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

Curr Med Res Opin. 2011 Aug;27(8):1659-68. doi: 10.1185/03007995.2011.595782. Epub 2011 Jun 30.

Abstract

Aim: 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].

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atorvastatin
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / physiopathology
  • Cholesterol, LDL / blood*
  • Disease-Free Survival
  • Female
  • Glomerular Filtration Rate / drug effects*
  • Heptanoic Acids / administration & dosage*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Kidney / physiopathology*
  • Male
  • Metabolic Syndrome* / blood
  • Metabolic Syndrome* / complications
  • Metabolic Syndrome* / drug therapy
  • Metabolic Syndrome* / mortality
  • Metabolic Syndrome* / physiopathology
  • Middle Aged
  • Prospective Studies
  • Pyrroles / administration & dosage*
  • Uric Acid / blood*

Substances

  • Cholesterol, LDL
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Uric Acid
  • Atorvastatin

Associated data

  • ClinicalTrials.gov/NCT00416741