The predictive value of serum Dickkopf-1, Dickkopf-3 level to coronary artery disease and acute coronary syndrome

Background: Previous studies have already confirmed the association between Dickkopf (Dkk) protein and the occurrence and progression of atherosclerosis. However, there is limited clinical evidence regarding the serum levels of Dickkopf-1 (Dkk1) and Dickkopf-3 (Dkk3) in relation to atherosclerotic cardiovascular disease (ASCVD), particularly acute coronary syndrome (ACS). Materials and methods: A total of 88 healthy volunteers and 280 patients with coronary artery disease (CAD) undergoing coronary angiography for angina between October 2021 and October 2022, including 96 cases of stable angina (SA), 96 of unstable angina (UA) and 88 of acute myocardial infarction (AMI) were included finally. The serum concentrations of Dkk1 and Dkk3 were measured using electrochemiluminescence of Meso Scale Discovery. The predictive value of single or combined application of serum Dkk1 and Dkk3 in CAD and ACS were evaluated. Results: The serum levels of Dkk1 were significantly higher in the SA group, UA group, and AMI group compared to the control group. Multivariable logistic regression analysis demonstrated that elevated serum Dkk1 levels were independent predictive factors for increased risk of CAD and ACS (OR = 1.027, 95%CI = 1.019-1.034, p < 0.001; OR = 1.045, 95%CI = 1.028-1.053, p < 0.001, respectively). Receiver operating characteristic curve (ROC) analysis showed that the optimal cutoff value of serum Dkk1 for predicting ACS was 205 ng/dl, with a sensitivity of 82.6% and specificity of 96.6%. The area under the curve (AUC) was 0.930 (95%CI: 0.899-0.961, p < 0.001). Regarding Dkk3, serum Dkk3 levels were elevated in CAD patients compared to the healthy control group, and significantly higher in ACS patients compared to SA patients. Serum Dkk3 was significantly associated with increased risk of CAD and ACS (OR = 1.131, 95%CI = 1.091-1.173, p < 0.001; OR = 1.201, 95%CI = 1.134-1.271, p < 0.001, respectively). ROC curve analysis showed that the optimal cutoff value of serum Dkk3 for predicting ACS was 50.82 ng/ml, with a sensitivity of 85.9% and specificity of 87.5%. The AUC was 0.925 (95%CI: 0.894-0.956, p < 0.001). When serum Dkk1 and Dkk3 are combined as predictive factors for ACS, the AUC was 0.975. Conclusion: Serum levels of Dkk1 and Dkk3 are significantly associated with an increased risk of CAD and ACS, and they possess predictive value for CAD and ACS. The combination of serum Dkk1 and Dkk3 is a superior predictive factor for CAD and ACS.