title: High-sensitivity ST2 for prediction of adverse outcomes in chronic heart failure.
abstract: BACKGROUND
  Soluble ST2 reflects activity of an interleukin-33-dependent cardioprotective signaling axis and is a diagnostic and prognostic marker in acute heart failure. The use of ST2 in chronic heart failure has not been well defined. Our objective was to determine whether plasma ST2 levels predict adverse outcomes in chronic heart failure in the context of current approaches.
  
  
  RESULTS
  We determined the association between ST2 level and risk of death or transplantation in a multicenter, prospective cohort of 1141 chronic heart failure outpatients. Adjusted Cox models, receiver operating characteristic analyses, and risk reclassification metrics were used to assess the value of ST2 in predicting risk beyond currently used factors. After a median of 2.8 years, 267 patients (23%) died or underwent heart transplantation. Patients in the highest ST2 tertile (ST2 >36.3 ng/mL) had a markedly increased risk of adverse outcomes compared with the lowest tertile (ST2 ≤22.3 ng/mL), with an unadjusted hazard ratio of 3.2 (95% confidence interval [CI], 2.2 to 4.7; P<0.0001) that remained significant after multivariable adjustment (adjusted hazard ratio, 1.9; 95% CI, 1.3 to 2.9; P=0.002). In receiver operating characteristic analyses, the area under the curve for ST2 was 0.75 (95% CI, 0.69 to 0.79), which was similar to N-terminal pro-B-type natriuretic peptide (NT-proBNP) (area under the curve, 0.77; 95% CI, 0.72 to 0.81; P=0.24 versus ST2) but lower than the Seattle Heart Failure Model (area under the curve, 0.81 (95% CI, 0.77 to 0.85; P=0.014 versus ST2). Addition of ST2 and NT-proBNP to the Seattle Heart Failure Model reclassified 14.9% of patients into more appropriate risk categories (P=0.017).
  
  
  CONCLUSIONS
  ST2 is a potent marker of risk in chronic heart failure and when used in combination with NT-proBNP offers moderate improvement in assessing prognosis beyond clinical risk scores.
authors.affiliation: Penn Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. bonnie.ky@uphs.upenn.edu
authors.forename: Bonnie
authors.initials: B
authors.lastname: Ky
authors.forename: Benjamin
authors.initials: B
authors.lastname: French
authors.forename: Kristin
authors.initials: K
authors.lastname: McCloskey
authors.forename: J Eduardo
authors.initials: JE
authors.lastname: Rame
authors.forename: Erin
authors.initials: E
authors.lastname: McIntosh
authors.forename: Puja
authors.initials: P
authors.lastname: Shahi
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Dries
authors.forename: W H Wilson
authors.initials: WH
authors.lastname: Tang
authors.forename: Alan H B
authors.initials: AH
authors.lastname: Wu
authors.forename: James C
authors.initials: JC
authors.lastname: Fang
authors.forename: Rebecca
authors.initials: R
authors.lastname: Boxer
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Sweitzer
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Levy
authors.forename: Lee R
authors.initials: LR
authors.lastname: Goldberg
authors.forename: Mariell
authors.initials: M
authors.lastname: Jessup
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Cappola
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D002908:Chronic Disease; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000401:mortality / Q000601:surgery; D016027:Heart Transplantation; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D011956:Receptors, Cell Surface / Q000097:blood*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014481:United States
chemical_list: D015415:Biomarkers; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain