Platelet Activity & Cardiovascular Events following Vascular Surgery

血小板活性

• 批准号: 8723272
• 负责人: Jeffrey S Berger
• 金额: $ 62.81万
• 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 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8723272
• 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; 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; follow-up; high risk; improved; insight; modifiable risk; mortality; new therapeutic target; novel; novel diagnostics; prevent; prospective; public health relevance; 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（由申请人提供）：外周动脉疾病在美国是一种高度流行的疾病，是心血管发病率和全因死亡率的重要原因。虽然血管外科手术通常用于提高患者生存率和生活质量，但患者发生围手术期不良心血管事件的风险较高。血管手术后，患者长期心血管事件的风险仍然增加。传统的危险因素在区分血管手术后心血管风险方面的能力有限，并且大多数是不可修改的。病理学和临床研究一致表明，血小板是一个主要的罪魁祸首的发病机制， 动脉粥样硬化血栓形成我们提出了一种新的，可靠的，可重复的测量增加血小板活性，从而允许调查这一临床相关的和潜在的可修改的心血管危险因素在这个非常高的风险人群。研究假设血小板 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。我们还将血小板活性与基因组表达谱相关联，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评估方法，用于危险分层，可用作诊断和治疗干预的目标。拟定研究是一项前瞻性观察性队列研究，入组350例非急诊下肢开放性血管手术前受试者。将在血管手术前后测量血小板活性，并将其与30天和长期心血管事件相关。30天主要终点为死亡、心肌梗死、卒中和肌钙蛋白I >0.1ng/ml。长期主要终点为死亡、心肌梗死或卒中。次要终点是大出血、血管血栓形成、每个个体终点和心血管死亡。将探索外周动脉疾病患者血小板活性升高的机制;将12例血小板活性升高患者的分离血小板mRNA和microRNA表达谱与12例血小板活性正常患者进行比较。这项研究将提供新的数据，以解决现有的知识差距，有关血小板活性测量和心血管事件之间的关联，并将确定是否存在一个独特的血小板RNA表达谱在外周动脉疾病受试者与血小板活性增加。从本研究中获得的数据将使用潜在可修改的风险因素在血管手术前识别高风险受试者。这些数据将提供对调节血小板活性的分子机制的深入了解，并产生用于风险分层的新型诊断测试，以及用于改善接受血管手术的外周动脉疾病患者的临床结局的新型治疗靶点。