Does Hypertension Mediate the Association of the Serum Uric Acid-to-Albumin Ratio with Mortality in U.S. Adults? A Prospective Cohort Study

(1) Background: The uric acid-to-albumin ratio (UAR) has emerged as a potential inflammation and oxidative stress biomarker for cardiovascular health; however, its association with mortality risk in the general population and the mediating role of hypertension remain understudied. (2) Methods: The data set comprised 52,534 participants aged 18 years and older from the National Health and Nutrition Examination Survey (NHANES) database, collected between 1999 and 2018. UAR was calculated as the ratio of uric acid (mg/dL) to albumin (g/dL). Covariates included demographic factors, lifestyle variables, and health conditions. The primary outcome was all-cause mortality, with specific-cause mortality as a secondary outcome. Cox proportional hazard models and restricted cubic spline regression (RCS) were used to assess the correlation between UAR levels and risk of death, and mediation analysis was performed to evaluate the role of hypertension in the UAR-mortality relationship.(3) Results: Higher UAR levels were significantly associated with an increased risk of all-cause mortality (hazard ratio [HR], 1.91; 95% confidence interval [CI], 1.77-2.05) and specific cause-related mortalities, particularly heart disease and nephropathy. A strong association was observed between hypertension and mortality (HR, 1.44; 95% CI, 1.36-1.53). The results of the mediation analysis indicated that hypertension played a role in mediating the relationship between UAR and mortality. The mediation effect estimate was -14.34 (95% CI: -18.02, -10.67), p<0.0001, and the proportion mediated by hypertension was 6.09%. This suggests that UAR has a direct impact on mortality, independent of its effect on hypertension. (4) Conclusions: The results of our study indicate a significant correlation between UAR, hypertension, and mortality. This suggests that UAR may serve as a potential biomarker for early risk identification and an antioxidant target for further clinical interventions.