Epidemiology of Venous Thrombosis and Pulmonary Embolism

描述（由申请方提供）：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。我们在此建议对ARIC和CHS队列进行为期4年的前瞻性研究，即我们独特且信息丰富的血栓栓塞病因学纵向研究（LITE）。我们在前一个项目期间有几个重要的发现，其中三个最重要的是（1）在前瞻性研究中首次确定血浆纤维蛋白片段D-二聚体（纤维蛋白转换的标志物）与未来VTE的风险呈正相关，（2）再次前瞻性验证因子VIII和血管性血友病因子是VTE的强风险因子，和（3）证明肥胖和糖尿病是重要的VTE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继续期间通过添加新病例和测试新假设来建立这些发现。我们的目标是 1. 将LITE研究中的VTE事件随访再延长4年，预计将使当前VTE事件数量（n=335）增加47%（至n=493），并对每个病例进行1次对照采样。在新病例和对照中，我们将测量在LITE中已经发现的重要分析物（凝血因子V Leiden、凝血酶原G20210 A变体、D-二聚体和TAFI），作为联合分析的协变量。 2. 使用诊断前血液和DNA标本，对493例VTE病例和828例对照的整个样本进行巢式病例对照研究，以确定VTE与几种新型血浆止血因子和遗传标记物的前瞻性相关性。 3. 对VTE发病率和我们尚未充分探讨的潜在风险因素（或相互作用）进行纵向分析：饮食、虚弱、激素替代疗法和肥胖相互作用。 4. 目的：研究动态血D-二聚体和同型半胱氨酸水平，以更好地了解其与VTE发生的关系。 继续这项全面的前瞻性研究将为VTE的病因学提供更多重要的流行病学见解。这可能导致预防或治疗VTE的新策略。

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.