Epidemiology of Venous Thromboembolism

静脉血栓栓塞（VTE）是一种常见的疾病，导致大量的发病率、成本和死亡率，但这种疾病的流行病学的几个方面仍未被探索。本提案的主要目的是评估静脉血栓栓塞的潜在可改变的生活方式预测因素及其与生化和遗传决定因素的联合关系。研究将确定静脉血栓栓塞的初始发生和复发的决定因素。该研究设计是一项前瞻性队列研究，涉及77118人，基于美国卫生专业人员的四项大型随机试验的汇总信息，这些试验收集了详细的风险因素信息，并使用了共同的策略来前瞻性地识别和验证静脉血栓栓塞病例。这些试验是：医生健康研究I和II，包括29,071名美国男性医生，其中22,071名自1982年第一次试验开始以来一直被跟踪；妇女健康研究，包括39,876名女性保健专业人员，平均随访时间为10年；女性抗氧化剂心血管研究包括8,171名患有心血管疾病或心血管疾病高风险的女性卫生专业人员，她们将平均随访8年。大约75%的参与者在基线时收集了存档的血液样本，并将用于评估生化和遗传风险标记，包括V Leiden因子、凝血酶原基因G20210A突变、高同型半胱氨酸血症和抗心磷脂抗体。该研究将评估这些标志物和潜在可改变因素（包括体重指数、激素替代疗法、体力活动和阿司匹林使用）与风险的联合关系。研究人群将包括1000多例静脉血栓栓塞病例，其中750例有血液样本。大样本、前瞻性设计、高随访率、详细可靠的长期暴露和结局信息、大量亚群的血液样本的可用性，加上相对较低的成本，使这些队列成为研究静脉血栓栓塞风险决定因素的宝贵和独特资源。这项工作的结果可能会导致静脉血栓栓塞预防的新策略。

Venous thromboembolism (VTE) is a common condition causing substantial morbidity, cost and mortality, yet several aspects of the epidemiology of this disease remain unexplored. The major aim of this proposal is to evaluate potentially modifiable lifestyle predictors of VTE and their joint associations with biochemical and genetic determinants. Studies will identify determinants of both initial occurrence of VTE as well as recurrence among persons with a prior event. The study design is a prospective cohort study of 77,118 persons based on pooling information from four large randomized trials of US health professionals that have collected detailed risk factor information and have used common strategies to prospectively identify and validate cases of VTE. These trials are: Physicians' Health Studies I and II including 29,071 US male physicians, of whom 22,071 have been followed since the initiation of the first trial in 1982; the Women's Health Study including 39,876 female health professionals who will have an average of 10 years of follow-up; and the Women's Antioxidant Cardiovascular Study including 8,171 female health professionals with prevalent cardiovascular disease or at high risk of cardiovascular disease who will have an average of 8 years of follow-up. Archived blood samples were collected from approximately 75 percent of participants at baseline and will be used to assess biochemical and genetic markers of risk including factor V Leiden, the G20210A mutation in the prothrombin gene, hyperhomocysteinemia, and anticardiolipin antibodies. The study will assess the joint association with risk of these markers and potentially modifiable factors including body mass index, hormone replacement therapy, physical activity, and aspirin use. The study population will include over 1,000 incident cases of VTE, including 750 with blood samples. The large size, prospective design, high follow-up rates, detailed and reliable long-term exposure and outcome information, and the availability of blood specimens on a large subgroup, combined with the relatively low cost, make these cohorts a valuable and unique resource for studying determinants of risk of VTE. The results of this work may lead to new strategies for VTE preventio.