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Introduction: Stroke risk more than doubles each decade after the age of 55. In patients with intracranial atherosclerosis (ICAS), the SAMMPRIS study showed that individuals 60 years or older had a higher risk of recurrent stroke or death (17%) than younger patients (12%) despite intensive medical management (IMM). In prior studies, an antiangiogenic profile has been associated with higher rates of failure to IMM in stroke. The purpose of this study is to evaluate the hypothesis that aging is an independent predictor of higher circulating levels of antiangiogenic factors endostatin and angiostatin in ICAS.Methods: Prospective observational longitudinal study of circulating angiogenic factors in 74 patients with ICAS treated medically. Patients with ICAS greater than 70% had angiostatin and endostatin measured in duplicate via ELISA at baseline and were followed for 6 months. Mixed model analysis was performed for the outcome variables endostatin and angiostatin. Predictor variables included age, gender, smoking history, hypertension (HTN), hyperlipidemia (HLD), Diabetes 2, obesity, coronary artery disease (CAD) and peripheral artery disease (PAD). Classification and regression tree (CART) analysis were used to select the threshold age for the longitudinal model.Results: Age was a significant independent predictor of higher levels of endostatin (p=0.002) and angiostatin (p<0.001). Age older than 52 was significantly associated with higher levels of endostatin (p=0.03), and age older than 70 with higher levels of angiostatin (p=0.005). Additional significant factors associated with higher levels of antiangiogenic circulating factors included PAD, HTN, HLD, and obesity.Conclusion: Aging is a significant independent predictor of elevated antiangiogenic circulating factors, which are associated to failure to IMM in ICAS. Antiangiogenesis can potentially represent a common path for multimorbidity of advanced age.