Epidemiology of Venous Thrombosis and Pulmonary Embolism

描述（由申请人提供）：静脉血栓栓塞（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原因。在此，我们建议对我们独特且信息丰富的血栓栓塞病因学纵向调查（LITE）进行为期4年的延续，这是一项针对ARIC和CHS队列的前瞻性研究。我们在之前的项目期间有几个重要的发现，其中最重要的三个是：(1)在前瞻性研究中首次发现血浆纤维蛋白片段d -二聚体（纤维蛋白周转的标志）与未来静脉血栓栓塞的风险正相关，(2)再次前瞻性地首次证实，VIII因子和血管性血血病因子是静脉血栓栓塞的强烈危险因素。(3)证明肥胖和糖尿病是重要的静脉血栓栓塞危险因素，但大多数其他动脉疾病危险因素，包括纤维蛋白原和c反应蛋白，不是。我们计划在LITE继续期间通过增加新病例和测试新假设来建立这些发现。我们的目标是

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.