Longitudinal association between serum urate and subclinical atherosclerosis: The Coronary Artery Risk Development in Young Adults (CARDIA) study

Objective: The aim of the present study was to determine whether serum urate (sUA) concentration is positively associated with subclinical atherosclerosis, independent of body mass index (BMI), amongst generally healthy adults. Design and setting: The CARDIA study followed 5115 Black and White individuals aged 18-30 years in 1985-1986 (year 0). Subclinical atherosclerosis comprised coronary artery calcified plaque (CAC; years 15, 20 and 25), and maximum common carotid intima-media thickness (IMT; year 20). sUA (years 0, 10, 15 and 20) was modelled as gender-specific quartiles that were pooled. Discrete-time hazard regressions and generalized linear regressions were used for analyses. Results: Mean sUA concentration was lower in women than in men and increased with age. Adjusting for demographic and lifestyle factors, the highest versus lowest quartile of sUA at year 0 was associated with a 44% [95% confidence interval (CI) 20%, 73%] greater risk of CAC progression from years 15 to 25 (P_trend < 0.001), which was attenuated by adjustment for BMI at year 0 (P_trend = 0.45). A stronger association was found between sUA at year 15 and CAC progression at year 20 or 25 (hazard ratio 2.07, 95% CI 1.66, 2.58 for the highest versus lowest sUA quartile P_trend < 0.001), which was attenuated, but remained significant with additional adjustment for BMI at year 15 (P_trend = 0.01). A greater increment in sUA concentration from year 0 to year 15, independent of change in BMI, was related to a higher risk of CAC progression (P_trend < 0.001). Similar associations were found between sUA and IMT, but only in men. Conclusion: sUA may be an early biomarker for subclinical atherosclerosis in young adults; starting in early middle age, sUA predicts subclinical atherosclerosis independently of BMI.