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

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 m²; 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.

Trial registration: ClinicalTrials.gov identifier: NCT00416741.

Keywords::

• Cardiovascular events
• Metabolic syndrome
• Multifactorial treatment
• Renal function
• Serum uric acid

Key messages::

• (1) A long-term, target-driven, intensive intervention aiming at multiple risk factors in patients with metabolic syndrome (MetS) but without diabetes or cardiovascular disease (n = 1123) is feasible and substantially reduces the prevalence of MetS components and the estimated cardiovascular disease risk. (2) Renal function improved and serum uric acid levels decreased with atorvastatin treatment during a 3-year follow-up, mainly in patients with stage 3 chronic kidney disease (n = 349), and this might have contributed to the reduction in cardiovascular events in the group with a more aggressive low density lipoprotein cholesterol target (<100 mg/dl). (3) The use of multifactorial treatment with appropriate drugs at appropriate doses along with a high compliance to this treatment might reduce the cardiovascular morbidity and mortality associated with the obesity and MetS epidemic.

Transparency

Declaration of funding

This study was conducted under the auspice of the Hellenic Atherosclerosis Society and was sponsored by Pfizer Hellas through an independent research grant.

Declaration of financial/other interest

V.G.A., A.K., E.S.G., K.P., V.N., G.B., K.T., T.A., and E.N.L. have disclosed that they have no relevant financial relationships to disclose. D.P.M. has disclosed that he is a consultant to MSD. He has also been sponsored by and is on the speakers’ bureau for MSD and Genzyme, and has received research grants from MSD, Genzyme and Astra Zeneca. CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors thank Dr A Papageorgiou, for carrying out the statistical analysis.

The authors also thank all the physicians of the Assessing The Treatment Effect in Metabolic syndrome without Perceptible diabeTes (ATTEMPT) Collaborative group for providing patient data: Achimastos A, Anagnostis P, Bilianou E, Basdekas S, Giovas P, Chimonas T, Griva T, Florentin M, Foundakis G, Giannakopoulou V, Gianoglou G, Giouleme O, Gossios TD, Kakafika A, Kapnia E, Kargiotis K, Kolovou G, Liberi S, Liopirakis A, Lioudaki E, Michailidou K, Mitsiou E, Pagourelias ED, Petridis D, Pappas S, Theocharidou E, Tolias D, Tsakoudakis N.