Abdominal aortic aneurysm disease is a common and lethal health problem of older Americans. Substantialevidence links sedentary existence and resulting pro-inflammatory aortic conditions to the pathogenesis ofAAA disease. Insights derived from investigations in animal models and high risk patient groups and care ofAAA patients have help define our LONG TERM OBJECTIVE; to identify, validate and apply effective nonsurgicaltherapies to the treatment of AAA disease. The purpose of this proposal is to test the ability of lowerextremity exercise to reduce AAA risk, limit small aneurysm progression and modify biologic markers ofdisease.We have two SPECIFIC AIMS:First, we will perform a cross-sectional correlation study to determine whether lifetime physical activity andmeasured exercise capacity represent independent risk factors for AAA disease. These studies will test ourhypothesis that aortic diameter and activity level will be independently and inversely related; that is, abdominalaorta size adjusted for age, will be increased in A) inidividuals completing questionnaires indicating persistentlylow levels of physical activity or B) have reduced exercise capacity as defined by clinical testing. Second, wewill perform a prospective, randomized controlled longitudinal trial of exercise to suppress small AAAprogression. The impact of training will be monitored by both serial surveillance ultrasound imaging andsurrogage biologic markers and imaging of disease progression. This will test our hypothesis that supervisedexercise 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 thenew diagnosis of small AAA disease, measure aortic diameter in a large cohort of patients with previouslydefined exercise capacity, and apply supervised exercise training to an additional cohort of small aneurysmpatients.This application is RELEVANT to public health in that we will test a new and low risk method of preventing thedevelopment or progression of AAA disease, a potentially life threatening condition. In addition, we will developa framework to test, measure and compare the effectiveness of future novel therapies.
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