Abdominal aortic aneurysm disease is a common and lethal health problem of older Americans. Substantial evidence links sedentary existence and resulting pro-inflammatory aortic conditions to the pathogenesis of AAA disease. Insights derived from investigations in animal models and high risk patient groups and care of AAA patients have help define our LONG TERM OBJECTIVE;to identify, validate and apply effective nonsurgical therapies to the treatment of AAA disease. The purpose of this proposal is to test the ability of lower extremity exercise to reduce AAA risk, limit small aneurysm progression and modify biologic markers of disease. We have two SPECIFIC AIMS: First, we will perform a cross-sectional correlation study to determine whether lifetime physical activity and measured exercise capacity represent independent risk factors for AAA disease. These studies will test our hypothesis that aortic diameter and activity level will be independently and inversely related;that is, abdominal aorta size adjusted for age, will be increased in A) inidividuals completing questionnaires indicating persistently low levels of physical activity or B) have reduced exercise capacity as defined by clinical testing. Second, we will perform a prospective, randomized controlled longitudinal trial of exercise to suppress small AAA progression. The impact of training will be monitored by both serial surveillance ultrasound imaging and surrogage biologic markers and imaging of disease progression. This will test our hypothesis that supervised exercise training will reduce AAA expansion rates and/or diminish surrogate markers of disease progression. To ACHIEVE THESE AIMS we will apply analyze life time physical activity to several hundred patients with the new diagnosis of small AAA disease, measure aortic diameter in a large cohort of patients with previously defined exercise capacity, and apply supervised exercise training to an additional cohort of small aneurysm patients. This application is RELEVANT to public health in that we will test a new and low risk method of preventing the development or progression of AAA disease, a potentially life threatening condition. In addition, we will develop a framework to test, measure and compare the effectiveness of future novel therapies.
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