Objective To investigate the correlation between circulating exosomal miR-485-3p, miR-32- 5p expression, and the incidence of early onset coronary heart disease (CHD). Methods This study retrospectively included 50 patients with a confirmed diagnosis of early onset CHD from October 2023 to May 2024 as the observation group and 50 matched, healthy individuals without CHD as the control group. Demographic and clinical data were collected and compared. Multivariate logistic regression analysis was applied to evaluate the significant predictors of early - onset CHD. Additionally, Spearman correlation analysis was used to assess the relationship between plasma exosomal miR 485-3p, miR-32-5p levels, and CHD occurrence and severity, indicated by the Gensini score. The diagnostic utility of exosomal miR-485-3p and miR-32-5p, individually and combined, was assessed using receiver operating characteristics (ROC) curve analysis. Results The observation group exhibited significantly higher proportions of family history of CHD, smoking history, low density lipoprotein (LDL) levels, miR-485-3p, miR325p, and Gensini scores than the control group (P<0.05). Logistic regression analysis indicated that smoking history, family history of CHD, LDL, miR-485-3p, and miR-32-5p were key risk factors for early onset CHD, the OR values were 6. 997 (95% CI: 1.578-31.027), 16.671 (95% CI: 1.666166.799), 2.632 (95% CI: 1.060-6.537), 12. 717 (95% CI: 2. 629 61.505), 6.000 (95% CI: 1.83919.571). respectively. Positive correlations were found between early onset CHD and elevated levels of circulating exosomal miR-485-3p and miR-32-5p (r=0.525 and 0. 548, respectively; P< 0.05), as well as between the Gensini score and these two exosomal miRNAs (r=0.485 and 0.506, respectively; P < 0.05). The ROC curve analysis yielded the area under ROC curve (AUC) values of 0. 927 and 0. 936 for miR-485-3p and miR-32-5p, respectively, with a combined predictive AUC of 0.957. Conclusion Circulating exosomal miR 485-3p and miR-32-5p are upregulated in early onset CHD, demonstrating positive correlations with both disease incidence and coronary lesion severity. These miRNAs may serve as predictive biomarkers for early onset CHD, with higher diagnostic accuracy when combined. [ABSTRACT FROM AUTHOR]