Circulating Antiangiogenic Profile Predicts Lower Degrees of Neovascularization After Indirect Revascularization With Encephaloduroarteriosynangiosis (EDAS) in Patients With Intracranial Atherosclerosis (ICAS)

Objective: To evaluate the hypothesis that circulating pro and antiangiogenic profiles predict the degree of angiographic neovascularization in patients undergoing EDAS for the treatment of symptomatic ICAS. Methods: This is a prospective observational study of circulating angiogenic factors in patients with arterial stenosis greater than 70% due to ICAS. All patients received intensive medical management. Patients with persistent symptoms underwent in addition EDAS revascularization. Twenty-one angiogenic factors were analyzed in serum samples collected at baseline, before surgery, using multiplex ELISA. All samples were run in duplicate and accepted as valid if the intersample variability was less than 20%. Patients have angiographic follow up 6 months after EDAS and a Neovascularization Index (NI) based on Perren grades and ASITN collaterals were calculated. Angiogenic profiles (APs) were defined using Principal Component Analysis (PCA). Seven profiles were selected for each time-point (Eigenvalue greater than 1.0). A regression model was built for the outcome variable NI using as predictor variables age, smoking history diabetes, and the 7 APs. Forward stepwise modeling with minimum BIC stopping rule was used to select the best fitted model. Results: Fifteen patients were enrolled. Mean age was 62.1 ± 12.3, 75% were females. The regression model demonstrated significant associations of age, diabetes and the AP 1-6 with the NI. Whole model P=0.023, Rsquare=0.93. The solution of the regression formula for the significant AP components revealed a strong negative association of the antiangiogenic factors endostatin and angiostatin (regression parameters -1.8 and -4.5, respectively, p=0.02). At 6 months follow up no patients had suffer strokes. Conclusion: In this prospective study of angiogenic factors in patients with ICAS undergoing EDAS revascularization, we have found that baseline levels of the antiangiogenic factors endostatin and angiostatin are significantly negatively associated to the degree of postoperative revascularization at 6 months. This finding supports the concept that neutralization of antiangiogenic factors may serve as a new pharmacological target to treat cerebral ischemia in patients with ICAS.