Abstract 135: Angiogenic Factors and Response to Intensive Medical Management in Atherosclerotic Intracranial Arterial Stenosis

Introduction: Intracranial atherosclerotic steno-occlusive disease (ICASD) is the most common cause of stroke worldwide accounting for 33-67% of stroke in countries with predominantly Asian, Hispanic, and Black populations and at least 10% of all strokes in the US. In this study we test the hypothesis that circulating angiogenic factor profiles are associated with response to medical management. Methods: This is a prospective cohort of participants in the Angiogenic Factors in Intracranial Arterial Stenosis (ANFIS) Study, age 30-80, with a diagnosis of 70-99% ICASD of a major intracranial artery. All patients had optimization of medical management. Failure of medical treatment was defined as presence of TIA or strokes within 30 days of enrollment. Angiogenic factors were isolated in peripheral blood: HBEGF, VEGF, VEGF-D, TGFB1, TGFB2, PDGFAA, PDGFBB, Endostatin, Angiostatin, and VEGFR2. A correlation matrix was used to group highly correlated factors. Multivariable logistic-regression models were prepared to estimate risk of medical management failure. Results: Thirty patients (53% female) age 28-86 (mean 62.5) were enrolled. There were 10 (33.3%) failures of medical management. Age, gender, ethnicity and race were not significantly different between responders and failures of medical treatment. The multivariate analysis showed that higher VEGFD levels were associated with reduced failure (OR=0.26 95%CI 0.06-0.63, p=0.02) and higher HBEGF was associated with increased failure (OR=2.52 95%CI 1.28-7.34, p=0.03). The multivariate logistic model including VEGFD, HBEGF, female sex and black race had 90% sensitivity and 75% specificity (AUC 0.87) in predicting failure of management. Conclusion: In patients with severe (>70%) ICASD, elevated circulating HBEGF levels were associated with failure of medical treatment, while elevated circulating VEGFD levels were associated with protection from TIA/stroke. Further evaluation of the role of these factors in stroke prevention and potential collateral formation could elucidate new pathways for the treatment of intracranial atherosclerotic disease.