Studies of Autoimmunity and Coronary Artery Disease

描述(由申请人提供)：结缔组织病(CTD)已被确定为冠状动脉疾病(CAD)的危险因素。患有CTD的患者，如类风湿性关节炎和系统性红斑狼疮，有很高的CAD患病率，并且在CAD发病时比预期的要年轻。有人提出，这些CTD和CAD之间的联系与炎症有关。此外，在CAD中已发现循环自身抗体，并推测CAD可能具有自身免疫功能。循环自身抗体在CTD发生之前就已存在，无症状个体中此类自身抗体的存在是未来临床CTD的预测指标。尽管CTD和CAD之间的关联已经建立，但临床前循环自身抗体和早期CAD之间的关联尚未被探索。这项拟议的研究将检验主要假设，即临床前CTD相关自身免疫的个体更有可能表现出亚临床CAD的后续发展。为了验证这一假设，利用现有的数据库提出了以下具体目标：1)确定1992年收集的储存血清中测量的自身免疫与2000年和2005年测量的亚临床CAD的后续发展之间的关联。2)评估1992年测量的自身免疫是否预示着未来C-反应蛋白(CRP)水平的升高，以及自身免疫与CAD之间的关系是否由CRP水平调节。这些目标将由西北大学风湿病学系和预防医学系的一个调查小组来实现。研究人员将利用之前建立的一项研究，即青年冠状动脉风险发展(CARDIA)研究，这是一项自1985年以来跟踪调查的5108名受试者的前瞻性队列，目的是开发新的心脏风险因素。CARDIA研究拥有广泛的流行病学数据库和过去20年来从3500人中连续收集和存储的血清，是这项拟议研究的理想资源。

DESCRIPTION (provided by applicant): Connective tissue diseases (CTD) have been identified as risk factors for coronary artery disease (CAD). Patients with CTD such as rheumatoid arthritis and systemic lupus erythematosus have a high prevalence of CAD and are younger than expected at the onset of CAD. It has been proposed that the association between these CTD and CAD is related to inflammation. Furthermore, circulating autoantibodies have been identified in CAD and it has been hypothesized that CAD may have autoimmune features. Circulating autoantibodies exist prior to CTD development and the presence of such autoantibodies in asymptomatic individuals is a predictor of future clinical CTD. Although the association between CTD and CAD has been established, an association between pre-clinical circulating autoantibodies and early CAD has not yet been explored. The proposed study will test the primary hypothesis that individuals with pre-clinical CTD related autoimmunity are more likely to demonstrate subsequent development of sub-clinical CAD. To test this hypothesis, the following Specific Aims are proposed using an existing database: 1) Determine the association between autoimmunity measured in stored sera collected in 1992 and the subsequent development of sub-clinical CAD measured in 2000 and 2005. 2) Assess whether autoimmunity measured in 1992 predicts future increased levels of C-reactive protein (CRP) and whether the relationship between autoimmunity and CAD is mediated by CRP level. These aims will be accomplished by a team of investigators within the Division of Rheumatology and Department of Preventive Medicine at Northwestern University. The investigators will utilize a previously established study, the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective cohort of 5108 subjects followed since 1985 for development of novel cardiac risk factors. With its extensive epidemiologic database and stored serum collected serially and available from 3500 individuals over the past 20 years, the CARDIA study is an ideal resource for this proposed study.