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（由申请人提供）：在美国，周围动脉疾病是一种高度普遍的疾病，也是心血管发病率和全因死亡率的重要原因。尽管通常执行血管外科手术以改善患者的生存和生活质量，但患者的围手术期心血管事件的风险越高。血管手术后，患者仍然有长期心血管事件的风险增加。传统的风险因素的限制能力有限，其在血管手术后鉴别心血管风险的能力受到限制，并且大多是不可修道的。病理和临床研究一致表明，血小板是造成罪魁祸首的主要罪魁祸首。 动脉粥样硬化。我们提出了一种新型，可靠且可重复的血小板活性的测量，从而可以研究这种非常高风险的人群中这种临床相关且潜在地与心血管危险因素的研究。研究假设是血小板 血管手术前的活性测量与30天的心血管事件有关。我们进一步假设术后测量的血小板活性独立且与长期心血管事件显着相关。我们还将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。长期的目标是确定对血小板活动的临床有用评估，用于风险分层，该评估也可以用作诊断和治疗干预措施。拟议的研究将是一项前瞻性观察队列研究，在下肢的非紧急开放性血管手术之前，招募了350名受试者。血小板活性将在血管手术前后进行测量，并将与30天和长期心血管事件相关。 30天的主要终点将是死亡，心肌梗塞，中风和肌钙蛋白I> 0.1ng/ml。长期的主要终点将是死亡，心肌梗塞或中风。次要终点是主要出血，血管血栓形成，每个终点和心血管死亡。将探索血小板活性增加的周围动脉疾病患者的机制；在12例血小板活性增加的患者中，分离的血小板mRNA和microRNA表达谱将与12例正常血小板活性的患者进行比较。这项研究将提供新的数据，以解决有关血小板活性测量与入射心血管事件之间关联的现有差距，并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。从这项研究中获得的数据将在血管手术前使用潜在的可修改风险因素鉴定高风险受试者。这些数据将提供有关调节血小板活性的分子机制，并对风险分层进行新的诊断测试，这是一种新的治疗靶标，以改善接受血管手术的周围动脉疾病患者的临床结局。