Thrombophilia In Cryptogenic Stroke (THICK) Study

描述(由申请人提供)： 应聘者的计划/培训： 应聘者计划成为一名独立的临床调查员，专注于与心脑血管疾病的血液学、血管和心脏决定因素相关的以患者为中心的研究。培训将包括临床研究中的正式流行病学课程工作，以及在密切指导下完成研究方案。 环境：威尔·康奈尔医学院的心脏科和公共卫生系将提供有组织的指导。纽约长老会医院的超声心动图实验室、公共卫生部和综合临床研究中心将提供研究支持。课程作业将在哥伦比亚大学公共卫生学院进行。 研究：缺血性中风构成了惊人的公共卫生负担，但其原因往往无法确定，尽管进行了彻底的评估。尽管卵圆孔未闭(PFO)已被确定为年轻患者不明原因卒中的危险因素，但绝大多数PFO不是致病的。最近，随着大量静脉血栓前因子的发现，可能增加矛盾栓塞术风险的潜在关键致病因素已经出现。各种动脉促凝血因子也可以通过独立于PFO的机制来解释隐源性卒中的一个重要部分。有证据表明，静脉和动脉血栓形成可能是缺血性中风的重要危险因素，尤其是在年轻人中。然而，它们在不明原因中风人群中的意义还没有得到充分的研究。血栓形成参与隐源性卒中的病因学研究，不仅有助于阐明疾病的发病机制，而且有助于确定合适的治疗策略。这些都是非常重要的，因为只有有限的数据来指导对这类患者进行终生抗凝、外科关闭PFO或无限期抗血栓治疗的决定。我们提出了一项前瞻性病例对照研究，以检验1)静脉血栓形成是否是隐源性卒中的独立危险因素；2)静脉血栓形成是PFO致病的重要共同决定因素；3)动脉血栓形成在解释隐源性卒中中具有显著作用。此外，还将调查血栓形成、血栓形成和传统心血管危险因素之间的相互作用，以及血栓形成和其他潜在的心脏栓塞源。

DESCRIPTION (provided by applicant): Candidate's Plans/Training: The candidate plans a career as an independent clinical investigator focusing on patient oriented research related to hematologic, vascular and cardiac determinants of cardiovascular/cerebrovascular disease. Training will include formal epidemiological course work in clinical research and closely mentored completion of the research protocol. Environment: The Cardiology Division and Department of Public Health at Weill Cornell Medical College will provide structured mentoring. The Echocardiography Laboratory, Department of Public Health, and General Clinical Research Center at the New York Presbyterian Hospital will provide research support. Coursework will be undertaken at the Columbia School of Public Health. Research: Ischemic stroke constitutes a public health burden of staggering proportions, yet its cause often cannot be determined despite thorough evaluation. Although patent foramen ovale (PFO) has been identified as a risk factor for unexplained stroke in younger patients, the overwhelming majority of PFOs are not pathogenic. Potentially key co-determinants of PFO pathogenicity have emerged with recent identification of a host of venous prothrombotic factors that could heighten the risk of paradoxical embolization. Various arterial procoagulant factors could also explain an important fraction of cryptogenic strokes, through mechanisms independent of PFO. There is evidence that venous and arterial thrombophilias may be important risk factors for ischemic stroke, especially in young subjects. Their significance in populations with unexplained stroke, however, has not been sufficiently studied. Involvement of thrombophilias in the etiology of cryptogenic stroke would not only illuminate the mechanism of disease, but would also help define appropriate therapeutic strategies. These are of immense importance because there are limited data to guide the decision to institute life-long anticoagulation, surgical closure of PFO, or indefinite antithrombotic therapy for such patients. We propose a prospective case-control study to examine whether 1) venous thrombophilias are independent risk factors for cryptogenic stroke; 2) venous thrombophilias are important co-determinants of PFO pathogenicity; and 3) arterial thrombophilias have a prominent role in explaining cryptogenic stroke. Interactions among thrombophilias, thrombophilias and traditional cardiovascular risk factors, and thrombophilias and other potential cardiac sources of embolism will also be investigated.