Metabolic Factors Mediate the Association Between Serum Uric Acid to Serum Creatinine Ratio and Cardiovascular Disease

BACKGROUND: The serum uric acid/serum creatinine ratio (SUA/SCr), which represents renal function‐normalized SUA, is associated with diverse adverse outcomes. The aim of this study was to investigate the association between SUA/SCr and cardiovascular disease (CVD), and determine whether and to what extent this association is mediated by cardiometabolic factors. METHODS AND RESULTS: This prospective study enrolled 96 378 participants from the Kailuan study without stroke and myocardial infarction at baseline (2006). Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Mediation analyses were conducted to separately explore the mediating effects of cardiometabolic factors on the association between SUA/SCr and CVD. During median follow up of 11.01 years, 6315 (6.55%) individuals developed incident CVD. After adjustment for potential confounders, the highest quartile of SUA/SCr was associated with the highest risk of CVD (HR, 1.15; 95% CI, 1.07–1.23), stroke (HR, 1.16; 95% CI, 1.07–1.26), ischemic stroke (HR, 1.12; 95% CI, 1.02–1.22), and hemorrhagic stroke (HR, 1.36; 95% CI, 1.11–1.65), but not with myocardial infarction (HR, 1.07; 95% CI, 0.92–1.25). The association was consistent across different degrees of kidney function and glucose tolerance statuses. Additionally, the association between high SUA/SCr and CVD was partially mediated by triglycerides (30.74%), body mass index (BMI) (19.52%), total cholesterol (15.06%), hs‐CRP (high‐sensitivity C‐reactive protein) (13.06%), diastolic blood pressure (11.75%), and blood glucose (−16.38%). CONCLUSIONS: SUA/SCr and CVD were positively associated. Furthermore, this association was partially mediated through blood lipids, BMI, blood pressure, hs‐CRP, and blood glucose.