Studies of Autoimmunity and Coronary Artery Disease

描述（由申请方提供）：结缔组织疾病（CTD）已被确定为冠状动脉疾病（CAD）的风险因素。 CTD患者（如类风湿性关节炎和系统性红斑狼疮）的CAD患病率较高，并且CAD发病时比预期的年轻。已经提出这些CTD和CAD之间的关联与炎症有关。此外，循环自身抗体已被确定在CAD和它已被假设，CAD可能有自身免疫功能的特点。在CTD发展之前存在循环自身抗体，并且在无症状个体中存在此类自身抗体是未来临床CTD的预测因子。虽然CTD和CAD之间的关联已经确立，但临床前循环自身抗体和早期CAD之间的关联尚未探索。拟议的研究将检验主要假设，即临床前CTD相关自身免疫性个体更有可能表现出亚临床CAD的后续发展。为了检验这一假设，使用现有数据库提出了以下具体目的：1）确定在1992年收集的储存血清中测量的自身免疫性与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可预测未来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流变学系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，年轻人冠状动脉风险发展（CARDIA）研究，自1985年以来，对5108例受试者进行了前瞻性队列研究，以研究新的心脏风险因素。由于其广泛的流行病学数据库和储存的血清连续收集，并在过去20年中从3500个人，心脏研究是一个理想的资源，这项拟议的研究。

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.