Cardiac Imaging of Thoracic Fat and Aortic Stiffness in Older High Risk Patients

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DESCRIPTION (provided by applicant): The candidate is an Instructor in the Section on Gerontology and Geriatric Medicine in the Department of Internal Medicine. Her previous research focused on the effects of exercise training on changes in cardiovascular disease risk factors in older persons. Receipt of this K01 award will provide training in imaging, epidemiology, and vascular biology/mechanics, thereby equipping her with the skills necessary to become an independent researcher in the field of cardiovascular aging. Research: The proposed research will be an ancillary study to the Vascular Stiffness and Pulmonary Edema Study, a prospective study examining the association between dobutamine stress-induced changes in aortic stiffness and flash pulmonary edema warranting hospital admission in older high risk patients. The major aims of the present study are to 1) quantify the relationship between pericardial and perivascular adipose tissue (PCAT, PVAT) and dynamic changes in aortic stiffness in response to dobutamine-induced stress and 2) determine whether PCAT and PVAT predict cardiac events over a mean follow-up of 3.5 years. Potential mechanisms underlying the association between PCAT and PVAT and the outcomes will also be examined, including the possibility of a local effect that is perhaps mediated by adipocyte-derived factors (i.e. adipokines). Of particular interest is adiponectin, which is expressed in both PCAT and PVAT and has potent effects on cardiovascular function and insulin action. The hypotheses are that PCAT and PVAT will be positively associated with dynamic changes in aortic stiffness and that higher levels will be associated with an increased risk of future cardiac events. We also anticipate that these relationships will be independent of traditional risk factors, as well as abdominal visceral fat, adiponectin, and insulin resistance. This K01 award will provide the candidate with protected research time and mentored training to learn the technical and statistical methods to test these specific aims. The knowledge she acquires during the conduct of this study will ultimately provide her with expertise in the application of MRI to the assessment of interventions designed to alter the trajectory of age- related changes in vascular function and cardiovascular disease risk. Environment: There is an enriched research and training environment in aging-related studies within the WFU School of Medicine. The successful completion of the candidate's research and career goals will be guided by a highly-qualified, multidisciplinary team of mentors and consultants with expertise in epidemiology (Drs. Kritchevsky and Ding), cardiac imaging (Dr. Hundley), regional body fat distribution (Drs. Nicklas and Ding), cardiovascular aging (Dr. Kitzman), and biostatistics (Dr. Leng). PUBLIC HEALTH RELEVANCE: This study will help to refine the relationship between obesity and cardiovascular disease risk by determining the importance of fat around the heart and blood vessels in relation to aortic stiffness and risk of future cardiac events. This knowledge will be useful in developing randomized controlled trials of interventions that may reduce the morbidity, mortality, and health care costs associated with cardiovascular diseases.