Serum uric acid and cardiovascular disease according to metabolic risk factors: the Korean Heart Study

Abstract

Background and Aims: The aims of this epidemiological study was to characterize the association between serum uric acid (SUA) levels and the incidence of cardiovascular disease (CVD) in a large, sample of the Korean general population without or and without metabolic risk factors. Given the correlation with hypertension, inflammation, endothelial dysfunction, insulin resistance, and obesity, uric acid has recently been proposed to play a role as a risk factor for CVD, but the evidence is discordant. However, most studies have examined the relation of CVD with hyperuricemia, or have focused upon populations with existing morbidity.

Methods: The Korean Heart Study (KHS) enrolled 465,233 Korean adults who visited one of 18 health centers across the country between January1996 and December 31, 2004. In this study, a total of 322,467 Koreans, without CVD in the KHS who had baseline, SUA measurements were analyzed. Metabolic risk factors were defined using the modified National Cholesterol Education Program-Adult Treatment Panel III criteria, except for waist circumference. All statistical tests were 2-sided, and statistical significance was accepted for p-values < 0.05. Hazard ratios and 95% confidence intervals for CVD events were determined according to SUA quintiles using multivariable Cox proportional hazard models.

Results: The median follow-up was 9.5 years and we assessed the associations of SUA and CVD events (27,009 cases) after adjusting for potential confounders. Cox proportional hazards models were calculated to evaluate SUA by quintiles, as a predictive marker for CVD. SUA levels > 6.8mg/dL in men and > 4.8mg/dL in women were independently associated with an increased risk of CVD incidence; the adjusted hazard ratio (HR) for the highest versus lowest quintile of SUA was 1.22 (95% CI, 1.16-1.28) in men and 1.27 (95% CI, 1.19-1.35) in women. When stratified by conventional metabolic risk factors, SUA was significantly associated with ischemic heart disease (IHD) within CVD. However, in a subgroup analysis of participants without diabetes, the HR for IHD increased to 1.27 (95% CI, 1.14-1.41) in men and 1.51 (95% CI, 1.29-1.77) in women, and these findings showed a clear dose-response relationship.

Conclusions: Elevated serum uric acid levels were associated with IHD, independently of conventional CVD risk factors and metabolic syndrome. The increased risk of IHD associated with hyperuricemia was consistent across most subgroups. Hyperuricemia may increase the risk of IHD, particularly in females. Further research is needed to broadly evaluate the causal effects of multiple biomarkers on cardiovascular disease and metabolic risk traits using data from large-scale cohorts or GWAS including many different genetic variants.