Increased serum homocitrulline concentrations are associated with the severity of coronary artery disease

Clin Chem Lab Med. 2015 Jan;53(1):103-10. doi: 10.1515/cclm-2014-0642.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Citrulline / analogs & derivatives*
  • Citrulline / blood
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / diagnostic imaging
  • Cross-Sectional Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Radiography


  • homocitrulline
  • Citrulline