LAUSR

Serum uric acid (SUA) is increasingly recognised as an important predictor of cardiovascular disease (CVD) and total mortality. However, the levels of SUA that discriminate across the different strata of risk for CVD and total mortality remain unknown, complicating the identification of subjects at high or low mortality risk for SUA in clinical practice. In this study we used a large Italian population comprising >3ehz748.0326 subjects to assess the threshold of SUA that increases the risk of total and CVD mortality. The URic Acid Right for heArt Health (URRAH) study is a regional-basis multicentre cohort study which collected data from prospective studies and databases from different hypertension centres, including subjects with at least one measure of SUA and a follow-up of about 20 years. Total mortality was defined as mortality for any causes, cardiovascular mortality as death due to fatal myocardial infraction, stroke or heart failure. Multivariate dichotomic logistic and Cox regression models were used to confirm the relationship between SUA and mortality status both from cardiovascular and any causes, while ROC curves were used to identify the threshold of SUA that better discriminated people at higher or lower mortality risk. A total of 22.275 subjects had SUA and mortality information. Logistic regression identified a direct and strong association between SUA and an increased risk of total (OR 1.176, 95% CI 1.127–1.227) and CVD (OR 1.147, 95% CI 1.093–1.203) mortality, independently of other CVD risk factors (age, BMI, LDL cholesterol, diagnosis of diabetes, hypertension, chronic kidney disease, alcohol consumption and smoking). Cox models confirmed the presence of an independent association between SUA and any causes (HR 1.123, 95% CI 1.090–1.567) and CVD (HR 1.124, 95% CI 1.081–1.169) mortality. ROC curve analysis identified a cut-off value od SUA [(4.79 mg/dL (95% CI 4.7–5.4 mg/dl)] able to discriminate total mortality status, and a different one [(5.60 mg/dL (95% CI 5.09–5.89 mg/dl)] able to identify CVD mortality status. Multivariate Cox analysis adjusted for confounders confirmed that subjects with SUA >4.79 mg/dl had a significantly higher total mortality (HR 1.293, 95% CI 1.181–1.416) compared to those with SUA <4.79 mg/dl, independently of covariables. Similarly, subjects with SUA >5.60 mg/dl had a significantly higher CVD mortality (HR 1.428, 95% CI 1.273–1.600) than those with SUA <5.60 mg/dl after adjustment for the same confounders. Levels of SUA that increase the risk of total and CVD mortality are significantly lower than those commonly used for the definition of hyperuricemia in clinical practice. Our data provide the first large evidence of a level of “cardiovascular” SUA that might be used in clinical practice to identify subjects at greater risk of total and CVD mortality.