Abstract: Objective:To explore the changes and clinical significance of peripheral blood miR-146a and miR-155 levels in patients with coronary heart disease and severe periodontitis.Methods:Thirty-two patients with coronary heart disease and severe periodontitis (group A) admitted to the hospital from January 2020 to January 2023 were selected, another 54 patients with severe chronic periodontitis admitted to the same hospital during the same period (group B) were selected, another 45 healthy individuals were selected as the control group. The levels of miR-146a and miR-155 in peripheral blood of three groups were compared. The univariate analysis of factors affecting the occurrence of coronary heart disease in patients with severe periodontitis, and logistic regression analysis of the influencing factors. The receiver operating curve (ROC) was used to analyze the value of miR-146a and miR-155 levels in predicting the occurrence of coronary heart disease in patients with severe periodontitis. Results: The levels of miR-146a in peripheral blood of group A and group B were higher than those of the control group (P<0.05), and the levels of miR-146a in peripheral blood of group A were higher than those of group B (P<0.05). The peripheral blood miR-155 levels in group A and group B were lower than those in the control group (P<0.05), and the peripheral blood miR-155 levels in group A were lower than those in group B (P<0.05). The body mass index, serum CRP, and peripheral blood miR-146a levels of patients in group A were higher than those in group B (P<0.05), while the education years and peripheral blood miR-155 levels of patients in group A were lower than those in group B (P<0.05). Logistic multivariate regression analysis showed that serum CRP, peripheral blood miR-146a, and miR-155 levels were independent risk factors for the occurrence of coronary heart disease in patients with severe periodontitis (P<0.05). ROC analysis showed that the optimal cutoff points for miR-146a and miR-155 levels in peripheral blood predicting the occurrence of coronary heart disease in patients with severe periodontitis were 1.84 and 0.60, sensitivity was 81.25% and 84.37%, the specificity was 83.33% and 72.22%, and the area under the curve (AUC) was 0.857 and 0.766, respectively. The sensitivity, specificity, and AUC of the combination of the two were 81.25%, 98.15%, and 0.942, respectively. Conclusion: The miR-146a and miR-155 levelsin peripheral blood may experience abnormal changes in patients with coronary heart disease and severe periodontitis, clinical testing of peripheral blood miR-146a and miR-155 levels can serve as sensitive indicators for predicting the occurrence of coronary heart disease in patients with severe periodontitis, and the combined predictive value is higher.