Genotypic Impact on Outcomes after CABG Surgery

基因型对 CABG 手术后结果的影响

• 批准号: 7109406
• 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 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7109406
• 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..

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项目成果

Pharmacogenetics of anesthetic and analgesic agents.

麻醉剂和镇痛剂的药物遗传学。

• DOI: 10.1097/00000542-200503000-00028
• 发表时间: 2005
• 期刊: Anesthesiology
• 影响因子: 8.8
• 作者: Palmer,StephenN;Giesecke,NMartin;Body,SimonC;Shernan,StantonK;Fox,AmandaA;Collard,CharlesD
• 通讯作者: Collard,CharlesD

Profilin-1 is expressed in human atherosclerotic plaques and induces atherogenic effects on vascular smooth muscle cells.

• DOI: 10.1371/journal.pone.0013608
• 发表时间: 2010-10-25
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Caglayan E;Romeo GR;Kappert K;Odenthal M;Südkamp M;Body SC;Shernan SK;Hackbusch D;Vantler M;Kazlauskas A;Rosenkranz S
• 通讯作者: Rosenkranz S

Genetic influences on cardiac surgical outcomes.

遗传对心脏手术结果的影响。

• DOI: 10.1053/j.jvca.2004.11.048
• 发表时间: 2005
• 期刊: Journal of cardiothoracic and vascular anesthesia
• 影响因子: 2.8
• 作者: Fox,AmandaA;Shernan,StantonK;Body,SimonC;Collard,CharlesD
• 通讯作者: Collard,CharlesD

Genomics: risk and outcomes in cardiac surgery.

基因组学：心脏手术的风险和结果。

• DOI: 10.1016/j.anclin.2008.04.002
• 发表时间: 2008
• 期刊: Anesthesiology clinics
• 作者: Perry,TjorviE;Muehlschlegel,JochenD;Body,SimonC
• 通讯作者: Body,SimonC

Common genetic variants on chromosome 9p21 predict perioperative myocardial injury after coronary artery bypass graft surgery.

• DOI: 10.1016/j.jtcvs.2009.06.032
• 发表时间: 2010-02
• 期刊: JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
• 影响因子: 6
• 作者: Liu, Kuang-Yu;Muehlschlegel, Jochen D.;Perry, Tjoervi E.;Fox, Amanda A.;Collard, Charles D.;Body, Simon C.;Shernan, Stanton K.
• 通讯作者: Shernan, Stanton K.