Abstract
Background: The association between the uric acid to albumin ratio (UAR) and mortality in the general population remains poorly understood. This study aimed to investigate the associations of UAR with all-cause and cardiovascular mortality among American adults. Methods: The study population comprised 19190 U.S. adults from the National Health and Nutrition Examination Survey (NHANES) conducted between 2003 and 2018. Mortality outcomes were ascertained through linkage to National Death Index (NDI) records, with follow-up extending to December 31, 2019. Multivariate Cox proportional hazards regression models with restricted cubic splines and trend analyses were utilized to assess the association between UAR and both all-cause and cardiovascular mortality. Subgroup analyses were conducted to assess whether the association between UAR and mortality varied across different demographic and clinical groups. Results: During a median follow-up period of 98 months, 2296 all-cause deaths were recorded, including 597 deaths related to cardiovascular disease (CVD). After multivariable adjustment, no linear trends were observed between UAR and either all-cause or CVD mortality. Kaplan-Meier curves revealed a significant increase in both all-cause and CVD mortality with associated with higher UAR levels (p for log-rank test < 0.001 for both). Restricted cubic spline models indicated a J-shaped nonlinear association between UAR and both all-cause and CVD mortality, with inflection points at UAR levels of 1.40 for all-cause mortality and 1.88 for CVD mortality. Specifically, UAR values exceeding these inflection points were positively associated with mortality (HR 2.11, 95% CI = 1.74-2.55 for all-cause mortality; HR 5.21, 95% CI = 3.06-8.87 for CVD mortality). Conversely, UAR values below the inflection points were inversely associated with all-cause mortality (HR 0.68, 95% CI = 0.50-0.93) but not significantly associated with CVD mortality (HR 1.07, 95% CI = 0.73-1.58). This association remained consistent across subgroup analyses stratified by sex, age, race, diabetes, hypertension, BMI, and smoking status, with no significant interactions between these characteristics and UAR (p for interaction > 0.05). Conclusion: This study identified a significant association between the UAR and both all-cause and CVD mortality in the general population. A J-shaped nonlinear association was observed, with inflection points at UAR levels of 1.40 for all-cause mortality and 1.88 for CVD mortality.