BackgroundThe association between insulin resistance and the comorbidity of ASCVD with hyperuricemia remains to be further explored. This study utilizes several insulin resistance indicators, including HOMA-IR, METS-IR, TyG, TyG-WHtR, TyG-WC, and TyG-BMI, to assess insulin resistance levels and investigate their association with the comorbidity of ASCVD and hyperuricemia in the study population.MethodsThis cross-sectional study included 16,092 participants from the National Health and Nutrition Examination Survey conducted between 2005 and 2018. Participants younger than 20 years old and those with missing data for exposure-related indicators were excluded. Six insulin resistance-related traditional and novel indicators—HOMA-IR, METS-IR, TyG, TyG-WC, TyG-WHtR, and TyG-BMI—were used as exposure factors, while the outcome was ASCVD with hyperuricemia. This study's analyses incorporated sample weights, clustering, and stratification to account for the complex multi-stage stratified probability sampling design employed in NHANES.ResultsA total of 523 patients were diagnosed with ASCVD with hyperuricemia. The results were adjusted for different covariates. METS-IR showed a consistent positive correlation with the outcome in all models, with model 3 indicating that for each unit increase, the OR was 1.04 (95% CI: 1.03–1.05, p