title: Clinical differences between total PAPP-A and measurements specific for the products of free PAPP-A activity in patients with stable cardiovascular disease.
abstract: OBJECTIVE
  We have previously reported that increases in total pregnancy-associated plasma protein-A (PAPP-A) which are thought to be indicative of vulnerable plaques and thus poor outcomes predict outcomes in patients with stable coronary artery disease. We hypothesized that the determination of CT- and NT-fragments of insulin-like growth factor binding protein 4 (CT- and NT-IGFBP4) which should be indicative of free PAPP-A would result in better performance.
  
  
  METHODS
  In 229 stable cardiovascular patients with indication for heart catheterization after performance of a stress test and an echocardiogram, CT- and NT-IGFBP4 were measured. Their values were investigated in relation to clinical characteristics, findings of noninvasive investigations, laboratory data and coronary angiography as well as to outcomes after a follow-up of 1094±307days.
  
  
  RESULTS
  CT-IGFBP4 values were independently predicted by patients with B-type (p=0.0069) or complex coronary lesions (p=0.0445). B-type and vulnerable coronary lesions were independently predicted by levels of CT-IGFBP4≥a cutoff of 31.55ng/mL derived from ROC analysis (p=0.0090 and 0.0480). NT-IGFBP4 was not predictive of coronary characteristics. Both IGFBP4 fragments were strongly dependent on age and renal function and were not predictive of outcomes.
  
  
  CONCLUSIONS
  Despite the relation of CT-IGFBP4 to a more severe coronary artery disease, CT- and NT-IGFBP4, in contrast to our report based on total PAPP-A, failed to predict any long-term outcomes in patients with stable cardiovascular disease. Further knowledge about the interaction of the PAPP-A-insulin-like growth factor system is needed to explain values of IGFBP4 fragments in these patients.
authors.affiliation: Interventionelle Kardiologie Spandau, Berlin, Germany; Universitätsmedizin Berlin, Charite Campus Mitte, Berlin, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Schulz
authors.affiliation: HyTest Ltd., Intelligate 6th floor, Joukahaisenkatu 6, 20520 Turku, Finland.
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Postnikov
authors.affiliation: HyTest Ltd., Intelligate 6th floor, Joukahaisenkatu 6, 20520 Turku, Finland.
authors.forename: Tatiana I
authors.initials: TI
authors.lastname: Smolyanova
authors.affiliation: HyTest Ltd., Intelligate 6th floor, Joukahaisenkatu 6, 20520 Turku, Finland.
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Katrukha
authors.affiliation: Universitätsmedizin Berlin, Charite Campus Mitte, Berlin, Germany.
authors.forename: Ingolf
authors.initials: I
authors.lastname: Schimke
authors.affiliation: Mayo Clinic and Medical School, Rochester, MN, USA. Electronic address: jaffe.allan@mayo.edu.
authors.forename: Allan S
authors.initials: AS
authors.lastname: Jaffe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*
chemical_list: D018974:Insulin-Like Growth Factor Binding Protein 4; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human
keywords: IGF fragments; PAPP-A