ST2 Levels Research Articles

Relationship between soluble protein ST2 (sST2) levels and microvascular complications in a cohort of patients with type 1 diabetes

AimTo determine the association and the prognostic value of soluble ST2 (sST2) levels in the development of diabetic retinopathy (DR), diabetic macular oedema (DMO) or diabetic nephropathy (DN), in a cohort of patients with type 1 diabetes (T1D). MethodsA total of 269 individuals with T1D (154 males and 115 females) were recruited. The overall mean age was 43.2±14.9 years, and the diabetes duration was 17.1±12.1 years. Levels of sST2 in serum were evaluated, and the presence as well as the degree of DR, DMO and DN was recorded. Additionally, other clinical and analytical parameters including demographic variables were recovered from patients’ electronic health record. Ten years later, the presence and stage of DR, DMO and DN were again recorded under the same criteria.The association between previously mentioned parameters with DR and DN was analysed by univariate and multivariate logistic regression. The variables in the final multivariate models were adjusted from complete models via backward elimination and maintained only when significant. ResultsAn increase of 10ng/ml in the levels of sST2 was associated with a 1.50 (1.02–2.19) and 1.48 (1.05–2.08) prevalence odds ratio (OR) in DMO and DR, respectively. There was no association between sST2 levels and DN. Meanwhile, sST2 levels did not display a prognostic effect in any of the microangiopathic diabetic complications studied. ConclusionsLevels of sST2 are associated with the presence of DR and DMO, they do not seem to be predictive for the development or deterioration of DR, DMO or DN.

Soluble Isoform of ST2 is a Cardiac Inducer of Collagen Deposition in an Ex Vivo Model of Obesity

IntroductionOne of the main cardiac mechanosensor is the IL‐33/ST2L complex composed by the allarmin IL‐33 released into extracellular space by damaged cells during cardiac overload and its receptor, ST2L, which their binding promotes cell survival and anti‐fibrotic signaling. After damage, to stop IL‐33/ST2L signal, resident cardiac cells release sST2, the soluble isoform of transmembrane receptor of ST2, which sequesters IL‐33, functioning as a decoy receptor and blocking its signal. In obesity, the sST2 become over express especially by hypertrophic fat cells. The aim of our study is to evaluate in an ex vivo model of obesity the role of sST2 in the promotion of collagen production by cardiac cells.MethodsTen obese nondiabetic male Zucker rats (OB) (fa/fa‐, 10 weeks of age) and 10 lean littermates (L) (Fa/+) at the age of 25 weeks were weighted and scarified according to Italian Ministry of Health Authorization (N°325/2015PR of 2015/04/05) and their heart and visceral adipose tissue (VAT) were collected for the analysis. VAT biopsies were cut in 30mg pieces and added into a co‐culture system with H9C2 for 6‐24 and 48 hours. At each time points, cells and culture medium were collected. In all samples were evaluated ST2 by ELISA and collagen were quantified by quantitative Sircol assay for measurement of both acid‐soluble and pepsin‐soluble collagens.ResultsOB cardiac biopsies showed higher protein level of both ST2 and collagen than L rats (p<0.02 and p<0.002 respectively) and the rat weight positively correlates with ST2 cardiac protein level (p<0.05). Co‐culture data demonstrated that OB VAT promotes ST2 releases in both cardiac and fat cells, resulting an incremental increase of sST2 release in cell culture medium than L VAT in time. sST2 quantification in correspondent H9C2 co‐cultured lysate is more incremented in OB than L H9C2 after 48h.total collagen quantification in co‐culture medium resulted higher in OB than L (p<0.05).ConclusionOur results demonstrated in a co‐culture system that obesity promotes sST2 increase in the heart and this promotes collagen releases by cardiac cells, suggesting sST2 role in activation of pro‐fibrotic signaling and detrimental heart remodeling.

EVALUATION OF QUALITY OF LIFE INDICATORS IN NSTEMI PATIENTS DEPENDING ON PLASMA LEVEL ST2, NATURE OF CORONARY ARTERIES LESION AND OTHER CLINICAL CHARACTERISTICS

Introduction. The prevalence of myocardial infarction and its leading role in the structure of overall and cardiovascular mortality encourages the search for predictors of adverse disease and the search for optimal means to prevent adverse events and improve the quality of life of this category of patients. The aim of the study – to evaluate quality of life in NSTEMI patients based on plasma ST2 levels, the nature of coronary artery disease, and other clinical characteristics. Research Methods. The study involved 200 patients with NSTEMI aged 38 to 80 years. All patients were examined according to the current treatment protocol for patients with acute myocardial infarction without ST segment elevation, plasma ST2 levels were determined and quality of life was assessed using the MIDAS-35 questionnaire. Results and Discussion. Spearman's rank correlation showed that the level of physical activity (the first subscale of MIDAS-35) of patients with NSTEMI is directly correlated with the presence of frequent ventricular extra­systoles and paroxysms of ventricular tachycardia recorded during ECG monitoring on day 1 of NSTEMI, the seve­rity of coronary artery lesions and plasma ST2 levels determined on the 1st day of hospitalization. Similar patterns are found in subscales 2, 4, 5. Subscale 6 revealed the presence of a correlation only with the presence of frequent ventricular tachycardia. Subscales 3 and 7 did not show correlations with the studied parameters. Conclusions. Elevated ST2 levels, hemodynamically significant coronary artery lesions and the presence of acute arrhythmias in the early period of NSTEMI have been found to significantly affect quality of life as determined by the MIDAS-35 questionnaire. The impact on remodeling processes and the strategy of early invasive treatment in patients with NSTEMI will not only reduce the likelihood of complications, but also improve the quality of life of this category of patients.

Influence of ST2 level on the development of acute arrhythmias in NSTEMI

Abstract Funding Acknowledgements Type of funding sources: None. Purpose To determine the structure and relationship of cardiac arrhythmias in NSTEMI patients based on plasma ST2 level. Methods We studied 90 patients with NSTEMI aged from 35 to 79 years (mean 60.7 ± 0.8, median - 61, interquartile range 54 and 69). Plasma ST2 level was determined and analyzed in the NSTEMI patients group, the gradations of the ST2 level and the correlation with cardiac arrhythmias. All of the research corresponds to the principles of the Declaration of Helsinki of the World Medical Association. Results. Using the variation statistics method, the ST2 level gradations group were selected. Thus, the relatively low (RL) corresponded to less than 25, and the relatively high (RH) level of ST2 to more than 75 persons in the group, respectively. For patients in the main group, these levels were <26 and> 56 ng / ml, respectively. Instead, the relatively moderate (or intermediate) ST2 level (RM) for these patients was 26-56 ng / ml. It has been determined that the most frequent rhythm disturbances were observed in the RM and RH risk groups, and more often in the RM risk group, probably due to a larger number of observations (Tab. 1). At that time, the total duration of ventricular tachycardia (VT) episodes, regardless of the number of patients, was at RH risk group. The same was observed with episodes of ST-depression. Conclusions. Despite the number of observations, the risk of VT and ST-depression is significantly higher in patients at RH risk group. This should be taken into account when predicting the risk of complications in patients with NSTEMI. Abstract Figure. Tab. 1

Persistently elevated levels of sST2 after acute coronary syndrome are associated with recurrent cardiac events

Purpose Higher soluble ST2 (sST2) levels at admission are associated with adverse outcome in acute coronary syndrome (ACS) patients. We studied the dynamics of sST2 over time in post-ACS patients prior to a recurrent ACS or cardiac death. Methods We used the BIOMArCS case cohort, consisting of 187 patients who underwent serial blood sampling during one-year follow-up post-ACS. sST2 was batch-wise quantified after completion of follow-up in a median of 8 (IQR: 5–11) samples per patient. Joint modelling was used to investigate the association between longitudinally measured sST2 and the endpoint, adjusted for gender, GRACE risk score and history of cardiovascular diseases. Results Median age was 64 years and 79% were men. The 36 endpoint patients had systematically higher sST2 levels than those that remained endpoint free (mean value 29.6 ng/ml versus 33.7 ng/ml, p-value 0.052). The adjusted hazard ratio for the endpoint per standard deviation increase of sST2 was 1.64 (95% confidence interval: 1.09–2.34; p = 0.019) at any time point. We could not identify a steady or sudden increase of sST2 in the run-up to the combined endpoint. Conclusion Asymptomatic post-ACS patients with persistently higher sST2 levels are at higher risk of recurrent ACS or cardiac death during one-year follow-up.

Expression of Hypersensitive Troponin I and Soluble ST2 in Acute Organophosphorus Pesticide Poisoning.

The role of soluble growth stimulating gene 2 protein and highly sensitive cardiac troponin in the diagnosis of early myocardial injury caused by acute organophosphorus pesticide poisoning was studied. 171 inpatients with AOPP were divided into three experimental groups according to their mild, moderate, and severe conditions. 20 healthy people were selected as the control group. The levels of cTnI, HS-CTNI, NT proBNP, and ST2 were measured at the 4th and 12th hours after the experiment. The measured data were expressed by mean standard deviation. The independent sample t-test was used for the detection between the two groups, and one-way ANOVA was used for the analysis and comparison between multiple groups. The relevant data were analyzed by Spearman correlation test (P < 0.05). The levels of cTnI and HS cTnI in the experimental group increased with the extension of time and the deepening of poisoning degree; four hours after admission, ST2 and NT proBNP water in the control group and the experimental group increased significantly on average. According to the analysis of the data, there was a positive correlation between HS TnI and ST2 in patients with AOPP (r = 0.938, P < 0.001, r = 0.827, P < 0.001). The more serious the disease, the higher the concentrations of HS TnI and ST2, and the more serious the myocardial injury.

A Preclinical Rat Model of Heart Failure With Preserved Ejection Fraction With Multiple Comorbidities.

Heart failure with preserved ejection fraction (HFpEF) is a common complex clinical syndrome for which there are currently few evidence-based therapies. As patients with HFpEF very often present with comorbidities comprising the metabolic syndrome, we hypothesized, that metabolic syndrome could lead over time to the development of diastolic dysfunction and HFpEF. Obesity-prone rats were exposed to high-fat diet and compared to obesity-resistant rats fed with standard chow. Phenotyping of metabolic syndrome, associated with echocardiographic and cardiac hemodynamic measurements, was performed after 4 and 12 months. Blood and myocardial tissue sampling were performed for pathobiological evaluation. High-fat diet in obesity-prone rats elicited metabolic syndrome, characterized by increased body and abdominal fat weights, glucose intolerance and hyperlipidemia, as well as increased left ventricular (LV) systolic pressure (after 12 months). This was associated with LV diastolic dysfunction (assessed by increased LV end-diastolic pressure) and pulmonary hypertension (assessed by increased right ventricular systolic pressure). Echocardiography revealed significant concentric LV hypertrophy, while LV ejection fraction was preserved. LV remodeling was associated with cardiomyocyte hypertrophy, as well as myocardial and perivascular fibrosis. Circulating levels of soluble ST2 (the interleukin-1 receptor-like) markedly increased in rats with HFpEF, while plasma NT-proBNP levels decreased. RNA-sequencing analysis identified clusters of genes implicated in fatty acid metabolism and calcium-dependent contraction as upregulated pathways in the myocardium of rats with HFpEF. High-fat diet during 12 months in obesity-prone rats led to the development of a relevant preclinical model of HFpEF with multiple comorbidities, suitable for investigating novel therapeutic interventions.

Correlation of Suppression of Tumourigenicity 2 with hsCRP, NT-proBNP and Left Ventricular Ejection Fraction in Patients with Myocardial Infarction

Introduction: Soluble Suppression of Tumourigenicity 2 (sST2) represents a clinically relevant biomarker and has predictive evidence in acute Myocardial Infarction (MI) and predicts cardiovascular death and risk of heart failure development in these patients. The data about the correlation of sST2, N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) and high-sensitivity C-reactive protein (hsCRP)in the Indian population is lacking. Aim: To find a correlation of ST2 level at the time of admission with NT-proBNP, hsCRP and Left Ventricular Ejection Fraction (LVEF) in patients with MI, and the association of ST2 levels with mortality. Materials and Methods: This longitudinal observational study was conducted at Poona Hospital and Research Centre, Pune, Maharashtra, India, between June 2018 and August 2019, among 75 myocardial infarction patients above 18 years of age. ST2, NT-proBNP and hsCRP levels were checked within 6 hour of hospitalisation. The primary outcome measures were to study the correlation of ST2 levels at the time of admission with hsCRP, NT-proBNP and LVEF. The secondary outcome measures were to study the association of ST2 levels with in-hospital and onemonth mortality. The medians of continuous variables of two groups and three groups were-tested using the Mann-Whitney U test and Kruskal-Wallis H test respectively. The correlation analysis was performed using Spearman’s method. Results: The mean age of the study population was 57.8±7.2 years. The mortality rate was 60% (12/75). ST2 levels showed a statistically significant positive correlation with NT-proBNP (r =0.703, p-value=0.001) and hsCRP (r=0.873, p-value=0.001), whereas, ST2 levels showed a negative correlation with LVEF (r=- 0.711, p-value=0.001) in MI patients. The median ST2 levels were significantly higher in-hospital (215.3 ng/dL vs 94 ng/dL) and one month (219.5 ng/dL vs 92.0 ng/dL) mortality as compared to survived MI patients. Conclusion: ST2 levels showed a statistically significant positive correlation with NT-proBNP and hsCRP and were associated with in-hospital and one month mortality in MI patients.

Serum CD40L, ST2, IL-6, and CRP serving as biomarkers for acute coronary syndrome

To analyze the diagnostic value of CD40 ligand (CD40L), soluble growth stimulating expression gene 2 protein (ST2), interleukin-6 (IL-6), and C-reactive protein (CRP) are used in patients with acute coronary syndrome (ACS). Serum samples were collected from 259 ACS patients admitted to our hospital. Additionally, 119 healthy individuals who received physical examination in the hospital at the same time period were included as normal control. The levels of CD40L, ST2, IL-6, and CRP in 259 patients with ACS and 119 healthy subjects were detected by ELISA. The levels of CD40L, ST2, IL-6, and CRP were significantly increased in unstable angina (UA) patients, while ST2, CRP, and IL-6 were significantly elevated in acute myocardial infarction (AMI) patients. Pearson correlation analysis showed that ST2 was also closely related to CRP in ACS patients, while ST2 was positively correlated with creatine kinase (CK), creatine kinase isoenzyme (CK-MB), and troponin I (cTnI) in AMI patients. The levels of glucose (GLU) and low-density lipoprotein cholesterol (LDL-c) were significantly decreased, while the levels of high-density lipoprotein cholesterol (HDL-c) were significantly increased in AMI patients treated with stent implantation. Furthermore, the level of serum CD40 L was significantly elevated in coronary heart disease (CHD) patients treated with stent implantation, while the levels of ST2 and IL-6 in AMI patients treated with the stent implantation decreased significantly. The levels of inflammatory factors significantly changed in patients with ACS. These inflammatory factors may involve in the pathological progression of ACS and can be used as diagnostic indexes for ACS.

THE LEVEL OF GROWTH STIMULATING FACTOR EXPRESSED BY GENE 2 AND TROPONIN I IN THE BLOOD PLASMA OF NSTEMI PATIENTS DEPENDING ON DIFFERENT CLINICAL CHARACTERISTICS

The aim of the study is to evaluate the relationship between ST2 and Troponin I with various clinical and instrumental parameters. Materials and methods: We examined 200 patients with NSTEMI aged 38 to 80 years, who were urgently hospitalized in the Vinnytsya Regional Clinical Center of Cardiovascular Pathology. All patients underwent laboratory testing of ST2 and Troponin I levels in plasma by enzyme-linked immunosorbent assay on the first day of hospitalization before coronary angiography. Results: Elevations in ST2 levels were significantly higher in patients with acute heart failure (Killip III) and the presence of acute arrhythmias, diabetes mellitus, and smoking. The increase in Troponin I was associated primarily with the nature of changes in the ECG, stratification on the GRACE score and the presence of concomitant arterial hypertension. Conclusions: Determination of ST2 and Troponin I before coronary angiography makes it possible to predict the course of NSTEMI and make appropriate therapeutic corrections to prevent complications.

MARKER DIAGNOSTIC HEART FAILURE PROGRESSION IN THE POST-INFARCTION PERIOD.

The aim: To study the relationship between the concentration of copeptin, NT-proBNP, ST2 and indicators of myocardial remodeling, the dynamics of these indicators in order to predict the occurrence of decompensated heart failure (HF) in patients with acute myocardial infarction (AMI). Materials and methods: The study is based on the results of the examination of 160 patients with MI, including 120 patients with decompensated CHF II A-B stage according to Vasylenko-Strazhesko classification of (FC) III-IV (according to NYHA) and 40 patients with MI without signs of decompensated CHF, as well as 20 medically healthy individuals. The level of copeptin, NT-proBNP, ST2 were determined. Results: In patients with signs of decompensated HF there were significantly higher levels of NT-proBNP in the blood serum that amounted to (950.38±3.15) pg/ml, in patients without decompensated HF after MI (580.15±3.03) pg/ml compared to healthy individuals (111.20±3.47) pg/ml (p<0.05). The mean value of copeptin concentration in patients with decompensated CHF was recorded (18.11±0.12) pg/ml, compared to (12.03±0.14) pg/ml in patients with MI without signs of CHF decompensation. Conclusions: The most significant for clinical and prognostic assessment of the post-infarction period complicated by decompensated HF is the response of the patient's body to dosed physical exertion and the levels of NT-prpBNP, copeptin and ST2.

THE ROLE OF NT-PROBNP AND ST2 BIOMARKERS IN PATIENTS WITH ACUTE CORONARY SYNDROME

The aim: To determine the diagnostic value of serum levels of ST2 in patients with the acute coronary syndrome (ACS) and its correlation with NT-proBNP levels. Materials and methods: NT-proBNP and ST2 concentration in serum of patients was measured on admission to the hospital and on the 10th day of the treatment using NT-proBNP ELISA (Biomedica, Slovakia) and Presage ST2 assay (Critical Diagnostics, USA), respectively. Results: Statistically significant direct correlations (p&lt;0.05). The simultaneous increase of ST2 and NT-proBNP serum levels above their threshold in patients with ACSelST (sensitivity – 92.5 %, specificity – 74.2 %, AUC – 0.893, р&lt;0.05) indicated a significant risk of cardiovascular (CV) complications of acute myocardial infarction (AMI) during the inpatient period, e.g. acute heart failure, acute LV aneurysm, recurrent AMI, as well as rhythm and conductivity disturbances. Conclusions: The data suggest that both ST2 and NT-proBNP may prove useful in predicting unfavorable prognosis during the inpatient care of AMI, as the simultaneous increase of these biomarkers above their threshold values indicates a significant risk of CV complications.

PROSPECTS OF MELDONIUM AND FOLIC ACID USING TO IMPROVE THE CONDITION OF PATIENTS WITH ISCHEMIC HEART DISEASE AND CONCOMITANT HYPERTENSION

Coronary heart disease (CHD) is a leading cause of high mortality, disability and reduced quality of life for patients. At the heart of coronary heart disease - ischemia and activation of oxidative stress. With concomitant hypertension, the condition of patients and the prognosis for the course of their disease deteriorates significantly. The prognosis of coronary heart disease, the occurrence of new hospitalizations or deaths from cardiovascular disease can be further assessed by monitoring ST2 and malonic dialdehyde (MDA). Traditional treatment of coronary heart disease does not always guarantee the achievement of the desired clinical results. That is why it is advisable to use in the complex treatment of patients with coronary heart disease and concomitant hypertension cytoprotectors and drugs that have antioxidant properties, such as meldonium and folic acid.&#x0D; The aim of the research. Detect anti-ischemic activity in meldonium and folic acid and evaluate the effect of these drugs on the level of ST2, MDA in the blood in patients with coronary heart disease and concomitant hypertension.&#x0D; Materials and methods. The research included 80 patients (women - 4, men - 76, aged 57,7 ± 9,8 years) with diagnoses of coronary heart disease: stable angina, functional class II-III (FC), chronic heart failure (CHF) I-IIa, FC II-III ", with concomitant arterial hypertension II-III stages, 2-3 degrees, risk 4 (very high), CHF I-IIa, FC II-III". Patients were divided into 4 groups of 20 patients, respectively: 1) patients who, in addition to basic therapy, were prescribed folic acid at a dose of 0.8 mg / d for six months; 2) patients who, in addition to basic treatment, were prescribed meldonium at a dose of 750.0 mg / d for six months; 3) patients who, in addition to basic treatment, were prescribed folic acid at a dose of 0.8 mg / d and meldonium at a dose of 750.0 mg / d for six months; 4) patients who were prescribed only basic antianginal, disaggregating, hypolipidemic treatment.The number of anginal attacks and doses of nitroglycerin during the day were determined, the results of the test with a 6-minute walk and the plasma concentration of ST2 and MDA before and after 6 months of treatment with meldonium and folic acid were evaluated.&#x0D; Results. Found anti-ischemic activity in meldonium and its combination with folic acid. The combination of these drugs as an adjunct to basic therapy significantly reduced the concentration of ST2. Both drugs alone or in combination reduced the concentration of MDA in the blood of patients.&#x0D; Conclusions. Our research showed the presence of anti-ischemic activity in meldonium, both when added to the basic therapy of patients with coronary heart disease and concomitant hypertension, and when used together with folic acid. In the groups of patients where these drugs and their combinations were used, the frequency of anginal attacks and the number of doses of nitroglycerin used during the day were significantly reduced.&#x0D; The combined use of folic acid and meldonium when added to the basic therapy after 6 months significantly reduced the concentration of ST2 in the blood. Folic acid and meldonium showed pronounced antioxidant properties. At separate adding of these medications to basic therapy or their combined adding significantly decreased the concentration of MDA - a marker of oxidative stress.&#x0D; Therefore, we consider it appropriate to use folic acid and meldonium in the complex treatment of patients with coronary heart disease with stable angina and concomitant hypertension.

Differences in maternal soluble ST2 levels in the third trimester of normal pregnancy versus preeclampsia.

BackgroundPreeclampsia is associated with intense inflammatory response in pregnancy, and soluble ST2 (sST2) is pathologically increased in this condition. No data exist regarding maternal sST2 levels in normal pregnancy versus preeclampsia in areas of southeast Asia with an ethnic Malay predominance.Materials and MethodsPatients were sorted into normal pregnancy or preeclampsia. Patients with a history of allergic, inflammatory, or malignant disease were excluded. One sample was taken per patient; all samples were taken during the third trimester of pregnancy. Thirty samples from each group were enrolled in the study, totaling 60 samples. Soluble ST2 levels in maternal plasma were measured using the Presage® ST2 Assay according to manufacturer instructions, and data was analyzed using SPSS 23.ResultsPatients in the preeclampsia group were significantly older than those in the normal pregnancy group (p = 0.01). Most patients with preeclampsia presented as early-onset (n = 23). Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly higher (p < 0.001) in the preeclampsia group. Mean sST2 level in the preeclampsia group (85.89 ng/ml) was significantly higher than the normal pregnancy group mean (38.3 ng/ml) during the third trimester (p < 0.001). This study also found a correlation between sST2 and preeclampsia (p < 0.001, r = 0.480), SBP (p < 0.001, r = 0.407), and DBP (p = 0.007, r = 0.342), while preeclampsia was found to be the best explanatory variable of sST2 levels (r = 0.468, p < 0.001). sST2 level> 63.66 ng/ml has sensitivity 50% and specificity 93.3%, with AUC of 0.78 [95% CI 0.66 – 0.90], p < 0.001. The sST2 > 63.66 ng/ml has an OR of 14.0 [95% CI 2.82 – 69.6], p < 0.001 for preeclampsia. The dose-response relationship between sST2 level and preeclampsia was linear.ConclusionSoluble ST2 levels were increased in both normal pregnancy and preeclampsia but were significantly higher in patients with preeclampsia. Preeclampsia was also found to be the best explanatory variable for the increase of sST2 levels in ethnic Malay predominance.

Early cardiopulmonary resuscitation on serum levels of myeloperoxidase, soluble ST2, and hypersensitive C-reactive protein in acute myocardial infarction patients.

BACKGROUNDPrompt and effective cardiopulmonary resuscitation (CPR) can promote the recovery of spontaneous circulation to some extent and can save patients’ lives. The minimum target of cardiac resuscitation is the restoration of spontaneous circulation (ROSC). However, owing to prolonged sudden cardiac arrest, there is relatively high mortality within 24 h after cardiac resuscitation. Moreover, severe cerebral anoxia can deteriorate the prognosis of patients. Therefore, it is important to adopt an effective clinical evaluation of acute myocardial infarct (AMI) patients’ prognosis after cardiac resuscitation for the purpose of prevention and management.AIMTo investigate early CPR effects on human myeloperoxidase (MPO), soluble ST2 (sST2), and hypersensitive C-reactive protein (hs-CRP) levels in AMI patients.METHODSIn total, 54 patients with cardiac arrest caused by AMI in our hospital were selected as the observation group, and 50 other patients with AMI were selected as the control group. The differences in serum levels of MPO, sST2, and hs-CRP between the observation group and the control group were tested, and the differences in the serum levels of MPO, sST2, and hs-CRP in ROSC and non-ROSC patients, and in patients who died and in those who survived, were analyzed.RESULTSSerum levels of MPO, sST2, hs-CRP, lactic acid, creatine kinase isoenzyme (CK-MB), and cardiac troponin I (cTnI) were significantly higher in the observation group than in the control group (P < 0.05). Serum levels of MPO, sST2, hs-CRP, lactic acid, CK-MB, and cTnI in the observation group were lower after CPR than before CPR (P < 0.05). In the observation group, MPO, sST2, hs-CRP, lactic acid, CK-MB, and cTnI serum levels were lower in ROSC patients than in non-ROSC patients (P < 0.05). MPO, sST2, hs-CRP, and lactic acid serum levels of patients who died in the observation group were higher than those of patients who survived (P < 0.05). The areas under receiver operating characteristic curve predicted by MPO, sST2, hs-CRP, lactic acid, CK-MB, and cTnI were 0.616, 0.681, 0.705, 0.704, 0.702, and 0.656, respectively (P < 0.05). The areas under receiver operating characteristic curve for MPO, SST2, hs-CRP, and lactic acid to predict death were 0.724, 0.800, 0.689, and 0.691, respectively (P < 0.05). Logistic regression analysis showed that MPO, sST2, and hs-CRP were the influencing factors of ROSC [odds ratios = 1.667, 1.589, and 1.409, P < 0.05], while MPO, sST2, hs-CRP, and lactic acid were the influencing factors of death (odds ratios = 1.624, 1.525, 1.451, and 1.365, P < 0.05).CONCLUSIONSerum levels of MPO, sST2, hs-CRP, and lactic acid have a certain value in predicting recovery and prognosis of patients with ROSC.

Abstract 10697: Both ST2 and BNP Predicts Atrial Fibrillation Independently of Heart Failure but BNP is Stronger When Used in Combination

Background: ST2, a novel marker of fibrosis in heart failure, may be a marker in Atrial fibrillation (AF) due to the role of fibrosis in AF. There is paucity of data suggesting the association of ST2 with AF. Hypothesis: To examine the association of ST2 with AF and its incremental value over traditional biomarkers. Methods: 619 unselected patients presenting to a Cardiology service had BNP and ST2 sent. They included patients with heart failure, acute coronary syndromes, elective cardioversion for AF and cardiac catheterisation. Results: Their characteristics are shown in Table1. Both ST2 and BNP levels were significantly higher in patients with heart failure, chronic kidney disease (CKD) and AF. The AF group (30%) were older and had higher prevalence of heart failure and CKD. Both ST2 and BNP were associated with AF in both univariable (Table 2) and multi-variable models, and remained independent predictors when adjusted for risk factors (Table 3 Model 2). However, ST2 loses significance when BNP is added to the model (Table 2 Model 3). While ST2 levels were significantly higher in males, there was no significant interaction when stratified by sex (interaction p=0.31). Conclusions: Both ST2 and BNP are independent predictors of AF even after adjustment for other clinical factors. When ST2 is used in combination with BNP, raised BNP appears to be a stronger predictor of AF than ST2.

Abstract 11416: The Prognostic Impact of Myocardial Fibrosis Biomarkers for Atrial Fibrillation in a Heart Failure Population

Introduction: Several studies suggest that circulating biomarkers of myocardial fibrosis are associated with worse prognosis of atrial fibrillation (AF). Hypothesis: Here, we aimed to evaluate the prognostic impact of myocardial fibrosis biomarkers for atrial fibrillation in a heart failure (HF) population Methods: Three-hundred-and-twenty-one patients hospitalized for HF (mean age 75 years; 32% women) were screened for co-existing AF and a proximity extension assay including estimation of 7 proteins associated with myocardial fibrosis; Metalloproteinase inhibitor 4 (TIMP-4), Soluble interleukin 1 receptor-like 1 (ST-2), Galectin 3 (Gal-3), Growth/differentiation factor 15 (GDF-15) and Matrix metalloproteinase 2, 3 and 9 (MMP-3, MMP-3 and MMP-9 respectively). Associations between AF and proteins were cross-sectionally studied in multivariable logistic regression models. Furthermore, associations between protein plasma levels, mortality and re-hospitalization risk were analyzed using multivariable Cox regression analysis adjusted for age sex, prevalent diabetes, smoking, body mass index (BMI), systolic blood pressure (SBP) and New York heart association classification (NYHA-class). Results: One-hundred-and-ninety-seven patients (61%) had prevalent AF at hospitalization. In multivariate logistic regression models, the prevalence of atrial fibrillation was significantly associated with increased plasma levels of TIMP-4, GDF-15, ST-2, MMP-2 and MMP-9. In the fully adjusted Cox regression model, increased plasma levels of 5 proteins yielded significant associations with mortality; TIMP4 (p=0,022 HR;1,46 CI95%1,06-2,01), GDF 15 (p=0,028; HR1,29; CI95% 1,03-1,63), Gal-3 (p=0,017; HR1,64;CI95% 1,09-2,47), ST2 (p=0,002; HR;1,43; CI95%1,14-1,80) and MMP3 (p=0,011; HR;1,29; CI95% 1,06-1,58). Further, increased levels of TIMP4 was significantly associated with rehospitalization (p=0,001; HR 1,58; C95% 1,19-2,08). Conclusions: We have demonstrated that increased plasma levels of plasma proteins related to myocardial fibrosis are associated with the risk of mortality in hospitalized HF patients, independently of traditional risk factors.

Prognosis value of serum soluble ST2 level in acute ischemic stroke and STEMI patients in the era of mechanical reperfusion therapy.

Soluble form suppression of tumorigenicity 2 (sST2) is known to have prognostic value in ST-elevation myocardial infarction (STEMI) and could impact mortality after acute ischemic stroke (AIS). However, before considering sST2 as a therapeutic target, the kinetics of release and its association with adverse clinical events in both STEMI and AIS patients have to be determined. We prospectively enrolled 251 STEMI patients, treated with primary percutaneous coronary intervention, and 152 AIS patients treated with mechanical thrombectomy. We evaluated the level of sST2 in patient sera at five time point (admission, 4, 24, 48h and 1month from admission for STEMI patients and admission, 6, 24, 48h and 3months from admission for AIS patients). Major adverse clinical events (MACE) (all-cause death, acute myocardial infarction, stroke or hospitalization for heart failure) in STEMI patients and all-cause death in AIS patients were recorded during a 12-month follow-up. Mean age of the study population was 59 ± 12 and 69 ± 15years in STEMI and AIS patients, respectively. In STEMI patients, sST2 peaked 24h after admission (25.5ng/mL interquartile range (IQR) [14.9-29.1]) whereas an earlier and lower peak was observed in AIS patients (16.8ng/mL IQR [15.2-18.3] at 6h). Twenty-five (10.0%) STEMI patients experienced a MACE and 12 (7.9%) AIS patients had all-cause death within the first 12months. A high level of sST2 at 24h was associated with MACE in STEMI patients (hazard ratio (HR) = 2.5; 95% confidence interval (CI) [1.1-5.6], p = 0.03) and all-cause death in AIS patients (HR = 11.7; 95% CI [3.8-36.2], p < 0.01) within the first 12months. The study highlights that sST2 levels at 24h are associated with an increased risk to adverse clinical events in both diseases.

Association macrophage subpopulation with cardiac biomarkers in patients with acute decompensated ischemic heart failure with reduced ejection fraction

Abstract Objective To determine the association macrophage subpopulation with cardiac biomarkers (interleukin (IL)-1β, IL-6, IL-10, highly sensitive C-reactive protein (hsCRP), tumor necrosis factor alpha (TNF-α), troponin I, interferon gamma (IFN-γ), plasma brain natriuretic peptide (BNP), and N-terminal fragment of precursor protein brain-type natriuretic peptide (NT-proBNP), soluble interleukin 1 receptor-like 1 (ST2)) in patients with acute decompensated ischemic heart failure with reduced ejection fraction. Methods This open-label, nonrandomized, single-center, prospective trial was registered at clinicaltrials.gov (#NCT02649517) and included 25 patients (84% men, LVEF of 29.17±9.4%) with ADHF. Inclusion criteria were ADHF, not earlier than 6 months after optimal surgery (PCI or/and CABG) and optimal drug treatment for ADHF according to ESC guidelines. Invasive coronary angiography was performed in all patients to exclude the progression of coronary atherosclerosis. All patients underwent endomyocardial biopsy (EMB) with immunohistochemically analysis for diagnostic myocarditis. Macrophage infiltration in the heart was assessed by double immunofluorescence. CD68 was a marker for the cells of the macrophage lineage, CD80 was considered as M1-like macrophage and CD163, CD206, stabilin-1 were as M2-like macrophage biomarkers. Each area was evaluated in 5 random fields. On admission serum levels of IL-1β, IL-6, IL-10, hsCRP, TNF-α, troponin I, IFN-γ, ST2, BNP, and NT-proBNP were measured using enzyme-linked immunosorbent assay (ELISA). The double immunofluorescence has not been performed in 4 patients. Results An association was found between CD68+/CD80+ macrophages and level of TNF-α (r=0.512, p=0.042) in all patient. After EMB, all patients were divided into 2 groups. Group 1 comprised 16 patients (64%) with myocarditis; group 2 comprised 9 patients (36%) without myocarditis. In group 1 the association was found between CD68+/CD80+ macrophages and the level of troponin I (r=0.874, p=0.05). Besides, the association was revealed CD68-/CD206+ macrophages with the level of hsCRP (r= - 0.755, p=0.03), and CD163-/CD206+ macrophages with the level of IL-6 (r=0.843, p=0,009) in group 1. CD68-/stabilin-1 macrophages were in direct correlation with level of NT-proBNP (r=0.790, p=0.02) and in inverse correlation with level of troponin I (r= - 0.711, p=0.05) in group 1. In group 2 the association was found between CD68-/CD206+ macrophages and the level of ST2 (r=0.0.537, p=0.037). Conclusion Our data suggest that many associations identified between M1-like macrophages (CD 68+/CD 80+), M2-like macrophages (CD68-/CD206+, CD163-/CD206+) and markers of inflammation (hsCRP, IL-6) and myocardial damage (NT-proBNP, troponin I) in patients with myocarditis. Whereas in patients without myocarditis, only the association of M2-like macrophages (CD68-/CD206+) with the ST2 level was revealed, probably due to the continuing unfavorable remodeling of the heart. Funding Acknowledgement Type of funding sources: None.

IL-33 receptor expression on myeloid and plasmacytoid dendritic cells after allergen challenge in patients with allergic rhinitis

The diversity of immune responses in allergic diseases is critically mediated by dendritic cells (DCs), including myeloid and plasmacytoid DCs. Allergen inhalation increased the release of IL-33 from patients with allergic rhinitis (AR), which affecting the downstream cells by binding to its receptor (ST2). However, the effects of inhaled allergens on the expression of ST2 by DCs and IL-33 on the function of mDCs are unknown. The levels of ST2+mDCs and ST2+pDCs in the blood from patients with AR and healthy subjects were examined using flow cytometry. Moreover, the patients were challenged using the allergens and the levels of ST2+mDCs and ST2+pDCs were investigated at different time points. We found that there were higher levels of ST2+ mDCs and ST2+ pDCs in patients with AR, and these levels were further increased 0.5 h after allergen inhalation. Additionally, the type 2 immune response was upregulated after challenge. IL-33 treatment increased the expression of ST2 on mDCs. Our study demonstrated that ST2 was upregulated on DCs after allergen inhalation and that mDCs responded directly to IL-33 through ST2, suggesting that the IL-33/ST2 axis might play an important role in the pathogenesis of allergic rhinitis by DCs.