title: Role of ST2 in non-ST-elevation acute coronary syndrome in the MERLIN-TIMI 36 trial.
abstract: OBJECTIVE
  We investigated the prognostic performance of ST2 with respect to cardiovascular death (CVD) and heart failure (HF) in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) in a large multinational trial.
  
  
  BACKGROUND
  Myocytes that are subjected to mechanical stress secrete ST2, a soluble interleukin-1 receptor family member that is associated with HF after STE-ACS.
  
  
  METHODS
  We measured ST2 with a high-sensitivity assay in all available baseline samples (N=4426) in patients enrolled in the Metabolic Efficiency With Ranolazine for Less Ischemia in the Non-ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36), a placebo-controlled trial of ranolazine in NSTE-ACS. All events, including cardiovascular death and new or worsening HF, were adjudicated by an independent events committee.
  
  
  RESULTS
  Patients with ST2 concentrations in the top quartile (>35 μg/L) were more likely to be older and male and have diabetes and renal dysfunction. ST2 was only weakly correlated with troponin and B-type natriuretic peptide. High ST2 was associated with increased risk for CVD/HF at 30 days (6.6% vs 1.6%, P<0.0001) and 1 year (12.2% vs 5.2%, P<0.0001). The risk associated with ST2 was significant after adjustment for clinical covariates and biomarkers (adjusted hazard ratio CVD/HF 1.90, 95% CI 1.15-3.13 at 30 days, P=0.012; 1.51, 95% CI 1.15-1.98 at 1 year, P=0.003), with a significant integrated discrimination improvement (P<0.0001). No significant interaction was found between ST2 and ranolazine (Pinteraction=0.15).
  
  
  CONCLUSIONS
  ST2 correlates weakly with biomarkers of acute injury and hemodynamic stress but is strongly associated with the risk of HF after NSTE-ACS. This biomarker and related pathway merit further investigation as potential therapeutic targets for patients with ACS at risk for cardiac remodeling.
authors.affiliation: TIMI Study Group, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. pkohli@partners.org
authors.forename: Payal
authors.initials: P
authors.lastname: Kohli
authors.forename: Marc P
authors.initials: MP
authors.lastname: Bonaca
authors.forename: Rahul
authors.initials: R
authors.lastname: Kakkar
authors.forename: Anastacia Y
authors.initials: AY
authors.lastname: Kudinova
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Scirica
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Murphy
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.forename: Richard T
authors.initials: RT
authors.lastname: Lee
authors.forename: David A
authors.initials: DA
authors.lastname: Morrow
mesh_terms: D000083:Acetanilides / Q000627:therapeutic use; D054058:Acute Coronary Syndrome / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000401:mortality; D004562:Electrocardiography; D005260:Female; D006333:Heart Failure / Q000175:diagnosis; D006439:Hemodynamics; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000378:metabolism; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010879:Piperazines / Q000627:therapeutic use; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D000069458:Ranolazine; D011956:Receptors, Cell Surface / Q000097:blood*; D018570:Risk Assessment
chemical_list: D000083:Acetanilides; D015415:Biomarkers; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D010879:Piperazines; D011956:Receptors, Cell Surface; D020097:Natriuretic Peptide, Brain; D000069458:Ranolazine
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