Methods and resultsIndividual data of patients from the Biomarkers In Heart Failure Outpatient Study (BIOS) Consortium with sST2, hs‐cTnT, and NT‐proBNP measured were analysed. The primary endpoint was a composite of 1 year cardiovascular death and HF hospitalization. The secondary endpoints were 5 year cardiovascular and all‐cause death. The cohort included 4540 patients (age 67 ± 12 years, left ventricular ejection fraction 33 ± 13%, 1111 women, 25%). Women showed lower sST2 (24 vs. 27 ng/mL, P < 0.001) and hs‐cTnT level (15 vs. 20 ng/L, P < 0.001), and similar concentrations of NT‐proBNP (1540 vs. 1505 ng/L, P = 0.408). Although the three biomarkers were confirmed as independent predictors of outcome in both sexes, the optimal prognostic cut‐off was lower in women for sST2 (28 vs. 31 ng/mL) and hs‐cTnT (22 vs. 25 ng/L), while NT‐proBNP cut‐off was higher in women (2339 ng/L vs. 2145 ng/L). The use of sex‐specific cut‐offs improved risk prediction compared with the use of previously standardized prognostic cut‐offs and allowed to reclassify the risk of many patients, to a greater extent in women than men, and for hs‐cTnT than sST2 or NT‐proBNP. Specifically, up to 18% men and up to 57% women were reclassified, by using the sex‐specific cut‐off of hs‐cTnT for the endpoint of 5 year cardiovascular death.ConclusionsIn patients with chronic HF, concentrations of sST2 and hs‐cTnT, but not of NT‐proBNP, are lower in women. Lower sST2 and hs‐cTnT and higher NT‐proBNP cut‐offs for risk stratification could be used in women.

Effect of β-blocker therapy on the level soluble ST2 protein in the blood serum in patients with heart failure with preserved and mildly reduced ejection fraction

Aim. To study the prognostic value of high serum concentration of soluble ST2 protein (sST2) in the development of cardiovascular events after endovascular myocardial revascularization and the possibility of using this biomarker as a target for β-blocker therapy in patients with chronic heart failure (CHF) with preserved (HFpEF) and mildly reduced (HFmrEF) left ventricular ejection fraction.Materials and methods. The study included 72 patients (aged 57–69 years, 81.94% were men) with class I–III CHF of ischemic etiology with HFpEF and HFmrEF. The patients were admitted to the cardiology department for endovascular myocardial revascularization. Before myocardial revascularization, serum concentrations of sST2 and N-terminal pro-brain natriuretic peptide (NT-proBNP) in all patients were analyzed by enzyme-linked immunosorbent assay (ELISA). Doses of β-blockers used in all patients were recalculated into a total daily dose equivalent to metoprolol succinate. Patients were divided into 2 groups depending on the median equivalent dose of metoprolol succinate (“high” ≥ 100 mg / day and “low” &lt; 100 mg / day).Results. In patients of group 1, the serum concentration of sST2 was 30.7% higher (p &lt; 0.001) than in patients of group 2 (40.26 [34.39; 48.92] ng /ml and 27.9 [23.05; 35.27] ng / ml, respectively), the serum NT-proBNP level in group 1 was 22.8% higher (p = 0.049) than in group 2 (167 [129; 330] ng / ml vs. 129 [125; 147] ng / ml, respectively). In patients receiving an equivalent dose of metoprolol succinate &lt; 100 mg / day, the incidence of cardiovascular events was 34% higher (p = 0.002) than in patients receiving an equivalent dose of metoprolol succinate ≥ 100 mg/day. The ROC analysis showed that serum sST2 level ≥ 34.18 ng / ml (sensitivity 78.0%, specificity 90.0%, area under the curve (AUC) 0.906; p &lt; 0.0001) predicts a high risk of cardiovascular events within one year. However, the serum NT-proBNP level was not an informative predictor of cardiovascular events. Conclusion. It was confirmed that increased sST2 serum concentration has high prognostic value in the development of cardiovascular events within a year after endovascular myocardial revascularization. The possibility of using this biomarker as a target for β-blocker therapy in patients with HFpHF and HFmrEF was substantiated. Aggressive use of β-blockers in the group of patients with HFpEF and HFmrEF and sST2 overexpression is preferable in order to reduce the incidence of cardiovascular events.

Soluble ST2 as a Potential Biomarker for Risk Assessment of Pulmonary Hypertension in Patients Undergoing TAVR?

Background: Severe aortic valve stenosis (AS) is associated with pulmonary hypertension (PH) and has been shown to limit patient survival. Soluble suppression of tumorigenicity-2 (sST2) is a cardiovascular biomarker that has proven to be an important prognostic marker for survival in patients undergoing transcatheter aortic valve replacement (TAVR). The aim of this study was to assess the importance of the sST2 biomarker for risk stratification in patients with severe AS in presence or absence of PH. Methods: In 260 patients with severe AS undergoing TAVR procedure, sST2 serum level concentrations were analyzed. Right heart catheter measurements were performed in 152 patients, with no PH detection in 43 patients and with PH detection in 109 patients. Correlation analyses according to Spearman, AUROC analyses and Kaplan–Meier curves were calculated. Results: Patients with severe AS and PH showed significantly higher serum sST2 concentrations (p = 0.006). The sST2 cut-off value for non-PH patients regarding 1-year survival yielded 5521.15 pg/mL, whereas the cut-off value of PH patients was at a considerably higher level of 10,268.78 pg/mL. A cut-off value of 6990.12 pg/mL was related with a significant probability of PH presence. Survival curves showed that patients with severe AS and PH not only had higher 1-year mortality, but also that increased levels of sST2 plasma concentration were associated with earlier death. Conclusion: sST2 definitely has the potential to provide information about the presence of PH in patients with severe AS, in a noninvasive way.

Higher serum sST2 is associated with increased left atrial low-voltage areas and atrial fibrillation recurrence in patients undergoing radiofrequency ablation.

To conduct a comprehensive analysis of prospectively measuring the concentration of soluble suppression of tumorigenicity 2 (sST2) to predict left atrial (LA) low-voltage areas (LVAs) and atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFA). This was a prospective cohort study. A total of 84 patients, including 54 paroxysmal AF cases and 30 persistent AF cases who underwent RFA, were recruited. Electroanatomical voltage mapping determined the extent of LVAs. The serum level of sST2 was measured by enzyme-linked immunosorbent assay. All patients were followed for 12months after the RFA procedure to verify AF recurrence. The concentration of sST2 measured in the sample was 17.90-198.77pg/mL, and the range of LA LVAs was 0-85.6%. The sST2 level positively correlated with LVAs (r = 0.40; P = 0.005). When comparing the top and bottom quartile, sST2 is significantly associated with LA LVAs (OR = 1.833, 95% CI: 1.582-2.011, P = 0.004). When compared with the 1st quartile group, the multivariable adjusted hazard ratios for AF recurrence after RFA were 1.57 (95% CI: 1.182-1.795) for the 4th quartile group, 1.44 (95% CI: 1.085-1.598) for the 3rd quartile group, and 1.27 (95% CI: 0.954-1.318) for the 2nd quartile group. The AF-free survival rates of patients with 1st quartile and 4th quartile sST2 levels after ablation were 95% and 59.6%, respectively (Log Rank test, P = 0.027). Elevated sST2 levels of AF patients were associated with higher LA LVAs and a significantly increased risk of recurrence. The circulating sST2 concentration might be a pre-diagnostic marker of AF recurrence after RFA.

A Comparative Analysis of Novel Biomarkers in Sepsis and Cardiovascular Disease

(1) Background: Sepsis still represents a major health care challenge, with mortality rates exceeding 25% in the western world. To further improve outcomes in this patient collective, new cardiovascular biomarkers present a promising opportunity as they target the paramount prognostic processes in sepsis: inflammation and ischemia. However, in contrast to cardiovascular diseases, a detailed analysis of novel biomarkers in sepsis is still lacking. (2) Objective: In this project, we aimed to perform a comparative analysis of biomarker levels in ischemic cardiovascular disease and sepsis. Analyzed markers comprised soluble suppression of tumorigenicity 2 (sST2; hemodynamics and inflammation), growth-differentiation factor 15 (GDF-15; injury, remodelling), soluble urokinase-type plasminogen activator receptor (suPAR; inflammation and remodeling) and heart-type fatty acid binding protein (H-FABP; myocardial ischemia). (3) Methods: In total, 311 patients were included in the study: 123 heart-failure (HF) patients, 60 patients with ST-segment elevation myocardial infarction (STEMI) and 53 sepsis patients. A total of 75 patients without coronary artery disease or signs of heart failure served as a control group. Plasma samples were analyzed by use of ELISA after informed consent. (4) Results: Patients with sepsis showed significantly increased plasma levels in all tested biomarkers compared to cardiovascular disease entities (sST2, suPAR, GDF-15: p &lt; 0.001; H-FABP: compared to HF p &lt; 0.001) and controls (sST2: 7.4-fold, suPAR: 3.4-fold, GDF-15: 6.5-fold and H-FABP: 15.3-fold increased plasma levels, p &lt; 0.001). Moreover, in patients with sepsis, serum concentrations of sST2 and suPAR were significantly elevated in patients with HF and patients with STEMI (sST2: HF: 1.6-fold increase and STEMI: 2.5-fold increase, p &lt; 0.001; suPAR: HF: 1.4-fold increase, p &lt; 0.001 and STEMI: 1.4-fold increase, p &lt; 0.01), whereas plasma levels of GDF-15 and H-FABP were markedly elevated in patients with STEMI only (GDF-15: 1.6-fold increase, H-FABP: 6.4-fold increase, p &lt; 0.001). (5) Conclusions: All tested novel cardiac biomarkers showed significantly elevated levels in sepsis patients. Interestingly, a secretion pattern similar to STEMI was observed with regards to sST2 and HFABP. Thus, by providing an assessment tool especially covering the cardiovascular component of the disease, novel biomarkers offer a promising tool in sepsis patients.

Diagnostic Value of sST2, VCAM-1, and Adiponectin in Patients with Breast Cancer to Predict Anti-Tumour Treatment-Related Cardiac Events: A Pilot Study.

The present exploratory study investigated the diagnostic value of inflammatory markers in patients with breast cancer to predict anti-tumour treatment-related cardiac events. Twenty-one patients with breast cancer were enrolled in this prospective observational study and followed over 6 months. Transthoracic echocardiography and measurement of cardiac (N-terminal prohormone of brain natriuretic peptide (NT-proBNP), troponin I (TnI)) and inflammatory biomarkers (vascular adhesion molecule 1 (VCAM-1), soluble suppression of tumorigenesis-2 (sST2), adiponectin) was performed at 3-month intervals (baseline, follow-up, final visit). Cardiac events were defined as decrease in left ventricular ejection fraction (LVEF, decrease by 10% or <50%) or increase in global longitudinal strain (GLS, increase by 15% or > -16%), as a more sensitive marker of LV function. Cardiac deterioration was observed in 9 out of 21 patients (event group). While LVEF did not differ significantly between the two groups (event vs. no event) at any visit, GLS was significantly higher during follow-up (follow-up: event -16 ± 3.3% vs. no event -18 ± 1.6%, p = 0.04; final visit: event -16 ± 2.1% vs. no event -19 ± 1.9%, p = 0.003). NT-proBNP was numerically higher in patients with a cardiac event during all visits, with NT-proBNP negatively correlated with LVEF and MAPSE (both r = -0.33, p = 0.02), whereas GLS (r = 0.40, p = 0.006), TnI (r = 0.44, p = 0.001), and VCAM-1 (r = 0.48, p = 0.003) showed a positive association with NT-proBNP. In comparison, higher VCAM-1 and sST2 concentrations were detected in the event group at both baseline and the final visit, with a significant difference for baseline (VCAM-1: p = 0.02; sST2: p = 0.03). Adiponectin was also lower in patients with a treatment-related event. Thresholds for VCAM-1 >762 ng/mL and sST2 >18.7 ng/mL, as detected by ROC analysis, correlated best with the primary endpoint. Cardiac events during anti-tumour treatment in patients with breast cancer are relatively common. Inflammatory markers such as VCAM-1 or sST2 were associated with an increased likelihood for occurrence of a treatment-related event, which may therefore hold the promise to better identify patients at high risk.

Soluble ST2 and All-Cause Mortality in Patients with Chronic Obstructive Pulmonary Disease-A 10-Year Cohort Study.

Chronic obstructive pulmonary disease (COPD) is an inflammatory condition with constantly increasing mortality rates. Interleukin (IL)-33 and its decoy receptor, soluble suppression of tumorigenicity 2 (sST2), play a central role in the inflammatory response during infection. sST2 was suggested as a factor in the pathogenesis of COPD and emerged as a predictor of mortality in other non-communicable diseases. The role of sST2 as a predictor of mortality remains unclear in COPD yet. In this cohort study, we measured circulating concentrations of IL-33 and sST2 in the serum of patients with stable COPD (n = 59), patients with acute exacerbation of COPD (n = 29) and smoking (n = 20) and non-smoking controls (n = 20), using commercially available ELISAs, and investigated the prognostic role of sST2 in stable COPD. sST2 levels were significantly higher in COPD patients and smokers compared with non-smoking controls. We identified systolic blood pressure, forced expiratory volume in 1 s (FEV1% predicted), neutrophil count, lactate dehydrogenase and pack-years index as independent predictors of sST2 levels. During a median follow-up time of 10.6 years, 28 patients (47.5%) died. sST2 was an independent predictor of all-cause mortality in patients with COPD with a hazard ratio of 2.9 (95% CI 1.1–8.4, p = 0.035) per one standard deviation after adjustment for age, sex, pack-years, FEV1% predicted and C-reactive protein (CRP). sST2 concentrations are associated with severity of disease and long-term outcome in patients with COPD.

Development of an ultra-sensitive human IL-33 biomarker assay for age-related macular degeneration and asthma drug development

BackgroundOver the past decade, human Interleukin 33 (hIL-33) has emerged as a key contributor to the pathogenesis of numerous inflammatory diseases. Despite the existence of several commercial hIL-33 assays spanning multiple platform technologies, their ability to provide accurate hIL-33 concentration measurements and to differentiate between active (reduced) and inactive (oxidized) hIL-33 in various matrices remains uncertain. This is especially true for lower sample volumes, matrices with low hIL-33 concentrations, and matrices with elevated levels of soluble Interleukin 1 Receptor-Like 1 (sST2), an inactive form of ST2 that competes with membrane bound ST2 for hIL-33 binding.ResultsWe tested the performance of several commercially available hIL-33 detection assays in various human matrices and found that most of these assays lacked the sensitivity to accurately detect reduced hIL-33 at biologically relevant levels (sub-to-low pg/mL), especially in the presence of human sST2 (hsST2), and/or lacked sufficient target specificity. To address this, we developed and validated a sensitive and specific enzyme-linked immunosorbent assay (ELISA) capable of detecting reduced and total hIL-33 levels even in the presence of high concentrations of sST2. By incorporating the immuno-polymerase chain reaction (iPCR) platform, we further increased the sensitivity of this assay for the reduced form of hIL-33 by ~ 52-fold. Using this hIL-33 iPCR assay, we detected hIL-33 in postmortem human vitreous humor (VH) samples from donors with age-related macular degeneration (AMD) and found significantly increased hIL-33 levels when compared to control individuals. No statistically significant difference was observed in aqueous humor (AH) from AMD donors nor in plasma and nasosorption fluid (NF) from asthma patients compared to control individuals.ConclusionsUnlike existing commercial hIL-33 assays, our hIL-33 bioassays are highly sensitive and specific and can accurately quantify hIL-33 in various human clinical matrices, including those with high levels of hsST2. Our results provide a proof of concept of the utility of these assays in clinical trials targeting the hIL-33/hST2 pathway.

Soluble ST2 concentrations associate with in-hospital mortality and need for mechanical ventilation in unselected patients with COVID-19

ObjectiveSoluble ST2 (sST2) reflects inflammation, endothelial dysfunction and myocardial fibrosis, is produced in the lungs and is an established biomarker in heart failure. We sought to determine the role of...

Heart failure with preserved left ventricular ejection fraction in patients with obstructive sleep apnea syndrome: prognostic value of biomarkers.

Aim To study the role of soluble ST2 (sST2), N-terminal pro-brain natriuretic peptide (NT-proBNP), and С-reactive protein (CRP) in patients with chronic heart failure and preserved left ventricular ejection fraction (CHF with pLVEF) and syndrome of obstructive sleep apnea (SOSA) in stratification of the risk for development of cardiovascular complications (CVC) during one month of a prospective observation.Material and methods The study included 71 men with SOSA with an apnea/hypopnea index (AHI) &gt;15 per hour, abdominal obesity, and arterial hypertension. Polysomnographic study and echocardiography according to a standard protocol with additional evaluation of left ventricular myocardial fractional changes and work index were performed for all patients at baseline and after 12 months of observation. Serum concentrations of sST2 , NT-proBNP, and CRP were measured at baseline by enzyme-linked immunoassay (ELISA).Results The ROC analysis showed that the cutoff point characterizing the development of CVC were sST2 concentrations ≥29.67 ng/l (area under the curve, AUC, 0.773, sensitivity 65.71 %, specificity 86.11 %; p&lt;0.0001) while concentrations of NT-proBNP (AUC 0.619; p=0.081) and CRP (AUC 0.511; р=0.869) were not prognostic markers for the risk of CVC. According to data of the ROC analysis, all patients were divided into 2 groups based on the sST2 cutoff point: group 1 included 29 patients with ST2 ≥29.67 ng/l and group 2 included 42 patients with ST2 &lt;29.67 ng/l. The Kaplan-Meyer analysis showed that the incidence of CVC was higher in group 1 than in group 2 (79.3 and 28.6 %, respectively, p&lt;0.001). The regression analysis showed that adding values of AHI and left ventricular myocardial mass index (LVMMI) to sST2 in the model increased the analysis predictive significance.Conclusion Measuring sST2 concentration may be used as a noninvasive marker for assessment of the risk of CVC development in patients with CHF with pLVEF and SOSA within 12 months of observation. Adding AHI and LVMMI values to the model increases the predictive significance of the analysis.