Exploring the predictive values of CRP and lymphocytes in coronary artery disease based on a machine learning and Mendelian randomization

Purpose: To investigate the predictive value of leukocyte subsets and C-reactive protein (CRP) in coronary artery disease (CAD). Methods: We conducted a Mendelian randomization analysis (MR) on leukocyte subsets, C-reactive protein (CRP) and CAD, incorporating data from 68,624 patients who underwent coronary angiography from 2010 to 2022. After initial screening, clinical data from 46,664 patients were analyzed. Techniques employed included propensity score matching (PSM), logistic regression, lasso regression, and random forest algorithms (RF). Risk factors were assessed, and the sensitivity and specificity of the models were evaluated using receiver operating characteristic (ROC) curves. Additionally, survival analysis was conducted based on a 36-month follow-up period. Results: The inverse variance weight (IVW) analysis showed that basophil count (OR 0.92, 95% CI: 0.84-1.00, P = 0.048), CRP levels (OR 0.87, 95% CI: 0.73-1.00, P = 0.040), and lymphocyte count (OR 1.10, 95% CI: 1.04-1.16, P = 0.001) are significant risk factors for CAD. Using LASSO regression, logistic regression, and RF analysis, both CRP and lymphocyte counts were consistently identified as risk factors for CAD, prior to and following PSM. The ROC curve analysis indicated that the combination of lymphocyte and CRP levels after PSM achieves a higher diagnostic value (0.85). Survival analysis revealed that high lymphocyte counts and low CRP levels are associated with a decreased risk of Major Adverse Cardiovascular Events (MACE) (P < 0.001). Conversely, a higher CRP level combined with lymphocyte counts correlates with a poorer prognosis. Conclusion: There is a causal relationship between lymphocytes, CRP and CAD. The combined assessment of CRP and lymphocytes offers diagnostic value for CAD. Furthermore, high CRP levels coupled with low lymphocyte counts are associated with a poor prognosis.