Abstract 14564: Inverse Association Between Serum Vascular Endothelial Growth Factor-C Levels and the Severity of Arteriosclerotic Obliterans in Men
Background: Vascular endothelial growth factor-C (VEGF-C) plays a key role in lymphangiogenesis. Recently, we demonstrated that VEGF-C is closely associated with dyslipidemia and atherosclerosis. However, the direct relationship between VEGF-C and atherosclerotic diseases in humans is unknown.
Methods and Results: We carried out a cross-sectional study involving 116 male patients with arteriosclerotic obliterans (ASO) and 25 male controls who have no apparent cardiovascular diseases. Serum levels of VEGF-C were measured. Patients were divided into three groups according to the severity of ASO: Control, mild ASO (Fontaine 1+2, n=97), and severe ASO (Fontaine 3+4, n=19). VEGF-C levels were significantly lower in severe and mild ASO compared with Control. Multiple logistic regression analysis, including established risk factors (age, hypertension, diabetes, dyslipidemia, and current smoking) and VEGF-C levels, revealed that the VEGF-C level was independently and inversely associated with severe ASO (odds ratio, 0.34 for 1-SD increase; 95% confidence interval [CI], 0.16-0.78 ; P = 0.01). Next, we examined the predictive value of VEGF-C in patients with mild ASO. The primary outcome was major adverse cardiac events (MACE). Patients were followed up over 30 months. The median follow-up was 263 (IQR: 83-435) days. During the follow-up period, MACE developed in a total of 36 patients (37%). Patients were divided into two groups based on the optimal cut-off value of VEGF-C determined employing receiver operating characteristic curve analysis: low-VEGF-C (<4078 pg/mL, n=41) and high-VEGF-C (>=4078 pg/mL, n=58). In Kaplan-Meier analysis, low-VEGF-C had a significantly higher event rate compared with high-VEGF-C (P = 0.02, by log-rank test). Furthermore, multivariate Cox proportional hazard analysis, including established risk factors and low-VEGF-C, revealed that low-VEGF-C was independently associated with MACE (hazard ratio, 2.10; 95% CI, 1.05-4.23; P = 0.04).
Conclusions: Low VEGF-C levels were significantly associated with the baseline severity of ASO. The low VEGF-C level was also associated with MACE in patients with mild ASO. A low VEGF-C value may serve as a marker of the severity of ASO as well as the risk of future cardiovascular events.
- © 2013 by American Heart Association, Inc.