title: Temporal course of pregnancy-associated plasma protein-A in angioplasty-treated ST-elevation myocardial infarction patients and potential significance of concomitant heparin administration.
abstract: Pregnancy-associated plasma protein-A (PAPP-A) is a putative plaque instability marker. In acute coronary syndromes, the disrupted culprit plaque contains abundant PAPP-A, and circulating PAPP-A levels predict clinical outcomes. Determinants of circulating PAPP-A levels, however, are not fully understood, and the potential role of concomitant heparin administration has not previously been evaluated. The purposes of the present study were to evaluate in-hospital levels of PAPP-A compared with other circulating biomarkers in patients with acute myocardial infarctions and to explore the potential impact of concomitant heparin administration on PAPP-A levels in an animal experiment. Group A comprised 84 patients with ST elevation myocardial infarctions (STEMIs) who were treated with heparin and transferred for primary percutaneous coronary intervention. Plasma samples were obtained at the time of primary percutaneous coronary intervention, twice within the next 24 hours, and subsequently daily during hospitalization. Levels of PAPP-A, troponin T, soluble cluster of differentiation 163, N-terminal-pro-brain natriuretic peptide, and high-sensitivity C-reactive protein were determined. PAPP-A levels were also determined in 2 historical cohorts not given heparin: 14 patients with STEMIs (group B) and 56 patients with non-ST elevation myocardial infarctions (group C). The impact of concomitant heparin administration on the clearance of PAPP-A from the circulation was also explored in mice. In group A, PAPP-A levels were increased in the initial plasma sample in 95% of patients presenting within 3 hours of symptom onset, whereas increased levels of troponin T, soluble cluster of differentiation 163, N-terminal-pro-brain natriuretic peptide, and high-sensitivity C-reactive protein were detectable in 45%, 15%, 50%, and 35% of patients, respectively. Compared with group A, lower levels of PAPP-A were observed in the initial plasma samples drawn in groups B (p = 0.07) and C (p <0.001) not given heparin. In the animal experiment, concomitant heparin administration resulted in increased levels of PAPP-A and delayed clearance of PAPP-A from the circulation. In conclusion, PAPP-A is markedly elevated in the earliest hours after the onset of symptoms in patients with STEMIs treated with heparin and primary percutaneous coronary intervention, and in animal studies, heparin administration is associated with a significant increase in PAPP-A levels, presumably because of the detachment of PAPP-A from the vessel wall. If future studies confirm that concomitant heparin administration also increases PAPP-A levels in humans, the prognostic role of PAPP-A in patients with STEMIs needs to be reevaluated.
authors.affiliation: Department of Cardiology B, Aarhus University Hospital, Denmark. christian_juhl_terkelsen@hotmail.com
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Terkelsen
authors.forename: Claus
authors.initials: C
authors.lastname: Oxvig
authors.forename: Bjarne L
authors.initials: BL
authors.lastname: Nørgaard
authors.forename: Simon
authors.initials: S
authors.lastname: Glerup
authors.forename: Tina S
authors.initials: TS
authors.lastname: Poulsen
authors.forename: Jens F
authors.initials: JF
authors.lastname: Lassen
authors.forename: Holger J
authors.initials: HJ
authors.lastname: Møller
authors.forename: Leif
authors.initials: L
authors.lastname: Thuesen
authors.forename: Erling
authors.initials: E
authors.lastname: Falk
authors.forename: Torsten T
authors.initials: TT
authors.lastname: Nielsen
authors.forename: Henning R
authors.initials: HR
authors.lastname: Andersen
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000379:methods*; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000503:physiopathology / Q000628:therapy; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D006493:Heparin; D011266:Pregnancy-Associated Plasma Protein-A