Abstract 10861: Serum Levels of VEGF-C, but not VEGF-A, are Inversely Correlated with Systolic Dysfunction

Background: Vascular endothelial growth factor-A (VEGF-A) plays a pivotal role in cardiac angiogenesis and is required for preventing the transition from compensatory left ventricular hypertrophy (LVH) to heart failure (HF). Vascular endothelial growth factor-C(VEGF-C), a homologue of the VEGF family, plays a key role in lymphangiogenesis. However, the relationship between VEGF-C and HF is unknown. Methods and Results: We carried out a cross-sectional study involving 401 outpatients whose New York Heart Association functional classes were stable for at least 3 months. We performed echocardiography and calculated the left ventricular ejection fraction (LVEF) and left ventricular mass index (LVMI). Serum levels of N-terminal pro- brain natriuretic peptide(NT-proBNP), VEGF-A, and VEGF-C were determined employing specific enzyme-linked immunosorbent assays. Patients were divided into three groups: those with systolic dysfunction (HF+; LVEF 116 in males, >104g/m 2 in females), and those without LVH or systolic dysfunction (Control). There were no significant differences in the body mass index and prevalence of a male gender and dyslipidemia among the three groups. Age was greater and hypertension, diabetes, and chronic kidney disease were more prevalent in HF+ than Control. Levels of NT-pro BNP were significantly higher in HF+ than Control and LVH+. Conversely, those of VEGF-C were significantly lower in HF+ than Control ( P = 0.005) and LVH+ ( P = 0.027), whereas those of VEGF-A were similar among the three groups. Multivariate logistic regression analyses, including age, a male gender, hypertension, diabetes, dyslipidemia, current smoking, obesity, chronic kindey disease, NT-proBNP, and either of VEGF-C or VEGF-A, revealed that diabetes (odds ratio [95% CI]: 9.7 [1.97-47.9], P = 0.0005), obesity (13.0 [2.7-63.5], P = 0.029), NT-proBNP (5.9 [2.8-12.4], P P = 0.029), but not VEGF-A, were independently associated with systolic dysfunction. Conclusions: Low serum levels of VEGF-C, but not VEGF-A, were independently associated with systolic dysfunction. VEGF-C signaling might be involved in the pathophysiology of HF in humans.