Abstract

Background: Programmed Death-1(PD-1) and its ligand, PD-L1 regulate T cell proliferation and secretion of cytokines, leading to immunotolerance. A previous experimental study reported increased expression of PD-L1 in myocardium. Hence, PD-L1 could be associated with atherosclerotic cardiovascular disease (ASCVD). We hypothesized that serum soluble PD-L1 (sPD-L1) could be associated with cardiovascular events. We prospectively investigated the association between the serum levels of sPD-L1 and cardiovascular outcomes in patients with ASCVD. Methods: We prospectively measured sPD-L1 in patients with ASCVD admitted to Kumamoto University Hospital using a commercially available enzyme-linked immunosorbent assay kit and observed the occurrence of cardiovascular events between December 2017 and June 2019. The primary outcome was a composite of death from any cause, death from cardiovascular causes, nonfatal myocardial infarction, unstable angina pectoris, stroke, and heart failure hospitalization. We excluded patients complicated with cancer, hemodialysis, active collagen diseases, and inflammatory diseases. Results: Finally, 446 patients with ASCVD were enrolled. Median follow-up period was 322 days. A total of 153 events were recorded. Kaplan-Meier curve revealed that the higher sPD-L1 group (sPD-L1 ≧155pg/dL, median) showed significantly higher rate of cardiovascular events than the lower sPD-L1 group (19.2% vs. 28.1%, log-rank test: P =0.044). Univariate Cox proportional hazards analysis showed that creatinine, low density-lipoprotein cholesterol, B-type natriuretic peptide (BNP), and higher sPD-L1 (≧155pg/dL) were significantly associated with cardiovascular events. Multivariable Cox proportional hazards analysis by significant factors from univariate analysis identified that higher sPD-L1 [hazard ratio (HR): 1.699, 95% confidence interval (CI): 1.023-2.823, P =.041) and BNP (HR: 1.001, 95% CI: 1.000-1.001, P =0.036) were significantly and independently associated with cardiovascular events. Conclusions: The higher levels of sPD-L1 were significantly associated with near future cardiovascular events in patients with ASCVD, suggesting sPD-L1 could be a novel prognostic predictor in patients with ASCVD.

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