Abstract
BACKGROUND: In-stent neoatherosclerosis (ISNA) is the leading cause of in-stent restenosis (ISR) and stent thrombosis, often signifying stent placement failure. Prior studies have demonstrated an association between uric acid (UA) levels and ISNA, while high-density lipoprotein (HDL) dysfunction may contribute to both target lesion revascularization and ISNA progression. However, no comprehensive study has evaluated the combined role of UA and HDL in ISNA. The UA to HDL ratio (UHR), an integrative metabolic-inflammatory biomarker, has been studied across various cardiovascular and metabolic disorders. This study examines the association between UHR and ISNA and assesses whether UHR predicts ISNA more accurately than UA or HDL alone. METHODS: We conducted a retrospective cross-sectional study using clinical data from the Affiliated Hospital of Zunyi Medical University (2014–2025). Multivariable logistic regression models were employed to assess the association between the UHR and ISNA, with adjustments for clinically relevant confounders. Potential nonlinear relationships were examined using restricted cubic spline (RCS) regression with three knots. To validate the predictive utility of UHR, we performed subgroup analyses stratified by sex, age and comorbidities, along with ROC curve analysis to determine the optimal cutoff value and area under the curve (AUC). RESULTS: In multivariable regression analysis of 514 participants, each unit increase in UHR was associated with a 14.1% increased risk of ISNA (OR 1.141, 95% CI 1.113–1.170; P < 0.001). This association remained significant after adjusting for gender, age, smoking status, diabetes mellitus, hypertension, chronic kidney disease, prior stroke history, triglyceride levels, relevant medication use, as well as stent type, lesion location, and pre-dilation. RCS regression confirmed a linear relationship (P for non-linearity = 0.517). This positive correlation was consistent across most subgroups, further supporting the reliability of the findings. ROC analysis revealed that UHR had superior predictive performance for ISNA (AUC 0.793, 95% CI 0.753–0.832) compared to UA (AUC 0.760) and HDL (AUC 0.688), supporting its potential clinical utility. CONCLUSIONS: In OCT-diagnosed ISR patients, elevated UHR levels showed both independent association with NA development and superior predictive performance compared to UA and HDL alone. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-026-05640-z.