title: Relationship between inflammatory cytokines and uric acid levels with adverse cardiovascular outcomes in patients with stable coronary heart disease.
abstract: BACKGROUND
  So far it is unclear whether the association between serum uric acid (SUA), inflammatory cytokines and risk of atherosclerosis is causal or an epiphenomenon. The aim of the project is to investigate the independent prognostic relationship of inflammatory markers and SUA levels with adverse cardiovascular outcomes in a patient population with stable coronary heart disease (CHD).
  
  
  METHODS
  SUA, C-reactive protein (CRP) and interleukin (IL)-6 were measured at baseline in a cohort of 1,056 patients aged 30-70 years with CHD. Cox proportional hazards model was used to determine the prognostic value of these markers on a combined CVD endpoint during eight year follow-up after adjustment for covariates.
  
  
  RESULTS
  For 1,056 patients with stable coronary heart disease aged 30-70 years (mean age 58.9 years, SD 8.0) follow-up information and serum measurements were complete and n = 151 patients (incidence 21.1 per 1000 patients years) experienced a fatal or non-fatal CVD event during follow-up (p-value = 0.05 for quartiles of SUA, p = 0.002 for quartiles of CRP, p = 0.13 for quartiles of IL-6 in Kaplan-Meier analysis). After adjustment for age, gender and hospital site the hazard ratio (HR) for SUA increased from 1.37 to 1.65 and 2.27 in the second, third, and top quartile, when compared to the bottom one (p for trend <0.0005). The HR for CRP increased from 0.85 to 0.98 and 1.64 in the respective quartiles (p for trend 0.02). After further adjustment for covariates SUA still showed a clear statistically significant relationship with the outcome (p for trend 0.045), whereas CRP did not (p for trend 0.10).
  
  
  CONCLUSIONS
  The data suggest that compared to inflammatory markers such as CRP and IL-6 serum uric acid levels may predict future CVD risk in patients with stable CHD with a risk increase even at levels considered normal.
authors.affiliation: Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany. dietrich.rothenbacher@uni-ulm.de
authors.forename: Dietrich
authors.initials: D
authors.lastname: Rothenbacher
authors.forename: Andrea
authors.initials: A
authors.lastname: Kleiner
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.forename: Paola
authors.initials: P
authors.lastname: Primatesta
authors.forename: Lutz P
authors.initials: LP
authors.lastname: Breitling
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001499:Bayes Theorem; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D003327:Coronary Disease / Q000097:blood* / Q000175:diagnosis / Q000401:mortality; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012306:Risk; D014527:Uric Acid / Q000097:blood*
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D014527:Uric Acid; D002097:C-Reactive Protein