Serum Uric Acid Levels, but Not rs7442295 Polymorphism of SCL2A9 Gene, Predict Mortality in Clinically Stable Coronary Artery Disease

Abstract

Serum uric acid (SUA) has been associated with cardiovascular disease, but up to now whether SUA is an independent cardiovascular risk factor or merely a disease-related epiphenomenon remains still controversial. within the framework of the Verona Heart Study, we prospectively followed 703 subjects with angiographically demonstrated and clinically stable coronary artery disease between May 1996 and March 2007. At baseline, SUA levels were measured in all the patients. Genotype data of SCL2A9 rs7442295 polymorphism, which has been associated with SUA by genome-wide association studies, were available for 686 subjects (97.6%). After a median follow-up of 57 months, 116 patients (16.5%) had died, 83 (11.8%) because of cardiovascular causes. Patients with hyperuricemia, defined by SUA levels above the 75th percentile (≥0.41 mmol/L), had an increased total and cardiovascular mortality rate than those with SUA below this threshold level (23.3% vs 14.1%, P = 0.048 and 19.4% vs 9.2%, P = 0.001, respectively, by Kaplan-Meier with Log-Rank test). These associations were confirmed by Cox regression after adjustment for sex, age, other predictors of mortality, coronary revascularization, and drug therapies at discharge (hazard ratio for total mortality 1.87 [1.05-3.34], P = 0.033; hazard ratio for cardiovascular mortality 2.09 [1.03-4.25], P = 0.041). Although associated with SUA levels, rs7442295 polymorphism did not predict total or cardiovascular mortality. our data support that SUA may be a prognostic cardiovascular biomarker, predicting total and cardiovascular mortality in the setting of secondary prevention of coronary artery disease. On the other hand, SCL2A9 gene polymorphism, notwithstanding a clear influence on SUA levels, was not associated with mortality.