title: Increased serum homocitrulline concentrations are associated with the severity of coronary artery disease.
abstract: BACKGROUND
  Carbamylation is a non-enzymatic post-translational modification of proteins that has been recently identified as a non-traditional risk factor for atherosclerosis. The aim of this study was to determine whether serum homocitrulline (HCit), a characteristic carbamylation-derived product, was related to the presence and the severity of coronary artery disease (CAD).
  
  
  METHODS
  Forty-five control subjects and 109 patients were included in this cross-sectional study. After coronary angiography, the patients were classified as non-CAD patients (patients with normal arteries, n=33) and CAD patients (n=76). The severity of CAD was then evaluated using the Gensini scoring system. Serum total HCit concentrations were determined by LC-MS/MS.
  
  
  RESULTS
  Serum HCit concentrations were significantly (p<0.001) higher in CAD patients than in control or non-CAD subjects. The receiver operating characteristic curve analysis showed an area under the curve equal to 0.908 (95% confidence interval, 0.853-0.964, p<0.001) and a threshold HCit concentration of 0.16 mmol/mol Lys for predicting the presence of CAD (78.9% sensitivity and 78.8% specificity). HCit concentrations significantly (p<0.001) increased concomitantly with the severity of CAD and were positively correlated with Gensini scores (r=0.725, p<0.001) as well as with the number of stenotic coronary arteries (p<0.001). Furthermore, in a multiple stepwise regression analysis, HCit was significantly (p<0.001) and independently associated with the presence of CAD, the Gensini score, and the number of stenotic arteries (standardized β values of 0.525, 0.722, and 0.642, respectively).
  
  
  CONCLUSIONS
  Our results demonstrate that serum HCit concentrations are increased during CAD and are positively associated with the severity of the disease.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Jaisson
authors.forename: Mohsen
authors.initials: M
authors.lastname: Kerkeni
authors.forename: Izabella C R
authors.initials: IC
authors.lastname: Santos-Weiss
authors.forename: Faouzi
authors.initials: F
authors.lastname: Addad
authors.forename: Mohammed
authors.initials: M
authors.lastname: Hammami
authors.forename: Philippe
authors.initials: P
authors.lastname: Gillery
mesh_terms: D016022:Case-Control Studies; D002956:Citrulline / Q000031:analogs & derivatives* / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011859:Radiography
chemical_list: C001352:homocitrulline; D002956:Citrulline