Early Noninvasive Detection of Myocardial Microbascular Dysfunction in Diabetes

描述(由申请人提供)：本提案的目的是促进Angela Taylor医学博士的科学发展，因为她正在发展独立的临床研究生涯。弗吉尼亚大学将在克里斯托弗·克莱默博士的指导下为泰勒博士提供理想的环境，在那里研究糖尿病早期冠状动脉疾病的成像和治疗。II型糖尿病在美国已经成为一种流行病。死于心血管疾病的人数是一般人口的2到4倍。最近的试验表明，仅有传统的危险因素并不能完全预测疾病负担，特别是在疾病过程的早期，用目前的非侵入性成像技术衡量。在显性冠状动脉疾病之前，心肌微血管功能异常和动脉壁非闭塞性斑块聚集，这两种情况都可以进行侵入性测量。已有研究表明，与糖尿病和代谢综合征相关的风险因素可预测侵入性测量。然而，目前的非侵入性技术没有能力可靠地测量这些早期异常。心脏磁共振(CMR)提供了一种非侵入性技术，能够直接评估心脏内的微血管功能。我们的初步数据显示，与对照组相比，糖尿病患者在显性冠状动脉狭窄之前的微血管功能降低。这项研究的目的是证明CMR可以可靠地诊断早期非闭塞性冠状动脉疾病。受试者将接受危险因素测量，用血管内超声直接对动脉壁成像，并用CMR无创性测量微血管功能。具体目标包括证明冠状动脉疾病的风险因素预测有创和无创的测量，风险因素的改善导致有创和非有创的测量的改善，以及CMR预测有创的结果。相关性(参见说明)：心血管疾病的早期非侵入性检测机制将有可能在疾病过程的早期确定哪些风险因素影响最大，从而定制治疗并降低成本，提供更安全的诊断机制，并及早治疗冠心病，预防未来的事件，从而有助于显著改善公共卫生。(摘要结束)

DESCRIPTION (provided by applicant): The purpose of this proposal is to foster the scientific development of Angela Taylor, M.D. as she develops an independent clinical research career. The University of Virginia will provide Dr. Taylor with the ideal setting under the mentorship of Dr. Christopher Kramer in which to investigate the imaging and treatment of early coronary artery disease in diabetes. Type II diabetes has become an epidemic in the United States. Death from cardiovascular disease is 2 to 4 fold the general population. Recent trials have demonstrated that traditional risk factors alone are not completely predictive of disease burden as measured with current noninvasive imaging technology particularly early in the disease process. Overt coronary artery disease is preceded by abnormalities in myocardial microvascular function and nonocclusive plaque accumulation in the artery wall both of which can be measured invasively. It has been shown that risl< factors associated with diabetes and the metabolic syndrome predict invasive measurements. However, current noninvasive technology does not have the ability to reliably measure these early abnormalities. Cardiac Magnetic Resonance (CMR) provides a noninvasive technology capable of directly assessing microvascular function within the heart. Our preliminary data shows a reduction of microvascular function in diabetes prior to overt coronary stenoses as compared to controls. The purpose of this study will be to demonstrate that CMR can reliably diagnose early nonocclusive coronary artery disease. Subject will undergo risk factor measurement, direct imaging of the artery wall with intravascular ultrasound, and noninvasive measurement of microvascular function with CMR. Specific aims include demonstrating that risk factors for coronary artery disease predict invasive and noninvasive measurements, that improvements in risk factors result in improvements in invasive and noninvasive measurements, and that CMR predicts invasive findings. RELEVANCE (See instructions): An eariier noninvasive mechanism of detection of cardiovascular disease will provide the potential to determine which risk factors have the greatest effect early in the disease process thus tailoring therapy and reducing costs, to offer a safer diagnostic mechanism, and to treat coronary disease eariier preventing future events thus contributing to significant improvements in public health. (End of Abstract)