Vitamin D as a mediator in the J-shaped association between serum uric acid and all-cause and cardiovascular mortality in patients with cardiovascular–kidney–metabolic syndrome: A prospective cohort study

The relationship between serum uric acid (UA) and mortality in patients with cardiovascular-kidney-Metabolic (CKM) syndrome remains unclear. We hypothesized that elevated UA increases mortality nonlinearly and is partly mediated by vitamin D. Using NHANES data (2007-2016) from 25,979 adults with CKM stages 0 to 4, we performed Cox regression, threshold analysis, and causal mediation analysis. During a median follow-up of 93.0 months, 2264 all-cause and 689 cardiovascular deaths occurred. A J-shaped relationship existed between UA and mortality. Each 1 mg/dL increase in UA increased fully adjusted risks of all-cause (HR = 1.06, 95% CI: 1.02-1.09) and cardiovascular mortality (HR = 1.11, 95% CI: 1.04-1.18). Thresholds were identified at 6.6 mg/dL and 7.1 mg/dL. Participants aged ≤60 years showed higher all-cause mortality risk (HR = 1.15, 95% CI: 1.06-1.25). Serum 25(OH)D negatively correlated with UA (β = -0.064, P < .00001) and mediated 14.55% of its effect on all-cause mortality. High UA beyond specific thresholds predicts mortality in CKM syndrome, partially mediated by vitamin D. Interventions on UA and vitamin D may improve outcomes.