7. PROJECT SUMMARY/ABSTRACT: For over two decades, the annual cardiovascular disease (CVD) mortality rate has been higher for women as compared to men, yet obstructive coronary artery disease (CAD) is less prevalent in women. Coronary angiography is the gold standard for diagnosing obstructive CAD and remains a cornerstone of modern CVD care, but it cannot identify diffuse atherosclerosis and small-vessel disease. These may contribute to adverse CVD events, including heart failure, from resultant coronary vasomotor dysfunction, microvascular disease, and myocardial ischemia. Thus, even patients without significant obstructive CAD may be at high risk for adverse CVD events. CANDIDATE: Dr. Viviany Taqueti is an early career cardiologist, imager, and physician- scientist at Brigham and Women's Hospital in Boston, MA with a longstanding interest in endothelial and cardiomyocyte function and vascular inflammation. Her goal is to become an independent clinical investigator and leader in leveraging imaging data from a breadth of study designs to better define ischemic heart disease phenotypes and pathophysiology, ultimately to inform future therapeutic trials. This K23 application presents a comprehensive training plan including structured mentorship (with Dr. Marcelo Di Carli), a well-developed advisory committee (with Drs. Paul Ridker, Scott Solomon, and Bairey Merz), and a tailored didactic curriculum in advanced statistical and imaging methods, which together will provide Dr. Taqueti with the skills necessary to achieve this goal and transition into a successful independent investigator. ENVIRONMENT: The Cardiovascular Imaging Group at Brigham and Women's Hospital offers exposure to a diverse range of faculty members in the Departments of Radiology and Medicine who are engaged in basic, clinical, and population health research, and provides a unique environment for cross-departmental collaborations. BWH is a world- class center for myocardial perfusion positron emission tomography (PET) imaging and noninvasive quantification of coronary flow reserve (CFR). Importantly, its leadership is dedicated to protecting Dr. Taqueti's time for research and career development activities, and to foster her development as an independent translational investigator. Dr. Taqueti will also have access to resources at the Harvard Catalyst Clinical and Translational Science Center and the Harvard School of Public Health. RESEARCH SUMMARY: The objective of this proposal is to utilize a novel, noninvasive imaging method of quantifying coronary blood flow to understand mechanisms of CVD outcomes in women and men across the anatomic CAD spectrum. Coronary flow reserve (CFR), calculated as the ratio of hyperemic to rest myocardial blood flow as quantified noninvasively by positron emission tomography (PET), is an integrated noninvasive measure of large and small vessel CAD and myocardial ischemia, and identifies patients at risk for CVD death independently of angiographic d...