Serum uric acid and the trajectory of cardiometabolic multimorbidity: a prospective study conducted with data from the UK Biobank

OBJECTIVE: This study aimed to investigate the role of serum uric acid (SUA) in disease progression from baseline to first cardiometabolic disease (FCMD), subsequent cardiometabolic multimorbidity (CMM), and mortality. METHODS: We conducted a prospective analysis using UK Biobank data (n = 418,765). CMM was defined as the coexistence of at least at least two cardiometabolic conditions out of type 2 diabetes (T2D), ischemic heart disease (IHD), and stroke. Multi-state models were employed to analyze the associations between SUA levels and disease transitions across different stages, including disease-specific analyses for individual cardiometabolic diseases. RESULTS: During follow-up, 54,946 participants developed FCMD, of whom 6,260 progressed to CMM. Each 1 mg/dL increase in SUA was associated with higher risks of FCMD [HR: 1.08 (1.07, 1.09)], transition from FCMD to CMM [HR: 1.07 (1.05, 1.10)], and all-cause mortality from all states [HR 1.04 (1.03, 1.05) from baseline to death; HR 1.03 (1.01, 1.05) from FCMD to death; HR 1.08 (1.03, 1.12) from CMM to death]. When FCMD was further divided into IHD, stroke, and T2D, we found that SUA played different roles in disease-specific transitions even within the same stage, with the strongest associations observed for incident T2D [HR: 1.15 (1.14, 1.17)] and stroke-to-CMM progression [HR: 1.11 (1.04, 1.18)]. These associations remained robust across sensitivity analyses and were stronger in younger participants (< 60 years). CONCLUSIONS: Elevated SUA levels serve as a potential marker across the entire trajectory of cardiometabolic disease progression. These findings suggest the importance of SUA monitoring and management in preventing cardiometabolic disease progression.