Abstract 15495: Serial Measurement of Vascular Endothelial Growth Factor-D in Heart Failure: The PREHOSP-CHF Study

Abstract

Background: Vascular endothelial growth factor-D (VEGF-D) is a secreted glycoprotein that can act as lymphangiogenic and angiogenic growth factors. We recently reported that VEGF-D appeared to be a prognostic marker for major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death or heart failure hospitalization (HF), in patients with HF. However, the prognostic value of changes of VEGF-D is unknown. Methods: The PREHOSP-CHF study is a nationwide prospective survey of patients with HF in Japan. Serum VEGF-D levels were measured in 203 patients (mean age, 75 years; male, 62%; mean ejection fraction, 45%) at both baseline and 6-month follow-up. We set the cut-off level of VEGF-D as 366 pg/ml, based on the ROC analysis of the entire cohort of the PREHOSP-CHF study. We defined increased VEGF-D as transition from low VEGF-D to high VEGF-D and decreased VEGF-D as transition from high to low. We investigated the association of changes of VEGF-D levels with the incidence of MACE after 6 months. Results: Mean VEGF-D levels at baseline and 6-month follow-up were 449±199 pg/ml and 519±230 pg/ml, respectively. During the 2-year follow-up, 18 patients developed MACE before 6-month follow-up, and 42 patients developed MACE after 6-month follow up. Based on levels of VEGF-D at baseline, patients with high VEGF-D showed significantly higher incidence of MACE than those without. After excluding the patients developed MACE before 6-month follow-up, 11 of 105 patients with high VEGF-D moved to the low VEGF-D group at 6-month follow-up, and 34 of 78 patients with low VEGF-D moved to the high VEGF-D group. Landmark analysis after 6 months showed that incidence of MACE was significantly higher in patients with increased VEGF-D than those without in the low VEGF-D group, and tended to be lower in patients with deceased VEGF-D than those without in the high VEGF-D group. After adjustment for ejection fraction, N-terminal B-type natriuretic peptide levels, and VEGF-D levels at baseline, increased VEGF-D were also significantly associated with the incidence of MACE after 6 months (hazard ratio per 10 pg/ml increase, 1.02; 95% confidence interval 1.00-1.03; P=0.04). Conclusions: In patients with HF, changes in VEGF-D might serve as a prognostic marker for MACE.