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。6万多人 每年在美国接受心脏手术，使他们活得更长，更充实。 但如果手术过程因中风而复杂化，死亡率将增加10倍。克伦德南博士是一位 心胸麻醉师致力于改善老年人心脏手术后的临床结局 成人和这个NIA GEMSSTAR提案旨在为他提供结构化的指导， 成为围手术期衰老研究的领导者所需的培训。他建立了一个合作 导师团队由Adit Ginde博士领导，他是一名急诊医学医师和一家大型 PETAL网络临床试验，有3,000名参与者，由Robert Schwartz博士提供共同指导， 公认的老龄化研究领导者方法学顾问包括Alex Kaizer博士（生物统计学）和Dr. Kirk汉森（血栓形成）。该提案利用了已建立的指导团队的集体专业知识 以及科罗拉多大学安舒茨医学中心独特的环境， 在一所大型公立研究型大学的背景下建立心脏手术转诊中心。这些充足的 这些资源将使Clendenen博士能够解决降低经导管主动脉瓣置换术后卒中风险的关键障碍。 瓣膜置换术，一项大型回顾性队列研究，收集了来自19个州50家机构的数据 （多中心围手术期结局组，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 年龄相关血小板高反应性与TAVR联合MPOG后院内卒中之间的关系（目的1）， 确定TAVR对衰老相关血小板高反应性的不利影响， 队列（目标2）。这些具体的目标要求克伦德南博士发展分析大型数据集的专业知识， 老化研究他将通过有针对性的专业发展计划（包括课程作业）来实现这一目标 生物统计学、临床研究设计和衰老研究。完成拟议项目将提供 必要的指导，培训和经验，使Clendenen博士成为领导者， 围手术期老化研究，以改善经导管主动脉瓣置换术后的结局。