Venous Thromboembolism Sequelae in a Population-based Inception Cohort

项目概要/摘要 每年有近100万美国人经历第一次静脉血栓栓塞（VTE），其中包括深静脉血栓栓塞。 静脉血栓形成（DVT）和肺栓塞（PE）。VTE通常被视为急性事件， 抗凝剂可治疗，较少关注慢性不良VTE后遗症或康复。的成年人 发生过VTE事件的患者在治疗后的前12个月内发生不良VTE后遗症的风险较高 事件，包括患者相关症状（如呼吸困难、疼痛和肿胀）和不良临床 结局（VTE复发和死亡）。迄今为止的研究表明， 发生在DVT后，但对PE事件后的后遗症的关注要少得多。 此外，几乎所有关于DVT和PE后后遗症的研究都是在 使用维生素K拮抗剂抗凝，而不是使用新的直接口服抗凝剂（DOAC）， 目前主要用于实践。在临床上，我们缺乏方法来确定成人最大的风险，不利的静脉血栓栓塞 如何预防这些后遗症。是否有几个很有前途的生物标志物， 用于临床测量（脑利钠肽、D-二聚体和肌钙蛋白），或是否可改变暴露量 如抗凝剂类型或体力活动与不良VTE后遗症相关 明白在拟议的研究中，我们将描述患者相关症状和不良临床反应， VTE后前12个月内多个时间点的结局，并将评价生物标志物和可修改的 与这些VTE后遗症相关的风险因素。为了实现这一目标，我们将创造一个新的预期人口- 一项基于Kaiser Permanente华盛顿的初始队列研究， 系统在华盛顿州。我们的初步研究支持日常事件识别的可行性 成人入组者中的VTE病例，我们预计在33个月内约有957名合格成人患有经验证的VTE 注册。在约380名知情同意的成人中重新收集数据将包括：1）2周和1、3、6周时的调查， 静脉血栓栓塞后12个月收集静脉血栓栓塞后症状的信息，2）腕戴式加速计， 客观测量VTE后12个月的体力活动和静息心率，以及3）采血 在发生VTE的4周内测量3种预先指定的生物标志物。这些研究数据将被合并 利用丰富的电子健康档案数据，实现3个科学目标：（1）表征患病模式 VTE发生后2周和1、3、6和12个月的症状以及12个月内的临床结局 （2）评估在4个月内收集的血液中测量的关键生物标志物水平的相关性 VTE事件发生后的3周;（3）评估后遗症的可改变风险因素，包括VTE抗凝剂 类型和体力活动水平。这项研究将填补对患者重要的关键知识空白， 提供临床负担性VTE后遗症的患病率估计值，并确定可能的病因 和可改变的风险因素，可以在未来的干预措施中针对。

PROJECT SUMMARY / ABSTRACT Nearly 1 million Americans each year experience a first venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). VTE is typically viewed as an acute event that is treatable by anticoagulants, with less focus on chronic adverse VTE sequelae or on rehabilitation. Adults who have experienced an incident VTE may be at high risk for adverse VTE sequelae in the first 12 months after their event, including patient-relevant symptoms (such as dyspnea, pain, and swelling) and adverse clinical outcomes (VTE recurrence and death). Research to-date has characterized the post-thrombotic syndrome occurring post-DVT, but there has been much less attention given to sequelae following an incident PE. Furthermore, almost all research about sequelae after both DVT and PE has been in the context of anticoagulation with vitamin K antagonists rather than with newer direct oral anticoagulants (DOACs), which are now primarily used in practice. Clinically, we lack methods to identify adults at greatest risk of adverse VTE sequelae and how to prevent these sequelae. Whether several promising biomarkers that are readily available for clinical measurement (brain natriuretic peptide, D-dimer, and troponin), or, whether modifiable exposures such as anticoagulant type or physical activity are associated with adverse VTE sequelae is incompletely understood. In the proposed research, we will characterize patient-relevant symptoms and adverse clinical outcomes at multiple timepoints in the first 12 months post-VTE and will evaluate biomarkers and modifiable risk factors in relation to these VTE sequelae. To accomplish this, we will create a new prospective population- based inception cohort study based in Kaiser Permanente Washington, an integrated healthcare delivery system in Washington State. Our preliminary research supports the feasibility of daily identification of incident VTE cases among adult enrollees, and we anticipate ~957 eligible adults with validated VTE across 33 months of enrollment. De novo data collection in ~380 consenting adults will include: 1) surveys at 2 weeks and 1, 3, 6, and 12 months post-VTE to collect information on post-VTE symptoms, 2) wrist-worn accelerometers to objectively measure physical activity and resting heart rate in the 12 months post-VTE, and 3) blood collection within 4 weeks of the incident VTE to measure 3 pre-specified biomarkers. These study data will be combined with rich electronic health record data to accomplish 3 scientific aims: (1) Characterize the prevalence pattern of symptoms at 2 weeks and 1, 3, 6, and 12 months post-incident VTE and clinical outcomes over the 12 months of follow-up; (2) evaluate the associations of key biomarker levels measured in blood collected within 4 weeks of the incident VTE; and, (3) evaluate modifiable risk factors for sequalae, including VTE anticoagulant type and physical activity level. This research will fill critical knowledge gaps that are important to patients by providing estimates of the prevalence of clinically burdensome VTE sequelae and identifying possible etiologic and modifiable risk factors that can be targeted in future interventions.