Uric acid-based nutritional and inflammatory biomarkers for predicting cardiovascular-kidney-metabolic syndrome and mortality: a population-based study with external validation

Abstract

Uric acid-to-HDL cholesterol ratio (UHR) and uric acid-to-albumin ratio (UAR) are emerging composite biomarkers of nutrition and metabolic inflammation. This study investigates and compares their associations with advanced cardiovascular-kidney-metabolic (CKM) syndrome and all-cause mortality. This cross-sectional study included 17,833 adults from NHANES 2001-2020, with external validation in a clinical cohort of 300 hospitalized patients. Weighted logistic regression, restricted cubic spline (RCS), ROC curve, and Cox regression analyses were performed. Both UHR and UAR were significantly elevated in patients with advanced CKM syndrome (both P < 0.001) and independently associated with increased CKM risk (UHR: OR = 1.07, 95%CI: 1.06-1.09; UAR: OR = 1.08, 95%CI: 1.06-1.10). Nonlinear associations were observed for both biomarkers, with inflection points at 9.46 for UHR and 15.79 for UAR (both P for nonlinear < 0.001). In ROC analysis, UAR slightly outperformed UHR in the NHANES cohort (AUC: 0.640 vs. 0.602), whereas UHR showed superior performance in the clinical cohort (AUC: 0.787 vs. 0.686). Both biomarkers remained independently associated with all-cause mortality after full adjustment. UHR and UAR are independently associated with advanced CKM syndrome and have complementary clinical utility. UAR may be preferred for early screening, whereas UHR may be better suited for CKM diagnosis and metabolic risk stratification. Their combined use may facilitate prognosis evaluation and mortality risk warning.