title: Inflammation and asymmetric dimethylarginine for predicting death and cardiovascular events in ESRD patients.
abstract: BACKGROUND
  Endothelial dysfunction as assessed by asymmetric dimethylarginine (ADMA) and inflammation has been consistently linked to atherosclerosis, death, and cardiovascular (CV) events in ESRD patients. Inflammation amplifies the effect of ADMA on the severity of atherosclerosis in ESRD patients, but it is still unknown whether inflammation and ADMA interact in the high risk of death and CV events in this population.
  
  
  METHODS
  In a cohort of 225 hemodialysis patients, we investigated the interaction between inflammatory biomarkers (C-reactive protein and IL-6) and ADMA as predictors of death and CV events over an extended follow-up (13 years).
  
  
  RESULTS
  During follow-up, 160 patients died, and 123 had CV events. With crude and multiple Cox regression analyses, an interaction was found between inflammation biomarkers and ADMA for explaining death and CV events in ESRD patients. The adjusted hazard ratios (HRs) for death (HR, 2.18; 95% confidence interval [CI], 1.34 to 3.54) and CV outcomes (HR, 2.59; 95% CI, 1.47 to 4.55) of patients with C-reactive protein and ADMA above the median were higher than expected in the absence of interaction under the additive model (1.15 and 1.97, respectively) and significantly higher than in patients with only one biomarker above the median. Data analyses carried out by stratifying patients according to IL-6 provided similar results.
  
  
  CONCLUSIONS
  These data support the hypothesis that inflammation amplifies the risk of death and CV events associated with high ADMA levels in ESRD. These analyses further emphasize the need for intervention studies to attenuate inflammation and high ADMA levels in this population.
authors.affiliation: CNR-IBIM, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Reggio Calabria, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tripepi
authors.forename: Francesco
authors.initials: F
authors.lastname: Mattace Raso
authors.forename: Eric
authors.initials: E
authors.lastname: Sijbrands
authors.forename: Mohamed Sidy
authors.initials: MS
authors.lastname: Seck
authors.forename: Renke
authors.initials: R
authors.lastname: Maas
authors.forename: Rainer
authors.initials: R
authors.lastname: Boger
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Witteman
authors.forename: Francesco
authors.initials: F
authors.lastname: Rapisarda
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Malatino
authors.forename: Francesca
authors.initials: F
authors.lastname: Mallamaci
authors.forename: Carmine
authors.initials: C
authors.lastname: Zoccali
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000276:immunology / Q000401:mortality*; D016009:Chi-Square Distribution; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology / Q000401:mortality*; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D007558:Italy / Q000453:epidemiology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000276:immunology / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D006435:Renal Dialysis / Q000009:adverse effects / Q000401:mortality; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; C018524:N,N-dimethylarginine; D002097:C-Reactive Protein; D001120:Arginine