title: Biomarkers and Coronary Lesions Predict Outcomes after Revascularization in Non-ST-Elevation Acute Coronary Syndrome.
abstract: BACKGROUND
  Risk stratification in non-ST-elevation acute coronary syndrome (NSTE-ACS) is currently mainly based on clinical characteristics. With routine invasive management, angiography findings and biomarkers are available and may improve prognostication. We aimed to assess if adding biomarkers [high-sensitivity cardiac troponin T (cTnT-hs), N-terminal probrain-type natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15)] and extent of coronary artery disease (CAD) might improve prognostication in revascularized patients with NSTE-ACS.
  
  
  METHODS
  In the PLATO (Platelet Inhibition and Patient Outcomes) trial, 5174 NSTE-ACS patients underwent initial angiography and revascularization and had cTnT-hs, NT-proBNP, and GDF-15 measured. Cox models were developed adding extent of CAD and biomarker levels to established clinical risk variables for the composite of cardiovascular death (CVD)/spontaneous myocardial infarction (MI), and CVD alone. Models were compared using c-statistic and net reclassification improvement (NRI).
  
  
  RESULTS
  For the composite end point and CVD, prognostication improved when adding extent of CAD, NT-proBNP, and GDF-15 to clinical variables (c-statistic 0.685 and 0.805, respectively, for full model vs 0.649 and 0.760 for clinical model). cTnT-hs did not contribute to prognostication. In the full model (clinical variables, extent of CAD, all biomarkers), hazard ratios (95% CI) per standard deviation increase were for cTnT-hs 0.93(0.81-1.05), NT-proBNP 1.32(1.13-1.53), GDF-15 1.20(1.07-1.36) for the composite end point, driven by prediction of CVD by NT-proBNP and GDF-15. For spontaneous MI, there was an association with NT-proBNP or GDF-15, but not with cTnT-hs.
  
  
  CONCLUSIONS
  In revascularized patients with NSTE-ACS, the extent of CAD and concentrations of NT-proBNP and GDF-15 independently improve prognostication of CVD/spontaneous MI and CVD alone. This information may be useful for selection of patients who might benefit from more intense and/or prolonged antithrombotic treatment. ClinicalTrials.gov Identifier: NCT00391872.
authors.affiliation: Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; daniel.lindholm@ucr.uu.se.|Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lindholm
authors.affiliation: Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.|Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Stefan K
authors.initials: SK
authors.lastname: James
authors.affiliation: Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Bertilsson
authors.affiliation: Division of Cardiovascular Health and Disease, Heart, Lung and Vascular Institute, Academic Health Center, Cincinnati, OH.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital and Harvard Clinical Research Institute, Boston, MA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.affiliation: Department of Internal Medicine III, Cardiology, University Hospital Heidelberg, Germany.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Giannitsis
authors.affiliation: Department of Medicine, Stanford University, Stanford, CA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.affiliation: AstraZeneca Research and Development, Mölndal, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Himmelmann
authors.affiliation: Department of Cardiology, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Frederic
authors.initials: F
authors.lastname: Kontny
authors.affiliation: Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.|Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.
authors.forename: Agneta
authors.initials: A
authors.lastname: Siegbahn
authors.affiliation: INSERM-Unité 1148, Paris, France.|Assistance Publique-Hôpitaux de Paris; Département Hospitalo-Universitaire FIRE, Hôpital Bichat, Paris, France.|Université Paris-Diderot, Sorbonne-Paris Cité, Paris, France.|NHLI Imperial College, ICMS, Royal Brompton Hospital, London, UK.
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
authors.affiliation: Department of Cardiovascular Science, University of Sheffield, Sheffield, UK.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.affiliation: Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.|Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Matthijs A
authors.initials: MA
authors.lastname: Velders
authors.affiliation: Henry Ford Heart and Vascular Institute, Detroit, MI.
authors.forename: W Douglas
authors.initials: WD
authors.lastname: Weaver
authors.affiliation: Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.|Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000175:diagnosis / Q000628:therapy*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects; D017023:Coronary Angiography; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D009204:Myocardial Revascularization; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D018570:Risk Assessment; D016896:Treatment Outcome; D020107:Troponin T / Q000097:blood*
chemical_list: D015415:Biomarkers; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D010446:Peptide Fragments; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain