Development and validation of a machine learning model for predicting vulnerable carotid plaques using routine blood biomarkers and derived indicators: insights into sex-related risk patterns

BACKGROUND: Early detection of vulnerable carotid plaques is critical for stroke prevention. This study aimed to develop a machine learning model based on routine blood tests and derived indices to predict plaque vulnerability and assess sex-specific risk patterns across biomarker value ranges. METHODS: We retrospectively included 1701 hospitalized patients from Suzhou Municipal Hospital (2019-2020), selected from an initial cohort of 10,028 individuals. All patients underwent carotid ultrasound, with vulnerable plaques identified using predefined imaging criteria. A total of 30 laboratory variables-including blood count, coagulation, and biochemistry-were extracted, alongside derived indices such as triglyceride-glucose index (TyG), atherogenic index of plasma (AIP), neutrophil-to-lymphocyte ratio (NLR) and others. Features were standardized and selected based on statistical and clinical relevance. Five machine learning models were trained using a 7:3 train-test split and evaluated by cross-validation. Model performance was assessed using AUC, sensitivity, and specificity. The best model was interpreted using SHapley Additive exPlanations (SHAP) analysis. Sex differences were explored using Mann-Whitney U tests and restricted cubic spline (RCS) modeling across value intervals. RESULTS: The Random Forest model showed the highest predictive performance (AUC = 0.847; 95% CI 0.791-0.895; specificity = 89.4%; sensitivity = 64.2%). SHAP analysis identified gender, age, fibrinogen, NLR, creatinine, fasting blood glucose, uric acid to high-density lipoprotein ratio (UHR), TyG, systemic inflammation response index (SIRI), and lymphocyte count as top predictors. Significant sex-specific differences in SHAP values were observed for key biomarkers, including age, UHR, TyG, SIRI, and others. RCS modeling further revealed distinct sex-related patterns in plaque vulnerability across biomarker value ranges. CONCLUSION: A Random Forest model integrating routine blood markers and derived indices accurately predicted vulnerable carotid plaques. The results underscore the importance of sex-specific risk assessment, highlighting differential effects of key biomarkers across genders and value intervals.