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Expression and clinical significance of CD69 and early growth response (EGR1) in plasma of patients with coronary heart disease (CHD) were investigated. A total of 194 patients with CHD and 130 healthy subjects, respectively, were selected as CHD and control group, clinical data were collected and coronary angiography was performed. RT-qPCR was used to detect the expression of EGR1. Flow cytometry was used to detect the expression level of CD69 and the receiver operating characteristic curve was used to analyze the values of relative expression of CD69 and EGR1. The relative expression of CD69 in plasma of patients with CHD was higher than that in control group, while the relative expression of EGR1 was lower than that in control group. The relative expression of EGR1 in plasma of patients with CHD was negatively correlated with lipoprotein a [Lp(a)] and high sensitive C-reactive protein (hs-CRP) (r=−0.394 and −0.524, P<0.05), and the relative expression of CD69 in peripheral blood was positively correlated with [Lp(a)] and hs-CRP (r=0.352 and 0.402, P<0.05). The area under curve (AUC) of the relative expression of CD69 in peripheral blood of patients with CHD in evaluating the course of the disease of patients was 0.889 (95% CI: 0.822–0.958). The AUC of the relative expression of EGR1 in plasma in evaluating the course of the disease of patients was 0.933 (95% CI: 0.867–0.978). By the combined detection of CD69 and EGR1, it was found that the AUC was 0.954 (95% CI: 0.887–0.982). The expression level of EGR1 in plasma of patients with CHD decreased, while the expression level of CD69 increased, and both of them were related to the severity of the disease of patients, which could be used as an indicator to evaluate the progression of the patients' conditions. [ABSTRACT FROM AUTHOR]