Platelet Activity & Cardiovascular Events following Vascular Surgery

血小板活性

• 批准号: 9324303
• 负责人: Jeffrey S Berger
• 金额: $ 47.76万
• 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 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9324303
• 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; 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; Pathologic; Patients; Pattern; Perioperative; Peripheral arterial disease; Phenotype; Postoperative Period; Procedures; Production; Prognostic Marker; Proteins; Publishing; Quality of life; RNA; Reproducibility; Risk; Risk Factors; Risk stratification; Stroke; Therapeutic Intervention; Thrombosis; Troponin I; United States; Vascular Diseases; Vascular Surgical Procedures; activity marker; atherothrombosis; cardiovascular risk factor; clinical investigation; clinically relevant; cohort; comparative; diagnostic biomarker; differential expression; follow-up; high risk; high risk population; improved; insight; modifiable risk; mortality; new therapeutic target; novel; novel diagnostics; prevent; profiles in patients; prospective; public health relevance; sex; targeted treatment; 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非常普遍的疾病，也是心血管疾病发病率和全因死亡率的一个重要原因。尽管血管外科手术通常是为了提高患者的生存率和生活质量，但患者发生围手术期心血管不良事件的风险较高。血管手术后，患者发生长期心血管事件的风险仍然增加。传统的危险因素在血管手术后区分心血管风险的能力有限，而且大多是不可改变的。病理学和临床研究一致表明，血小板是糖尿病发病机制的罪魁祸首。 动脉粥样硬化血栓形成。我们提出了一种新颖、可靠且可重复的血小板活性增加测量方法，从而可以在这一高危人群中研究这一临床相关且可能可改变的心血管危险因素。研究假设是血小板 血管手术前的活动测量与 30 天心血管事件独立且显着相关。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着相关。我们还将血小板活性与基因组表达谱关联起来，以确定控制血小板活性的分子机制。长期目标是确定临床上有用的血小板活性评估，以进行风险分层，也可用作诊断和治疗干预的目标。拟议的研究将是一项前瞻性观察性队列研究，在下肢非紧急开放血管手术前招募 350 名受试者。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 天的主要终点是死亡、心肌梗塞、中风和肌钙蛋白 I >0.1ng/ml。长期主要终点是死亡、心肌梗塞或中风。次要终点是大出血、血管血栓形成、各个终点和心血管死亡。将探讨外周动脉疾病患者血小板活性增加的机制；将 12 名血小板活性增加的患者中分离的血小板 mRNA 和 microRNA 表达谱与 12 名血小板活性正常的患者进行比较。这项研究将提供新的数据，以解决有关血小板活性测量与心血管事件之间关联的现有知识差距，并将确定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使用潜在可改变的风险因素在血管手术前识别高风险受试者。这些数据将深入了解调节血小板活性的分子机制，并产生新的风险分层诊断测试和新的治疗目标，以改善接受血管手术的外周动脉疾病患者的临床结果。

项目成果

Perioperative antiplatelet therapy and cardiovascular outcomes in patients undergoing joint and spine surgery.

接受关节和脊柱手术的患者的围手术期抗血小板治疗和心血管结局。

• 发表时间: 2016-12
• 作者: Smilowitz, Nathaniel R;Oberweis, Brandon S;Nukala, Swetha;Rosenberg, Andrew;Stuchin, Steven;Iorio, Richard;Errico, Thomas;Radford, Martha J;Berger, Jeffrey S
• 通讯作者: Berger, Jeffrey S

Trends in Perioperative Venous Thromboembolism Associated with Major Noncardiac Surgery.

与主要非心脏手术相关的围手术期静脉血栓栓塞的趋势。

• 发表时间: 2017-07
• 作者: Smilowitz, Nathaniel R;Gupta, Navdeep;Guo, Yu;Maldonado, Thomas S;Eikelboom, John W;Goldhaber, Samuel Z;Bangalore, Sripal;Berger, Jeffrey S
• 通讯作者: Berger, Jeffrey S

Co-existence of vascular disease in different arterial beds: Peripheral artery disease and carotid artery stenosis--Data from Life Line Screening(®).

不同动脉床血管疾病的共存：外周动脉疾病和颈动脉狭窄——来自生命线筛查（®）的数据。

• 发表时间: 2015-08
• 影响因子: 5.3
• 作者: Razzouk, Louai;Rockman, Caron B;Patel, Manesh R;Guo, Yu;Adelman, Mark A;Riles, Thomas S;Berger, Jeffrey S
• 通讯作者: Berger, Jeffrey S

Association Between Anemia, Bleeding, and Transfusion with Long-term Mortality Following Noncardiac Surgery.

贫血、出血和输血与非心脏手术后长期死亡率之间的关系。

• 发表时间: 2016-03
• 作者: Smilowitz, Nathaniel R;Oberweis, Brandon S;Nukala, Swetha;Rosenberg, Andrew;Zhao, Sibo;Xu, Jinfeng;Stuchin, Steven;Iorio, Richard;Errico, Thomas;Radford, Martha J;Berger, Jeffrey S
• 通讯作者: Berger, Jeffrey S

Perioperative bleeding and thrombotic risks in patients with Von Willebrand disease.

冯·维勒布兰德病患者的围手术期出血和血栓形成风险。

• 发表时间: 2017-07
• 影响因子: 4
• 作者: Smilowitz, Nathaniel R;Gupta, Navdeep;Guo, Yu;Bangalore, Sripal;Berger, Jeffrey S
• 通讯作者: Berger, Jeffrey S