BACKGROUND: Coronary artery disease (CAD) is a leading cause of cardiovascular morbidity and mortality. Exosomal microRNAs (miRNAs) play a role in vascular atherosclerosis and are involved in the pathophysiology of CAD. This study aimed to validate the associations of eight exosomal miRNAs with CAD and assess their relevance to disease severity. METHODS: A total of 875 participants who underwent elective coronary angiography were enrolled between January 2022 and August 2023. Blood samples were collected during angiography, and exosomal miRNAs were analyzed using quantitative polymerase chain reaction (qPCR). Only miRNAs with detection rates above 50% and reproducible results were included. Differential expression was evaluated using the Wilcoxon rank-sum test (also known as the Mann-Whitney U test), with statistical significance set at p <
0.05. RESULTS: Participants in the severe CAD group (with significant three-vessel disease) were older and had a higher incidence of hypertension than those in the non-CAD group (with patent coronary arteries). miRNA-382-3p was significantly upregulated in patients with severe CAD, correlating with the presence of disease. miRNA-3613-3p and miRNA-185-5p exhibited variable expression patterns, warranting further investigation. miRNA-200a-3p expression did not significantly differ between the groups, whereas miRNA-432-5p, miRNA-125a-5p, miRNA-151a-3p, and miRNA-328-3p had low detection rates, limiting their analytical utility. CONCLUSIONS: miRNA-382-3p is associated with severe CAD and may contribute to understanding disease mechanisms and therapeutic development. Further studies are necessary to validate its clinical significance and broader application.