Cohort study of repeated measurements of serum urate and risk of incident atrial fibrillation

Background-Current evidence on the association between serum urate and risk of atrial fibrillation (AF) is limited by crosssectional designs and 1-time measurement of serum urate. The roles of serum urate, gout-related inflammation, and systemic inflammation in the etiology of AF are currently unknown. This gap is important, given that systemic inflammation is a recognized risk factor for AF. Methods and Results-We conducted a prospective cohort study of 123 238 Chinese patients from 2006 to 2014. Serum urate concentrations were measured in 2006, 2008, 2010, and 2012. Incident AF cases were identified via biennial 12-lead ECG assessment. We used a Cox proportional hazards model to examine the sex-specific associations of cumulative average serum urate and changes in serum urate accounting for baseline level with risk of incident AF. We also assessed the joint associations of serum urate and high-sensitivity C-reactive protein levels. Comparing extreme categories, participants with the highest quintile of serum urate had 1.91-fold higher risk of AF (adjusted hazard ratio: 1.91; 95% CI, 1.32-2.76; P=0.001 for trend). Participants with both high serum urate and high-sensitivity C-reactive protein had 2.6-fold elevated risk of incident AF compared with those with normal levels of serum urate and high-sensitivity C-reactive protein (adjusted hazard ratio: 2.63; 95% CI, 1.63-4.23). Conclusions-High serum urate levels and increases in serum urate over time were associated with increased risk of incident AF. Patients with high levels of both serum urate and high-sensitivity C-reactive protein had substantially higher risk of AF.