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Background & objectives: Diabetes mellitus (DM) is characterized by increase in blood glucose levels due to defective insulin secretion or insulin sensitivity. Interleukins (ILs) are known to play an important role in the pathogenesis of DM. The aim of this study was to investigate the serum concentration of IL-33 and its receptor soluble ST2 (sST2) in patients with diabetes and draw a correlation between their serum levels and different standard glycaemic indices of patients affected with type-2 diabetes with or without metabolic syndrome. Methods: Thirty type-2 diabetic individuals and 30 healthy controls were recruited for this study. Serum and plasma were separated by centrifugation of blood for quantitative measurement of IL-33, sST2 and other biochemical parameters. Results: It was observed that serum IL-33 levels were significantly less and sST2 levels were significantly high in type-2 diabetic individuals as compared to healthy controls. A significant correlation between the serum IL-33 concentration and fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels were also found. Additionally, data also elucidated that serum levels of high-density lipoprotein, low-density lipoprotein or triglyceride in type-2 diabetics did not influence the serum levels of IL-33 and sST2, thereby excluding these factors as the major drivers of changes in serum IL-33 and sST2 concentration. Interpretation & conclusions: This study demonstrated alteration in serum levels of IL-33 and sST2 in type-2 diabetic individuals. Further mechanistic studies, focusing on the progression of type-2 diabetes could elucidate the involvement of IL-33 in the cellular acquisition of insulin resistance as observed in type-2 diabetics
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Objective To investigate the effects of Sacubitril/Valsartan on amino terminal probrain natriuretic peptide (NT-proBNP),high sensitivity C-reactive protein (hs-CRP),soluble suppression of tumorigenicity 2(sST2)levels and on left ventricular(LV)structure in NYHA Ⅳ heart failure with reduced ejection fraction(HFrEF) patients.Methods A total of 67 HFrEF patients with NYHA Ⅳ were randomly divided into the control group (n =30)receiving conventional medical treatment,and the observation group(n=32)receiving Sacubitril/Valsartan instead of ACEI(or ARB if ACEI induced cough) in conventional medical treatment.NT-proBNP levels were determined by fluorescer-enhanced chemiluminescence.hs CRP levels were detected by latecx enhanced immunoturbidimetric assay.sST2 levels were determined by enzyme-linked immunosorbent assay (ELISA).The modified Simpson method was used to detect left ventricular end-diastolic diameter (LVEDD),LV posterior wall(LVPW)and LV ejection fraction(LVEF).Two groups of patients were treated and followed-up for 6 months.Results Clinical efficacy was better in the observation group than in the control group(effective rate,20 cases or 61.3％ vs.8 cases or 26.7％,P＜0.05).As compared with the control group,the observation group of patients had an increased LVEF[(46.7±9.2) ％ vs.(41.8±8.0)％,P＜0.05]and a decreased LVEDD[(52.6±6.7)mm vs.(58.8±7.5)mm,P＜0.05].After vs.before treatment,NT-proBNP,hs-CRP and sST2 levels were decreased in both control and observation groups [(1 427 ± 219) μg/L vs.(2 615 ± 273)μg/L,(1.14 ± 1.02) mg/L vs.(1.55±1.38)mg/L,(0.30±0.12)μg/L vs.(0.41±0.10)μg/L,all P＜0.05],and the decrements were much more in the observation group than in the control group (P＜0.05).The annual accumulated frequence and duration of hospitalization were less in the observation group than in the control group[(0.8±0.6)times vs.(1.8±1.0) times,(10.2±5.8)d vs.(16.5±7.2)d,P＜0.05].The maintenance dose of tolasemide was lower in the observation group than in the control group [(15.2±8.4)mg vs.(20.6±10.8)mg,P＜0.05].Conclusions Sacubitril/valsartan therapy is safe and effective and it can reduce hs-CRP and sST2 levels and improve the ventricular remodeling in HFrEF patients of HYHA Ⅳ.
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Objective To study the predictive value of serum soluble ST2 (sST2) in patients with sepsis.Methods A total of 63 patientswith sepsis and 30 healthy subjects as a control group in the emergency Department,Beijing Hospital,National Center of Gerontology,were enrolled in the study.Serum sST2 concentrations were measured by ELISA method.Patients were divided into sepsis group (n=44) and septic shock group (n=19).According to 28-day mortality after the diagnosis of sepsis,patients were divided into death group (n=18) and survival group (n=45).Respiratory rate,oxygenation index,white blood cell count,procalcitonin (PCT),C reactive protein (CRP),serum creatinine (CRE),total bilirubin (TBIL) of patients and control subjects were measured.SPSS 23.0 software was used for the statistical analyses.The measurement data was analyzed by t test and the enumeration data was analyzed by Chi square test.The survival status was analyzed by Logistic binary regression analysis and ROC curve analysis.Results The serum sST2 level (1 382.12±384.07) pg/mL in sepsis group was significantly higher than that in control group (569.28±163.46) pg/mL (P＜0.05).in septic shock group,28-day mortality rate (63.16％) and serum sST2 level (1 675.49±457.59) pg/mL was higher than those in sepsis group (13.64％) (1255.44 ± 265.70) pg/ml (P＜0.05).The PCT (16.37±16.36) ng/mL and serum sST2 level (1794.47±335.18)pg/mL in death group were higher than those in survival group (P＜0.05).The ROC curve showed that the AUC of sST2 was larger than that of PCT (0.917 vs.0.884),the sensitivity was higher than that of PCT (88.9％ vs.72.2％),and the specificity was lower than that of PCT (82.2％ vs.93.3％).The combination AUC of sST2 and PCT was 0.944.Conclusions Serum sST2 has a certain value in the diagnosis of sepsis,and can be used to predict the prognosis of patients with sepsis.The higher the sST2 value,the worse the prognosis.Compared with PCT,sST2 is more sensitive in the prognosis of sepsis,but the specificity is not high enouph.The measurement of sST2 level coupled with PCT level may be more useful.
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BACKGROUND AND OBJECTIVES: We aimed to investigate the relationship between the recurrence of atrial fibrillation (AF) and fibrosis marker soluble ST2 (sST2) in patients with nonvalvular paroxysmal AF (PAF). METHODS: We prospectively included 100 consecutive patients with PAF diagnosis and scheduled for cryoballoon catheter ablation for AF (47 males, 53 females; mean age 55.1±10.8 years). sST2 plasma levels were determined using the ASPECT-PLUS assay on ASPECT Reader device (Critical Diagnostics). The measurement range of these measurements was 12.5–250 ng/mL. Patients had regular follow-up visits with 12-lead electrocardiogram (ECG), medical history, and clinical evaluation. Twenty-four hours Holter ECG monitoring had been recorded 12 months after ablation. RESULTS: AF recurrence was detected in 22 patients after 1 year. Age, smoking history, diabetes mellitus,hypertension frequency, angiotensin converting enzyme inhibitor-angiotensin receptor blocker use, CHA2DS2VASc and HAS-BLED scores, serum sST2 level, left atrium (LA) end-diastolic diameter, LA volume and LA volume index were related to AF recurrence. In multivariable logistic regression analysis, sST2 was found to be only independent parameter for predicting AF recurrence (odds ratio, 1.085; p=0.001). Every 10-unit increase in sST2 was found to be associated with 2.103-fold increase in the risk of AF recurrence. The cut-off value of sST2 obtained by receiver operating characteristic curve analysis was 30.6 ng/mL for prediction of AF recurrence (sensitivity: 77.3%, specificity: 79.5%). The area under the curve was 0.831 (p < 0.001). CONCLUSIONS: sST2, which is associated with atrial fibrosis, can be thought to be a useful marker for detection of patients with high-grade fibrosis who will get less benefit from cryoablation.
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Female , Humans , Male , Atrial Fibrillation , Catheter Ablation , Catheters , Cryosurgery , Diagnosis , Electrocardiography , Fibrosis , Follow-Up Studies , Heart Atria , Logistic Models , Peptidyl-Dipeptidase A , Plasma , Prospective Studies , Recurrence , ROC Curve , Sensitivity and Specificity , Smoke , SmokingABSTRACT
Objective@#Diagnostic efficacy of serum markers is low for heart failure patients with preserved left ventricular ejection fraction (HF-pEF) as compared to heart failure patients with reduced left ventricular ejection fraction.We sought to explore the diagnostic value of serum levels of soluble ST2 (sST2) combined with interleukin-33 (IL-33) for the diagnosis of HF-pEF in this study.@*Methods@#A total of 376 patients with HF-pEF (HF group), 376 matched-control patients without heart failure who shared similar clinical characteristics (non-HF group) were included in the study.Another 500 healthy individuals were recruited for assessing the normal ranges of IL-33 and sST2.Serum levels of NT-proBNP were measured by chemi-luminescence assay, while IL-33 and sST2 were measured by enzyme linked immunosorbent assay.@*Results@#Serum levels of IL-33 and sST2 were not normally distributed in healthy population.Serum concentrations of IL-33 and sST2 were significantly higher in HF-pEF patients than in patients in non-HF group (median, IL-33: 0.437 μg/L vs. 0.127 μg/L, P<0.01; sST: 0.118 μg/L vs. 0.067 μg/L, P<0.01). The area under receiver operating characteristic curve (AUC) of sST2 for detecting HF-pEF was 0.763 (95%CI 0.729-0.795, P<0.01), with 71.01% sensitivity and 66.75% specificity, the AUC was 0.884 (95%CI 0.859-0.908, P<0.01), with 80.05% sensitivity and 81.91% specificity in patients with serum IL-33 higher than 0.117 μg/L (median level of serum IL-33 in healthy individuals, n=306). The AUC of NT-proBNP for detecting HF-pEF was 0.83, with 74.73% sensitivity and 84.57% specificity.The AUC of sST2 for detecting HF-pEF was significantly higher than NT-proBNP in population with high serum IL-33 (AUC: 0.88 vs. 0.83, P<0.01).@*Conclusion@#Serum sST2 could serve as a satisfactory biomarker for HF-pEF diagnosis, especially for patients with high serum IL-33 concentrations.
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BACKGROUND: Soluble ST2 (sST2) has emerged as a biomarker of heart failure. Previous studies indicated 35 ng/mL of sST2 as the clinically prognostic cut-off value. This study aims to establish reference intervals in a Korean population using an sST2 assay and to evaluate the applicability of the cut-off value. METHODS: From March to May 2014, sST2 levels were assayed in serum samples of 255 cardio-healthy Koreans (128 men and 127 women) using the Presage ST2 ELISA kit (Critical Diagnostics, USA). The reference interval for sST2 was defined using the nonparametric percentile method according to the CLSI EP28-A3c guideline. RESULTS: The median sST2 concentrations were 23.8 ng/mL (interquartile range (IQR), 19.0-28.7), 26.6 ng/mL (IQR, 21.0-30.9), and 21.9 ng/mL (IQR, 17.3-26.5) for the entire cohort, men, and women, respectively. sST2 levels were significantly higher in men than in women (P<0.0001). The 97.5th percentile upper reference limits for sST2 were 43.8 ng/mL, 49.6 ng/mL, and 35.4 ng/mL for the cohort, men, and women, respectively. Gender-specific upper reference limits were similar to limits reported by other studies. CONCLUSIONS: We suggest that gender-specific reference intervals should be used for the Korean population, as application of a single cut-off value of 35 ng/mL may be overcautious of the possibility of false positivity, especially in men.
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Female , Humans , Male , Cohort Studies , Enzyme-Linked Immunosorbent Assay , Heart Failure , MethodsABSTRACT
Heart failure is a serious and terminal stage of various cardiovascular diseases,is one of the most important heart diseases,and it also the most common reason for hospitalization.In recent years,studies on new markers in the diagnosis,treatment and prognosis of heart failure have made great progress,such as B-type brain natriuretic peptide can partially reflect hemodynamic imbalance,troponin can indicate cardiomyocyte injury,soluble ST2 and galectin-3 indicate myocardium remodeling and fibrosis,C-reactive protein,cystatin C and procalcitonin,and copeptin have significant prognostic value for outcomes,microRNA in the regulation of gene expression influence heart failure.
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BACKGROUND: A biomarker that is of great interest in relation to adverse cardiovascular events is soluble ST2 (sST2), a member of the interleukin family. Considering that metabolic syndrome (MetS) is accompanied by a proinflammatory state, we aimed to assess the relationship between sST2 and left ventricular (LV) structure and function in patients with MetS. METHODS: A multicentric, cross-sectional study was conducted on180 MetS subjects with normal LV ejection fraction as determined by echocardiography. LV hypertrophy (LVH) was defined as an LV mass index greater than the gender-specific upper limit of normal as determined by echocardiography. LV diastolic dysfunction (DD) was assessed by pulse-wave and tissue Doppler imaging. sST2 was measured by using a quantitative monoclonal ELISA assay. RESULTS: LV mass index (β=0.337, P<0.001, linear regression) was independently associated with sST2 concentrations. Increased sST2 was associated with an increased likelihood of LVH [Exp (B)=2.20, P=0.048, logistic regression] and increased systolic blood pressure [Exp (B)=1.02, P=0.05, logistic regression]. Comparing mean sST2 concentrations (adjusted for age, body mass index, gender) between different LV remodeling patterns, we found the greatest sST2 level in the group with concentric hypertrophy. There were no differences in sST2 concentration between groups with and without LV DD. CONCLUSIONS: Increased sST2 concentration in patients with MetS was associated with a greater likelihood of exhibiting LVH. Our results suggest that inflammation could be one of the principal triggering mechanisms for LV remodeling in MetS.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Age Factors , Area Under Curve , Blood Pressure , Body Mass Index , Cross-Sectional Studies , Echocardiography, Doppler , Enzyme-Linked Immunosorbent Assay , Hypertrophy, Left Ventricular/diagnostic imaging , Interleukin-1 Receptor-Like 1 Protein/analysis , Linear Models , Logistic Models , Metabolic Syndrome/metabolism , ROC Curve , Sex Factors , Ventricular Function, Left/physiology , Ventricular Remodeling/physiologyABSTRACT
PURPOSE: Soluble ST2 (sST2) is an emerging prognostic biomarker in patients with cardiovascular disease (CVD). A recent study showed that sST2 predicted incident hypertension. High sensitive C-reactive protein (hsCRP) has been a widely-used biomarker for risk-stratifying in CVD. We compared the abilities of sST2 and hsCRP to predict high risk coronary artery calcium score (CACS). MATERIALS AND METHODS: The CACS was assessed by cardiac computed tomography, and sST2 was measured in 456 subjects enrolled in the Mapo-gu community cohort. In accordance with the 2013 ACC/AHA guidelines, we defined the high risk CACS group as individuals with a CACS ≥300 Agatston units (AU). RESULTS: There were 99 (21.7%) subjects with a CACS ≥300 AU. There was a strong correlation between log sST2 and log hsCRP (r=0.128, p=0.006), and both log sST2 and log hsCRP showed significant associations with CACS (r=0.101, p=0.031 for sST2, r=0.101, p=0.032 for hsCRP). In net reclassification improvement (NRI) analysis, the NRI for hsCRP over sST2 was significant [continuous NRI 0.238, 95% confidence interval (CI) 0.001–0.474, integrated discrimination index (IDI) 0.022, p=0.035], while the NRI for sST2 over hsCRP was not significant (continuous NRI 0.212, 95% CI -0.255–0.453, IDI 0.002, p=0.269). CONCLUSION: sST2 does not improve net reclassification for predicting a high risk CACS. Using hsCRP provides superior discrimination and risk reclassification for coronary atherosclerosis, compared with sST2.
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Humans , Atherosclerosis , C-Reactive Protein , Calcium , Cardiovascular Diseases , Cohort Studies , Coronary Artery Disease , Coronary Vessels , Discrimination, Psychological , HypertensionABSTRACT
Objective: To study the correlations between galectin-3, soluble ST2 (sST2) levels and chronic heart failure (CHF) classiifcation, traditional HF indicator and short-term death in relevant patients. Methods: This research included 2 groups: CHF group, containing 142 relevant patients treated in our hospital from 2014-02 to 2015-10 and Control group, containing 85 normal subjects from physical examination at the same period of time. Based on NYHA criterion, the patients were classiifed in NYHA grade II, III and IV respectively. Blood levels of N-terminal brain natriuretic peptide (NT-ProBNP), high-sensitivity C reactive protein (hs-CRP) and ultrasonic morphology were examined upon admission; protein expressions of galectin-3 and sST2 were assessed by ELISA. Results: The patients with NYHA grade III and IV had increased levels of galectin-3 and soluble sST2; galectin-3, sST2 were positively related to NT-ProBNP, hs-CRP and LVEDD, while negatively related to LVEF. Logistic regression analysis indicated that galectin-3 and sST2 were related to short-term death in CHF patients,P<0.05. Area under ROC curve of galectin-3 and sST2 for diagnosing CHF were 0.738 and 0.771,P<0.01. Conclusion: Galectin-3 and sST2 levels were related to traditional HF indicator and could be used for CHF diagnosis in relevant patients.
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ObjectiveTo study the changes and clinical significance of serum heart-type fatty acid-binding protein (H-FABP) and soluble ST2 protein (sST2) in children with chronic heart failure (CHF).MethodsThirty-nine children with CHF and 30 healthy children were recruited. Serum levels of H-FABP and sST2 were determined by ELISA, The left ventricular ejection fraction (LVEF) and fractional shortening of the left ventricle (LVFS) were measured by two-dimensional echocardiog-raphy.ResultsIn 39 children with CHF, 15 males and 24 females, aged 2 months to 14 years, included 27 cases of endocardial ifbroelastosis (EFE) and 12 cases of dilated cardiomyopathy (DCM). According to the cardiac functional grading standard, the children with CHF were divided into 10 cases with cardiac function II, 15 cases with cardiac function III, and 14 cases with cardiac function IV. The mean levels of H-FABP, sST2 and NT-Pro-BNP in children with CHF at stage of heart failure and heart failure remission were statistically higher than those in the healthy children (allP0.05). The Spearman correlation analysis showed that, in children with CHF at stage of heart failure, the serum H-FABP level was positively correlated with NT-Pro-BNP, sST2 and cardiac function (r=0.402、0.621、0.644,P<0.05). Serum sST2 level was positively correlated with NT-Pro-BNP and cardiac function (r = 0.501、0.678,P<0.05), and was negatively correlated with LVEF and LVFS (r=?0.340、?0.329, P<0.05).ConclusionsH-FABP and sST2 are involved in the development of heart failure. H-FABP and sST2 can be used as reference indices for clinical diagnosis and assessment of CHF.
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Interleukin (IL)-33 is an important mediator of innate immunity. Behcet's disease (BD) is an autoinflammatory disorder characterized by hyperactivity of the innate immune response. We measured serum levels of IL-33 and its receptor soluble ST2 (sST2) in patients with BD to investigate their association with disease activity. Serum levels of both IL-33 and sST2 were higher in patients with BD compared with those in normal controls (IL-33: 594.48+/-175.04 pg/mL in BD and 224.23+/-56.64 pg/mL in normal controls [P=0.048], sST2: 99.01+/-15.92 pg/mL in BD and 23.56+/-3.25 pg/mL in normal controls [P<0.001]). IL-33 and sST2 expression in skin tissue, as shown by immunohistochemistry, was higher in patients with BD compared with that in the normal controls. Serum sST2 level correlated significantly with the BD currently active form (BDCAF), Iranian BD dynamic activity measure (IBDDAM), erythrocyte sedimentation rate and C-reactive protein. Multiple linear regression showed that serum sST2 was an independent factor associated with IBBDAM (regression coefficient, 0.374; P=0.004), and BDCAF (regression coefficient, 0.236; P=0.047). These results demonstrate that IL-33 and sST2 are highly expressed in patients with BD and that serum sST2 is an independent factor associated with IBDDAM and BDCAF, suggesting a potential role for sST2 as a surrogate marker of disease activity in patients with BD.