title: Increased soluble ST2 predicts long-term mortality in patients with stable coronary artery disease: results from the Ludwigshafen risk and cardiovascular health study.
abstract: BACKGROUND
  Soluble suppression of tumorigenicity 2 (sST2) has emerged as a strong prognostic biomarker in patients with heart failure and myocardial infarction. The aim of this study was to evaluate the long-term prognostic value of sST2 in patients with stable coronary artery disease (CAD).
  
  
  METHODS
  sST2 plasma concentrations were measured in 1345 patients with stable CAD referred for coronary angiography at a single tertiary care center. The primary endpoint was all-cause mortality.
  
  
  RESULTS
  During a median follow-up time of 9.8 years, 477 (36%) patients died. The median sST2 plasma concentration at baseline was significantly higher among decedents than survivors (21.4 vs 18.5 ng/mL; P < 0.001). In multivariate Cox proportional hazards regression analysis, sST2 was an independent predictor of all-cause mortality (risk ratio 1.16 per 1-SD increase in log-transformed values; 95% CI 1.05-1.29; P = 0.004). In the same multivariate analysis, amino-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) were also independent predictors, whereas galectin-3 was not. Patients with sST2 in the highest quartile (>24.6 ng/mL) displayed a 2-fold increased risk of death in univariate analysis, which was attenuated but remained significant in a fully adjusted model (risk ratio 1.39; 95% CI 1.10-1.76; P = 0.006). Further analysis showed that the prognostic impact of sST2 was additive to NT-proBNP and hs-cTnT. Using a multibiomarker approach combining these 3 complementary makers, we demonstrated that patients with all 3 biomarkers in the highest quartiles had the poorest outcome.
  
  
  CONCLUSIONS
  In this cohort of patients with stable CAD, increased sST2 was an independent predictor of long-term all-cause mortality and provided complementary prognostic information to hs-cTnT and NT-proBNP.
authors.affiliation: Department of Laboratory Medicine, Konventhospital Barmherzige Brueder Linz, Linz, Austria;
authors.forename: Benjamin
authors.initials: B
authors.lastname: Dieplinger
authors.forename: Margot
authors.initials: M
authors.lastname: Egger
authors.forename: Meinhard
authors.initials: M
authors.lastname: Haltmayer
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.forename: Hubert
authors.initials: H
authors.lastname: Scharnagl
authors.forename: Guenther
authors.initials: G
authors.lastname: Silbernagel
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
authors.forename: Winfried
authors.initials: W
authors.lastname: Maerz
authors.forename: Thomas
authors.initials: T
authors.lastname: Mueller
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000401:mortality*; D005260:Female; 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; D011446:Prospective Studies; D020033:Protein Isoforms / Q000097:blood; D011956:Receptors, Cell Surface / Q000097:blood*; D020107:Troponin T / Q000097:blood
chemical_list: D015415:Biomarkers; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D010446:Peptide Fragments; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain