title: Effect of statins versus untreated dyslipidemia on serum uric acid levels in patients with coronary heart disease: a subgroup analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study.
abstract: BACKGROUND
  Little is known about the effect of dyslipidemia on serum uric acid (SUA) levels, and less is known about the effect of statin treatment on them. The GREek Atorvastatin and Coronary-heart-disease Evaluation study suggested that a mean atorvastatin dose of 24 mg/d achieves the National Cholesterol Educational Program treatment goals and significantly reduces morbidity and mortality in patients with coronary heart disease (CHD) in comparison to the usual care. Here, we report the time course of SUA levels in usual-care patients undertreated for their dyslipidemia (12% were administered statins) in comparison to structured-care patients treated with atorvastatin in the vast majority (98%).
  
  
  METHODS
  Mean on-study SUA levels (up to 48 months) were compared with those at baseline by using analyses of variance to assess differences over time within and between treatment groups. Cox multivariate analysis was used to investigate whether changes in SUA levels during the study were clinically relevant.
  
  
  RESULTS
  All patients had normal renal function at baseline; serum creatinine (SCr) levels less than 1.3 mg/dL (<115 micromol/L) and moderately elevated SUA levels (mean, 7.1 +/- 0.9 [SD] mg/dL [425 +/- 52 micromol/L]; upper normal limit, 7.0 mg/dL [415 micromol/L]). Usual-care patients (n = 800) showed an increase in SUA levels by 3.3% ( P < 0.0001). Structured-care patients (n = 800) had an 8.2% reduction in SUA levels ( P < 0.0001). In all patients not administered diuretics (n = 1,407), SUA level changes showed a positive correlation with changes in SCr levels ( r = 0.82; P < 0.0001) and an inverse correlation with estimated glomerular filtration rate ( r = -0.77; P < 0.0001). After adjustment for 19 predictors of all CHD-related events, Cox multivariate analysis involving backward stepwise logistic regression showed a hazard ratio (HR) of 0.89 (95% confidence interval [CI], 0.78 to 0.96; P = 0.03) with every 0.5-mg (30-micromol/L) reduction in SUA level, an HR of 0.76 (95% CI, 0.62 to 0.89; P = 0.001) with every 1-mg (60-micromol/L) reduction, an HR of 1.14 (95% CI, 1.03 to 1.27; P = 0.02) with every 0.5-mg increase, and an HR of 1.29 (95% CI, 1.17 to 1.43; P = 0.001) with every 1-mg increase in SUA levels.
  
  
  CONCLUSIONS
  Data suggest that SUA level is an independent predictor of CHD recurrent events. Atorvastatin treatment significantly reduces SUA levels in patients with CHD, thus offsetting an additional factor associated with CHD risk.
authors.affiliation: Atherosclerosis Unit, Aristotelian University, Hippocration Hospital, Thessaloniki, Greece. athyros@med.auth.gr
authors.forename: Vasilios G
authors.initials: VG
authors.lastname: Athyros
authors.forename: Moses
authors.initials: M
authors.lastname: Elisaf
authors.forename: Athanasios A
authors.initials: AA
authors.lastname: Papageorgiou
authors.forename: Athanasios N
authors.initials: AN
authors.lastname: Symeonidis
authors.forename: Anthimos N
authors.initials: AN
authors.lastname: Pehlivanidis
authors.forename: Vasilios I
authors.initials: VI
authors.lastname: Bouloukos
authors.forename: Haralambos J
authors.initials: HJ
authors.lastname: Milionis
authors.forename: Dimitri P
authors.initials: DP
authors.lastname: Mikhailidis
mesh_terms: D000368:Aged; D000069059:Atorvastatin; D003327:Coronary Disease / Q000097:blood* / Q000188:drug therapy*; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000097:blood* / Q000188:drug therapy*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D014527:Uric Acid / Q000097:blood*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011758:Pyrroles; D014527:Uric Acid; D000069059:Atorvastatin; D003404:Creatinine