CHADSS: Chagas Disease Scan Study

CHADSS：恰加斯病扫描研究

• 批准号: 8740565
• 负责人: Karen L Furie
• 金额: $ 32.21万
• 依托单位: FEDERAL UNIVERSITY OF BAHIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8740565
• 关键词: Accounting; Acute; Address; Affect; Anti-Inflammatory Agents; Anti-inflammatory; Aspirin; Atherosclerosis; Atrial Fibrillation; Biological Markers; Blood Tests; Blood Vessels; Brain; Brain imaging; Brazil; Cardiac; Cardiomyopathies; Caregivers; Chagas Disease; Characteristics; Chronic; Chronic Phase; Coagulation Process; Commit; Congestive Heart Failure; Coupled; Data; Development; Diagnostic; Dilated Cardiomyopathy; Disease; Economics; Embolism; Etiology; Fever; Fibrin; Gelatinase B; Genetic; Goals; Grant; Health Status; Heart Diseases; Heart failure; Hemostatic Agents; Impaired cognition; Incidence; Individual; Infarction; Infection; Inflammation; Inflammatory; Interleukin-6; International; Ischemic Stroke; Latin America; Left; Link; Magnetic Resonance Imaging; Metalloproteases; Methods; Morphologic artifacts; Neprilysin; Nerve Degeneration; Orosomucoid; Outcome; Parasitic infection; Patients; Peptides; Pharmaceutical Preparations; Phase; Platelet Activation; Population; Prevalence; Preventive; Production; Productivity; Prophylactic treatment; Public Health; Quality of life; Research; Research Infrastructure; Resources; Risk; Risk Factors; Role; Scanning; Secondary Myocardial Diseases; Signal Transduction; Source; Staging; Stratification; Stroke; Stroke prevention; Surrogate Endpoint; System; Testing; Therapeutic; Trypanosoma cruzi; United States; Vascular Diseases; Warfarin; White Matter Hyperintensity; Work; aging population; atherogenesis; cerebral atrophy; cost; disability; effective therapy; endothelial dysfunction; high risk; neuroimaging; novel; older patient; social; therapeutic target; young adult

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.

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，可用于应对人口老龄化的资源有限。中风发病率的主要原因之一是高度流行的恰加斯病，这是一种寄生虫感染，影响了大约 1800 万人，也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带来中风风险：结构性心脏病和慢性炎症。尽管炎症与缺血性中风风险增加和预后较差有关，但其作用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，增加全身纤维蛋白的产生和血小板活化。脑萎缩也与慢性炎症有关。因此，患有南美锥虫病继发性心肌病的成年人，无论年轻还是年老，发生心源性栓塞和神经退行性变的风险都较高。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 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协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存在独立于心肌病的关联。认知障碍和脑萎缩也与恰加斯病相关，与心肌病无关。生物标志物口腔类粘蛋白、脑啡肽酶、白细胞介素 6 (IL-6) 和基质金属蛋白酶 9 (MMP-9) 被确定为恰加斯病的诊断和治疗靶点。作为这一阶段的一部分，我们将实现三个具体目标：（1）建立恰加斯充血性心力衰竭（CM）患者中风风险的脑磁共振成像标记； (2) 确定生物标志物是否可以预测 Chagasic CM 患者的卒中风险； (3) 评估抗血小板治疗在降低 Chagasic CM 患者微栓塞率方面的疗效。该项目的长期目标是建立对恰加斯病患者中风风险分层和中风结果预测的非侵入性方法。这项工作还将促进巴西中风预防和管理的新型抗锥虫、抗炎和抗血栓策略的开发。