Background/Purpose: Elevated serum urate concentration (hyperuricemia) is considered to be a key risk factor for developing gout.  However, the relationship between serum urate and incident gout is unclear, with variation in estimates of risk depending on different published studies.  We undertook the largest individual participant data analysis to date to examine the relationship between serum urate concentration and incident gout.

Methods: Publically available cohort studies with both baseline serum urate and incident gout data were identified through a systematic search of PubMed and the Database of Genotype and Phenotype, and individual participant data were extracted for analysis.  Kaplan-Meier plots were generated and the cumulative incidence of gout was calculated according to the baseline serum urate category.  We evaluated the relation of serum urate categories (<6mg/dL as referent group) to risk of gout using Cox proportional hazards modelling, adjusted for potential confounders (age, sex, ethnicity, cohort). 

Results: Four cohorts with publically available data were identified (Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, and the Original and Offspring cohorts of the Framingham Heart Study), with a total of 18,889 participants who were gout-free at baseline, mean (SD) 11.2 (4.2) years of follow-up, and 212,363 total patient-years included in the analysis.  The overall cumulative incidence (95% CI) of gout by 5 years was 1.1 (0.9-1.3)%, by 10 years was 2.4 (2.2-2.6)% and by 15 years was 3.2 (2.8-3.6)%.  The cumulative incidence at each time point varied according to baseline serum urate concentrations, with 15 year cumulative incidence (95% CI) ranging from 1.1 (0.9-1.4)% for <6mg/dL to 48.6 (30.5-66.6)% for 10mg/dL or more (Figure and Table).  Compared with baseline serum urate <6mg/dL, the adjusted hazard ratio (95% CI) for baseline serum urate 6.0-6.9 mg/dL was 2.7 (2.0-3.6), for 7.0-7.9 mg/dL was 6.6 (5.0-8.8), for 8.0-8.9 mg/dL was 14.9 (11.1-20.1), for 8.0-8.9 mg/dL was 29.7 (20.8-42.3), and for 10mg/dL or more was 64.0 (42.5-96.1).

Conclusion: Serum urate is a strong concentration-dependent predictor of incident gout. Nonetheless, only about half of those with serum urate concentrations of 10mg/dL or more develop gout over 15 years, implying a role for additional factors in the pathogenesis of gout and a long duration of hyperuricemia preceding the onset of clinical gout. This analysis provides cumulative incidence estimates to guide discussions with hyperuricemic individuals about their risk of developing gout over time.