title: Pregnancy-associated plasma protein A and its endogenous inhibitor, the proform of eosinophil major basic protein (proMBP), are related to complex stenosis morphology in patients with stable angina pectoris.
abstract: BACKGROUND
  The metalloproteinase pregnancy-associated plasma protein-A (PAPP-A) has been implicated in coronary plaque disruption. Its endogenous inhibitor, the proform of eosinophil major basic protein (proMBP), may also play a role in this process. Atheromatous plaque disruption often presents as complex angiographic lesions. We sought to assess whether PAPP-A, proMBP, and PAPP-A/ProMBP ratio are markers of angiographic plaque complexity in patients with chronic stable angina.
  
  
  RESULTS
  We studied 396 stable angina patients (age 63+/-10 years, 230 men) of whom 289 had angiographically documented coronary artery disease (> or =75% stenosis). All coronary stenoses > or =30% diameter reduction (n =531 in 322 patients) were assessed and classified as complex (n =228) or smooth (n =303) by previously validated criteria. PAPP-A, proMBP, and C-reactive protein (hs-CRP) serum levels were measured by ELISA. Patients with complex coronary stenoses had a significantly (P<0.001) higher PAPP-A/proMBP ratio (3.1+/-1.2 versus 2.7+/-0.8x10(-3)) and PAPP-A levels (5.9+/-1.6 versus 5.1+/-1.4 mIU/L) than those without. On univariate analysis, male gender (P<0.001), age (P<0.001), previous history of myocardial infarction (P=0.013), reduced ejection fraction (P<0.001), severe coronary artery disease (P<0.001), aspirin treatment (P<0.001), PAPP-A levels (P<0.001), and PAPP-A/proMBP ratio (P<0.001) were correlated with the number of complex stenoses. Multiple regression analysis showed that male gender, age, severe coronary artery disease, and PAPP-A/proMBP ratio were independent predictors of the number of angiographically complex stenoses.
  
  
  CONCLUSIONS
  In patients with stable angina, PAPP-A and PAPP-A/proMBP ratio are associated with angiographic plaque complexity.
authors.affiliation: Department of Cardiac and Vascular Sciences, St George's Hospital Medical School, London, UK.
authors.forename: Juan
authors.initials: J
authors.lastname: Cosin-Sales
authors.forename: Michael
authors.initials: M
authors.lastname: Christiansen
authors.forename: Paul
authors.initials: P
authors.lastname: Kaminski
authors.forename: Claus
authors.initials: C
authors.lastname: Oxvig
authors.forename: Michael T
authors.initials: MT
authors.lastname: Overgaard
authors.forename: Della
authors.initials: D
authors.lastname: Cole
authors.forename: David W
authors.initials: DW
authors.lastname: Holt
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Kaski
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D000925:Anticoagulants / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D015415:Biomarkers; D001798:Blood Proteins / Q000502:physiology*; D002097:C-Reactive Protein / Q000032:analysis; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D023921:Coronary Stenosis / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D018450:Disease Progression; D047093:Eosinophil Major Basic Protein; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D011237:Predictive Value of Tests; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D011498:Protein Precursors / Q000097:blood / Q000502:physiology*; D011509:Proteoglycans / Q000097:blood / Q000502:physiology*; D012307:Risk Factors; D013318:Stroke Volume
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D001798:Blood Proteins; D011498:Protein Precursors; D011509:Proteoglycans; C074129:PRG2 protein, human; D002097:C-Reactive Protein; D047093:Eosinophil Major Basic Protein; D011266:Pregnancy-Associated Plasma Protein-A; D001241:Aspirin