title: Plasma asymmetric dimethylarginine predicts death and major adverse cardiovascular events in individuals referred for coronary angiography.
abstract: BACKGROUND
  Elevated plasma level of asymmetric dimethylarginine (ADMA) was reported to be associated with endothelial dysfunction and atherosclerotic risk factors. We assessed the prognostic value of plasma ADMA levels in 997 consecutive individuals referred for coronary angiography from July 2006 to June 2009.
  
  
  METHODS
  ADMA was measured by high performance liquid chromatography. All subjects were followed for a median period of 2.4years for the occurrence of all-cause mortality, major adverse cardiovascular events (MACE, defined as cardiovascular death, non-fatal myocardial infarction and stroke), and MACE plus clinically-driven target vessel revascularization (TVR).
  
  
  RESULTS
  Plasma ADMA levels were significantly higher in patients with significant coronary artery disease (CAD) (≥50% stenosis, n=655) than those with insignificant CAD (20-50% stenosis, n=272) and normal coronary artery (<20% stenosis, n=70) (0.47±0.10μmol/l vs 0.44±0.10μmol/l vs 0.42±0.08μmol/l, p <0.001). By multivariate analysis, plasma ADMA level was identified as a significant independent risk factor of significant CAD (OR: 1.29, 95% CI: 1.10-1.50; p=0.002). Moreover, multivariate Cox regression analysis showed that, comparing with the ADMA tertile I, the highest ADMA tertile was a significant independent predictor for all adverse long-term clinical outcomes. Notably, plasma ADMA level remained associated with the long-term outcomes in non-diabetic individuals, but not in those with diabetes (interaction p=0.04 for MACE plus TVR).
  
  
  CONCLUSIONS
  Our findings suggest that elevated plasma ADMA level might be a risk factor of significant CAD, and might predict worse long-term clinical outcomes in subjects referred for cardiac catheterization, especially in non-diabetic individuals.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Tse-Min
authors.initials: TM
authors.lastname: Lu
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Chung
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Lin
authors.forename: Chiao-Po
authors.initials: CP
authors.lastname: Hsu
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000401:mortality*; D017023:Coronary Angiography / Q000379:methods*; D003643:Death; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012017:Referral and Consultation; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C018524:N,N-dimethylarginine; D001120:Arginine