title: Prognostic significance of biomarkers in predicting outcome in patients with coronary artery disease and left ventricular dysfunction: results of the biomarker substudy of the Surgical Treatment for Ischemic Heart Failure trials.
abstract: BACKGROUND
  Patients with heart failure and coronary artery disease often undergo coronary artery bypass grafting, but assessment of the risk of an adverse outcome in these patients is difficult. To evaluate the ability of biomarkers to contribute independent prognostic information in these patients, we measured levels in patients enrolled in the biomarker substudies of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Patients in STICH Hypothesis 1 were randomized to medical therapy or coronary artery bypass grafting, whereas those in STICH Hypothesis 2 were randomized to coronary artery bypass grafting or coronary artery bypass grafting with left ventricular reconstruction.
  
  
  RESULTS
  In substudy patients assigned to STICH Hypothesis 1 (n=606), plasma levels of soluble tumor necrosis factor-α receptor-1 (sTNFR-1) and brain natriuretic peptide (BNP) were highly predictive of the primary outcome variable of mortality by univariate analysis (BNP: χ(2)=40.6; P<0.0001 and sTNFR-1: χ(2)=38.9; P<0.0001). When considered in the context of multivariable analysis, both BNP and sTNFR-1 contributed independent prognostic information beyond the information provided by a large array of clinical factors independent of treatment assignment. Consistent results were seen when assessing the predictive value of BNP and sTNFR-1 in patients assigned to STICH Hypothesis 2 (n=626). Both plasma levels of BNP (χ(2)=30.3) and sTNFR-1 (χ(2)=45.5) were highly predictive in univariate analysis (P<0.0001) and in multivariable analysis for the primary end point of death or cardiac hospitalization. In multivariable analysis, the prognostic information contributed by BNP (χ(2)=6.0; P=0.049) and sTNFR-1 (χ(2)=8.8; P=0.003) remained statistically significant even after accounting for other clinical information. Although the biomarkers added little discriminatory improvement to the clinical factors (increase in c-index ≤0.1), net reclassification improvement for the primary end points was 0.29 for BNP and 0.21 for sTNFR-1 in the Hypothesis 1 cohort, and 0.15 for BNP and 0.30 for sTNFR-1 in the Hypothesis 2 cohort, reflecting important predictive improvement.
  
  
  CONCLUSIONS
  Elevated levels of sTNFR-1 and BNP are strongly associated with outcomes, independent of therapy, in 2 large and independent studies, thus providing important cross-validation for the prognostic importance of these 2 biomarkers.
authors.affiliation: Department of Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA. Arthur.feldman@temple.edu
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Feldman
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Mann
authors.forename: Lilin
authors.initials: L
authors.lastname: She
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bristow
authors.forename: Alan S
authors.initials: AS
authors.lastname: Maisel
authors.forename: Dennis M
authors.initials: DM
authors.lastname: McNamara
authors.forename: Ryan
authors.initials: R
authors.lastname: Walsh
authors.forename: Dorellyn L
authors.initials: DL
authors.lastname: Lee
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Wos
authors.forename: Irene
authors.initials: I
authors.lastname: Lang
authors.forename: Gretchen
authors.initials: G
authors.lastname: Wells
authors.forename: Mark H
authors.initials: MH
authors.lastname: Drazner
authors.forename: John F
authors.initials: JF
authors.lastname: Schmedtje
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Pauly
authors.forename: Carla A
authors.initials: CA
authors.lastname: Sueta
authors.forename: Michael
authors.initials: M
authors.lastname: Di Maio
authors.forename: Irving L
authors.initials: IL
authors.lastname: Kron
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Velazquez
authors.forename: Kerry L
authors.initials: KL
authors.lastname: Lee
mesh_terms: D015415:Biomarkers / Q000097:blood*; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000097:blood* / Q000401:mortality*; D006801:Humans; D015999:Multivariate Analysis; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D017063:Outcome Assessment, Health Care; D011379:Prognosis; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000097:blood*
chemical_list: D015415:Biomarkers; D047888:Receptors, Tumor Necrosis Factor, Type I; D020097:Natriuretic Peptide, Brain
keywords: bypass graft; cardiovascular disease; heart failure