title: Association of asymmetric dimethylarginine levels with treadmill-stress-test-derived prognosticators.
abstract: BACKGROUND
  Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide production. The purpose of this study was to assess the correlation between ADMA and treadmill stress test outcome parameters with known prognostic value, in patients with intermediate risk for coronary artery disease (CAD).
  
  
  METHODS
  Study participants were referred for treadmill exercise stress test (EST) due to symptoms of suspected CAD. Participants with prior history of CAD, cerebrovascular events, peripheral artery disease, systemic inflammatory disease or use of anti-inflammatory agents were excluded. ADMA levels were measured before EST.
  
  
  RESULTS
  The study prospectively enrolled 209 individuals (165 males, aged 58.1±10.9). A significant negative correlation was detected between ADMA and maximal exercise time (r=-0.556, p<0.001), metabolic equivalents (METs) (r=-0.555, p<0.001) and Duke treadmill score (DTS) (r=-0.347, p<0.001). Subjects who exercised to ≥10 METs (n=114) had lower ADMA levels than those who achieved <7 METs (n=30) (0.58±0.06 vs 0.87±0.08μmol/L, p<0.001), and those with DTS<5 (n=63) had higher ADMA (0.75±0.19 vs 0.64±0.15μmol/L, p<0.001) compared to those with DTS ≥5 (n=146). In multivariable analysis, ADMA remained an independent predictor of DTS (R(2)=0.210; beta=-10.5; 95% confidence interval -14.9 to -6.2; adjusted p<0.001) and METs (R(2)=0.500; beta -8.5; 95% confidence interval -9.7 to -6.0; adjusted p<0.001) after adjustment for age, BMI, gender, diabetes, smoking status, dyslipidemia, hypertension and family history of premature CAD.
  
  
  CONCLUSIONS
  ADMA is correlated to EST parameters with proven prognostic value. This implies that ADMA itself might be a useful prognosticator in patients with suspected CAD.
authors: Department of Cardiology, Athens General Hospital "G. Gennimatas", Athens, Greece; Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT, USA.
authors: Spyridon
authors: S
authors: Deftereos
authors: Department of Cardiology, Athens General Hospital "G. Gennimatas", Athens, Greece.
authors: Georgios
authors: G
authors: Bouras
authors: Department of Cardiology, Athens General Hospital "G. Gennimatas", Athens, Greece.
authors: Dimitrios
authors: D
authors: Tsounis
authors: Department of Cardiology, Athens General Hospital "G. Gennimatas", Athens, Greece.
authors: Charalampos
authors: C
authors: Papadimitriou
authors: 1st Department of Cardiology, University of Athens Medical School, Hippokration Hospital, Athens, Greece.
authors: George
authors: G
authors: Hatzis
authors: Department of Cardiology, Athens General Hospital "G. Gennimatas", Athens, Greece.
authors: Konstantinos
authors: K
authors: Raisakis
authors: Department of Cardiology, Athens General Hospital "G. Gennimatas", Athens, Greece; Hellenic Center for Disease Control and Prevention, Athens, Greece.
authors: Vasiliki
authors: V
authors: Panagopoulou
authors: Department of Cardiology, Athens General Hospital "G. Gennimatas", Athens, Greece.
authors: Andreas
authors: A
authors: Kaoukis
authors: Hellenic Open University, Patras, Greece.
authors: Antonis
authors: A
authors: Ioannidis
authors: Department of Cardiology, Athens General Hospital "G. Gennimatas", Athens, Greece.
authors: Gerasimos
authors: G
authors: Deftereos
authors: Department of Cardiology, Athens General Hospital "G. Gennimatas", Athens, Greece; Hellenic Center for Disease Control and Prevention, Athens, Greece.
authors: Charalampos
authors: C
authors: Kossyvakis
authors: 1st Department of Cardiology, University of Athens Medical School, Hippokration Hospital, Athens, Greece.
authors: Antonis S
authors: AS
authors: Manolis
authors: Department of Cardiology, University of Patras Medical School, Patras, Greece.
authors: Dimitrios
authors: D
authors: Alexopoulos
authors: 1st Department of Cardiology, University of Athens Medical School, Hippokration Hospital, Athens, Greece.
authors: Christodoulos
authors: C
authors: Stefanadis
authors: Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT, USA.
authors: Michael W
authors: MW
authors: Cleman
authors: Department of Cardiology, Athens General Hospital "G. Gennimatas", Athens, Greece; Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT, USA; Hellenic Center for Disease Control and Prevention, Athens, Greece. Electronic address: ggiann@med.uoa.gr.
authors: Georgios
authors: G
authors: Giannopoulos
mesh_terms: D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood / Q000503:physiopathology; D005080:Exercise Test / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C018524:N,N-dimethylarginine; D001120:Arginine
keywords: ADMA; Biomarker; Coronary artery disease; Prognosis; Stress test