Serum Urate and Incident Cardiovascular Disease: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Abstract

ObjectiveThere is controversy about whether serum urate (sUA) predicts future cardiovascular disease (CVD) independently of classical risk factors, and the age at which any prediction starts. We studied the sUA-CVD association among generally healthy adults.MethodsCARDIA recruited 5115 black and white individuals aged 18–30 years in 1985–1986 (year-0). Fatal and nonfatal CVD events by year 27 (n = 164) were ascertained during annual contacts and classified using medical records. The association with sUA (year-0, 10, 15 and 20) was modeled using Cox proportional hazards regression, pooling over gender-specific quartiles.ResultsMean sUA concentration was higher in men than women, but increased over time in both genders. Those with elevated sUA had worse metabolic profiles that substantially deteriorated over time. Adjusting for demographic and lifestyle factors (the minimal model), baseline sUA concentration was positively associated with incident CVD (hazard ratio (HR) per mg/dL = 1.21; 95% confidence interval: 1.05, 1.39; P = 0.005). This positive association attenuated to nonsignificance in the full model accounting simultaneously for classical CVD risk factors (HR = 1.09; 0.94, 1.27; P = 0.24). Both the minimal and full models appeared to show stronger associations (than year-0 sUA) between year-10 sUA and incident CVD (HR = 1.27 and 1.12, respectively), but sUA was not statistically significant in the full model. Despite fewer events, year-15 sUA showed a significant sUA-CVD association pattern, with minimal model association magnitude comparable to year-10, and remained significant in the full model (HR = 1.19; 1.02, 1.40; P = 0.03). Hyperuricemia at year-15 strongly predicted CVD risk (HR = 2.11; 1.34, 3.33; P = 0.001), with some attenuation in the full model (HR = 1.68; P = 0.04).ConclusionssUA may be an early biomarker for CVD in adults entering middle age. The prediction of CVD by sUA appeared to strengthen with aging. The potential complex relation of sUA with deterioration of a cluster of metabolic abnormalities warrants future exploration.

Hyperuricemia and smoking in young adults suspected of coronary artery disease ≤ 35 years of age: a hospital-based observational study

“…The recent study concerning on the relationship between HUA and CAD in patients ≤35 years of age (the 2015 CARDIA study) showed that after adjusting for demographic and lifestyle factors, the baseline SUA concentration was positively associated with the prevalence of CVD (HR, 1.21; 95% CI, 1.05–1.39; p  = 0.005). This positive association was not significant in the full model due to the simultaneous effects of traditional risk factors (HR, 1.09; 95% CI, 0.94–1.27; p  = 0.24) [14]. This conclusion was similar to our findings.…”

Interactive effect of serum uric acid and total bilirubin for cardiovascular disease in Chinese patients with type 2 diabetes

“…Several prospective studies consistently demonstrated the positive relationship between SUA level and risk of cardiovascular diseases in general populations815. However, the association was inconsistent in patients with diabetes323334.…”

“…In this regard, high uric acid levels and low bilirubin concentrations were observed to be associated with CVD89. Uric acid is a metabolic end product of purine metabolism in humans and possesses pro-oxidant and antioxidant dual properties.…”

Uric acid, renal function and risk of hypoglycaemia in Chinese type 2 diabetes patients

“…These findings were robust after adjusting for multiple traditional risk factors for hypoglycaemia. Previous epidemiological or experimental studies reported that SUA was positively correlated with disorders of lipid metabolism, hemodynamic abnormalities [25], cardiovascular disease [26], pre-diabetes (i.e. impaired fasting glucose, mildly elevated HbA 1c , hyperinsulinemia and insulin resistance) [9,27] and diabetes [4,19].…”