ST2 In Patients Research Articles

INDICATORS NT-PROBNP and ST-2 IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION WITH ST-SEGMENT ELEVATION

INDICATORS NT-PROBNP and ST-2 IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION WITH ST-SEGMENT ELEVATION

GW27-e1166 The prognostic value of serum soluble ST2 in patients with acute myocardial infarction

In order to identify the value of prognosis, we assayed level of serum soluble ST2 (sST2) in AMI patients and analyzed the correlation with NT-proBNP, which can provide a theoretical basis for early intervention of AMI patients. ①A total of 56 AMI patients admitted to Cardiology Department of the

COMBINATION OF SST2 AND BNP IN PREDICTING THE MORTALITY OF ST- ELEVATION MYOCARDIAL INFARCTION

Background: Serum levels of ST2 are associated with prognosis in nonischemic heart failure, but the predictive value of ST2 in patients with ST elevation myocardial infarction is unknown. Methods: The study included 38 STEMI patients at Interventional Cardiology department of Cho ray hospital. Correlation analysis was used to identify the relationship between the cardiac outcomes within 30 days from the onset of chest pain and sST2 value. Results: ST2 levels were measured in serum from 38 patients with STEMI. Baseline levels of ST2 were significantly higher in those patients who died (<35 ng/ml versus >35 ng/mL, P=0,01) or developed new congestive heart failure (< 35 ng/ml versus > 35 ng/mL, P=0.002) by 30 days. In an analysis of outcomes at 30 days by ST2 quartiles, both death (P=0.01) and the combined death/heart failure end point (p=0.001) showed a significant graded association with levels of ST2. Furthermore, when sST2 > 35 ng/ml and BNP > 500 pg/ml showed a tightly relationship with cardiac outcomes within 30 days (P<0,0001). Conclusions: Serum levels of the interleukin-1 receptor family member ST2 predict mortality and heart failure in patients with STEMI. These data suggest that ST2 and BNP are the useful biomarker in short-term prognosis of cardiac events in STEMI. Key words: sST2, BNP, STEMI, cardiac outcomes

Biologic Variability of Soluble ST2 in Patients With Stable Chronic Heart Failure and Implications for Monitoring

Soluble ST2 (sST2) is a novel biomarker implicated in myocardial remodeling and fibrosis. Recent studies in normal subjects have suggested that the biologic variability (BV) of sST2 is significantly lower than that of the B-type natriuretic peptides and N-terminal pro B-type natriuretic peptide (NTproBNP). It may, consequently, be a better biomarker for monitoring patients with chronic heart failure (CHF). To date, no published studies have examined the BV of sST2 in a heart failure population. Blood samples from 50 outpatients with pharmacologically optimized stable CHF and persistent left ventricular dysfunction (ejection fraction <40%) were collected at baseline, 1hour, 1month, 3months, and 6months. Using log-transformed data, mean intra-individual coefficients of variation (CVI) and subsequent reference change values were calculated for both NTproBNP and sST2. Results demonstrate significantly lower CVI and reference change values for sST2 compared with NTproBNP at 1month (12.02 [36%] vs 36.75 [103%]), p <0.001, 3months (12.23 [36%] vs 40.98 [114%]), p <0.001, and 6months (16.41 [47%] vs 46.02 [128%]), p <0.001. In conclusion, the BV of sST2 is significantly lower than that of NTproBNP in patients with CHF. These results support previous indications that sST2 may be a better biomarker for monitoring such patients.

Contribution of Blastocystishominis subtypes and associated inflammatory factors in development of irritable bowel syndrome.

Blastocystis hominis with worldwide distribution is a human intestinal protozoa found in all countries. There have been differences in the severity of the pathogenesis of various Blastocystis spp. and a concomitant variation in the plasma concentration of the cytokines in patients with irritable bowel syndrome. In the present study, we aimed to demonstrate the contribution of B. hominis subtypes in the development of irritable bowel syndrome. Stool samples were collected from patients with gastrointestinal disorders. All samples were evaluated through native-lugol method. Total DNA was extracted. A PCR protocol was developed to amplify a specific region of the SSU ribosomal DNA (rDNA) gene. Serum levels of IL-6 and TNF-α were determined by immunoassay methods. The ClustalW algorithm was applied to align and blast the nucleotide sequences of the amplified region of the SSU rDNA gene. To evaluate the phylogenetic and molecular evolutionary of the nucleotide sequences, we used the MEGA software. In this study, we found 26 haplotypes of B. hominis in the studied samples which were collectively belong to five subtypes (ST1, ST2 in patients without irritable bowel syndrome vs. ST3 and two unknown subtypes in patients with irritable bowel syndrome). Result of ELISA showed a high level of IL-6 and TNF-α in the serum of patients with irritable bowel syndrome. The genetic heterogeneity of B. hominis and the existence of different subtypes of the protozoan in patients with IBS may shed light to the fact that some subtypes of parasites may involve in the pathogenesis of IBS.

Potential role of the IL-33/ST2 axis in celiac disease.

The IL-33/ST2 axis has been implicated in the pathogenesis of several tissue-specific autoimmune diseases. Celiac disease (CD) is the only autoimmune disease in which both the major genetic factors (HLA-DQ2/DQ8) and etiologic ones (dietary gluten) for susceptibility are known. We have measured serum levels and determined intestinal tissue expression of IL-33 and its receptor soluble ST2 in patients with CD to investigate their association with disease activity. Serum and tissue levels of both IL-33 and sST2 were significantly higher in patients with CD compared with those in control patients without CD. We show that toxic peptides extracted from barley and wheat gliadin significantly stimulate the production of IL-33 and ST2 in cultured peripheral blood mononuclear cell from celiac patients, strongly implicating the IL-33/ST2 axis in the pathogenesis of CD. The higher levels of IL-33 and its receptor ST2 in tissue and serum reflect an active inflammatory state and may represent a potential biomarker for disease activity. A better understanding of IL-33/ST2 release, mode of action, and regulation will be crucial to develop therapeutics that target the IL-33/ST2 pathway to treat CD.Cellular & Molecular Immunology advance online publication, 7 September 2015; doi:10.1038/cmi.2015.85.

Increased levels of soluble ST2 in patients with active newly diagnosed ANCA-associated vasculitis.

Objective. ST2, a member of the interleukin-1 receptor family, is selectively expressed on Th2 cells and mediates important Th2 functions. IL-33 is a specific ligand of ST2. The aim of the study was to determine whether serum levels of soluble ST2 (sST2) or IL-33 predict activity of the disease in patients with ANCA-associated vasculitides (AAV). Methods. 139 AAV patients and 62 controls were studied. IL-33 and sST2 in the blood were measured with a commercially available ELISA. Results. Newly diagnosed AAV patients had higher sST2 levels than controls (P < 0.01). Levels of sST2 were significantly higher in active newly diagnosed AAV patients than in patients with remission (P < 0.001). IL-33 levels were higher in AAV patients than in the control groups (P = 0.002). However, serum IL-33 levels were not increased in patients with active AAV compared to patients in remission. IL-33 levels were higher in patients with granulomatosis with polyangiitis than in patients with microscopic polyangiitis (P = 0.012). Conclusions. Serum sST2, but not serum IL-33, may be a marker of activity in AAV patients.

Level of galectin-3 and ST2 in ischemic chronic heart failure depending on the functional state of kidneys

Aim. The aim of the study was to investigate the characteristics of level markers of fibrosis galectin-3 (Gal-3), ST2 in patients with ischemic chronic heart failure (CHF) depending on the glomerular filtration rate.Methods and results. The study involved 113 patients with ischemic CHF. Depending on glomerular filtration patients were divided into 3 groups: those with normal function (≥90 ml/min/1.73 m2), mild (60-89 ml/min/1.73 m2) and moderate (30-59 ml/min/1.73 m2) kidney dysfunction. It is established that in patients with ischemic CHF with moderate renal dysfunction level of Gal-3 is higher as compared with mild dysfunction and normal renal function (7.1 % and 53.6 %, respectively). The level of ST2 had about the same value in the groups of moderate and mild dysfunction, but was higher than in the group of normal renal function (11.7 % and 12.1 %, respectively). In the group of patients with ischemic CHF with moderate renal dysfunction correlation analysis showing that only Gal-3 revealed interrelationships of NT-proBNP (r=0,77; p=0,04), cystatin C (r=0,91; p=0.002).Conclusion. In patients with ischemic CHF with normal renal function revealed a strong correlation interrelationships between Gal-3, ST2 and the parameters of the structural remodeling of the left ventricle.

Measurement of serum soluble ST2 in patients with heart failure and its diagnostic value

Objective To measure serum soluble ST2 level in patients with heart failure and to evaluate its diagnostic value for heart failure.Methods We selected 192 heart failure patients who were hospitalized in the Cardiology Department of East Hospital,Tongji University during Jul.2009 to Dec.2010.The selected patients were divided into different groups according to the classification criterion of New York Heart Association(NYHA).The serum high-sensitivity C-reactive protein,brain natriuretic peptide,cardiac troponin I(cTnI),and creatine kinase isomer-MB were all examined after admission.All the patients received cardiac ultrasound examination.The soluble ST2 levels were determined by ELISA.Results The level of sST2 in heart failure patients was significantly higher than that in healthy controls(P=0.003).The diagnosis sensitivity and specificity of soluble ST2 for heat failure were 88.2% and 77.8%,respectively.Correlation analysis showed that sST2 value was correlated with B-type natriuretic peptide(r=0.427,P=0.01),high-sensitivity C-reactive protein(r=0.252,P=0.023),troponin(r=0.330,P=0.041) and left ventricular ejection fraction(r=-0.354,P=0.047).Conclusion ST2 is correlated with B-type natriuretic peptide,left ventricular ejection fraction and so on,and it can be used for diagnosis of heart failure.High ST2 level indicates poor short-term prognosis of heart failure patients.

Serial Monitoring of Soluble Interleukin Family Member ST2 in Patients with Acutely Decompensated Heart Failure

Objectives: To determine whether serial measures of the interleukin receptor family member soluble ST2 (sST2) provide additional prognostic information to baseline measures for long-term risk stratification of acutely decompensated heart failure (ADHF) patients. Methods: We prospectively enrolled 72 ADHF patients. Blood samples were collected to measure sST2 concentrations at presentation and on day 4 of hospitalization. All patients were clinically followed, and vital status was registered. Results: Between presentation and day 4, sST2 concentrations decreased from 62 ng/ml (interquartile range 38–105) to 44 ng/ml (interquartile range 26–72; p < 0.001). Both sST2 concentrations at presentation [hazard ratio (HR) 1.011, 95% confidence interval (CI) 1.005–1.016; p < 0.001] and on day 4 (HR 1.015, 95% CI 1.005–1.024; p = 0.003) were independent predictors of mortality. Patients with sST2 ≤76 ng/ml at presentation and ≤46 ng/ml on day 4 had the lowest mortality rates (3%), whereas those with both sST2 values above these cutoff points had the highest mortality (50%). C index and reclassification analyses demonstrated that the use of serial sST2 measures resulted in an improvement in the accuracy of mortality prediction. Conclusions: Among ADHF patients, sST2 concentrations tend to decrease following initiation of treatment and are prognostic both at presentation and during hospitalization. Serial sampling of sST2 adds prognostic information and may provide a basis for enhanced clinical decision making.

Serum IL-33 but not ST2 level is elevated in intermittent allergic rhinitis and is a marker of the disease severity.

BackgroundTh2 cells play an important role in intermittent allergic rhinitis (IAR). Interleukin (IL)-33 stimulates the production of Th2-associated cytokines. IL-33 binds to ST2 receptor which is highly expressed on mast cells and selectively on Th2 cells. IL-33 and ST2 might be involved in the Th2-mediated immune response.ObjectiveWe analyzed the serum level of IL-33 and its receptor ST2 in patients with IAR sensitive to grass and/or tree pollen to assess if the serum level of IL-33 and/or ST2 may be a marker of the disease severity.MethodsIL-33, ST2 and total immunoglobulin (Ig) E were measured in sera of patients with IAR sensitive to birch and/or grass pollen and in patients with controlled bronchial asthma and in non-allergic controls. IAR severity was assessed by total nasal symptom score.ResultsSerum levels of IL-33 in patients with IAR were comparable with patients with bronchial asthma and were significantly higher in patients with IAR (P = 0.0035) and in patients with bronchial asthma (P = 0.008) than in controls. Serum levels of IL-33 correlated with disease severity.ConclusionElevated level of IL-33 in sera of patients with IAR sensitive to tree and/or grass pollen and the correlation of IL-33 with the disease severity suggest that IL-33 is involved in the pathogenesis of intermittent allergic rhinitis.

ST2 Has Diagnostic and Prognostic Utility for All-Cause Mortality and Heart Failure in Patients Presenting to the Emergency Department With Chest Pain

BackgroundElevated ST2 predicts future heart failure and/or death in patients with pulmonary diseases, heart failure, acute dyspnea, and acute coronary syndromes. This study assesses both diagnostic and prognostic utility of ST2 in patients with chest pain. Methods and ResultsFrom November 2007 to April 2010, 995 patients attending the Emergency Department with chest pain were prospectively recruited. Troponin I (TnI), B-type natriuretic peptide (BNP), creatine kinase–myocardial band (CKMB), myoglobin, and ST2 were measured at 0 and 2 hours. The diagnostic utility of ST2 for heart failure and prognostic utility for primary outcome of death and/or heart failure by 18 months was assessed. Elevated ST2 had sensitivity 73.5% (55.8%–86.4%) and specificity 79.6% (79.0%–80.1%) for acute heart failure (n = 34) [compared with BNP sensitivity 88.2% (73.6%–95.3%), specificity 66.2% (65.7%–66.4%)]. Elevated ST2 conveyed risk of 18-month primary outcome (n = 110), with an adjusted hazard ratio (HR) of 1.9 (1.2–3.2), compared with BNP HR 2.8 (1.4–5.7), myoglobin HR 1.9 (1.1–3.3), TnI HR 1.7 (1.0–2.7), and CKMB HR 0.9 (0.5–1.7). When ST2 and BNP were both elevated, risk was greater than if either marker was elevated in isolation (P < .001). ConclusionsST2 was more specific for acute heart failure than BNP. ST2 is independently predictive of future death and/or heart failure and has incremental utility in combination with BNP.

Prognostic Utility of ST2 in Patients with Acute Dyspnea and Preserved Left Ventricular Ejection Fraction

Soluble ST2 (sST2), an interleukin-1 receptor family member, is an emerging risk indicator for patients with cardiovascular disease. We evaluated the prognostic role of sST2 for patients presenting to the emergency department with acute dyspnea, with a focus on those with preserved left ventricular ejection fraction (LVEF ≥50%), as risk stratification is often most complex in this subgroup. We conducted a post hoc analysis of 387 patients [39% female, mean (SD) age 57.6 (14.5) years] presenting to the emergency department with dyspnea and followed for 1 year (97% complete follow-up). We examined clinical data, concentrations of serum biomarkers [sST2, amino-terminal pro-B-type natriuretic peptide (NT-proBNP)], and transthoracic echocardiography. Patients had a median sST2 concentration of 38.4 U/mL [interquartile range (IQR) 25.5-64 U/mL]. Forty-six patients (12%) died during follow-up. Log sST2 [hazard ratio (HR) (95% CI) 2.85 (2.04-3.99), P < 0.001rsqb] and log NT-proBNP [1.28 (1.13-1.45), P < 0.001] concentrations were significant predictors of mortality at 1 year. After multivariate adjustment, only sST2 remained predictive of mortality [per log: 2.14 (1.37-3.38), P = 0.001]. In the subpopulation of individuals with normal systolic function (n = 200), only sST2 continued to predict mortality after multivariate adjustment [per log: 2.57 (1.12-5.91), P = 0.03]. Only NT-proBNP, but not sST2, concentrations correlated with multiple echocardiographic indices of left ventricular diastolic function. sST2 is a strong predictor of mortality in patients presenting with acute dyspnea, particularly those with preserved LVEF, and may be useful for triage and risk stratification of this challenging group.

Characteristics of the Novel Interleukin Family Biomarker ST2 in Patients With Acute Heart Failure

The purpose of this study was to examine the patient-specific characteristics of the interleukin-1 receptor family member ST2 in patients with acute heart failure (HF). ST2 signaling is involved in the process of cardiac fibrosis and hypertrophy. In all, 346 patients with acute HF had ST2 measured. Associations between ST2 and demographics, severity/type of HF, and other biomarkers were examined. Receiver-operator characteristic curves and multivariable Cox proportional hazards analyses evaluated the prognostic ability of ST2. The ST2 values correlated with the severity of HF (p < 0.001), left ventricular ejection fraction (r = -0.134; p = 0.014), creatinine clearance (r = -0.224; p < 0.001), B-type natriuretic peptide (r = 0.293; p < 0.001), amino terminal B-type natriuretic peptide (r = 0.413; p < 0.001), and C-reactive protein (r = 0.429; p < 0.001). ST2 was not associated with age, prior HF, or body mass index. The ST2 levels at presentation were higher among patients who died by 1 year. The area under the receiver-operator characteristic for death at 1 year was 0.71 (p < 0.001). In a multivariable Cox model containing established clinical and biochemical predictors (including natriuretic peptides), ST2 remained a predictor of mortality (hazard ratio: 2.04, 95% confidence interval: 1.30 to 3.24, p = 0.003), and was equally predictive in patients with HF and preserved or impaired systolic function. When both ST2 and natriuretic peptides were elevated, the highest rates of death were observed in cumulative hazard analysis (p < 0.001). In the presence of a low ST2 level, natriuretic peptides did not predict mortality. Consistent with its proposed role in a myocardial-specific response to stretch, ST2 has strong clinical and biochemical correlates in patients with acute HF. Prognostically, ST2 is powerful in acute HF and is synergistic with natriuretic peptides for this use.

Measurement of the Interleukin Family Member ST2 in Patients With Acute Dyspnea: Results From the PRIDE (Pro-Brain Natriuretic Peptide Investigation of Dyspnea in the Emergency Department) Study

The aim of this study was to examine the value of measurement of the interleukin-1 receptor family member ST2 in patients with dyspnea. Concentrations of ST2 have been reported to be elevated in patients with heart failure (HF). Five hundred ninety-three dyspneic patients with and without acute destabilized HF presenting to an urban emergency department were evaluated with measurements of ST2 concentrations. Independent predictors of death at 1 year were identified. Concentrations of ST2 were higher among those with acute HF compared with those without (0.50 vs. 0.15 ng/ml; p < 0.001), although amino-terminal pro-brain natriuretic peptide (NT-proBNP) was superior to ST2 for diagnosis of acute HF. Median concentrations of ST2 at presentation to the emergency department were higher among decedents than survivors at 1 year (1.08 vs. 0.18 ng/ml; p < 0.001), and in multivariable analyses, an ST2 concentration > or =0.20 ng/ml strongly predicted death at 1 year in dyspneic patients as a whole (HR = 5.6, 95% confidence interval [CI] 2.2 to 14.2; p < 0.001) as well as those with acute HF (hazard ratio [HR] = 9.3, 95% CI 1.3 to 17.8; p = 0.03). This risk associated with an elevated ST2 in dyspneic patients with and without HF appeared early and was sustained at 1 year after presentation (log-rank p value <0.001). A multi-marker approach with both ST2 and NT-proBNP levels identified subjects with the highest risk for death. Among dyspneic patients with and without acute HF, ST2 concentrations are strongly predictive of mortality at 1 year and might be useful for prognostication when used alone or together with NT-proBNP.

Serum levels of the interleukin-1 receptor family member ST2 predict mortality and clinical outcome in acute myocardial infarction.

Mechanically overloaded cardiomyocytes secrete a soluble interleukin-1 receptor family member called ST2. Serum levels of ST2 are associated with prognosis in nonischemic heart failure, but the predictive value of ST2 in patients with acute myocardial infarction is unknown. ST2 levels were measured in serum from 810 patients with acute myocardial infarction in the Thrombolysis In Myocardial Infarction (TIMI) 14 (362 patients) and Enoxaparin and TNK-tPA With or Without GPIIb/IIIa Inhibitor as Reperfusion Strategy in STEMI (ENTIRE)-TIMI 23 (448 patients) clinical trials. Baseline levels of ST2 were significantly higher in those patients who died (0.379 versus 0.233 ng/mL, P=0.0001) or developed new congestive heart failure (0.287 versus 0.233 ng/mL, P=0.009) by 30 days. In an analysis of outcomes at 30 days by ST2 quartiles, both death (P=0.001) and the combined death/heart failure end point (P=0.001) showed a significant graded association with levels of ST2; furthermore, in-hospital death (P=0.003) and death/heart failure (P=0.004) were also significantly associated with higher ST2 levels. In a logistic regression analysis that controlled for important clinical factors, increasing levels of ST2 remained associated with death at 30 days (P=0.047). ST2 levels rose during the first day after infarction and were maximal at 12 hours; ST2 levels at 12 hours were also independently associated with death at 30 days (P<0.001). Serum levels of the interleukin-1 receptor family member ST2 predict mortality and heart failure in patients with acute myocardial infarction. These data suggest that ST2 may be a useful biomarker and that this novel inflammatory receptor may play a role in cardiac pathophysiology.

Elevated soluble ST2 protein levels in sera of patients with asthma with an acute exacerbation.

Previous studies have reported that ST2 is preferentially expressed on Th2 cells and plays a critical part in controlling airway inflammation in murine models of asthma. However, the clinical role of ST2 in patients with bronchial asthma remains unclear. In our study, we examined 56 patients with atopic asthma in a nonattack phase and 200 nonatopic normal volunteers for healthy control, and analyzed the relationship of their serum ST2 levels to asthma severity, pulmonary function, and laboratory data. Of the 56 patients with atopic asthma, 30 exhibited asthmatic exacerbation, and their serum ST2 levels were also analyzed. The serum ST2 levels were low, but a statistical difference was found between patients with nonattack asthma and the healthy control group (p < 0.05). We also found a differential rise of serum ST2 level that correlates well with the severity of asthma exacerbation. Furthermore, the serum ST2 levels during asthma exacerbation statistically correlated with the percentage of predicted peak expiratory flow (r = -0.634, p = 0.004) and Pa(CO(2)) (r = 0.516, p = 0.003). These results suggest that soluble human ST2 protein in sera may be related to Th2-mediated allergic inflammation inducing acute exacerbation in patients with atopic asthma.