Abstract
BACKGROUND: Although serum uric acid (SUA) has been frequently linked to a range of cardiorenal diseases, its potential role in disease trajectories leading to incident sudden cardiac arrest (SCA) has not been previously explored using a multistate modeling approach.</p>
OBJECTIVE: This study aimed to investigate the long-term effect of SUA on SCA and the possible intermediate diseases.</p>
METHODS: Based on the UK Biobank cohort, the Cox proportional hazard model was applied to explore associations between SUA and SCA. Chronic kidney disease and acute kidney injury and major adverse cardiovascular events (MACEs) were selected as intermediate conditions, and a multistate model was used for trajectory analysis.</p>
RESULTS: A total of 468,427 participants were included. During a median follow-up of 14.5 years, 2972 participants developed SCA. The hazard ratios (HRs) for SCA were 1.12 (1.08-1.15) per 1 mg/dL increment of SUA. Restricted cubic spline demonstrated a significant positive and nonlinear correlation between SUA and risk of incident SCA (P for nonlinearity < .01). Most prominently, SUA and hyperuricemia could induce SCA by promoting transitions from baseline health to chronic kidney disease/acute kidney injury (HRs 1.10 and 1.29) and then to SCA (HRs 1.15 and 1.32). Less importantly, SCA could be developed through transitions from baseline health to MACE (HRs 1.05 and 1.14) and further to SCA (HRs 1.08 and 1.25).</p>
CONCLUSION: This study provides novel and compelling evidence that the long-term effect of SUA could promote the development of SCA, with renal insufficiency emerging as a more significant intermediate condition than MACE.</p>