CHADSS: Chagas Disease Scan Study

描述（由申请人提供）：中风是一个巨大的国际公共卫生问题，特别是在发展中国家，那里有有限的资源来提供老龄化人口。中风发病率的主要原因之一是高度流行的查加斯病，这是一种寄生虫感染，影响估计1 800万人，是拉丁美洲心力衰竭的主要原因。恰加斯病通过两种既定机制传递中风风险：结构性心脏病和慢性炎症。虽然炎症与缺血性卒中风险增加和预后不良相关，但其作用在很大程度上与动脉粥样硬化有关。慢性炎症可导致内皮功能障碍并刺激止血系统，增加全身纤维蛋白产生和血小板活化。脑萎缩也与慢性炎症有关。因此，成年人，年轻人和老年人，谁开发了继发性心肌病从恰加斯心脏栓塞和神经退行性变的风险较高。中风患者通常可以存活，但可能会留下严重的残疾，影响他们的健康状况，生产力和生活质量。这些因素也会影响护理人员。因此，中风的社会和经济后果是巨大的。在我们的R21规划资助期间，我们能够在巴西和美国的研究小组之间建立合作基础设施，并收集初步数据。我们发现恰加斯病和中风之间的联系与心肌病无关。认知障碍和脑萎缩也与查加斯病相关，独立于心肌病。类粘蛋白、脑啡肽酶、白细胞介素-6（IL-6）和基质金属蛋白酶-9（MMP-9）等生物标志物被确定为恰加斯病的诊断和治疗靶点。作为该阶段的一部分，我们将解决三个具体的目标：（1）建立脑磁共振成像标记物的中风风险的Chagglutinemergency心力衰竭（CM）患者;（2）以确定是否生物标志物可以预测中风风险的Chagglutinemergency CM患者;（3）评估抗血小板治疗的疗效，降低微栓塞率Chagglutinemergency CM患者。本项目的长期目标是建立非侵入性的方法对查加斯病患者进行卒中风险分层和卒中结局预测。这项工作还将促进巴西卒中预防和管理的新型抗锥虫、抗炎和抗血栓策略的开发。

DESCRIPTION (provided by applicant): 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 is the highly prevalent Chagas disease, a parasitic infection affecting an estimated 18 million individuals 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. Brain atrophy has also been associated with chronic inflammation. Adults, young and old, who develop a secondary cardiomyopathy from Chagas are therefore at higher risk of cardioembolism and neurodegeneration. 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. During our R21 planning grant period, we were able to establish a collaborative infrastructure between the research groups in Brazil and the United States and collect preliminary data. We found an association between Chagas disease and stroke that was independent of cardiomyopathy. Cognitive impairment and brain atrophy were also associated with Chagas disease independently of cardiomyopathy. Biomarkers orosomucoid, neprilysin, interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) were identified as diagnostic and therapeutic targets in Chagas disease. As part of this phase, we will address three specific aims: (1) to establish brain magnetic resonance imaging markers of stroke risk in patients with Chagasic congestive heart failure (CM); (2) to determine whether biomarkers can predict stroke risk in patients with Chagasic CM; and (3) to evaluate the efficacy of antiplatelet treatment in decreasing microembolization rate in patients with Chagasic CM. 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.