Abstract 10882: Serum Levels of Vascular Endothelial Growth Factor-C are Inversely Correlated with Future Cardiovascular Events

Abstract

Background: Vascular endothelial growth factor-A (VEGF-A) not only plays a pivotal role in angiogenesis but is also required to maintain cardiovascular integrity. However, a previous study showed that circulating levels of VEGF-A have only a minor impact on atherosclerosis. Vascular endothelial growth factor-C (VEGF-C), a homologue of the VEGF family, plays a key role in lymphangiogenesis. Recently, we demonstrated that VEGF-C, rather than VEGF-A, is closely related to dyslipidemia and atherosclerosis. However, the relationship between circulating levels of VEGF-C and cardiovascular disease is unknown.

Methods and Results: To examine the predictive value of serum VEGF-C, we performed a prospective cohort study involving 511 consecutive, stable outpatients who attended for primary or secondary prevention. Patients were followed up over 3 years. The primary outcome was major adverse cardiac events (MACEs), defined as all-cause mortality, hospitalization due to acute coronary syndrome, stroke, congestive heart failure, aortic disease, and coronary and peripheral revascularization. The median follow-up was 873 (IQR: 384-1,080) days. MACEs developed in a total of 61 patients (12%). Patients were divided into two groups based on the optimal cut-off value of VEGF-C (4021 pg/mL) determined by receiver operating characteristic curve analysis: low-VEGF-C (n=95, 68±9 y, male: 62%) and high-VEGF-C (n=416, 62±12 y, male: 49%). In Kaplan-Meier analysis, the event-free survival rate was significantly lower in low-VEGF-C than high-VEGF-C (P = 0.0007, by log-rank test). Multivariate Cox proportional hazard analysis revealed that the hazard ratios (95% confidence interval) of age, a male gender, hypertension, diabetes, dyslipidemia, current smoking, obesity, and low-VEGF-C were 1.06 (1.03-1.09, P = 0.0002), 1.65 (0.93-2.91), 1.51 (0.73-3.01), 1.21 (0.68-2.16), 1.10 (0.63-1.92), 2.22 (1.04-4.71, P = 0.039), 1.43 (0.83-2.44), and 1.89 (1.10-3.27, P = 0.022), respectively.

Conclusions: These findings suggest that low-VEGF-C is independently associated with MACEs even after adjustment for established risk factors. A low serum VEGF-C value may serve as a predictive marker of cardiovascular events.