Associations of serum uric acid-to-high density lipoprotein cholesterol ratio with age-related diseases and mortality among older population in the United States

Background: Older adults experience numerous physiological and socioeconomic changes that increase the risk of chronic diseases. The uric acid to high-density lipoprotein cholesterol ratio (UHR) has emerged as a potential biomarker for assessing various health conditions. This study aimed to investigate the relationship between UHR and the prevalence of age-related diseases and mortality in a nationally representative sample of older adults in the United States. Methods: This retrospective cohort study utilized data from the National Health and Nutrition Examination Surveys (NHANES) 2001-2016 including 17,968 participants aged >= 50 years. Mortality data were obtained through the National Death Index (NDI) until December 31, 2019. UHR was calculated by dividing serum uric acid (SUA) by high-density lipoprotein cholesterol (HDL-C). Statistical analyses included Kaplan-Meier, logistic regression models, COX regression, restricted cubic spline (RCS), receiver operating characteristic (ROC), net reclassification index (NRI), integrated discrimination improvement (IDI), and mediation analyses. Results: Significant positive associations were found between UHR levels and the incidence of hypertension, diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD). Higher UHR levels also correlated with increased cardiovascular and all-cause mortality. Non-linear regressions were observed between UHR and the morbidity of diabetes (p = 0.039), CVD (p = 0.036), all-cause mortality (p = 0.004), with a consistent inflection point at 0.1067478. Subgroup analyses indicated potential effect modifications by gender, BMI, alcohol and drug consumption. UHR outperformed SUA and HDL-C in predicting CVD, as demonstrated by ROC curves and validated by NRI and IDI scores. Mediation analysis indicated that renal impairment partially mediated the link between UHR and all-cause mortality (mediation ratio: 27.39 %). Conclusion: UHR was significantly associated with the incidence of age-related diseases and mortality in adults aged over 50 years. The study provided evidence that UHR may be a more effective predictor of CVD than SUA or HDL-C alone. Our findings highlighted the potential clinical utility of UHR as a diagnostic and prognostic tool in the older population. Further research is required to generalize conclusions and understand underlying mechanisms.