ST2 in Emergency Department Patients With Noncardiac Dyspnea
ABSTRACT Serum levels of soluble ST2, a member of the interleukin-1 receptor family, predict mortality in emergency department (ED) patients with dyspnea secondary to acute heart failure and acute coronary syndrome. Elevated levels of ST2 have also been described in pulmonary disease, but it is unclear if these are associated with adverse outcomes. The hypothesis for this study was that elevated ST2 levels would be associated with 180-day mortality and 180-day return ED visits or hospital readmission in patients presenting to the ED with noncardiac causes of dyspnea.
This prospective observational cohort study enrolled a convenience sample of patients presenting to a single academic tertiary care ED with a chief complaint of dyspnea. Exclusion criteria included dyspnea due to chest wall trauma, airway obstruction, and known cardiac etiology (new onset heart failure, prior heart failure with current brain natriuretic peptide > 500 pg/mL, presumed ischemic chest pain, elevated troponin, electrocardiogram changes indicating myocardial infarction or ischemia, heart transplant). ST2 levels were measured at ED presentation and compared between those with and without adverse outcomes. Staff were blinded to ST2 levels. Differences between groups were assessed using the Mann-Whitney U test.
Of the 82 patients enrolled, 45 (55%) were female, 48 (59%) were African American, and 34 (42%) were hospitalized. The most frequent ED or hospital diagnosis was chronic obstructive pulmonary disease (COPD) or asthma, in 29 (35%) patients. At 180 days, 36 of 81 patients (44%) had return ED visits, 21 of 81 patients (26%) were readmitted, and five of 82 patients (6%) were deceased. Median ST2 level was 227 ng/mL in patients who died versus 32 ng/mL in those who survived (difference = 195 ng/mL, 95% confidence interval [CI] = 48 to 342 ng/mL, p = 0.006). Median ST2 level was 59 ng/mL in readmitted patients versus 31 ng/mL in nonreadmitted patients (difference = 28 ng/mL, 95% CI = -3 to 60 ng/mL, p = 0.036). Median ST2 levels were 41 ng/mL in patients with return ED visits versus 31 ng/mL in those without return visits (difference = 10 ng/mL, 95% CI = -10 to 20 ng/mL, p = 0.23).
Patients with noncardiac dyspnea who died or required readmission to the hospital within 180 days had higher levels of ST2 compared with nonadmitted survivors. Further research into ST2 as a prognostic tool in pathologic processes not involving the heart, such as pulmonary disease, is warranted.
SourceAvailable from: Ken Yanagisawa[Show abstract] [Hide abstract]
ABSTRACT: In the course of studying the ST2 gene, which was initially found to be expressed specifically at the G0/G1 transitional state in BALB/c-3T3 cells and was one of the primary response genes, we found another ST2-related mRNA, designated as ST2L, in serum-stimulated BALB/c-3T3 cells in the presence of cycloheximide. Nucleotide sequence analysis of the cloned ST2L cDNA revealed that it had an open reading frame encoding a polypeptide of 567 amino acids. A 5' region (1,028 nucleotides) of ST2L cDNA was identical with the ST2 cDNA, and a unique 3' region encoded a putative transmembrane domain of 24 amino acids and a cytoplasmic domain of 201 amino acids. The ST2 gene product is highly similar to the extracellular portion of IL-1 receptors type 1 and type 2, and the ST2L gene product shows a marked similarity with entire IL-1 receptor type 1.FEBS Letters 03/1993; 318(1):83-7. DOI:10.1016/0014-5793(93)81333-U · 3.34 Impact Factor
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ABSTRACT: 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.American Journal of Respiratory and Critical Care Medicine 08/2001; 164(2):277-81. DOI:10.1164/ajrccm.164.2.2008120 · 11.99 Impact Factor
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ABSTRACT: We identified an interleukin-1 receptor family member, ST2, as a gene markedly induced by mechanical strain in cardiac myocytes and hypothesized that ST2 participates in the acute myocardial response to stress and injury. ST2 mRNA was induced in cardiac myocytes by mechanical strain (4.7+/-0.9-fold) and interleukin-1beta (2.0+/-0.2-fold). Promoter analysis revealed that the proximal and not the distal promoter of ST2 is responsible for transcriptional activation in cardiac myocytes by strain and interleukin-1beta. In mice subjected to coronary artery ligation, serum ST2 was transiently increased compared with unoperated controls (20.8+/-4.4 versus 0.8+/-0.8 ng/mL, P<0.05). Soluble ST2 levels were increased in the serum of human patients (N=69) 1 day after myocardial infarction and correlated positively with creatine kinase (r=0.41, P<0.001) and negatively with ejection fraction (P=0.02). These data identify ST2 release in response to myocardial infarction and suggest a role for this innate immune receptor in myocardial injury.Circulation 01/2003; 106(23):2961-6. · 14.95 Impact Factor