Abstract
BACKGROUND: Frailty represents a common condition among older individuals, linked to heightened vulnerabilities for negative health effects and death. The ratio of uric acid (UA) to high-density lipoprotein cholesterol (HDL-C) (UHR) serves as a novel indicator for inflammatory and oxidative processes, although its connections to frailty rates and death risks in frail elderly populations are still unexamined. Our research explored the relationships between UHR, frailty occurrence, and death results in frail older adults in the United States, along with evaluating the intermediary effects of eating habits. METHODS: Data from 11,751 participants (weighted n = 364.6 million individuals) across 12 NHANES cycles (1999-2023) were analyzed. UHR was calculated as [serum UA (mg/dL) / HDL-C (mg/dL)] × 100%. Frailty was assessed using a 49-item deficit accumulation index and participants needed to respond to a minimum of 39 out of 49 items. A frailty index ≥ 0.25 indicates frailty. Mortality data were linked from the National Death Index up to December 31, 2019. Dietary patterns were evaluated via the Mediterranean diet score, the Healthy Eating Index-2020, the Dietary Approaches to Stop Hypertension Index, the Planetary Health Diet Index-US, and the Dietary Inflammation Index (DII). Weighted multivariable logistic/Cox regressions, restricted cubic splines, threshold analyses, subgroup interactions, and mediation models were employed, adjusting for demographics, lifestyle, clinical covariates, and diverse diet scores. RESULTS: Higher UHR was associated with increased frailty risk (fully adjusted OR per unit: 1.07, 95% CI: 1.06-1.08) in a linear pattern (P(nonlinearity) = 0.640). In frail participants (n = 2,498; median follow-up 5.92 years), UHR predicted higher all-cause mortality (ACM; HR: 1.02, 95% CI: 1.01-1.03) and cardiovascular mortality (CVM; HR: 1.04, 95% CI: 1.02-1.05), with nonlinear U-shaped relationships (both P(nonlinearity) < 0.001) and thresholds at 9.07 (ACM) and 9.54 (CVM). Tertile analyses showed dose-dependent effects, with T3 vs. T1 yielding OR = 2.05 (frailty), HR = 1.28 (ACM), and HR = 1.51 (CVM). Associations of UHR and frailty were stronger in females (P(interaction) = 0.016), living alone (P(interaction) = 0.008), and alcohol consumers (P(interaction) = 0.048). No interaction effects of the subgroups were observed in the associations of UHR and mortality outcomes in frailty participants. Sensitive analysis revealed the robustness and generalizability of our findings. Exploratory analysis of dietary patterns in the UHR-frailty association demonstrated that dietary patterns mediated 1.35-5.06% of the UHR-frailty link, with DII exerting the largest effect (5.06%). CONCLUSIONS: Elevated UHR independently predicts frailty and mortality in elderly U.S. adults. As an accessible biomarker, UHR offers potential for early risk assessment and intervention in aging populations. Future trials should validate these findings and explore therapeutic targeting of UHR.