Endostatin as a Mediator between Enhelial Function and Cognitive Performance in Those at Risk for Vascular Cognitive Impairment

Abstract

Background: Patients with coronary artery disease have an increased risk for developing vascular cognitive impairment. Enhelial function is often diminished and has been associated with lower cognitive performance in these patients. The link between enhelial function and cognition in coronary artery disease is not fully understood. Angiogenesis may play a role in mediating the association between enhelial function and cognition since angiogenic processes rely heavily on the enhelium. Objective: The aim of this study was to determine if markers of angiogenesis mediate the relationship between enhelial function and cognition in coronary artery disease patients. Methods: In 50 participants with coronary artery disease, enhelial function was assessed using peripheral arterial tonometry. Vascular enhelial growth factor (pro-angiogenic) and endostatin (anti-angiogenic) were measured in peripheral serum samples. Cognition was assessed using the Montreal Cognitive Assessment. A mediation analysis, using a bias corrected inferential bootstrapping method with 10,000 permutations, was used to determine if vascular enhelial growth factor or endostatin mediated an association between peripheral arterial tonometry measures and cognitive performance on the Montreal Cognitive Assessment. Results: Endostatin, but not vascular enhelial growth factor, mediated a relationship between enhelial function and cognitive performance when controlling for total years of education, body mass index, coronary artery bypass graft, stent, diabetes, and diuretic use. This analysis was also significant when delayed recall was substituted for the overall score on the Montreal Cognitive Assessment. Conclusion: These results suggest that endostatin mediates an association between enhelial function and cognitive performance in coronary artery disease.