Objective: The purpose of this study was to identify circulating angiogenic factor profiles associated to success or failure of intensive medical treatment in ICAS patients.
Methods: Prospective observational study of circulating angiogenic factors in 72 patients with ICAS treated medically. Twenty-one pro and antiangiogenic factors were isolated from plasma in patients with intracranial arterial stenosis greater than 70% due to ICAS. Patients were followed for 6 months and mRS were collected. Failure to medical management was defined as presence of TIA or stroke within 30 days of presentation. Levels of angiogenic factors were determined by plasma multiplex sandwich ELISA. Samples were run in duplicate with variation coefficient lower than 20%. Angiogenic profiles (APs) were defined using Principal Component Analysis (PCA). Seven profiles were selected (Eigenvalue greater than 1.0). A logistic regression model was built for the outcome variable medical management failure/success using the 7 APs as predictors. An ordinal logistic regression model was built to predict the outcome variable mRS at 6 months using age, gender, baseline mRS and APs as predictors.
Results: Seventy-two patients with ICAS were included. Mean age was 61.8 (SD 12.3)yrs. There were 53% females. The predominant region of stenosis was the MCA. Of the 7 APs defined by PCA, the regression model identified AP-4 as significantly associated to failure of medical management (P=0.02). AP-4 was characterized by high levels of HGF and the anti-angiogenic factors VEGFR1, Endostatin, Angiostatin, VEGFR3, and TSP2. In the long-term follow up, AP-4 was positively associated with mRS, independently of baseline mRS and age (P=0.002).
Conclusion: In this extensive prospective study of angiogenic factors in patients with ICAS, a profile characterized by elevation of HGF and several circulating anti-angiogenic factors was strongly associated with failure to medical management and poor outcomes at 6 months.