This K 23 Career Development Award will accomplish the double objective of training the candidate in patient-oriented research, and advancing current knowledge of the relationship between inflammation and atherosclerosis. For the career development component, the candidate will participate in the Master of Science in Clinical Investigation program, established at her institution with funding from a K30 Award from the NHLBI. This outstanding program is tailored to the candidate's needs, and will provide an in depth exposure to study design, data management and analysis, research ethics and scientific writing. The candidate will benefit from a rich environment of national experts in epidemiology, vascular imaging, cardiology, neurology, rheumatology and biostatistics . The objective of the research component is to examine to what extent atherosclerosis and cardiovascular morbidity are explained by systemic inflammation in rheumatoid arthritis (RA), accounting for the competing influence of established cardiovascular risk factors. The candidate will pursue three Specific Aims: (1) To determine the extent of atherosclerosis that is explained by cumulative systemic inflammation in RA; (2) To determine the role of inflammation in the progression of atherosclerosis in patients with RA; and (3) To determine the role of ongoing inflammatory disease activity as a risk factor for cardiac and cerebrovascular atherothrombotic events in RA.
For Specific Aim 1, 680 members of an established cohort of RA patients will undergo two non-invasive procedures to measure atherosclerosis: high resolution B-mode ultrasound of the carotid intima- media thickness (IMT) and ankle-arm systolic blood pressure index. These measures will be compared to the severity of joint damage, which reflects cumulative inflammation in RA.
For Specific Aim 2, the candidate will examine the influence of inflammation on the progression of carotid IMT over three years.
For Specific Aim 3, the candidate will assess the influence of ongoing inflammatory disease activity on the incidence of cardiac and cerebrovascular events in the RA cohort. This research is a novel approach to understanding the contribution of inflammation to atherosclerosis, and will point the way for future research into the mechanisms of atherogenesis. In addition, it will have implications for the management of patients with RA and other inflammatory diseases, by extending the current indications for anti- inflammatory therapy to the prevention of atherosclerosis. This would ultimately lengthen life expectancy and improve the quality of life of people with inflammatory diseases.
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