title: Urinary asymmetric dimethylarginine (ADMA) is a predictor of mortality risk in patients with coronary artery disease.
abstract: BACKGROUND
  Asymmetric dimethylarginine (ADMA) causes endothelial dysfunction by inhibiting endothelial nitric oxide synthase. Elevated ADMA plasma levels comprise a major risk factor for coronary artery disease (CAD) and predict coronary events. ADMA is metabolised by dimethylarginine dimethylaminohydrolases (DDAHs) to citrulline and dimethylamine (DMA) and is partly excreted unchanged via the kidney. Unlike circulating ADMA, very little is known about urinary ADMA and DMA concentrations and a predictive value in CAD patients.
  
  
  RESULTS
  Seventy-seven consecutive patients admitted to hospital because of stable angina (mean age 65.9 ± 1.1 years) were enrolled and followed-up for 28 [1-28] months. All patients underwent cardiac catheterization and were divided into patients with no CAD or 1-3-vessel disease (CAD 1-3). Urinary ADMA levels (corrected for creatinine excretion) were lower in severely diseased patients (CAD 3, p<0.05) whereas the DMA/ADMA ratio was significantly increased (p<0.05 CAD 3 vs. CAD 0). In a stepwise multivariate regression analysis the ADMA/creatinine ratio correlated with cardiac function (r=0.5, p<0.0001) and LDL concentrations (r=0.27, p=0.01). A total of 12 patients died during follow-up, 9 due to cardiovascular causes. Importantly, low urinary ADMA concentrations predicted future cardiovascular death (p<0.01) and overall death (p<0.05).
  
  
  CONCLUSIONS
  In CAD patients low urinary ADMA concentrations are associated with impaired cardiac function and predict cardiovascular as well as all-cause mortality. The potential clinical value of urinary ADMA as a new biomarker for the diagnosis of CAD or cardiac dysfunction is intriguing, but warrants further studies.
authors.affiliation: Institut für Molekulare und Translationale Therapiestrategien (IMTTS), Medizinische Hochschule, Hannover, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Wolf
authors.forename: Johan M
authors.initials: JM
authors.lastname: Lorenzen
authors.forename: Sylvia
authors.initials: S
authors.lastname: Stein
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tsikas
authors.forename: Stefan
authors.initials: S
authors.lastname: Störk
authors.forename: Frank
authors.initials: F
authors.lastname: Weidemann
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.forename: Johann
authors.initials: J
authors.lastname: Bauersachs
authors.forename: Thomas
authors.initials: T
authors.lastname: Thum
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives* / Q000652:urine; D015415:Biomarkers / Q000652:urine; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000401:mortality* / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C018524:N,N-dimethylarginine; D001120:Arginine