title: Association between the changes in renal function and serum uric acid levels during multifactorial intervention and clinical outcome in patients with metabolic syndrome. A post hoc analysis of the ATTEMPT study.
abstract: OBJECTIVE
  To assess the effects of long-term multifactorial intervention on renal function and serum uric acid (SUA) levels and their association with estimated cardiovascular disease (eCVD) risk and actual CVD events.
  
  
  METHODS
  This prospective, randomized, target-driven study included 1123 subjects (45.6% men, age 45-65 years) with metabolic syndrome (MetS) but without diabetes or CVD. Patients were randomized to multifactorial treatment. Atorvastatin was titrated from 10-80 mg/day aiming at a low density lipoprotein cholesterol (LDL-C) target of <100 mg/dl (group A) or an LDL-C target of <130 mg/dl (group B). Changes in estimated glomerular filtration rate (eGFR) and SUA levels were recorded in all patients and in the subgroup with stage 3 chronic kidney disease (CKD; eGFR = 30-59 ml/min/1.73 m(2); n = 349). We used ANOVA to compare changes within the same group, unpaired Student t-test to compare results between groups at specific time points, and log-rank test to compare event free survival.
  
  
  RESULTS
  The eCVD-risk reduction was greater in group A. In the overall study population, eGFR increased by 3.5% (p < 0.001) and SUA levels fell by 5.6% (p < 0.001). In patients from group A with stage 3 CKD (group A1; n = 172), eGFR increased by 11.1% (p < 0.001) from baseline and by 7.5% (p < 0.001) in group B1 (n = 177; p < 0.001 vs. the change in group A1). The corresponding fall in SUA levels was 10.7% in group A1 (p < 0.001 vs. baseline) and 8.3% in group B1 (p < 0.001 vs. baseline and group A1). These changes were mainly attributed to atorvastatin treatment. Among the CKD stage 3 patients there were no CVD events in group A1, while 6 events occurred in group B1 (p = 0.014).
  
  
  CONCLUSIONS
  Multifactorial intervention in patients with MetS without established CVD improved renal function and reduced SUA levels. These changes were more prominent in stage 3 CKD patients and might have contributed to the reduction in eCVD risk and clinical events. Original study registration number [ClinicalTrials.gov ID: NCT00416741].
authors.affiliation: Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Vassilios G
authors.initials: VG
authors.lastname: Athyros
authors.forename: Asterios
authors.initials: A
authors.lastname: Karagiannis
authors.forename: Emmanouel S
authors.initials: ES
authors.lastname: Ganotakis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Paletas
authors.forename: Vassilios
authors.initials: V
authors.lastname: Nicolaou
authors.forename: George
authors.initials: G
authors.lastname: Bacharoudis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tziomalos
authors.forename: Theodore
authors.initials: T
authors.lastname: Alexandrides
authors.forename: Evangelos N
authors.initials: EN
authors.lastname: Liberopoulos
authors.forename: Dimitri P
authors.initials: DP
authors.lastname: Mikhailidis
mesh_terms: D000368:Aged; D000069059:Atorvastatin; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000401:mortality / Q000503:physiopathology; D008078:Cholesterol, LDL / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D008875:Middle Aged; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage*; D014527:Uric Acid / Q000097:blood*
chemical_list: D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D014527:Uric Acid; D000069059:Atorvastatin