Multi-Ethnic Study of Autoimmunity and Cardiovascular Disease

自身免疫和心血管疾病的多种族研究

• 批准号: 8434885
• 负责人: DARCY S MAJKA
• 金额: $ 42.91万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-10 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8434885
• 关键词: Address; African American; Age; Ancillary Study; Antibodies; Anticardiolipin Antibodies; Antinuclear Antibodies; Antiphospholipid Syndrome; Asians; Aspirin; Atherosclerosis; Attenuated; Autoantibodies; Autoimmune Process; Autoimmunity; Biological Markers; Blood Pressure; Body mass index; Calcium; Cardiolipins; Cardiovascular Diseases; Cardiovascular system; Caucasians; Caucasoid Race; Cessation of life; Cholesterol; Clinical; Connective Tissue Diseases; Coronary artery; Coronary heart disease; Data; Databases; Diabetes Mellitus; Disease Outcome; Elderly; Electron Beam; Epidemiology; Ethnic Origin; Evaluation; Event; Future; Gender; Glycoproteins; Heart Arrest; High Density Lipoproteins; Hispanics; Incidence; Individual; Inflammatory; Intercellular adhesion molecule 1; Interleukin-6; Lead; Low-Density Lipoproteins; Lupus; Measures; Mediating; Modeling; Myocardial Infarction; Observational Study; Participant; Pathogenesis; Patients; Peptide antibodies; Pharmaceutical Preparations; Population; Prevention Measures; Preventive; Preventive Medicine; Primary Prevention; Principal Investigator; Process; Questionnaires; Race; Research; Research Personnel; Resources; Rheumatoid Arthritis; Rheumatoid Factor; Rheumatology; Risk Factors; Sample Size; Secondary Prevention; Serum; Staging; Stroke; Systemic Lupus Erythematosus; Testing; Time; Universities; Work; X-Ray Computed Tomography; age group; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular risk factor; cigarette smoking; cohort; coronary artery calcification; cyclic citrullinated peptide; follow-up; immunoregulation; inflammatory marker; innovation; lipoprotein-associated phospholipase A(2); middle age; novel strategies; prospective; public health relevance; young adult

DESCRIPTION (provided by applicant): There is a well established association between clinically apparent coronary heart disease (CHD) and autoimmune connective tissue diseases (CTD) including rheumatoid arthritis and lupus, but the exact mechanism is not established. It has been proposed that the association between CTD and CHD is related to common inflammatory processes. CTD-related autoantibodies have been identified in individuals years before they develop rheumatoid arthritis and lupus, but most individuals with positive circulating autoantibodies do not develop clinical CTD. Circulating autoantibodies have also been identified in CHD, thus it has been hypothesized that autoimmunity may contribute to the pathogenesis of atherosclerosis. However, it is not definitively known if subclinical CTD-related autoantibodies are associated with atherosclerosis and future clinical CHD. Preliminary data from this team suggest that there is an association between CTD-related antibodies and subclinical atherosclerosis: We found that the presence of anti-22 glycoprotein I antibodies (anti-22-GPI) measured in stored serum from African American (AA) and Caucasian young adults was associated with coronary artery calcification (CAC) measured 8 and 13 years later. We wish to extend this innovative finding in order to 1) determine if this relationship exists in other race/ethnicity groups, in other age groups and with other autoantibodies and 2) confirm the temporal relationship between subclinical CTD-related autoantibodies and CAC and extend our work to assess the relationship with ensuing clinical cardiovascular disease (CVD) events. To test our hypothesis that subclinical CTD-related autoantibodies lead to subclinical atherosclerosis and clinical CVD, we propose the following Aims using an existing cohort of 6814 multi-ethnic middle-aged to elderly subjects who will have active CTDs ruled out by a questionnaire: 1) Determine the cross-sectional association between subclinical CTD-related autoantibodies measured in stored sera collected at baseline (years 2000-2001) and presence of CAC. 2) Determine the association between baseline subclinical CTD-related autoantibodies and incidence, as well as progression, of CAC over 2 and 4 years follow-up. 3) Determine the association between baseline autoantibodies and clinical CVD events over 10 years follow-up. 4) Assess whether autoantibodies are associated with higher levels of inflammatory markers, and whether the relationship between autoantibodies and CVD outcomes are mediated by differences in inflammatory markers. These Aims will be accomplished by a team of investigators in the Division of Rheumatology and Department of Preventive Medicine at Northwestern University. We will utilize the ongoing multicenter Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort of 6814 Caucasian, AA, Hispanic, and Asian subjects followed since 2000 to examine the early stages of CVD in a multi-ethnic population. With its stored sera, epidemiologic database, older age, and multi-ethnicity, MESA is an ideal resource for this proposed study, which may lead to new approaches for the prevention of CVD.

描述（由申请人提供）：临床上明显的冠心病（CHD）与包括类风湿性关节炎和狼疮在内的自身免疫性结缔组织疾病（CTD）之间存在明确的关联，但确切的机制尚未确定。有人提出 CTD 和 CHD 之间的关联与常见的炎症过程有关。与 CTD 相关的自身抗体在个体发展为类风湿性关节炎和狼疮前数年就已被发现，但大多数循环自身抗体呈阳性的个体不会发展为临床 CTD。在先心病中也发现了循环自身抗体，因此推测自身免疫可能有助于动脉粥样硬化的发病机制。然而，尚不清楚亚临床 CTD 相关自身抗体是否与动脉粥样硬化和未来临床 CHD 相关。该团队的初步数据表明，CTD 相关抗体与亚临床动脉粥样硬化之间存在关联：我们发现，在非洲裔美国人 (AA) 和白种人年轻人与 8 年后和 13 年后测量的冠状动脉钙化 (CAC) 相关。我们希望扩展这一创新发现，以便 1) 确定这种关系是否存在于其他种族/族裔群体、其他年龄组以及其他自身抗体中；2) 确认亚临床 CTD 相关自身抗体与 CAC 之间的时间关系，并扩展我们的研究致力于评估与随后的临床心血管疾病（CVD）事件的关系。为了检验我们的假设，即亚临床 CTD 相关自身抗体会导致亚临床动脉粥样硬化和临床 CVD，我们使用现有的 6814 名多种族中老年受试者队列提出以下目标，这些受试者将通过问卷排除活动性 CTD：1 ) 确定在基线（年）收集的储存血清中测量的亚临床 CTD 相关自身抗体之间的横断面关联2000-2001）以及 CAC 的存在。 2) 确定基线亚临床 CTD 相关自身抗体与 2 年和 4 年随访中 CAC 的发生率和进展之间的关联。 3) 确定基线自身抗体与 10 年随访期间临床 CVD 事件之间的关联。 4) 评估自身抗体是否与较高水平的炎症标志物相关，以及自身抗体与CVD结果之间的关系是否由炎症标志物的差异介导。这些目标将由西北大学风湿病科和预防医学系的一组研究人员来实现。我们将利用正在进行的动脉粥样硬化多中心多种族研究 (MESA)，该前瞻性队列自 2000 年以来跟踪调查了 6814 名白人、AA、西班牙裔和亚洲受试者，以检查多种族人群中 CVD 的早期阶段。 MESA 拥有储存的血清、流行病学数据库、较高的年龄和多种族，是这项拟议研究的理想资源，这可能会带来预防 CVD 的新方法。