Libman-Sacks Endocarditis and NPSLE

利布曼-萨克斯心内膜炎和 NPSLE

• 批准号: 7487058
• 负责人: CARLOS A ROLDAN
• 金额: $ 51.89万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7487058
• 关键词: Acute; Affect; Age; Anti-Inflammatory Agents; Anti-inflammatory; Anticoagulants; Antiphospholipid Antibodies; Brain; Brain Injuries; Brain Pathology; Brain imaging; Cardiac; Cardiovascular system; Carotid Artery Plaques; Central Nervous System Diseases; Cephalic; Cerebrum; Chorea; Clinical; Coagulation Process; Confusion; Data; Detection; Diagnosis; Diffusion weighted imaging; Disease; Disease remission; Echocardiography; Endocarditis; Experimental Designs; Future; Generations; Heart Diseases; Hemostatic Agents; Image; Image Analysis; Impaired cognition; Infarction; Inflammatory; Ischemic Brain Injury; Laboratories; Lesion; Longitudinal Studies; Lupus Erythematosus; Magnetic Resonance Imaging; Measurement; Methods; Mitral Valve; Modality; Morbidity - disease rate; Neurologic; Neuropsychiatric Systemic Lupus Erythematosus; Odds Ratio; Pathogenesis; Patients; Perfusion; Phase; Platelet Activation; Platelet aggregation; Population Research; Psychotic Disorders; Publishing; Recruitment Activity; Recurrence; Research Personnel; Resources; Role; Seizures; Severities; Stroke; Systemic Lupus Erythematosus; Techniques; Testing; Thick; Thromboembolism; Transesophageal Echocardiography; Transient Ischemic Attack; Weight; antithrombin III-protease complex; base; cohort; experience; improved; interest; mortality; neuroimaging; neuropsychiatry; prevent; programs; prospective; prothrombin fragment 1.2; sex

DESCRIPTION (provided by applicant): Background. Libman-Sacks endocarditis with vegetations is the most serious heart disease of systemic lupus erythematosus (SLE). Neuropsychiatric SLE (NPSLE) which includes stroke and transient ischemic .attacks is associated with increased morbidity and mortality. Our published data demonstrate that: 1) Libman-Sacks orthrombotic vegetations are detected by transesophageal echocardiography (TEE) in 35% of SLE patients; and 2) NPSLE affects 60% of patients. Our preliminary data in 37 patients with SLE demonstrate that: 1) 27 patients (73%) had NPSLE; 2) 14 (38%) had cerebral infarcts on MRI; 3) 22 (59%) had valve vegetations detected by TEE, mostly on the mitral valve (82%); 4) cerebral infarcts were more common in patients with than without NPSLE (48% vs. 10%, p = 0.056); 5) mitral valve vegetations were more common in patients with than without NPSLE (63% vs. 10%, p = 0.008); and of most importance, 6) mitral valve vegetations were the strongest independent predictor of NPSLE (odds ratio 15.3, 95% Cl 1.7 - 139, p = 0.005). Thus, thromboembolism from valve vegetations is likely a major cause of NPSLE. Hypothesis: Valve vegetations generate macro- and microemboli that occlude the medium and small cerebral vessels resulting in altered perfusion, ischemic brain injury, and NPSLE. Experimental. This is a prospective controlled cross-sectional and longitudinal study to determine the role of valve vegetations as a major cause of NPSLE. Patients will be recruited from our SLE cohort of 437 subjects. During the cross-sectional phase, 31 subjects with new or recurrent NPSLE, 31 subjects without NPSLE, and 20 age and sex matched controls will undergo: 1) TEE to detect valve vegetations; 2) transcranial Doppler for detection of microemboli; 3) carotid duplex to assess intimal-media thickness and carotid plaques; 4) assessment of SLE and NPSLE activity and severity; 5) neuropsychiatric testing; 6) assessment of coagulation and platelet activation by measurement of antiphospholipid antibodies, prothrombin fragments 1.2, thrombin-antithrombin III complexes, and platelet aggregation; and 7) cranial MRI, diffusion weighted imaging and perfusion weighted imaging for assessment of brain injury and cerebral perfusion. During the longitudinal phase of 48 months, 1) subjects with NPSLE in the remission phase; and 2) subjects with new or recurrent NPSLE will undergo repeat clinical, cardiovascular and cerebral imaging evaluations to further determine a temporal association of vegetations with microemboli, brain injury, and NPSLE. Significance. This integrated cardiovascular-brain imaging approach provides a powerful experimental design that will demonstrate a causal relationship of valve vegetations to the generation of microemboli, ischemic brain injury, arid thus, NPSLE. These findings will establish: 1) cardioembolism as a major cause of NPSLE; 2) new strategies for the diagnosis of valve disease and NPSLE; and 3) the scientific basis for a future trial of selective antithrombotic, anticoagulant, or anti-inflammatory therapy to prevent the progression and recurrence of valve vegetations and NPSLE.

简介(申请人提供)：背景。伴赘生物的Libman-Sack心内膜炎是系统性红斑狼疮(SLE)最严重的心脏病。神经精神性系统性红斑狼疮(NPSLE)包括中风和短暂性脑缺血发作，与增加的发病率和死亡率有关。我们公布的数据表明：1)经食道超声心动图(TEE)可在35%的SLE患者中发现Libman-Sack或血栓性赘生物；以及(2)NPSLE影响60%的患者。我们对37例系统性红斑狼疮患者的初步资料显示：1)非狼疮性狼疮27例(73%)；2)脑梗塞14例(38%)；3)TEE发现22例(59%)瓣膜赘生物，主要位于二尖瓣(82%)；4)脑梗塞多见于非狼疮性狼疮(48%vs 10%，p=0.056)；5)非狼疮性狼疮患者二尖瓣赘生物多见(63%vs 10%，p=0.008)；最重要的是，二尖瓣赘生物是NPSLE最强的独立预测因子(优势比15.3，95%CI1.7-139，p=0.005)。因此，瓣膜赘生物引起的血栓栓塞症可能是NPSLE的主要原因。假设：瓣膜赘生物会产生巨大和微小的栓子，阻塞中、小脑血管，导致血流灌注改变、缺血性脑损伤和NPSLE。实验性的。这是一项前瞻性、对照、横断面和纵向研究，旨在确定瓣膜肥大是NPSLE的主要原因。患者将从我们的437名SLE患者队列中招募。在横断期，31名新发或复发的NPSLE患者、31名没有NPSLE的患者和20名年龄和性别匹配的对照组将接受：1)TEE检测瓣膜赘生物；2)经颅多普勒检测微栓子；3)颈动脉双重成像评估内中膜厚度和颈动脉斑块；4)评估SLE和NPSLE的活动和严重程度；5)神经精神测试；6)通过测量抗磷脂抗体、凝血酶原片段1.2、凝血酶-抗凝血酶III复合体和血小板聚集来评估凝血和血小板激活；以及7)头颅MRI、加权成像和灌注成像评估脑损伤和脑灌注。在为期48个月的纵向阶段，1)处于缓解期的NPSLE患者；以及2)新发或复发的NPSLE患者将接受反复的临床、心血管和脑成像评估，以进一步确定植物与微栓子、脑损伤和NPSLE的时间相关性。意义重大。这一集成的心血管-脑成像方法提供了一个强大的实验设计，将证明瓣膜肥大与微栓子、缺血性脑损伤以及NPSLE的产生之间的因果关系。这些发现将确立：1)心脏栓塞是NPSLE的主要原因；2)诊断瓣膜疾病和NPSLE的新策略；3)未来进行选择性抗血栓、抗凝或抗炎治疗以防止瓣膜赘生物和NPSLE进展和复发的科学基础。