Longitudinal trajectories of serum uric acid and incident cardiovascular–kidney–metabolic syndrome components: Outcome-specific mediating role of adiposity in a large community-based cohort

Objective Serum uric acid links cardiovascular, kidney, and metabolic health; however, its role within the cardiovascular–kidney–metabolic syndrome framework is poorly understood, especially its long-term dynamics. We aimed to identify serum uric acid trajectories and investigate their outcome-specific associations with incident cardiovascular–kidney–metabolic components to clarify the mediating role of adiposity. Methods We analyzed data from 6052 participants (age ≥40 years) initially free from cardiovascular–kidney–metabolic components from a community-based cohort. Latent class growth analysis identified serum uric acid trajectories over a median 8-year follow-up. Generalized linear mixed models and causal mediation analysis were employed to assess associations with incident hypertension, hyperglycemia, and hypercholesterolemia as well as the role of body mass index. Results We identified “low-stable” (64.8%) and “high-increasing” (35.2%) serum uric acid trajectories. Compared with the “low-stable” group, the “high-increasing” group had elevated risks of incident hypertension (adjusted odds ratio: 1.26, 95% confidence interval: 1.15–1.37), hyperglycemia (adjusted odds ratio: 1.53, 95% confidence interval: 1.22–1.93), and hypercholesterolemia (adjusted odds ratio: 1.31, 95% confidence interval: 1.12–1.52). Mediation analysis revealed distinct pathways; the effect on hyperglycemia was predominantly mediated by body mass index (60.5%, p < 0.001), with the direct effect rendered non-significant. In contrast, body mass index was a partial mediator for hypertension (37.5%) but a suppressor for hypercholesterolemia (−18.1%), masking a stronger direct association. Conclusions Long-term serum uric acid trajectories are powerful predictors of incident cardiovascular–kidney–metabolic components; however, their impact is channeled through distinct, adiposity-dependent and adiposity-independent pathways. Monitoring serum uric acid dynamics, not just static levels, is crucial for early, stratified risk assessment of cardiovascular–kidney–metabolic syndrome.