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Introduction: Patients with stroke due to intracranial atherosclerosis (ICAS) are more likely to have coronary and peripheral vascular disease abnormalities than patients with other etiologies. We have found in prior studies that in patients with ICAS, an increased antiangiogenic profile was significantly associated with recurrent TIA and stroke. The purpose of this study is to evaluate the hypothesis that the previously identified profile of circulating antiangiogenic factors is associated with atherosclerotic multimorbidity in patients with ICAS.Methods: Prospective observational longitudinal study of circulating angiogenic factors in 74 patients with ICAS treated medically. Patients with ICAS greater than 70% had pro and antiangiogenic factors measured in duplicate via ELISA. Angiogenic profiles were defined by principle component analysis. A nominal logistic regression model was fit for the outcome variable atherosclerotic multimorbitdity, defined as the presence of atherosclerosis in more than one vascular bed. The predictor variables were age, gender, smoking history, hypertension, hyperlipedimia, and the profiles of circulating angiogenic factors.Results: An angiogenic profile characterized by high levels of HGF and the antiagiogenic factors endostatin, angiostatin, and VEGFR-1 was significantly associated to the presence of atherosclerotic multimorbidity (OR = 1.9; 95% CI = 1.2 - 3.3; p = 0.01). Smoking history, hypertension, and hyperlipidemia were poor predictors of atherosclerotic multimorbidity in this cohort. Commonly related risk factors for atherosclerosis were not associated with the predictive antiangiogenic profile.Conclusion: Our results indicate that antiangiogenesis is a stronger predictor of systemic atherosclerosis than classically recognized risk factors, and it may represent a common path for multimorbidity in patients with ICAS.