Coronary Flow Reserve to Assess Hidden Risk: Focus on Women, Heart Failure, and Inflammation

通过冠状动脉血流储备评估隐藏风险：关注女性、心力衰竭和炎症

• 批准号: 9224107
• 负责人: Viviany R Taqueti
• 金额: $ 19.98万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9224107
• 关键词: Advisory Committees; Anatomy; Ancillary Study; Angioplasty; Anti-Inflammatory Agents; Anti-inflammatory; Atherosclerosis; Blood flow; Boston; Bypass; Cardiac Myocytes; Cardiovascular Diseases; Cardiovascular system; Caring; Case Fatality Rates; Center for Translational Science Activities; Cessation of life; Clinical; Clinical Investigator; Clinical Sciences; Collaborations; Coronary; Coronary Angiography; Coronary Arteriosclerosis; Coronary Vessels; Data; Development; Diagnosis; Diffuse; Disease Outcome; EFRAC; Echocardiography; Environment; Event; Exposure to; Faculty; Fostering; Functional disorder; Future; Goals; Gold; Heart; Heart failure; Hospitals; Image; Impairment; Inflammation; Interleukin-1; Interleukin-6; Leadership; Lipids; Measures; Mediating; Medicine; Mentorship; Microvascular Dysfunction; Modernization; Myocardial; Myocardial Ischemia; Myocardial perfusion; National Heart, Lung, and Blood Institute; Patients; Physicians; Placebos; Population; Positron-Emission Tomography; Preventive Intervention; Public Health Schools; Radiology Specialty; Registries; Research; Research Design; Research Personnel; Resources; Rest; Risk; Risk stratification; Scientist; Severity of illness; Statistical Methods; Structure; Systemic Therapy; Testing; Therapeutic Intervention; Therapeutic Trials; Time; Training; United States National Institutes of Health; Vasomotor; Woman; Women' s Health; cardiovascular disorder risk; cardiovascular imaging; career; career development; catalyst; diagnosis standard; didactic education; disease phenotype; disorder risk; experience; high risk; imaging modality; improved; interest; member; men; mortality; non-invasive imaging; novel; patient registry; population health; public health relevance; research and development; research clinical testing; sex; skills; translational scientist; vascular inflammation

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 disease severity. This is especially important for women, in who diffuse atherosclerosis and microvascular dysfunction likely contribute to CVD outcomes, especially heart failure, but are often undiagnosed or misdiagnosed. Yet the exact relationship between impaired CFR and adverse CVD outcomes, particularly in the absence of obstructive CAD, is not well understood. Our central hypothesis is that excess CVD risk in women relative to men referred for coronary angiography is associated with impaired CFR independently of obstructive CAD, and that this increased risk may be mediated by increased myocardial strain and increased inflammation. Dr. Taqueti will apply state of the art analyses to two unique and complementary populations: a registry of patients undergoing PET myocardial perfusion for clinical evaluation of suspected CAD [CFR Registry]; and subjects from the Coronary Flow Reserve to Assess Cardiovascular Inflammation trial [CIRT-CFR], an ancillary study of the NHLBI sponsored multicenter Cardiovascular Inflammation Reduction Trial (CIRT) which will test whether reducing inflammation in stable CAD patients improves CFR. SPECIFIC AIMS: The following specific aims are proposed: (1) To identify the relationship between sex, CFR and angiographic disease severity in patients with suspected CAD [CFR Registry]; (2) To define the extent to which CVD risk in women relative to men is associated with impaired CFR, not obstructive CAD [CFR Registry]; and (3) To define the relationship between CFR, myocardial strain, and inflammation in women and men with stable CAD [CIRT-CFR]. By clarifying definitively the contribution of CFR to hidden CVD risk in women and men with varying levels of anatomic CAD, Dr. Taqueti will acquire the requisite experience and preliminary data for future R01-level studies employing this functional measure to select subjects for novel preventative and therapeutic interventions, including systemic therapy with anti-inflammatory, extreme lipid- lowering, and neurohormonal modulating agents. The proposed translational aims will help to define a new paradigm of ischemic heart disease with implications for diagnosis, risk stratification, and development of novel management strategies for a common, poorly recognized clinical problem with a disproportionate impact on women's health, an NIH strategic priority.

7.项目总结/摘要： 二十多年来，女性的心血管疾病（CVD）年死亡率一直较高， 与男性相比，阻塞性冠状动脉疾病（CAD）在女性中的患病率较低。冠状 血管造影术是诊断阻塞性CAD的金标准，并且仍然是现代CVD的基石 但它不能识别弥漫性动脉粥样硬化和小血管疾病。这些可能会导致不利的 心血管事件，包括心力衰竭，由冠状动脉血管功能障碍、微血管疾病， 和心肌缺血。因此，即使没有严重阻塞性CAD的患者， 不良CVD事件。候选人：Viviany Taqueti博士是一位早期职业心脏病专家、成像仪和医生- 马萨诸塞州波士顿布里格姆妇女医院的科学家，长期以来对内皮和 心肌细胞功能和血管炎症。她的目标是成为一名独立的临床研究者 在利用来自广泛研究设计的成像数据以更好地定义缺血性心脏病方面处于领先地位 表型和病理生理学，最终为未来的治疗试验提供信息。此K23应用程序提供了一个 全面的培训计划，包括结构化导师（与马塞洛·迪卡利博士一起），一个完善的 咨询委员会（与博士保罗Ridker，斯科特所罗门，和Bairey Merz），和量身定制的教学课程 在先进的统计和成像方法，这将共同提供塔奎蒂博士的技能， 以实现这一目标，并过渡到一个成功的独立调查员。环境：The 布里格姆妇女医院的心血管成像组提供了接触各种各样的教师 放射科和医学科的成员，他们从事基础，临床和人口 卫生研究，并提供了一个跨部门合作的独特环境。BWH是一个世界 心肌灌注正电子发射断层扫描（PET）成像和非侵入性 冠状动脉血流储备（CFR）的定量。重要的是，它的领导层致力于保护塔奎蒂博士的 研究和职业发展活动的时间，并促进她作为一个独立的发展， 翻译研究员Taqueti博士还将获得哈佛催化剂临床的资源， 转化科学中心和哈佛公共卫生学院。研究摘要：目标 该提案的一个重要目的是利用一种新的、非侵入性的定量冠状动脉血流的成像方法， 了解解剖CAD谱中女性和男性CVD结局的机制。冠状 血流储备（CFR），计算为充血心肌血流与静息心肌血流的比值， 正电子发射断层扫描（PET）是一种综合的非侵入性测量大， 小血管CAD和心肌缺血，并确定有CVD死亡风险的患者， 血管造影疾病严重程度。这对女性尤其重要，因为女性弥漫性动脉粥样硬化， 微血管功能障碍可能导致CVD结局，尤其是心力衰竭，但通常 未确诊或误诊然而，CFR受损和不良CVD结局之间的确切关系， 特别是在没有阻塞性CAD的情况下，还没有得到很好的理解。我们的核心假设是 女性相对于男性接受冠状动脉造影的CVD风险与CFR受损相关 独立于阻塞性CAD，这种风险增加可能是由心肌应变增加介导的 和炎症增加。Taqueti博士将运用最先进的分析技术， 人群：接受PET心肌灌注的患者登记研究，用于临床评价疑似 CAD [CFR登记研究];和来自冠状动脉血流储备的受试者，以评估心血管炎症 试验[CIRT-CFR]，一项NHLBI申办的多中心心血管炎症的辅助研究 减少试验（CIRT），将测试是否减少稳定CAD患者的炎症改善CFR。 具体目标：提出以下具体目标：（1）确定性别之间的关系，CFR 和疑似CAD患者的血管造影疾病严重程度[CFR登记研究];（2）定义 女性相对于男性的CVD风险与CFR受损相关，而与阻塞性CAD无关[CFR 登记];和（3）确定女性CFR、心肌应变和炎症之间的关系， 稳定型CAD男性患者[CIRT-CFR]。通过明确阐明CFR对隐藏的CVD风险的贡献， Taqueti博士将获得必要的经验， 未来R 01水平研究的初步数据，采用该功能测量选择受试者进行新的 预防性和治疗性干预措施，包括抗炎、高脂血症、 降低和神经激素调节剂。建议的翻译目标将有助于定义一个新的 缺血性心脏病的诊断、危险分层和新的 针对一种常见的、认识不足的临床问题的管理策略， 女性健康是NIH的战略重点