Abstract 16719: Vascular Endothelial Growth Factor-C and Mortality in Patients With Stable Coronary Artery Disease and Cancer: A Subanalysis of the ANOX Study

Abstract

Background: Recent basic studies suggest the importance of lymphatic vasculature as a therapeutic target in cardiovascular diseases, whereas clinical investigations of vascular endothelial growth factor-C (VEGF-C), a central player in lymphangiogenesis, have focused on its diagnostic possibilities for various malignancies. The expression levels in tumors and/or circulating levels of VEGF-C correlates with lymph node and distant metastasis, and poor prognosis. However, the relationship between VEGF-C and mortality in patients with stable coronary artery disease (CAD) and cancer is unknown. Methods: Serum VEGF-C levels were measured in 133 patients with stable CAD and cancer, enrolled in the development of novel biomarkers related to angiogenesis or oxidative stress to predict cardiovascular events (ANOX) study, and followed up for 3 years. The outcome was all-cause death. Results: During the follow-up, 43 patients (32%) died from any cause (10 patients from cardiovascular cause, and 25 patients from cancer). In Kaplan-Meier analysis, lowest quartile of VEGF-C was significantly associated with all-cause death (hazard ratio [HR], 2.6; 95% confidence interval [CI], 1.4-4.8, but not with cancer-related death (HR, 1.8; 95% CI, 0.8-4.2). After adjustment for established risk factors, low VEGF-C levels and the lowest quartile of VEGF-C were both significantly associated with all-cause death (HR for 1-SD increase, 0.67; 95% CI, 0.47-0.95; HR for values below the 25th percentile, 3.3; 95% CI, 1.7-6.3; respectively). Even after additional adjustment of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin-I, and high-sensitivity C-reactive protein, low VEGF-C levels and the lowest quartile of VEGF-C were both significantly associated with all-cause death (HR for 1-SD increase, 0.69; 95% CI, 0.48-0.99; HR for values below the 25th percentile, 2,7; 95% CI, 1.4-5.5; respectively). Conclusions: In patients with stable CAD and cancer, a low VEGF-C value was independently associated with all-cause mortality beyond established risk factors and standard cardiovascular biomarkers. These findings may indicate the difficulty to use elevated VEGF-C as a prognostic marker in patients with cancer.