complicated and multifactorial, because there are many confounding factors between UA and AF, such as race, sex, and any other risk factors.Our cross-sectional study in a large number of Japanese subjects undergoing health check-ups identified an independent association between UA and the prevalence of AF. 13 We could not, however, clarify the causal relationship between serum UA and AF, or determine the predictive value of UA for the incidence of AF because of its crosssectional design. Moreover, to our knowledge, research on the Japanese population has not demonstrated a relationship between baseline UA and new-onset AF. We therefore investigated this association by analyzing the stored examination data of a large number of Japanese subjects who underwent annual medical health check-ups.Background: The independent role of uric acid (UA) as a risk factor for atrial fibrillation (AF) has not been fully elucidated.
Methods and Results:We studied 111,566 subjects (53,416 men; 58,150 women) who underwent annual health check-ups. We divided them by sex into tertile of baseline UA. To investigate the predictive power of UA for new-onset AF, we performed Cox proportional hazard analysis including UA tertiles, body mass index, creatinine, smoking and drinking status, and presence of hypertension, diabetes, and dyslipidemia. During 4.1 years, 467 men (0.87%) and 180 women (0.31%) had AF (P<0.001). Cut-off points for tertiles of UA were as follows: women, ≤3.9, 4.0-4.8, and ≥4.9 mg/dL; men, ≤5.4, 5.5-6.4, and ≥6.5 mg/dL. Hazard ratio (HR) for third to first tertile was 1.74 (95% CI: 1.15-2.70; P=0.008), whereas there were no differences between tertiles in men. Rate of new-onset AF was significantly higher in the group with initially increased UA (ΔUA ≥0.3 mg/dL) than that with unchanged UA (ΔUA, −0.2 or +0.2 mg/dL) in the third tertile of baseline UA in both sexes.
Conclusions:Higher baseline UA was significantly associated with higher AF incidence in women. Initial increase in UA was significantly associated with AF incidence when baseline UA was ≥6.5 mg/dL in men, and ≥4.9 mg/dL in women.