Studies of Autoimmunity and Atherosclerosis

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DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) remains the leading cause of death in the USA. One in 3 Americans develop CVD and 910,000 die from CVD annually. Connective tissue diseases (CTD) have been identified as risk factors for coronary artery disease (CAD). Patients with CTDs such as rheumatoid arthritis and lupus have a high prevalence of CAD and are younger than expected at CAD onset. It has been proposed that the association between CTDs and CAD is related to inflammation. Furthermore, circulating autoantibodies have been identified in atherosclerosis, thus atherosclerosis may have autoimmune features. The presence of autoantibodies in asymptomatic individuals is a predictor of future clinical CTD. Although the association between CTD and CAD is established, an association between pre-clinical autoimmunity and CVD has not been explored. I am a rheumatologist/internist whose goal is to develop an independent clinical research career with a focus on the identification of pre-clinical autoimmune markers for the incidence of CVD. The proposed career development plan incorporates an intensive mentored, patient-oriented research experience in combination with a Master's Degree curriculum. I will work with my mentors to conduct projects examining autoimmune risk factors for CVD: 1) I will conduct ancillary studies in two prospective cohorts following young adults (CARDIA) and middle aged adults (MESA) for development of cardiac risk. I will gain hands on experience in study design and data collection as I examine the association between pre-clinical autoimmunity and sub-clinical atherosclerosis in the CARDIA subjects and a subset of the MESA subjects. 2) I will examine the associations between pre-clinical autoimmunity and evolution of traditional CVD risk factors. 3) I will use these preliminary data in an R01 application proposing to utilize the entire MESA cohort to further elucidate the mechanisms that mediate the association between autoimmunity and CVD. Relevance: The studies proposed here offer innovation to the study of cardiac risk. The large sample size and the extensive evaluation of autoantibodies will allow us to address the unique hypothesis that autoimmunity is a risk factor for sub-clinical atherosclerosis. If in fact, autoimmunity is found to be independently associated with atherosclerosis, then information gained from this study may be used in the future to identify pertinent risk factors for CAD so that primary and secondary prevention measures can be implemented.