The relationship between UHR and heart failure: insights from two large database studies

Heart failure (HF) is a major cardiovascular disease that causes high incidence and mortality rates worldwide. The uric acid to high-density lipoprotein ratio (UHR), as an emerging inflammatory and metabolic composite indicator, has recently been considered to be associated with various metabolic diseases. However, its value in predicting the risk of heart failure still requires further validation. This study aims to explore the association between the UHR indicator and the risk of heart failure by analyzing the nationally representative NHANES cohort and the MIMIC-IV clinical cohort. This study utilized the NHANES (1999–2018) database as the discovery cohort and the MIMIC-IV clinical cohort as the external validation cohort. Baseline characteristics of the two populations were first assessed, and ROC curves were plotted to evaluate the predictive value of UHR. Univariate analysis and variance inflation factor (VIF) were used for collinearity diagnostics. Subsequently, multivariate logistic regression models were employed to assess the independent association between UHR and heart failure, and restricted cubic spline (RCS) curves were used to evaluate the dose-response relationship between UHR and heart failure risk. To enhance the robustness of the results, inverse probability of treatment weighting (IPTW) was applied in the MIMIC-IV cohort to balance confounders between groups. Finally, sensitivity and subgroup analyses were conducted to verify the robustness of the conclusions. The discovery cohort (NHANES) included 48,762 participants (2,047 in the heart failure group), and the validation cohort (MIMIC-IV) included 238 participants (124 in the heart failure group). Multivariate Logistic analysis indicated that in the fully adjusted model (Model 2), a high UHR level (> 11.73) in the NHANES cohort was significantly associated with an increased risk of heart failure (OR = 1.45, 95%CI: 1.22–1.72, P < 0.001); in the MIMIC-IV cohort, a high UHR level (≥ 13.03) was also an independent risk factor for heart failure (OR = 2.02, 95%CI: 1.03–3.94, P = 0.04). Restricted cubic spline (RCS) analysis confirmed a nonlinear dose-response relationship in NHANES (P-nonlinear < 0.05), while a positive trend was observed in MIMIC-IV. Subgroup analysis showed that the association between UHR and heart failure was consistent across different age, BMI, and other stratifications. This study confirms that high UHR level is an independent predictor of heart failure risk and can serve as an auxiliary biomarker for clinical assessment of heart failure risk.