Stroke is an enormous international public health concern, particularly in the developing world where there are limited resources available to provide for an aging population. One of the main contributors to stroke incidence in Brazil is the highly prevalent Chagas disease, a parasitic infection affecting 14% of the population and a major cause of heart failure in Latin America. Chagas disease conveys stroke risk through two established mechanisms, structural cardiac disease and chronic inflammation. Although inflammation is associated with an increased risk of ischemic stroke and poorer outcome, its role has been largely linked to atherogenesis. Chronic inflammation can result in endothelial dysfunction and stimulate the hemostatic system, increasing systemic fibrin production and platelet activation. Adults, young and old, who develop a secondary cardiomyopathy from Chagas, are therefore at higher risk of cardioembolism. Stroke patients usually survive, but can be left with significant disability affecting their health status, productivity, and quality of life. These factors impact caregivers as well. Thus, the social and economic consequences of stroke are vast. The short term goals of this planning grant are to develop a multidisciplinary collaborative infrastructure of investigators and resources in the United States and Brazil to promote clinical stroke research, to provide training for emerging Brazilian clinical stroke researchers, and to determine the resources necessary to support this clinical research effort in future endeavors. As part of this development phase, we will collect pilot data to address two specific aims: (1) to elucidate which of the potential inflammatory and hemostatic markers of stroke risk are associated with chagasic cardiomyopathy, and (2) to determine the mechanism and outcome of stroke in patients with Chagas disease. The long-term goal of this project is to establish non-invasive methods of stroke risk stratification and prediction of stroke outcome in patients with Chagas disease. This work will also facilitate the development of novel anti-trypanosomal, anti-inflammatory, and antithrombotic strategies for stroke prevention and management in Brazil.
