Predictive value of uric acid-to-high-density lipoprotein cholesterol ratio for cardiometabolic multimorbidity in middle-aged and older adults: A nationwide prospective cohort study

Cardiometabolic multimorbidity (CMM) is an escalating public health challenge. The uric acid (UA)-to-high-density lipoprotein cholesterol (HDL-C) ratio (UHR) is a composite biomarker reflecting metabolic disturbance, but prospective evidence regarding the association between UHR and CMM remains limited. This prospective cohort study included 7435 adults aged ≥ 45 years from China Health and Retirement Longitudinal Study followed from 2011 to 2018. Cox proportional hazards models and restricted cubic spline analyses were used to examine the associations of UHR and cumulative UHR (CumUHR) with CMM. Receiver operating characteristic curves, net reclassification improvement, and integrated discrimination improvement were used to compare the incremental predictive performance of UHR and CumUHR with that of UA and HDL-C alone. Subgroup and sensitivity analyses were conducted to test the robustness of the findings. Among the 7435 participants, 1748 developed CMM. Kaplan-Meier analysis showed that the cumulative event rate of CMM increased progressively across UHR quartiles (log-rank + < .001). In the fully adjusted model, the highest UHR quartile (Q4) was associated with a significantly increased risk of CMM compared with the lowest quartile (Q1) (hazard ratio = 1.48, 95% confidence interval 1.27-1.77). When cumulative exposure was considered, elevated CumUHR remained an independent predictor of CMM (hazard ratio = 1.26, 95% confidence interval 1.15-1.39). Restricted cubic spline analyses further demonstrated significant nonlinear associations of both UHR and CumUHR with CMM risk, with inflection points observed around 8.5 for UHR and 35.7 for CumUHR. Furthermore, UHR and CumUHR showed better predictive performance for CMM than their individual components, with higher areas under the curve and significant improvements in net reclassification improvement and integrated discrimination improvement, whereas UA and HDL-C alone did not significantly improve these predictive indices. Higher UHR and CumUHR levels were independently associated with an increased risk of CMM in middle-aged and older adults. As composite indicators integrating UA and HDL-C, UHR and CumUHR may provide complementary information for cardiometabolic risk assessment and may help identify individuals at elevated risk of CMM when considered alongside established clinical risk factors.