NDT Advance Access published online on November 25, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn621
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Associations of serum uric acid with cardiovascular events and mortality in moderate chronic kidney disease
1 Department of Nephrology and Hypertension, Cleveland Clinic, Cleveland, OH 2 Medical Service, Salt Lake Veterans Affairs Healthcare System 3 Division of Nephrology & Hypertension, Salt Lake City, UT, USA
Correspondence and offprint requests to: Srinivasan Beddhu, 85 North Medical Drive East, Room 201, Salt Lake City, UT 84112, USA. Tel: +1-801-585-3810; Fax: +1-801-581-4750; E-mail: Srinivasan.beddhu{at}hsc.utah.edu
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Abstract |
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Background. It is unclear whether the presence of kidney disease modifies the associations of uric acid with cardiovascular events and death.
Methods. In the limited access, public use Atherosclerosis Risk In Communities (ARIC) database, associations of serum uric acid levels with cardiovascular events and death were analysed using a parametric proportional hazards model and the modification of these associations by the presence of CKD was assessed using a likelihood ratio test.
Results. Of the 15 366 ARIC participants included in this analysis, 461 had CKD (eGFR <60 ml/min/1.73 m2). In both non-CKD and CKD sub-groups, participants with hyperuricaemia (
7 mg/dl in men and 6 mg/dl in women) compared to those with normal serum uric acid levels had higher waist circumference and fasting serum insulin levels. In the entire cohort, in a multivariate parametric proportional hazards model, each mg/dl increase in serum uric acid was associated with an increased hazard of cardiovascular events (HR 1.09, 95% CI 1.05–1.12) and death. A multiplicative interaction term of serum uric acid and CKD when added to the above models was significant (P < 0.001). The likelihood ratio test of the models with and without the interaction term was also significant (P < 0.001). In the non-CKD population, a multivariate analysis after adjusting for comorbidities and metabolic syndrome showed a significant association between hyperuricaemia and mortality (HR 1.18, 95% CI 1.04–1.33) but not for cardiovascular events (HR 1.07, 95% CI 0.96–1.19). In the CKD population, the association was not significant for both mortality and cardiovascular events.
Conclusion. We conclude that hyperuricaemia is associated with insulin resistance and mortality in the non-CKD population. The presence of CKD attenuates the associations of uric acid with mortality. Interventional studies are warranted to establish the biological role of hyperuricaemia in mortality in non-CKD and CKD populations.
Keywords: cardiovascular events; chronic kidney disease; insulin resistance; mortality; uric acid
Received for publication: 1. 4.08
Accepted in revised form: 13.10.08