STUDIES OF AUTOIMMUNITY AND CORONARY ARTERY DISEASE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。结缔组织疾病（CTD）是已知的冠状动脉疾病（CAD）的危险因素。类风湿性关节炎和狼疮等CTD患者的CAD患病率很高。有人提出CTD和CAD之间的关联与炎症有关。此外，循环自身抗体已在CAD中发现，CAD可能具有自身免疫特征。无症状个体的循环自身抗体预测未来的临床CTD。虽然CTD和CAD之间的联系已经确立，但临床前自身抗体与早期CAD之间的关系尚未探讨。本研究将验证具有临床前CTD相关自身免疫的个体更有可能发展为亚临床CAD的假设。为了验证这一假设，我们将：1)确定1992年收集的血清中测量的自身免疫与2000年和2005年测量的亚临床CAD随后发展之间的关系。2)评估1992年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CRP是否介导自身免疫与CAD之间的关系。我们将利用在过去20年里由年轻人冠状动脉风险发展（CARDIA）研究连续收集的关于心脏风险、亚临床CAD和储存血清的广泛数据，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，以研究心脏风险因素的发展。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Connective tissue diseases (CTD) are known risk factors for coronary artery disease (CAD). Patients with CTD such as rheumatoid arthritis and lupus have a high prevalence of CAD. It has been proposed that the association between CTD and CAD is related to inflammation. Furthermore, circulating autoantibodies have been identified in CAD, and CAD may have autoimmune features. Circulating autoantibodies in asymptomatic individuals predict future clinical CTD. Although the association between CTD and CAD is established, an association between pre-clinical autoantibodies and early CAD has not been explored. This study will test the hypothesis that individuals with pre-clinical CTD related autoimmunity are more likely to develop sub-clinical CAD. To test this hypothesis, we will: 1) Determine the association between autoimmunity measured in sera collected in 1992 and the subsequent development of sub-clinical CAD measured in 2000 and 2005. 2) Assess whether autoimmunity in 1992 predicts future increased levels of C-reactive protein (CRP) and whether CRP mediates the relationship between autoimmunity and CAD. We will utilize the extensive data on cardiac risk, sub-clinical CAD, and stored serum collected serially over the past 20 years by the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective cohort of 5108 subjects followed since 1985 for development of cardiac risk factors.