Abstract 11462: Soluble Vascular Endothelial Growth Factor Receptor-1 as a Predictor of Cardiovascular Events in Stable Outpatients with Chronic Kidney Disease

Abstract

Background: Since chronic kidney disease (CKD) is a highly prevalent risk factor, it is necessary to efficiently extract a high-risk population from CKD patients. Vascular endothelial growth factor (VEGF) plays a role in endothelial integrity. The soluble VEGF receptor-1 (sFlt-1) is an endogenous inhibitor of VEGF. A recent study demonstrated that increased sFlt-1 levels are associated with endothelial dysfunction in CKD.

Methods and Results: To examine the prognostic value of serum sFlt-1 in comparison with N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hsCRP), we performed a prospective cohort study. A total of 490 stable outpatients, involving 396 without and 94 with CKD, were followed up over 3 years. The primary outcome was major adverse cardiac events (MACEs). The median follow-up was 878 (IQR: 385-1,080) days. MACEs developed in a total of 59 patients (12.0%). Patients were divided into two groups based on the optimal cut-off value of each biomarker determined by receiver operating characteristic curve (ROC) analyses. In Kaplan-Meier analyses, high-sFlt-1, high-NT-proBNP, and high-hsCRP groups were all significantly associated with MACEs. However, in non-CKD patients, high-NT-proBNP, but not high-sFlt-1 or high-hsCRP, was significantly associated with MACEs. In contrast, within CKD patients, high-sFlt-1, but not high-NT-pro-BNP or high-hsCRP, was significantly associated with MACEs (P = 0.0003, P = 0.08, P = 0.3 by log-rank test, respectively). Stepwise multivariate Cox proportional hazard analysis revealed that high-NT-proBNP, high-sFlt-1, and a history of cardiovascular disease, but not high-hsCRP, were independently associated with MACEs. Notably, within CKD patients, high-sFlt-1, but not high-NT-proBNP, high-hsCRP, or proteinuria, was independently associated with MACEs. Furthermore, time-dependent survival ROC analyses revealed that the area under the curve of sFlt-1 was superior to that of NT-proBNP both at 1 year and 2 years in CKD patients (0.71 vs. 0.52, P < 0.0001, 0.74 vs. 0.60, P < 0.0001, respectively).

Conclusions: These findings suggest that sFlt-1 serves as a better predictor of MACEs than NT-proBNP, hsCRP, and proteinuria in stable outpatients with CKD.