Abstract

Background: Programmed cell death (PD)-1 and its ligand (PD-L1) plays crucial roles in T-cell tolerance as immune checkpoint. Previous studies reported that increased serum levels of soluble PD-L1 (sPD-L1) reflect myocardial and vascular inflammation. However, little is known about the clinical relationship between sPD-L1 and acute coronary syndrome (ACS). We investigated the relation of sPD-L1 and ACS. Methods: We prospectively measured serum levels of sPD-L1 using a commercially available enzyme-linked immunosorbent assay kit in patients with coronary artery disease (CAD) and continuous non-CAD admitted to Kumamoto University Hospital between December 2017 and June 2019. All malignant diseases, patients who underwent hemodialysis, active collagen diseases, and severe infectious diseases were excluded. Results: Totally, 446 CAD patients [ACS, n=124; chronic coronary syndrome (CCS), n=322] and 24 non-CAD patients were analyzed. The levels of sPD-L1 were significantly higher in patients with ACS than those both with non-CAD and CCS {ACS, 188.7 (111.0-260.8) pg/mL, P<0.001 vs. non-CAD [83.5 (70.8-130.4) pg/mL]; and P=0.009 vs. CCS [144.2 (94.8-215.5) pg/mL], respectively}. Univariate logistic regression analysis identified that hypertension, dyslipidemia, current smoking, usage of aspirin, beta blockers, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and the levels of low density-lipoprotein cholesterol, high sensitive C-reactive protein, and high sensitive troponin-T levels were significant factors associated with ACS. sPD-L1 was also significantly associated with ACS [odds ratio (OR): 1.003, 95 % confidence interval (CI): 1.002-1.005, P=0.001]. Multivariable logistic regression analysis with nine significant factors identified from the univariate analysis revealed that sPD-L1 was significantly and independently associated with ACS (OR: 1.004, 95% CI: 1.002-1.006, P<0.001). Conclusions: This is the first clinical study to demonstrate the increased level of sPD-L1 in patients with CAD, and the significant association with ACS.

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