Genotypic Impact on Outcomes after CABG Surgery

基因型对 CABG 手术后结果的影响

• 批准号: 6941231
• 负责人: Simon C Body
• 金额: $ 16.09万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-12 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6941231
• 关键词: blood coagulation; clinical research; coronary bypass; fibrinolysis; genetic susceptibility; genotype; hemostasis; human subject; patient oriented research; phenotype; postoperative complications; tissue resource /registry

DESCRIPTION (provided by applicant): Activation of the coagulation and fibrinolytic pathways following cardiopulmonary bypass (CPB) and coronary artery bypass graft (CABG) surgery may result in specific, adverse clinical bleeding and arterial thrombotic clinical (ATC) outcomes. Accumulating evidence suggests that specific genotypes are associated with organ-specific outcomes after CPB, including cognitive dysfunction, renal compromise, and death. However, little is known of the role of allotypic coagulation and fibrinolytic gene variation in determining the frequency of adverse bleeding and ATC outcomes, including perioperative hemorrhage, MI, coronary artery graft failure and cardiac death following CABG surgery. The general aim of this proposal is to investigate whether specific coagulation and fibrinolytic genotypes and phenotypes are associated with an increased incidence of specific adverse, perioperative bleeding and ATC outcomes in humans undergoing CABG surgery requiring CPB. In order to accomplish this general aim, 3 specific aims are proposed. Specific Aim #1: Establish a robust perioperative blood sample repository and adverse clinical outcomes database of patients undergoing CABG surgery requiring CPB. Specific Aim #2: Establish whether specific coagulation and fibrinolytic phenotypes are predictive of adverse, perioperative bleeding and ATC outcomes in patients undergoing CABG surgery requiring CPB. Specific Aim #3: Establish the relationship between coagulation and fibrinolytic allotypes and adverse, perioperative bleeding and ATC outcomes in patients undergoing CABG surgery. The Applicant is a Cardiothoracic Anesthesiologist with twelve years experience in clinical management of cardiac patients, with a background in statistics and clinical trial design and execution. To build a foundation for future independent research, in addition to direct experience and training in basic molecular techniques, the Applicant will undertake a Master of Public Health degree at the Harvard School of Public Health. This will include didactic teaching in 1) Biostatistics, 2) Epidemiology of disease, 3) Bioinformatics, 4) Statistical methods in human genetics, and 5) Research ethics. The overall objective is to master genetic epidemiology and statistical methods for assessment of hereditary influences upon adverse outcomes and utilize these skills to conduct innovative patient-oriented clinical research. The career development and research plans will take advantage of the unique collection of statistical, epidemiological and genomic skills, and laboratory resources, notably in cardiovascular diseases, available within Brigham and Women's Hospital and the Harvard Medical School. Identification of specific coagulation and fibrinolytic genotypes and phenotypes associated with an increased incidence of specific adverse, perioperative bleeding and ATC outcomes in humans undergoing CABG surgery requiring CPB may improve preoperative patient risk stratification, preventative therapy and postoperative resource utilization..

描述（由申请人提供）： 心肺旁路（CPB）和冠状动脉搭桥术（CABG）手术后的凝血和纤维蛋白水解途径的激活可能会导致特定的，不良的临床出血和动脉凝血淋巴结临床（ATC）。积累的证据表明，特定的基因型与CPB后器官特异性结果有关，包括认知功能障碍，肾脏折衷和死亡。然而，知之甚少，关于同种型凝血和纤维蛋白水解基因变异在确定不良出血和ATC结局的频率中的作用，包括围手术期出血，MI，冠状动脉移植，冠状动脉移植和心脏死亡。该提案的总体目的是研究特定的凝血和纤维蛋白水解基因型和表型是否与需要CABG手术的人体中特定不良，围手术期出血和ATC结果的发生率增加有关。为了实现这一总体目标，提出了3个具体目标。具体目的＃1：建立一个强大的围手术期血液样本存储库和不良临床结果的数据库，该数据库正在接受需要CPB的CABG手术的患者。具体目标2：确定特定的凝血和纤维蛋白水解表型是否可以预测需要CPB的CABG手术患者的不良，围手术期出血和ATC结局。特定目标＃3：在接受CABG手术的患者中，建立凝血与纤维蛋白水解异型，围手术期出血和ATC结局之间的关系。申请人是一名心胸麻醉师，在心脏病患者的临床管理方面具有十二年的经验，具有统计和临床试验设计和执行背景。为了建立未来独立研究的基础，除了基本分子技术的直接经验和培训外，申请人还将在哈佛公共卫生学院攻读公共卫生硕士学位。这将包括1）生物统计学的教学，2）疾病流行病学，3）生物信息学，4）人类遗传学中的统计方法和5）研究伦理。总体目的是掌握遗传流行病学和统计方法，以评估遗传性影响不良后果的影响，并利用这些技能来进行创新的以患者为导向的临床研究。职业发展和研究计划将利用统计，流行病学和基因组技能以及实验室资源的独特收集，尤其是在心血管疾病中，在棕色，妇女医院和哈佛医学院内可用。鉴定特异性凝血和纤维蛋白水解基因型和表型与特定不良，围手术期出血的发生率增加和接受CABG手术中的ATC结局有关，需要CPB需要CPB，可以改善术前患者风险分层，预防治疗和术后资源利用。