Cumulative Serum Uric Acid Exposure and Its Time Course With the Risk of Incident Stroke

Abstract

BACKGROUND: Evidence on the longitudinal associations between serum uric acid (SUA) and stroke was limited and yielded inconsistent conclusions. We aimed to investigate the associations of cumulative SUA (cumSUA), incorporating the time course of cumSUA accumulation, with the risk of stroke. METHODS: The prospective cohort study enrolled 50 871 participants from Kailuan, China. CumSUA from 2006 to 2010 was derived by calculating the means of SUA values between consecutive examinations and multiplying by time intervals between visits. Time course of cumSUA accumulation was categorized as the slope of SUA versus time or by splitting the overall accumulation into an early (cumSUA 06-08 ) and late accumulation (cumSUA 08-10 ). Participants were classified by cumSUA quartiles, SUA slope (negative versus positive), and the combined median cumSUA (1105.21 μmol/L×year) with SUA slope, respectively. The associations with incident stroke between 2010 and 2019 were evaluated with competing risk model. RESULTS: During a median follow-up of 9.02 years, 2217 cases of incident stroke were identified. In the multivariable-adjusted model, a higher risk of stroke was observed in participants with the highest quartile versus the lowest quartile of cumSUA (subdistribution hazard ratio, 1.15 [95% CI, 1.01–1.31]), and those with a negative versus positive SUA slope (subdistribution hazard ratio, 1.09 [95% CI, 1.01–1.19]). Consistently, a later accumulation of SUA was not associated with the risk of stroke after adjustment for an early accumulation, indicating early accumulation may contribute more to the risk of stroke than later accumulation. When cumSUA was incorporated with its time course, those with changes in cumSUA suggesting early accumulation had elevated risk of stroke (subdistribution hazard ratio, 1.17 [95% CI, 1.03–1.33]). Similar results were observed for ischemic stroke. CONCLUSIONS: Incident stroke risk was associated with cumulative exposure to SUA and its accumulation time course. Early SUA accumulation resulted in a greater risk compared with later accumulation, underscoring the importance of early control of SUA to an optimal level.