Platelet Activity & Cardiovascular Events following Vascular Surgery

血小板活性

• 批准号: 8893130
• 负责人: Jeffrey S Berger
• 金额: $ 63.22万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-19 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8893130
• 关键词: Address; Age; Blood Platelets; Blood Vessels; Cardiovascular system; Cause of Death; Cessation of life; Clinical; Clinical Research; Cohort Studies; Cox Proportional Hazards Models; Data; Diagnosis; Diagnostic; Diagnostic tests; Enrollment; Event; Genetic Transcription; Genome; Goals; Health; Hemorrhage; Hour; Individual; Intervention; Investigation; Knowledge; Lower Extremity; Measurement; Measures; Mediator of activation protein; Messenger RNA; MicroRNAs; Molecular; Molecular Profiling; Morbidity - disease rate; Myocardial; Myocardial Infarction; Necrosis; Operative Surgical Procedures; Outcome; Pathogenesis; Patients; Pattern; Perioperative; Peripheral arterial disease; Phenotype; Population; Postoperative Period; Procedures; Production; Prognostic Marker; Proteins; Publishing; Quality of life; RNA; Risk; Risk Factors; Stratification; Stroke; Therapeutic Intervention; Thrombosis; Troponin I; United States; Vascular Diseases; Vascular Surgical Procedures; activity marker; atherothrombosis; cardiovascular risk factor; clinically relevant; cohort; comparative; differential expression; follow-up; high risk; improved; insight; modifiable risk; mortality; new therapeutic target; novel; novel diagnostics; prevent; prospective; sex; therapeutic target

DESCRIPTION (provided by applicant): Peripheral artery disease is a highly prevalent condition in the United States, and a significant cause of cardiovascular morbidity and all-cause mortality. Although vascular surgical procedures are commonly performed to improve patient survival and quality of life, patients are at heightened risk of adverse perioperative cardiovascular events. Following vascular surgery, patients remain at increased risk of long-term cardiovascular events. Traditional risk factors are limited in their ability to discriminate cardiovascular risk following vascular surgery and are mostly non-modifiable. Pathological and clinical studies consistently demonstrate that platelets are a major culprit in the pathogenesis of atherothrombosis. We propose a novel, reliable, and reproducible measurement of increased platelet activity, thus allowing investigation of this clinically relevant and potentially modifiabe cardiovascular risk factor in this very high-risk population. The study hypothesis is that platelet activity measurements before vascular surgery is independently and significantly associated with 30-day cardiovascular events. We further hypothesize that platelet activity measured postoperatively is independently and significantly associated with long-term cardiovascular events. We will also correlate platelet activity with the genome expression profile to determine molecular mechanisms controlling platelet activity. The long-term goal is to identify a clinically useful assessment of platelet activity for risk stratification that may be used as a diagnostic too and a target for therapeutic intervention. The proposed study will be a prospective observational cohort study enrolling 350 subjects before non- emergent open vascular surgery of the lower extremities. Platelet activity will be measured before and after vascular surgery and will be correlated with 30-day and long-term cardiovascular events. The 30-day primary endpoint will be death, myocardial infarction, stroke and troponin I >0.1ng/ml. The long-term primary endpoint will be death, myocardial infarction, or stroke. Secondary endpoints are major bleeding, vascular thrombosis, each individual endpoint, and cardiovascular death. The mechanism of increased platelet activity in patients with peripheral artery disease will be explored; isolated platelet mRNA and microRNA expression profile in 12 patients with increased platelet activity will be compared with 12 patients with normal platelet activity. This study will provide novel data to address existing gaps in knowledge regarding the association between platelet activity measurements and incident cardiovascular events, and will ascertain whether a unique platelet RNA expression profile exists in peripheral artery disease subjects with increased platelet activity. Data obtained from this study will identify high-risk subjects before vascular surgery using a potentially modifiable risk factor. These data will provide insight into the molecular mechanisms regulating platelet activity and yield novel diagnostic tests for risk stratification an novel therapeutic targets to improve clinical outcomes in patients with peripheral artery disease undergoing vascular surgery.

描述(申请人提供)：外周动脉疾病在美国是一种高度流行的疾病，也是心血管疾病和全因死亡的重要原因。虽然血管外科手术通常是为了改善患者的生存和生活质量，但患者在围手术期发生不良心血管事件的风险很高。血管手术后，患者长期心血管事件的风险仍在增加。传统的危险因素在区分血管手术后的心血管风险方面能力有限，而且大多是不可改变的。病理和临床研究一致表明，血小板是糖尿病发病的主要元凶。 动脉粥样硬化血栓形成。我们提出了一种新的、可靠的和可重复的血小板活性增加的测量方法，从而可以在这一非常危险的人群中研究这种临床上相关的和潜在的可修改的心血管危险因素。研究假设是，血小板 血管手术前的活动测量与30天的心血管事件独立且显著相关。我们进一步假设，术后测量的血小板活性与长期心血管事件独立且显著相关。我们还将把血小板活性与基因组表达谱联系起来，以确定控制血小板活性的分子机制。长期目标是确定一种临床上有用的血小板活性风险分层评估，该评估也可用作诊断和治疗干预的目标。这项拟议的研究将是一项前瞻性的观察性队列研究，纳入350名研究对象，在非急诊开放的下肢血管手术前进行。将在血管手术前后测量血小板活性，并将与30天和长期的心血管事件相关。30天的主要终点将是死亡、心肌梗死、中风和肌钙蛋白0.1 ng/ml。长期的主要终点将是死亡、心肌梗死或中风。次要终点是大出血、血管血栓、每个个体终点和心血管死亡。将探讨外周动脉疾病患者血小板活性升高的机制；将12例血小板活性增强的患者与12例血小板活性正常的患者的分离血小板mRNA和microRNA的表达谱进行比较。这项研究将提供新的数据来解决关于血小板活性测量和心血管事件之间的关联的现有知识空白，并将确定在血小板活性增加的外周动脉疾病受试者中是否存在独特的血小板RNA表达谱。从这项研究获得的数据将在血管手术前使用潜在的可改变的危险因素识别高危受试者。这些数据将为调节血小板活性的分子机制提供洞察力，并为风险分层提供新的诊断测试，这是改善接受血管手术的外周动脉疾病患者临床结果的新治疗靶点。