title: PAPP-A and IGFBP-4 fragment levels in patients with ST-elevation myocardial infarction treated with heparin and PCI.
abstract: OBJECTIVE
  Circulating levels of pregnancy-associated plasma protein-A (PAPP-A) predict outcome in patients with acute coronary syndrome (ACS). Unfortunately, administration of heparin to patients with ACS increases circulating PAPP-A, probably by a detachment of PAPP-A from cell surfaces, inducing a considerable bias when using PAPP-A as a biomarker. It remains unknown whether PAPP-A-derived N- and C-terminal fragments of insulin-like growth factor binding protein-4 (NT-IGFBP-4/CT-IGFBP-4) are acutely affected by the increase in PAPP-A.
  
  
  METHODS
  We prospectively included 78 patients with ST-segment elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI). Prior to PCI, patients were injected with 10,000IU of unfractionated heparin (UFH). Blood samples were collected immediately before PCI, but after UFH-injection, immediately after PCI and on day 1 and day 2. Plasma IGFBP-4, CT-IGFBP-4 and NT-IGFBP-4 levels were determined by specific, novel immunoassays, and PAPP-A and IGF-I by commercial immunoassays.
  
  
  RESULTS
  Plasma PAPP-A was strongly elevated upon STEMI, UFH-administration and PCI with mean concentrations (95%-confidence interval) pre-PCI, post-PCI, day 1, and day 2 of 13.0 (11.2;15.2), 14.8 (13.1;16.8), 1.03 (0.90;1.18), and 1.08 (0.92;1.28) μg/L, respectively (p<0.0001). Pre-PCI concentrations of IGFBP-4, CT-IGFBP-4 and NT-IGFBP-4 were 154 (142;166), 53 (47;60) and 136 (122;150) μg/L, and levels were unaltered post-PCI. Concentrations increased on day 1 by 63 (43;87)%, 69 (36;110)%, and 47 (21;79)%, respectively (p<0.0001), i.e. at a time point when PAPP-A levels had normalized.
  
  
  CONCLUSIONS
  Plasma IGFBP-4-fragment levels are not acutely altered in patients with STEMI treated with UFH and PCI. Thus, they possess potentials as prognostic markers in ACS patients.
authors.affiliation: Medical Research Laboratory, Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark; The Danish Diabetes Academy, Odense, Denmark. Electronic address: rikke.hjortebjerg@clin.au.dk.
authors.forename: Rikke
authors.initials: R
authors.lastname: Hjortebjerg
authors.affiliation: Department of Cardiology P, Gentofte University Hospital, Copenhagen, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Lindberg
authors.affiliation: Department of Cardiology P, Gentofte University Hospital, Copenhagen, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Hoffmann
authors.affiliation: Department of Cardiology P, Gentofte University Hospital, Copenhagen, Denmark; Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jan S
authors.initials: JS
authors.lastname: Jensen
authors.affiliation: Department of Molecular Biology and Genetics, Faculty of Science and Technology, Aarhus University, Aarhus, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Oxvig
authors.affiliation: Medical Research Laboratory, Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Bjerre
authors.affiliation: Medical Research Laboratory, Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D005260:Female; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis / Q000628:therapy*; D062645:Percutaneous Coronary Intervention / Q000639:trends; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D018974:Insulin-Like Growth Factor Binding Protein 4; D006493:Heparin; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human
keywords: Acute coronary syndrome (ACS); Biomarker; Cardiovascular disease; Heparin; IGF binding protein-4 (IGFBP-4); IGFBP-4 fragment; Insulin-like growth factor (IGF); Pregnancy-associated plasma protein-A (PAPP-A); ST-segment elevation myocardial infarction (STEMI)