Platelet Hyperreactivity as a Therapeutic Target for Reducing Stroke in Older Adults 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高反应性在 老年人经导管主动脉瓣置换术后卒中风险增加。超过6万人 每年在美国接受心脏手术，让他们活得更长、更有成就感 但如果中风使手术变得复杂，死亡率会增加10倍。克伦德宁博士是一位 心胸麻醉师致力于改善老年人心脏手术后的临床结果 这项NIA GEMSSTAR计划旨在为他提供结构化的指导和 成为围手术期衰老研究的领先者所需的培训。他已经开发出一种协作性的 由Adit Ginde博士领导的导师小组，他是一名急诊医生，也是一家大型 有3,000名参与者参加的Petal网络临床试验，由罗伯特·施瓦茨博士提供共同指导 公认的老龄化研究领域的领导者。方法论顾问包括Alex Kaizer博士(生物统计学)和Dr. 柯克·汉森(血栓症)。这项建议利用了一个已建立的指导团队的集体专业知识 科罗拉多大学安舒茨医学中心的独特环境包括 心脏手术转诊中心设在一所大型公立研究型大学。这些都很充足 资源将使Clendenen博士能够解决降低经导管主动脉插管术后中风风险的关键障碍 一项从19个州的50家机构收集数据的大型回溯性队列研究 (多中心围术期结局小组，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)。他将通过确定关联来实现这一点 增龄相关性血小板高反应性与TAVR合并MPOG后住院卒中的关系(目标1)和 前瞻性研究TAVR对衰老相关的血小板高反应性的不良影响 队列(目标2)。这些具体目标要求Clendenen博士在分析大型数据集和 老龄化研究。他将通过包括课程作业在内的专注的专业发展计划来实现这一点 生物统计学、临床研究设计和老龄化研究。拟建项目完成后，将提供 必要的指导、培训和经验，使克伦德宁博士成为 围术期老化研究以改善经导管主动脉瓣置换术后的预后。

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.