Association of uric acid to high-density cholesterol ratio (UHR) with biological age acceleration: evidence from NHANES 2009–2018

The global population is rapidly aging, presenting significant public health challenges, particularly with the increased risk of chronic diseases. Biological age acceleration refers to a faster-than-expected aging process, which is associated with an increased risk of age-related chronic diseases. Uric acid to high-density lipoprotein cholesterol ratio (UHR) is a novel biomarker that reflects metabolic disturbances and has been linked to various chronic conditions. Understanding the relationship between UHR and biological age acceleration, as well as its modifiable risk factors, is crucial for developing strategies aimed at promoting healthy aging and managing chronic diseases in older adults. Using data from a cohort study, the ratio of uric acid to high-density cholesterol (UHR), uric acid (UA), and high-density lipoprotein (HDL) were assessed in relation to biological age acceleration, including phenotypic age acceleration (PhAA) and Klemera-Doubal method age acceleration (KDM-AA), through multiple linear and logistic regression models, adjusted for demographic characteristics, lifestyle factors, and medical histories. Restricted cubic spline (RCS), subgroup, and interaction analyses were also conducted. Subgroups were stratified according to age (< 60 vs. ≥60 years), sex (male vs. female), race (Black vs. others), BMI (< 30 vs. ≥30), hypertension (yes/no), cardiovascular disease (yes/no), cancer (yes/no), and physical activity level (< 600, 600-3999, and ≥ 4000 min/week). The results reveal significant associations between elevated UHR, UA levels, reduced HDL cholesterol, and accelerated biological aging. RCS regression analyses revealed a complex relationship between UHR and age acceleration, with a non-linear association with PhAA and a linear relationship with KDM-AA. Subgroup analysis showed that the association between UHR and biological age acceleration remained robust across all groups. Interaction analyses revealed differential effects across subgroups, particularly among individuals with varying physical activity levels, cardiovascular disease, and hypertension status. This study demonstrates a significant positive association between UHR and markers of biological age acceleration. These findings suggest that UHR could serve as a potential biomarker for aging and chronic disease management in older adults, offering insights into strategies to reduce the burden of age-related conditions.