Vascular endothelial growth factor and its soluble receptor-1 as surrogate markers for subjects with high-risk of cardiovascular disease

Background: Vascular endothelial growth factor (VEGF) and its soluble receptor-1 (sVEGFR-1) can either act beneficially or adversely on cardiovascular health depending on the context. An understanding of VEGF regulation in subclinical atherosclerosis would help to identify individuals who may need more intensive efforts in risk modification as preventive measures. Subjects and Methods: The population in this study consisted of subjects without any modifiable risks and hypercholesterolemic subjects with low or high cardiovascular disease (CVD) risks. A total of 227 subjects were recruited from employees of the Electricity Generating Authority of Thailand and their cardiovascular risk factor history as well as clinical and laboratory data were collected. Plasma VEGF and sVEGFR-1 were measured using enzyme-linked immunosorbent assay. Results: Biphasic association between the sVEGFR-1-to-VEGF (R/V) ratio and the VEGF concentration indicated VEGF upregulation at concentrations above 12.99 pg/mL and VEGF entrapment at a concentration below this level. Rates of VEGF upregulation in low- and high-risk groups were respectively found to be 2.6-fold (P = 0.01) and 4.6-fold (P = 0.03) above the zero risk group. The R/V ratio, which is positively correlated to cholesterol level (P < 0.01), blood pressure and waist circumference (P < 0.1), was found to be associated with CVD risk severity in high-risk subjects (P = 0.028). At VEGF ≤18.58 pg/mL and R/V ratio >3.4, high-risk subjects compared to low-risk subjects had greater odds of being observed with severe risk scores (odds ratio = 8.2, P < 0.0001). Conclusions: VEGF upregulation in subjects with CVD risks is correctively controlled within the physiologic boundary and represents an attempt at vascular repair. Low VEGF levels and high R/V ratios in high-risk subjects are warning signs with respect to cardiovascular health and may indicate the need for more aggressive risk factor treatment in order to prevent the occurrence of undesirable cardiovascular events.