Venous Thromboembolism Sequelae in a Population-based Inception Cohort

项目摘要/摘要 每年有近100万美国人经历首次静脉血栓栓塞症(VTE)，其中包括深静脉血栓 静脉血栓形成(DVT)和肺栓塞(PE)。VTE通常被视为一种急性事件， 可用抗凝剂治疗，较少关注慢性不良VTE后遗症或康复。成年人 经历过VTE事件后的前12个月，VTE可能有很高的不良后遗症风险 他们的事件，包括与患者相关的症状(如呼吸困难、疼痛和肿胀)和不良的临床 结果(静脉血栓栓塞术复发和死亡)。到目前为止的研究已经表征了血栓形成后综合征 发生在DVT后，但对事件PE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拮抗剂而不是较新的直接口服抗凝剂(DOAC)进行抗凝，后者 现在主要用于实践中。临床上，我们缺乏方法来识别有最大风险的成年人的不良静脉血栓形成。 后遗症以及如何预防这些后遗症。几个有希望的生物标记物是否现成 用于临床测量(脑利钠肽、D-二聚体和肌钙蛋白)，或是否可修改暴露 如抗凝剂类型或体力活动与不良静脉血栓栓塞症后遗症相关不完全 明白了。在拟议的研究中，我们将描述与患者相关的症状和临床不良反应。 VTE后前12个月多个时间点的结果，并将评估生物标记物和可修改的 与这些VTE后遗症相关的危险因素。为了实现这一目标，我们将创造一个新的潜在人口- 基于华盛顿州Kaiser Permanente的初始队列研究，这是一项综合医疗保健服务 华盛顿州的系统。我们的初步研究支持了日常事件识别的可行性 成人参与者中的VTE病例，我们预计在33个月内约有957名符合条件的成年人患有有效的VTE 招生人数。对约380名同意的成年人进行的重新数据收集将包括：1)在2周和1、3、6、 和12个月后收集有关VTE后症状的信息，2)手腕佩戴的加速度计 客观测量VTE术后12个月的体力活动和静息心率，3)采血 在VTE事件发生后4周内测量3个预先指定的生物标志物。这些研究数据将结合在一起 利用丰富的电子健康档案数据实现3个科学目标：(1)描述流行模式 发生VTE后2周、1、3、6和12个月的症状和12个月内的临床结果 3个月的随访；(2)评估在4个月内采集的血液中测量的关键生物标志物水平的相关性 发生VTE的几周；以及，(3)评估后遗症的可修改危险因素，包括VTE抗凝剂 类型和体力活动水平。这项研究将通过以下方式填补对患者重要的关键知识空白 提供对临床负担沉重的静脉血栓栓塞症后遗症患病率的估计，并确定可能的病因 以及可在未来干预中有针对性的可改变的风险因素。

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.