Platelet Hyperreactivity as a Therapeutic Target for Reducing Stroke in Older Adults after Transcatheter Aortic Valve Replacement

血小板高反应性作为减少老年人经导管主动脉瓣置换术后中风的治疗目标

• 批准号: 10027770
• 负责人: Nathan Clendenen
• 金额: $ 15.55万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10027770
• 关键词: Address; Adult; Age; Aging; Anesthetics; Aorta; Aortic Valve Stenosis; Aspirin; Biochemical; Biometry; Blood Platelets; Cardiac; Cardiac Surgery procedures; Caring; Clinical; Clinical Data; Clinical Research; Clinical Trials Network; Colorado; Data; Databases; Development Plans; Disease; Elderly; Emergency Medicine; Enrollment; Environment; Goals; Guidelines; Health; Hemorrhage; Hospitals; In Vitro; Individual; Inflammation; Institution; Leukocytes; Measures; Medical center; Mentorship; Methodology; Mitochondria; Nested Case-Control Study; Outcome; Participant; Patients; Perioperative; Pharmaceutical Preparations; Physicians; Platelet Activation; Population; Postoperative Period; Prevention; Prevention strategy; Procedures; Prospective cohort; Records; Regimen; Research; Research Design; Resources; Retrospective cohort study; Risk; Role; Stroke; Structure; TNF gene; Testing; Therapeutic Embolization; Thrombosis; Time; Training; Training Support; Treatment Protocols; United States; Universities; aged; aortic valve; aortic valve replacement; biomedical referral center; career; clinical care; clopidogrel; cohort; design; disability; experience; improved; improved outcome; individual patient; large datasets; member; mitochondrial dysfunction; mortality; mortality risk; new therapeutic target; novel; novel therapeutics; patient response; post stroke; prospective; response; secondary outcome; stroke risk; therapeutic target; vascular injury; young adult

The long term goal of the proposal is to determine the role of aging-associated platelet hyperreactivity for increasing stroke risk after transcatheter aortic valve replacement in older adults. More than 60,000 people undergo cardiac surgery in the United States each year which allows them to live longer and more fulfilling lives, but if the procedure is complicated by stroke mortality increases up to 10-fold. Dr. Clendenen is a Cardiothoracic Anesthesiologist dedicated to improving clinical outcomes after cardiac procedures for older adults and this NIA GEMSSTAR proposal is designed to provide him with the structured mentorship and training necessary to become a leader in perioperative aging research. He has developed a collaborative mentorship team led by Dr. Adit Ginde who is an Emergency Medicine Physician and national PI for a large PETAL network clinical trial with 3,000 participants, with co-mentorship provided by Dr. Robert Schwartz, , a recognized leader in aging research. Methodological advisors include Dr. Alex Kaizer (Biostatistics) and Dr. Kirk Hansen (Thrombosis). This proposal leverages the collective expertise of an established mentorship team and the unique environment at the University of Colorado Anschutz Medical Center that incorporates a tertiary referral center for cardiac procedures in the setting of a large public research University. These ample resources will allow Dr. Clendenen to address key barriers to reducing stroke risk after transcatheter aortic valve replacement with a large retrospective cohort study collecting data from 50 institutions across 19 states (Multicenter Perioperative Outcomes Group, MPOG, n >14,000) and a prospective observational cohort with in depth platelet hyperreactivity analysis (n = 100). He will accomplish this by determining the association between aging associated platelet hyperreactivity and in-hospital stroke after TAVR with MPOG (Aim 1) and determining the detrimental effect of TAVR on aging-associated platelet hyperreactivity with the prospective cohort (Aim 2). These specific aims require Dr. Clendenen to develop expertise in analyzing large datasets and aging research. He will accomplish this with a focused Professional Development Plan including coursework on biostatistics, clinical study design, and aging research. Completion of the proposed project will provide the necessary mentorship, training, and experience required to allow Dr. Clendenen to become a leader in perioperative aging research to improve outcomes after transcatheter aortic valve replacement.

该提案的长期目标是确定与衰老相关的血小板过度反应性的作用 老年人经导管主动脉瓣置换后，卒中风险增加。超过60,000人 每年在美国接受心脏手术，这使他们能够寿命更长，更充实 生命，但是如果中风死亡率变得复杂，则增加了10倍。克伦登尼博士是 心胸麻醉师致力于改善临床结果后的临床结果 成人和这个Nia Gemsstar的建议旨在为他提供结构化指导和 成为围手术期衰老研究的领导者所必需的培训。他建立了合作 由Adit Ginde博士领导的指导团队，他是急诊医学医师和国家PI Petal网络临床试验与3,000名参与者，并由Robert Schwartz博士提供的会议， 公认的衰老研究领导者。方法论顾问包括Alex Kaizer博士（生物统计学）和博士。 柯克·汉森（Hansen）（血栓形成）。该建议利用了既定的指导团队的集体专业知识 以及科罗拉多大学安索兹大学医学中心的独特环境 大型公共研究大学的心脏程序转诊中心。这些足够 资源将使Clendenen博士能够解决转导主动脉后降低中风风险的关键障碍 通过大型回顾性队列研究替换阀门，从19个州的50个机构收集数据 （多中心围手术期结果组，MPOG，n> 14,000）和一个前瞻性观察队列 深度血小板高反应性分析（n = 100）。他将通过确定协会来实现这一目标 在与MPOG TAVR后衰老相关的血小板高反应性和院内中风（AIM 1）和 确定TAVR对衰老相关的血小板过度反应性的有害作用 队列（目标2）。这些具体目标要求克伦登嫩博士在分析大型数据集和 老化研究。他将通过一项重点的专业发展计划（包括课程工作）来实现这一目标 关于生物统计学，临床研究设计和衰老研究。拟议项目的完成将提供 允许克伦登嫩博士成为领导者所需的必要指导，培训和经验 围手术期衰老研究以改善经导管主动脉瓣置换后的结局。