title: Arginine bioavailability ratios are associated with cardiovascular mortality in patients referred to coronary angiography.
abstract: OBJECTIVE
  Arginine is the only source for nitric oxide (NO) synthesis. The bioavailability of NO plays a pivotal role in endothelial function and consequently in cardiovascular disease. The aim of the current study is to investigate the association of arginine bioavailability ratios with markers of endothelial function and cardiovascular mortality in patients referred to coronary angiography.
  
  
  METHODS
  We investigated 2236 patients recruited within the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study that were followed up for a median of 7.7 years. Arginine, ornithine and citrulline were chromatographically determined after precolumn-derivatisation followed by postcolumn continuous reaction with ninhydrin. Global arginine bioavailability (GABR) was calculated by arginine divided by the sum of ornithine plus citrulline.
  
  
  RESULTS
  We observed a significant rise in cardiovascular mortality with decreasing GABR and arginine to ornithine ratio quartiles. The adjusted Cox proportional HRs for GABR were 1.27 (0.88-1.83), 1.27 (0.89-1.80) and 1.75 (1.24-2.45) for the 3rd, the 2nd and the 1st quartile respectively in comparison to the 4th quartile. The HRs for the quartiles of the arginine to ornithine ratio were 1.83 (1.25-2.67), 2.17 (1.50-3.20) and 2.02 (1.39-2.92) respectively. Patients with type 2 diabetes mellitus had a significantly lower GABR than persons without diabetes (0.88 ± 0.23 vs. 0.94 ± 0.24, p<0.001). GABR was found to be inversely correlated with endothelial markers as VCAM-1 (r=-0.301, p<0.001) or ICAM-1 (r=-0.136, p<0.001).
  
  
  CONCLUSIONS
  GABR and the arginine to ornithine ratio are associated with markers of endothelial dysfunction and increased risk of cardiovascular mortality. Further studies are warranted to elucidate the pathobiology and clinical relevance of the arginine bioavailability ratios in cardio-metabolic diseases.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Graz, Austria. ha.sourij@medunigraz.at
authors.forename: Harald
authors.initials: H
authors.lastname: Sourij
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinitzer
authors.forename: Stefan
authors.initials: S
authors.lastname: Pilz
authors.forename: Tanja B
authors.initials: TB
authors.lastname: Grammer
authors.forename: Bernhard R
authors.initials: BR
authors.lastname: Winkelmann
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Boehm
authors.forename: Winfried
authors.initials: W
authors.lastname: März
mesh_terms: D000368:Aged; D001120:Arginine / Q000097:blood / Q000493:pharmacokinetics*; D002318:Cardiovascular Diseases / Q000401:mortality*; D002845:Chromatography / Q000379:methods; D002956:Citrulline / Q000097:blood; D017023:Coronary Angiography / Q000379:methods*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism; D009952:Ornithine / Q000097:blood; D016016:Proportional Hazards Models; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine; D009952:Ornithine