title: Characteristics of the novel interleukin family biomarker ST2 in patients with acute heart failure.
abstract: OBJECTIVE
  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).
  
  
  BACKGROUND
  ST2 signaling is involved in the process of cardiac fibrosis and hypertrophy.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Shafiq U
authors.initials: SU
authors.lastname: Rehman
authors.forename: Thomas
authors.initials: T
authors.lastname: Mueller
authors.forename: James L
authors.initials: JL
authors.lastname: Januzzi
mesh_terms: D000208:Acute Disease; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008297:Male; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D012720:Severity of Illness Index; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D015415:Biomarkers; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D011956:Receptors, Cell Surface; D017472:Receptors, Interleukin-1