Epidemiology of Venous Thrombosis and Pulmonary Embolism

静脉血栓形成和肺栓塞的流行病学

• 批准号: 7002648
• 负责人: AARON R FOLSOM
• 金额: $ 30.67万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7002648
• 关键词: ABO(H) blood groups; antifibrinolytic agents; carboxypeptidase; cardiovascular disorder epidemiology; cardiovascular disorder risk; clinical research; coagulation factor V; coagulation factor VII; disease /disorder etiology; enzyme linked immunosorbent assay; frail elderly; high performance liquid chromatography; homocysteine; hormone therapy; human genetic material tag; human middle age (35-64); human old age (65+); human subject; longitudinal human study; nutrient intake activity; obesity; prothrombin; pulmonary circulation obstruction; questionnaires; venous thrombosis; vitamin B6

DESCRIPTION (provided by applicant): Venous thromboembolism (VTE), comprising deep venous thrombosis and pulmonary embolism, is a major contributor to morbidity and mortality in the US. We propose here a 4-year continuation of our unique and informative Longitudinal Investigation of Thromboembolism Etiology (LITE), a prospective study within the ARIC and CHS cohorts. We have several important findings from the previous project period, the three most important being (1) identification for the first time in a prospective study that plasma fibrin fragment D-dimer, a marker of fibrin turnover, is positively and strongly associated with risk of future VTE, (2) verification, again for the first time prospectively, that factor VIII and von Willebrand factor are strong risk factors for VTE, and (3) demonstration that obesity and diabetes are important VTE risk factors, but that most other arterial disease risk factors, including fibrinogen and C-reactive protein, are not. We plan to build upon these findings during LITE continuation, by adding new cases and testing new hypotheses. Our aims are 1. To extend VTE event follow-up in the LITE Study for 4 more years, which is expected to increase the current number of VTE events (n=335) by 47 percent (to n=493), and to sample 1 control per case. In the new cases and controls, we will measure analytes found to be important in LITE already (factor V Leiden, prothrombin G20210A variant, D-dimer, and TAFI), to serve as covariates in combined analyses. 2. To conduct nested case-control studies in the entire sample of 493 VTE cases and 828 controls, using prediagnosis blood and DNA specimens, to determine the prospective associations of VTE with several novel plasma hemostatic factors and genetic markers. 3. To conduct longitudinal analyses of VTE incidence and potential risk factors (or interaction) that we have not yet fully explored: diet, frailty, hormone replacement therapy, and obesity interactions. 4. To study serial blood levels of D-dimer and homocysteine, to better understand their associations with VTE occurrence. Continuation of this comprehensive prospective study will provide additional important epidemiologic insights into the etiology of VTE. This could lead to new strategies for prevention or treatment of VTE.

描述(申请人提供)：静脉血栓栓塞症(VTE)，包括深静脉血栓形成和肺栓塞，是美国发病率和死亡率的主要贡献者。我们建议在ARIC和CHS队列中的前瞻性研究--血栓栓塞症病因学的独特和信息丰富的纵向调查(LITE)的基础上，继续进行为期4年的研究。我们从上一个项目期有了几个重要的发现，其中最重要的三个是(1)在一项前瞻性研究中首次确定作为纤维蛋白周转标志的血浆纤维蛋白片段D-二聚体与未来VTE的风险呈正相关，(2)再次前瞻性地验证了第VIII因子和von Willebrand因子是VTE的强烈风险因素，以及(3)证明肥胖和糖尿病是VTE的重要风险因素，但包括纤维蛋白原和C-反应蛋白在内的大多数其他动脉疾病风险因素不是。我们计划通过增加新的病例和测试新的假说，在Lite延续的过程中建立这些发现。我们的目标是 1.将LITE研究中的VTE事件随访延长4年，预计将使VTE事件的当前数量(n=335)增加47%(n=493)，并在每个病例中抽样1个对照。在新的病例和对照中，我们将测量已经在LITE中发现重要的分析物(因子V莱顿、凝血酶原G20210A变异体、D-二聚体和TAFI)，作为联合分析的协变量。 2.对493例VTE患者和828例对照进行巢式病例对照研究，利用诊断前的血液和DNA样本，确定VTE与几种新的血浆止血因子和遗传标记的前瞻性关联。 3.对VTE的发病率和潜在的危险因素(或交互作用)进行纵向分析，这些因素(或交互作用)是我们尚未充分探索的：饮食、虚弱、激素替代治疗和肥胖交互作用。 4.研究D-二聚体和同型半胱氨酸的动态变化，进一步了解其与VTE发生的关系。 这项全面的前瞻性研究的继续将为静脉血栓栓塞症的病因提供更多重要的流行病学见解。这可能导致预防或治疗静脉血栓栓塞症的新战略。