title: Effect of simvastatin on plasma asymmetric dimethylarginine concentration in patients with chronic kidney disease.
abstract: BACKGROUND
  The endogenous inhibitor of nitric oxide (NO) synthase, asymmetric dimethylarginine (ADMA), is a strong cardiovascular (CV) risk marker in patients with chronic renal insufficiency. Statins have pleiotropic effects and are currently considered as potential ADMA-lowering agents.
  
  
  METHODS
  We investigated the effect of simvastatin on plasma ADMA levels in 35 patients with chronic kidney disease (CKD) by performing a secondary analysis of a randomized double-blind placebo-controlled trial where patients were randomized to receive simvastatin or placebo for 6 months.
  
  
  RESULTS
  Plasma ADMA was higher in CKD patients (0.84 +/- 0.14 micromol/L) than in healthy subjects (0.69 +/- 0.10 micromol/L) (p<0.001). In CKD patients, ADMA at baseline was related directly with triglycerides (r=0.42, p=0.01) and inversely with HDL cholesterol (r=-0.37, p=0.03) and creatinine clearance (p=0.03). As expected, simvastatin caused significant reductions in total cholesterol, LDL cholesterol and triglycerides, as well as in C-reactive protein (CRP; -28%, p=0.001) and IL-6 (-20%, p=0.05) but failed to decrease plasma ADMA both in crude and adjusted analyses.
  
  
  CONCLUSIONS
  Simvastatin does not modify plasma ADMA. Because raised ADMA is known to prevent the favorable effect of statins on myocardial blood flow, cointerventions aimed at lowering or antagonizing ADMA may either prompt or potentiate the cardiovascular protective effect of simvastatin.
authors.affiliation: Nephrology Section, Department of Internal Medicine, University of Pisa, Pisa, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Panichi
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mantuano
authors.forename: Sabrina
authors.initials: S
authors.lastname: Paoletti
authors.forename: Samuele
authors.initials: S
authors.lastname: Santi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Manca Rizza
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Cutrupi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pizzini
authors.forename: Belinda
authors.initials: B
authors.lastname: Spoto
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tripepi
authors.forename: Carmine
authors.initials: C
authors.lastname: Zoccali
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D002908:Chronic Disease; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007674:Kidney Diseases / Q000097:blood*; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C018524:N,N-dimethylarginine; D001120:Arginine; D019821:Simvastatin