Libman-Sacks Endocarditis and NPSLE

利布曼-萨克斯心内膜炎和 NPSLE

• 批准号: 7281326
• 负责人: CARLOS A ROLDAN
• 金额: $ 58.25万
• 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/7281326
• 关键词: Acute; Affect; Age; Ally; Anti-Inflammatory Agents; Anti-inflammatory; Anticoagulants; Antiphospholipid Antibodies; Brain; Brain Injuries; Brain imaging; Cardiac; Cardiovascular system; Carotid Artery Plaques; Cephalic; Cerebrovascular Circulation; Cerebrum; Chorea; Clinical; Coagulation Process; Confusion; Coronary Arteriosclerosis; Data; Detection; Diagnosis; Diffusion weighted imaging; Disease; Disease remission; Echocardiography; Endocarditis; Experimental Designs; Future; Generations; Heart Diseases; Heart failure; Image; Image Analysis; Impaired cognition; Infarction; Injury; Ions; Ischemic Brain Injury; Lesion; Longitudinal Studies; Lupus Erythematosus; Magnetic Resonance Imaging; Measurement; Methodology; Methods; Mitral Valve; Modality; Morbidity - disease rate; Myocarditis; Neurologic; Neuropsychiatric Systemic Lupus Erythematosus; Odds Ratio; Pathogenesis; Pathology; Patients; Perfusion; Pericarditis; 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; 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.

描述（由申请人提供）：背景。Libman-Sacks心内膜炎伴赘生物是系统性红斑狼疮（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，与发病率和死亡率增加有关。我们发表的数据表明：1）经食管超声心动图（TEE）在35%的SLE患者中检测到Libman-Sacks或血栓性赘生物; 2）NPSLE影响60%的患者。37例SLE患者的初步资料显示：1）27例（73%）患者有NPSLE，2）14例（38%）MRI显示有脑梗死，3）22例（59%）TEE显示有瓣膜赘生物，主要发生在二尖瓣（82%）;（4）NPSLE患者脑梗死发生率高于非NPSLE患者（48% vs. 10%，p = 0.056）; 5）二尖瓣赘生物在有NPSLE的患者中比无NPSLE的患者更常见（63% vs. 10%，p = 0.008）;最重要的是，6）二尖瓣赘生物是NPSLE的最强独立预测因子（比值比15.3，95% CI 1.7 - 139，p = 0.005）。因此，瓣膜赘生物引起的血栓栓塞可能是NPSLE的主要原因。假设：瓣膜赘生物产生大栓子和微栓子，闭塞中小脑血管，导致灌注改变、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，旨在确定瓣膜赘生物作为NPSLE主要原因的作用。患者将从我们的437名受试者的SLE队列中招募。在横断面阶段，31名患有新发或复发性NPSLE的受试者、31名没有NPSLE的受试者以及20名年龄和性别匹配的对照者将经历：1）TEE以检测瓣膜赘生物; 2）经颅多普勒以检测微栓子; 3）颈动脉多普勒以评估内膜-中层厚度和颈动脉斑块; 4）评估SLE和NPSLE活动性和严重性; 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复合物和血小板聚集来评估凝血和血小板活化;和7）用于评估脑损伤和脑灌注的头颅MRI、扩散加权成像和灌注加权成像。在48个月的纵向阶段，1）缓解期的NPSLE受试者;和2）新发或复发NPSLE受试者将接受重复临床、心血管和脑成像评价，以进一步确定赘生物与微栓子、脑损伤和NPSLE的时间相关性。意义这种整合的心血管-脑成像方法提供了一种强大的实验设计，将证明瓣膜赘生物与微栓子、缺血性脑损伤以及NPSLE的产生之间的因果关系。这些调查结果将确定：1）心源性栓塞是NPSLE的主要原因; 2）诊断瓣膜疾病和NPSLE的新策略; 3）未来选择性抗血栓、抗凝或抗炎治疗试验的科学依据，以预防瓣膜赘生物和NPSLE的进展和复发。