ST2 in Emergency Department Chest Pain Patients With Potential Acute Coronary Syndromes

University of California, San Diego, San Diego, California, United States
Annals of emergency medicine (Impact Factor: 4.68). 09/2007; 50(2):153-8, 158.e1. DOI: 10.1016/j.annemergmed.2007.02.015
Source: PubMed


The emergency department (ED) evaluation of potential acute coronary syndrome patients is limited by the initial sensitivity of cell injury biochemical markers. Increased ST2, a protein thought to participate in the response to cardiovascular injury, has been noted to be prognostic in patients with acute myocardial infarction. We hypothesize that ST2 would be increased at presentation in ED chest pain patients with myocardial ischemia, thus allowing for the early identification of acute myocardial infarction, acute coronary syndrome, and 30-day adverse cardiovascular events, with an area under the receiver operator characteristic curve (AUC) for each outcome of greater than 0.7.
Patients aged 25 years or older and presenting to the ED with chest pain prompting an ECG were prospectively enrolled. ST2 was measured at presentation. Main outcomes were acute myocardial infarction, acute coronary syndrome, and 30-day events (death, acute myocardial infarction, or revascularization). Median ST2 values were calculated for patients with and without each outcome. The AUCs were calculated for each outcome. In a post hoc analysis, patients with outlying increased ST2 values were examined to determine possible alternative causes for ST2 expression.
There were 348 patients enrolled. The outcomes were acute myocardial infarction 17 patients (4.9%), acute coronary syndrome 39 (11.2%), and 30-day events 23 (6.6%). The AUCs for acute myocardial infarction, acute coronary syndrome, and 30-day events were 0.636, 0.630, and 0.579, respectively. ST2 did not predict acute myocardial infarction, acute coronary syndrome, or 30-day events. It was increased in a small number of patients with pulmonary disease, notably, pulmonary emboli, systemic infection or inflammation, and alcohol abuse.
ST2 was not of value in the evaluation of ED patients with potential acute coronary syndrome.

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    • "By adjusting for CAD, HF, atrial fibrillation, diabetes, hypertension, obesity, valvular disease, LV systolic dysfunction, and pulmonary and renal dysfunction, the Framingham Heart Study showed that male sex (p < 0.0001) and old age (p = 0.004) were related to higher sST2 concentrations[61]. Nevertheless, the measurement of sST2 in 348 patients presenting to the emergency department with chest pain sST2 was found to be increased in those suffering from pulmonary disease (obstructive sleep apnea, chronic obstructive pulmonary disease, asthma, pulmonary embolism, and pulmonary hypertension), systemic infection or inflammation, and alcohol abuse[62]. "
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    ABSTRACT: Cardiovascular diseases (CVD) are the major cause of death worldwide. The identification of markers able to detect the early stages of such diseases and/or their progression is fundamental in order to adopt the best actions in order to reduce the worsening of clinical condition. Brain natriuretic peptide (BNP) and NT-proBNP are the best known markers of heart failure (HF), while troponins ameliorated the diagnosis of acute and chronic coronary artery diseases. Nevertheless, many limitations reduce their accuracy. Physicians have tried to develop further detectable molecules in order to improve the detection of the early moments of CVD and prevent their development. Soluble ST2 (suppression of tumorigenicity 2) is a blood protein confirmed to act as a decoy receptor for interleukin-33. It seems to be markedly induced in mechanically overloaded cardiac myocytes. Thus, HF onset or worsening of a previous chronic HF status, myocardial infarct able to induce scars that make the myocardium unable to stretch well, etc, are all conditions that could be detected by measuring blood levels of soluble ST2. The aim of this review is to explore the possible role of ST2 derived-protein as an early marker of cardiovascular diseases, above all in heart failure and ischemic heart diseases.
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    ABSTRACT: Asthma is a chronic disease characterised by variable airflow obstruction, bronchial hyperresponsiveness and airways inflammation. At an immunological level Th2 inflammation and the presence of activated eosinophils and mast cells are key features of asthma. ST2, the receptor for the novel cytokine IL-33, is expressed upon Th2 lymphocytes and mast cells but its role in clinical and experimental asthma remains unclear. IL-33 has been shown to induce local and systemic eosinophilia when administered to the peritoneum of mice. In this thesis I have set out to test the hypothesis that the activation of mast cells by IL-33 acting on cell surface ST2 plays a critical role in allergic airways inflammation. I began by studying the function of ST2 on mast cells in vitro. I found that ST2 was expressed at an early stage of development, and correlated closely with the expression of the stem cell factor receptor (c-kit), a marker present on mast cells from a progenitor stage. Despite this mast cells generated form ST2 gene deleted mice proliferated and matured normally. When mast cells were activated by IL-33, acting in an ST2-dependent manner, pro-inflammatory cytokines and chemokines were released that have potential roles in asthma, specifically IL-6, IL-13, MIP-1α and MCP-1. To extend these findings I looked at the role of ST2 in allergic airways inflammation. I first optimised and validated an ovalbumin and adjuvant based ‘short’ twelve day model of murine asthma and demonstrated that ST2 gene deletion results in attenuated eosinophilic inflammation. In addition to being ST2 dependent it is possible that this adjuvant based short model is mast cell dependent, unlike longer adjuvant based models which are mast cell and ST2 independent. Therefore I went on to study an adjuvant-free model of asthma which has been demonstrated to be mast cell dependent. In this adjuvant-free model of asthma the airway inflammation was attenuated in ST2 gene deficient mice compared with wild type mice, while AHR was unaffected. There was an associated reduction in IgE production and thoracic lymph node recall Th2 cytokine responses. I then examined the effect of ST2 activation in the lungs. When IL-33 was administered directly to the airways of naïve mice it induced the features of experimental asthma. There was extensive eosinophilic inflammation within the lung tissue and airspaces. The Th2 cytokines IL-5 and IL-13, and the eosinophil chemoattractant chemokines eotaxin-1 and eotaxin-2 were detected at increased concentrations. Significant airways hyperresponsiveness was also generated. Using ST2 gene deleted mice I demonstrated that these effects were ST2 specific. Although I have shown that mast cells are activated by IL-33 in vitro, I used mast cell deficient mice to demonstrate that the eosinophilic inflammation generated by IL-33 is unaffected by the absence of mast cells. These data show that IL-33 can induce in the lungs the cardinal pathological characteristics of asthma, and that it appears to act upstream of other important mediators such as IL-13 and the eotaxins. Furthermore the IL-33 receptor ST2 is required in an adjuvant free model of asthma, which is more akin to human disease. Placing these findings in the context of recent evidence that IL-33 is released by structural cells in response to damage or injury suggests that IL-33 may play a key role in initiating the immunological features of clinical asthma. As a consequence of this position in the hierarchy of inflammation IL-33 offers a promising direct target for novel biological therapies in asthma.
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    ABSTRACT: We evaluated the association between ST2 concentrations and mortality at 1 year in 231 acutely dyspneic patients with pulmonary diseases seen in the emergency department. Blood concentrations of ST2 were ascertained; using 1-year survival as the reference standard, receiver operating characteristic curves with resultant area under the curve (AUC) were measured. Cox proportional hazards models identified independent predictors of 1-year death. Hazard curves compared rates of death as a function of ST2 concentration. Concentrations of ST2 were significantly higher in patients with pulmonary diseases compared with 153 subjects without cardiopulmonary disease (0.23 vs 0.11 ng/mL; P = .01). Among patients with pulmonary diseases, concentrations of ST2 were higher among decedents compared with survivors (1.14 ng/mL vs 0.19 ng/mL; P < .001). ST2 had an AUC of 0.72 as a predictor of death (P < .0001). An ST2 of 0.20 ng/mL had a hazard ratio for death of 6.1 (95% confidence interval, 1.8-21.0; P = .004). Compared with patients with lower ST2 concentrations, mortality rates for patients with an enrollment ST2 of 0.20 ng/mL or more diverged early and rose progressively in 1 year (P < .001). ST2 concentrations are frequently elevated in acute pulmonary diseases and are markedly prognostic for death by 1 year.
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