Abstract 3265: Serum Uric Acid as a Predictor of Cardiovascular Risk: The Treating to New Targets (TNT) Study
Background: Elevated serum uric acid (SUA) has been proposed as a cardiovascular (CV) risk factor and has been associated with impaired renal function. The current post hoc analysis of the TNT study investigates whether screening SUA is a significant predictor of CV risk, and whether reduction in SUA by atorvastatin (ATV) is associated with improved CV outcomes.
Methods: After 8 weeks open-label therapy with ATV 10 mg, 10,001 coronary heart disease (CHD) patients were randomized to double-blind therapy with ATV 10 mg or 80 mg and followed for a median of 4.9 years for the occurrence of major cardiovascular events (MCVE). SUA and estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation were assessed at screening, baseline and every 12 months. Screening SUA was evaluated as a predictor of MCVE using a Cox proportional hazards model. Change from baseline SUA was assessed as a time-dependent predictor of MCVE using the mean of all post-baseline SUA measurements prior to MCVE for each patient with or without adjustment for mean post-baseline change in eGFR.
Results: Screening SUA was a significant predictor of MCVE (HR 1.11 for every 1 mg/dL increase above the mean of 6.3 mg/dl, 95% CI 1.06 –1.16, P<0.0001). Over the course of the study, a 3.2% increase from baseline SUA was seen with ATV 10 mg versus a 2.0% decrease with ATV 80 mg (LS means difference −0.32, P<0.0001). Reduction in SUA from baseline was associated with a significant reduction in risk of MCVE (HR 0.90 for every 1 mg/dL decrease, 95% CI 0.83– 0.98, P=0.0155), with no treatment-by-SUA interaction (P=0.20). Mean % change in SUA correlated inversely with mean % change in eGFR from baseline (Pearson’s r = −0.37, P<0.0001). When adjusted for change in mean eGFR, the relationship between mean change in SUA and MCVE was no longer significant (P=0.32).
Conclusion: Screening SUA was a significant predictor of CV risk in TNT. Reduction in SUA with ATV 80 mg was associated with reduction in risk of MCVE. However, SUA risk prediction was not independent of on-treatment change in eGFR. This SUA-eGFR interaction may account for the variance in prior reports examining SUA as a CV risk factor and suggests the need to adjust for renal function when considering SUA in this role.