Studies of Autoimmunity and Coronary Artery Disease

描述（由申请人提供）：结缔组织疾病（CTD）已被确定为冠状动脉疾病（CAD）的危险因素。类风湿性关节炎和系统性红斑狼疮等CTD患者的CAD患病率很高，而且发病年龄比预期的要小。有人提出，这些CTD和CAD之间的关联与炎症有关。此外，在CAD中发现了循环自身抗体，并假设CAD可能具有自身免疫特征。循环自身抗体在CTD发展之前就存在，无症状个体中这种自身抗体的存在是未来临床CTD的预测因子。虽然CTD和CAD之间的联系已经建立，但临床前循环自身抗体和早期CAD之间的联系尚未探讨。拟议的研究将验证具有临床前CTD相关自身免疫的个体更有可能随后发展为亚临床CAD的主要假设。为了验证这一假设，使用现有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系。2)评估1992年自身免疫测量是否能预测未来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水平介导。这些目标将由西北大学风湿病学和预防医学系的一组研究人员完成。研究人员将利用先前建立的研究，即年轻人冠状动脉风险发展（CARDIA）研究，这是一项自1985年以来随访的5108名受试者的前瞻性队列研究，以研究新的心脏危险因素的发展。CARDIA研究拥有广泛的流行病学数据库和连续收集的3500人过去20年的血清，是本研究的理想资源。

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.