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.

描述（由申请人提供）：背景。 Libman-Sacks患有植被的心内膜炎是全身性红斑狼疮最严重的心脏病（SLE）。包括中风和短暂性缺血。攻击的神经精神SLE（NPSLE）与发病率和死亡率的增加有关。我们已发表的数据表明：1）35％的SLE患者在经食管的超声心动图（TEE）中检测到Libman-Sacks异性植物植被； 2）NPSE影响60％的患者。我们在37例SLE患者中的初步数据表明：1）27例（73％）患有NPSLE； 2）14（38％）在MRI上有脑梗塞； 3）22（59％）的瓣膜植被通过TEE检测到，主要是在二尖瓣上（82％）； 4）在患有NPSLE的患者中，脑梗塞更为普遍（48％比10％，P = 0.056）； 5）二尖瓣植被在患有NPSLE的患者中更为常见（63％vs. 10％，P = 0.008）；最重要的是，6）二尖瓣植被是NPSLE的最强独立预测指标（优势比15.3，95％Cl 1.7-139，p = 0.005）。因此，瓣膜植被的血栓栓塞可能是NPSLE的主要原因。假设：瓣膜植被会产生宏观和微栓塞，这些宏观和微栓塞阻塞了中脑和小脑血管，导致灌注，缺血性脑损伤和NPSLE改变。实验。这是一项前瞻性控制的横截面和纵向研究，以确定瓣膜植被作为NPSLE的主要原因的作用。将从我们的437名受试者的SLE队列中招募患者。在横截面阶段，有31名具有新的或经常性NPSLE的受试者，31名没有NPSLE的受试者以及20岁和性匹配的对照组将接受：1）TEE检测瓣膜植被； 2）用于检测微栓塞的经颅多普勒； 3）颈动脉复式，以评估内膜媒体厚度和颈动脉斑块； 4）评估SLE和NPSLE活动和严重程度； 5）神经精神病学测试； 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激活； 7）颅MRI，扩散加权成像和灌注加权成像，以评估脑损伤和脑灌注。在48个月的纵向阶段，1）在缓解阶段患有NPSLE的受试者； 2）具有新的或经常性NPSLE的受试者将经历重复的临床，心血管和脑成像评估，以进一步确定植被与微栓塞，脑损伤和NPSLE的时间关联。意义。这种综合的心血管脑成像方法提供了一种强大的实验设计，该设计将证明瓣膜植被与微栓塞，缺血性脑损伤的因果关系，因此，干旱。这些发现将确定：1）心脏栓塞作为NPSLE的主要原因； 2）诊断瓣膜疾病和NPS的新策略； 3）未来对选择性抗血栓形成，抗凝剂或抗炎疗法的科学基础，以防止瓣膜植被和NPSLE的进展和复发。