Prognostic Significance of Soluble PD-L 1 on Cardiovascular Outcomes in Patients with Coronary Artery Disease

Aims: Programmed cell death-1 (PD-1) and its ligand (PD-L1) regulate T cells, leading to immunotolerance. We previously demonstrated that patients with coronary artery disease (CAD) had increased circulating levels of soluble PD-L1 (sPD-L1). However, the prognostic significance of sPD-L1 on cardiovascular outcomes is unknown. In the present study, we evaluated the association between sPD-L1 and cardiovascular events in patients with CAD. Methods: We prospectively measured sPD-L1 in patients with CAD admitted to Kumamoto University Hospital between December 2017 and January 2020 and observed their cardiovascular event rate. The primary outcome was a composite of death from non-cardiovascular causes, death from cardiovascular causes, non-fatal myocardial infarction, unstable angina pectoris, revascularization, hospitalization for heart failure, and ischemic stroke. Results: Finally, 627 patients were enrolled, and 35 patients were lost to follow-up. The median follow-up duration was 522 days. In total, 124 events were recorded. The Kaplan-Meier curve showed that the event rate was higher in the higher sPD-L1 group (median >= 136 pg/dL) than in the lower sPD-L1 group (25.0% vs. 16.9%; p=0.028, log-rank test). Univariate Cox proportional hazards analysis showed that high-sensitivity C-reactive protein, an estimated glomerular filtration rate of <60 mL/min/1.73m(2), B-type natriuretic peptide, left ventricular ejection fraction, and sPD-L1 were significantly associated with cardiovascular events. Multivariable Cox proportional hazards analysis of factors that were significant in univariate analysis identified that sPD-L1 was significantly and independently associated with cardiovascular events (hazard ratio: 1.364, 95% confidence interval: 1.018-1.828, p=0.038). Conclusions: Higher sPD-L1 levels were significantly associated with future cardiovascular events in patients with CAD.