Objective To explore the association between serum uric acid levels and the cumulative incidence risk of atrial fibrillation, and to evaluate the predictive value of different uric acid levels for the onset of atrial fibrillation.

Methods A retrospective selection of 451 879 participants from the large-scale prospective epidemiological cohort UK Biobank, aged 40-69 years, all completed a median follow-up of 13.6 years. Participants were divided into groups based on the interquartile range of serum uric acid levels (Q1–Q4) related to gender and whether they were diagnosed with hyperuricemia. Cox proportional hazards model, sensitivity analysis, and other methods were used to compare baseline data and atrial fibrillation incidence during follow-up among each group of participants.

Results  Individuals with higher baseline uric acid levels tended to be older, more obese, and had lower education levels and a history of cancer, along with significantly higher levels of triglyceride, low-density lipoprotein cholesterol, and C-reactive protein, but lower high-density lipoprotein cholesterol levels (P<0.001); the highest uric acid group showed the highest diabetes prevalence (6.49%). Participants with higher serum uric acid levels (log-rank P<0.05) or diagnosed with hyperuricemia had significantly higher incidence of atrial fibrillation (P<0.001). After adjusting for potential confounders, compared to Q1 uric acid level group, the Q4 level was associated with a 20% increased risk of atrial fibrillation (HR=1.20, 95%CI 1.16–1.25). Each 74.7 μmol/L increase in uric acid level was associated with a 9% increased incidence risk of atrial fibrillation (HR=1.09, 95%CI 1.08–1.11). Individuals with hyperuricemia had a 20% increased incidence risk of atrial fibrillation (HR=1.20, 95%CI 1.17–1.24). A nonlinear association was observed between uric acid levels and the incidence risk of atrial fibrillation (P for nonlinearity <0.01). Subgroup analysis indicated significant heterogeneity of the risk effect across subgroups, with a higher risk associated with hyperuricemia in females.

Conclusions Elevated blood uric acid levels may increase the cumulative risk of atrial fibrillation, and this pathogenic effect is significantly correlated with age, race, cancer history, body mass index, and sex.