Studies of Autoimmunity and Coronary Artery Disease

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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.