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

描述（由申请人提供）：该候选人是内科老年医学和老年医学组的讲师。她之前的研究重点是运动训练对老年人心血管疾病危险因素变化的影响。获得K01奖将为她提供影像学、流行病学和血管生物学/力学方面的培训，从而使她具备成为心血管衰老领域独立研究人员所必需的技能。研究：拟议的研究将是血管僵硬和肺水肿研究的辅助研究，这是一项前瞻性研究，旨在研究多巴酚丁胺应激诱导的主动脉僵硬变化与老年高危患者住院的闪发性肺水肿之间的关系。本研究的主要目的是：1)量化心包和血管周围脂肪组织（PCAT， PVAT）与多巴酚丁胺诱导应激下主动脉僵硬度动态变化之间的关系；2)确定PCAT和PVAT是否能在平均3.5年的随访期间预测心脏事件。还将研究PCAT和PVAT之间关联的潜在机制以及结果，包括可能由脂肪细胞衍生因子（即脂肪因子）介导的局部效应的可能性。特别值得关注的是脂联素，它在PCAT和PVAT中均有表达，对心血管功能和胰岛素作用有强有力的影响。假设PCAT和PVAT与主动脉僵硬度的动态变化呈正相关，较高的水平与未来心脏事件的风险增加有关。我们还预计这些关系将独立于传统的危险因素，如腹部内脏脂肪、脂联素和胰岛素抵抗。该K01奖将为候选人提供受保护的研究时间和指导培训，以学习技术和统计方法来测试这些具体目标。她在这项研究中获得的知识最终将为她提供应用MRI评估干预措施的专业知识，这些干预措施旨在改变血管功能和心血管疾病风险与年龄相关的变化轨迹。环境：在WFU医学院有一个丰富的老龄相关研究和培训环境。成功完成候选人的研究和职业目标将由具有流行病学专业知识的高素质多学科导师和顾问团队指导。Kritchevsky和Ding)，心脏成像（Hundley博士），体脂区域分布(dr。Nicklas和Ding)，心血管老化（Kitzman博士）和生物统计学（Leng博士）。

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.