title: Limited Added Value of Circulating Inflammatory Biomarkers in Chronic Heart Failure.
abstract: This study sought to evaluate whether a panel of biomarkers improved prognostication in patients with heart failure (HF) and reduced ejection fraction of ischemic origin using a systematized approach according to suggested requirements for validation of new biomarkers.
  
  
  
  Modeling combinations of multiple circulating markers could potentially identify patients with HF at particularly high risk and aid in the selection of individualized therapy.
  
  
  
  From a panel of 20 inflammatory and extracellular matrix biomarkers, 2 different biomarker panels were created and added to the Seattle HF score and the prognostic model from the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) study (n = 1,497), which included conventional clinical characteristics and C-reactive protein and N-terminal pro-B-type natriuretic peptide. Interactions with statin treatment were also assessed.
  
  
  
  The two models-model 1 (endostatin, interleukin 8, soluble ST2, troponin T, galectin 3, and chemokine [C-C motif] ligand 21) and model 2 (troponin T, soluble ST2, galectin 3, pentraxin 3, and soluble tumor necrosis factor receptor 2)-significantly improved the CORONA and Seattle HF models but added only modestly to their Harrell's C statistic and net reclassification index. In addition, rosuvastatin had no effect on the levels of a wide range of inflammatory and extracellular matrix markers, but there was a tendency for patients with a lower level of biomarkers in the 2 panels to have a positive effect from statin treatment.
  
  
  
  In the specific HF patient population studied, a multimarker approach using the particular panel of biomarkers measured was of limited clinical value for identifying future risk of adverse outcomes.
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway. Electronic address: snymo@rr-research.no.
authors.forename: Ståle H
authors.initials: SH
authors.lastname: Nymo
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: John
authors.initials: J
authors.lastname: Kjekshus
authors.affiliation: British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom.
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.affiliation: Castle Hill Hospital, Hull York Medical School, University of Hull, Kingston-upon-Hull, United Kingdom.
authors.forename: John G F
authors.initials: JG
authors.lastname: Cleland
authors.affiliation: Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: John
authors.initials: J
authors.lastname: Wikstrand
authors.affiliation: scPharmaceuticals, Lexington, Massachusetts.
authors.forename: Pieter
authors.initials: P
authors.lastname: Muntendam
authors.affiliation: Roche Diagnostics, Penzberg, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Wienhues-Thelen
authors.affiliation: Department of Cardiovascular Research, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Latini
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Erik Tandberg
authors.initials: ET
authors.lastname: Askevold
authors.affiliation: Department of Cardiology, Akershus University Hospital, Lørenskog, Norway.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Gravning
authors.affiliation: Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Christen P
authors.initials: CP
authors.lastname: Dahl
authors.affiliation: Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Kaspar
authors.initials: K
authors.lastname: Broch
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.affiliation: Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; K. G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway.
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
mesh_terms: D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000401:mortality*; D002423:Cause of Death; D054421:Chemokine CCL21 / Q000097:blood; D002908:Chronic Disease; D043169:Endostatins / Q000097:blood; D037502:Galectin 3 / Q000097:blood; D037161:Galectins; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007249:Inflammation; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D009026:Mortality; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011379:Prognosis; D016016:Proportional Hazards Models; D000068718:Rosuvastatin Calcium / Q000627:therapeutic use; D000683:Serum Amyloid P-Component / Q000378:metabolism; D020107:Troponin T / Q000097:blood; D000099153:Pentraxins
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D002097:C-Reactive Protein; D054421:Chemokine CCL21; D043169:Endostatins; D037502:Galectin 3; D037161:Galectins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000072179:Interleukin-1 Receptor-Like 1 Protein; D016209:Interleukin-8; D020097:Natriuretic Peptide, Brain; D010446:Peptide Fragments; D000068718:Rosuvastatin Calcium; D000683:Serum Amyloid P-Component; D020107:Troponin T; D000099153:Pentraxins; C515478:CCL21 protein, human; C508606:CXCL8 protein, human; C079241:IL1RL1 protein, human; C428445:LGALS3 protein, human; C109794:pro-brain natriuretic peptide (1-76)
keywords: biomarkers; chronic ischemic heart disease; heart failure; inflammation; mortality; survival