title: Interleukin 33 and ST2 in non-ST-elevation myocardial infarction: comparison with Global Registry of Acute Coronary Events Risk Scoring and NT-proBNP.
abstract: BACKGROUND
  Soluble ST2 is a marker of biomechanical strain for which the natural ligand is interleukin 33 (IL-33). They have not been studied together in non-ST-elevation myocardial infarction (NSTEMI). We investigated their relationship with death, heart failure (HF) readmission, and reinfarction combined (termed major adverse cardiac events [MACE]) and, separately, in unselected patients using Global Registry of Acute Coronary Events Risk Scoring (GRACE-RS) and n terminal pro B type natriuretic peptide (NT-proBNP) as benchmark comparators.
  
  
  METHODS
  ST2 and IL-33 were measured in 577 patients 3 to 5 days after admission. Mean follow-up was 532 (150-1059) days, during which 156 patients (27%) reached the primary end point.
  
  
  RESULTS
  ST2 was higher in those who experienced MACE when compared with event-free survivors (median 782 pg/mL vs 596, P < .001), but there was no difference in IL-33 levels across any end point. Multivariate Cox regression analysis reveals that elevated ST2 is independently associated with increased risk of MACE during the long term (hazard ratio [HR] 2.01, P = .005). This relationship continues on further adjustment for either GRACE risk score or NT-proBNP individually but not on adjustment for both. ST2 also independently predicts reinfarction (HR 2.48, P = .03) and 30-day mortality (HR 4.43, P = .02, c-statistic 0.73, P < .001). Adding ST2 to GRACE or to NT-proBNP did not lead to significant improvements in the c-statistic for MACE for long-term follow-up (P = .27 and P = .57, respectively) or the net reclassification index. Neither IL-33 nor its ratio with ST2 was associated with study end points.
  
  
  CONCLUSIONS
  Elevated ST2 predicts adverse outcome in non-ST-elevation myocardial infarction but does not significantly improve risk stratification for established markers. Interleukin 33 was not related to adverse events.
authors.affiliation: Department of Cardiovascular Sciences and NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, University of Leicester, Leicester, UK. dhillonos@hotmail.com
authors.forename: Onkar S
authors.initials: OS
authors.lastname: Dhillon
authors.forename: Hafid K
authors.initials: HK
authors.lastname: Narayan
authors.forename: Paulene A
authors.initials: PA
authors.lastname: Quinn
authors.forename: Iain B
authors.initials: IB
authors.lastname: Squire
authors.forename: Joan E
authors.initials: JE
authors.lastname: Davies
authors.forename: Leong L
authors.initials: LL
authors.lastname: Ng
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000209:etiology; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000097:blood*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000097:blood* / Q000150:complications / Q000401:mortality; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011379:Prognosis; D012372:ROC Curve; D011956:Receptors, Cell Surface / Q000097:blood*; D018570:Risk Assessment
chemical_list: D015415:Biomarkers; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain