Abstract 15283: Soluble Vascular Endothelial Growth Factor Receptor-2 as a Predictor of Cardiovascular Events in Patients With Chronic Heart Failure
Background: Vascular endothelial growth factor (VEGF) is a key regulator of cardiac angiogenesis, and is required for preventing decompensated heart failure (HF). Soluble VEGF receptor-2 (sVEGFR-2) acts as an endogenous inhibitor of VEGF. Recently, we demonstrated that serum sVEGFR-2 levels are increased in subjects with metabolic syndrome in association with insulin resistance. However, the significance of sVEGFR-2 levels in patients with chronic HF (CHF) is unknown.
Methods and Results: To examine the prognostic value of sVEGFR-2, we performed a prospective cohort study involving 254 symptomatic patients with CHF. Patients were followed up over 2 years. The primary outcome was major adverse cardiovascular events (MACE) defined as cardiovascular death and hospitalization due to HF. Serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), VEGF, and sVEGFR-2 were determined employing specific enzyme-linked immunosorbent assays. Patients were divided into two groups based on the median of each biomarker (NT-pro BNP, 1,288 pg/mL; VEGF, 275 pg/mL; sVEGFR-2, 5987.5 pg/mL). The median follow-up was 275 (inter-quartile range, 93-495) days. MACE developed in a total of 60 patients (23.6%). In Kaplan-Meier analyses, high-NT-proBNP and low sVEGFR-2, but not high-VEGF, were significantly associated with MACE (P = 0.0006, P = 0.009, and P = 0.6 by log-rank test, respectively). Stepwise multivariate Cox proportional hazard analysis, including established risk factors, chronic kidney disease (CKD), previous hospitalization due to HF, high-NT-proBNP, high-VEGF, and low-sVEGFR-2, revealed that CKD (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.20-4.46; P = 0.013), high-NT-proBNP (HR, 2.08; 95%CI, 1.17-3.68; P = 0.012), and low-sVEGFR-2 (HR, 1.92; 95%CI, 1.13-3.25; P = 0.016) were independently associated with MACE. Receiver operating characteristic curve analyses for MACE revealed that the area under the curve (AUC) of established risk factors, CKD, previous HF, and high-NT-proBNP was 0.708. The addition of low-sVEGFR-2 further increased the AUC (0.719).
Conclusions: Unexpectedly, sVEGFR-2 levels were inversely associated with MACE. A low sVEGFR-2 value may serve as a predictor of MACE in patients with CHF.
- © 2013 by American Heart Association, Inc.