Risk Factors for Venous Thromboembolism in the Community

 描述（由申请人提供）：静脉血栓栓塞（VTE）是一个主要的健康问题。最近的外科医生行动呼吁将“VTE持续发生的原因”确定为该领域进展的关键障碍。该项目将在人群水平上解决这一问题，并通过开发和验证风险预测工具来改变初级和二级VTE预防的临床实践模式，以针对高VTE风险个体的特定子集。我们的具体目标将通过以下方式解决目前的知识差距：（目标1）估计（1a）（i）静脉血栓栓塞发病率和发作的长期趋势（ii）患病率和（iii）每种VTE风险因素的人群归因风险，以及（1b）估计（i）在多状态模型中对于偶发和复发性VTE以及VTE后死亡的转移概率，以及（ii）VTE后的生存趋势，以帮助告知公共政策;（目标2）推导并验证总体VTE复发预测评分，包括生殖系遗传变异（F5 rs6025，F2 rs1799963，ABO rs8176719）;和（目的3）分别推导和验证活动性癌症患者中（a）偶发性和（B）复发性VTE的风险和预测评分，包括血浆生物标志物，生殖系遗传变异，和癌组织促凝（组织因子）抗原表达。我们将使用以前完成的病例对照和病例队列研究的数据来得出风险和预测评分，并利用罗切斯特流行病学项目和马约诊所癌症登记处的纵向资源，分别对奥姆斯特德县的整个人群和一个大型的活动性癌症患者队列进行队列研究，以验证评分。在以下人群中识别高风险个体亚群的能力：a）一般人群（目标1），B）发生VTE的人群（目标2），以及c）活动性癌症人群（目标3），将有助于以具有成本效益和安全的方式进行有针对性的一级和二级VTE预防。

 DESCRIPTION (provided by applicant): Venous thromboembolism (VTE) is a major health problem. The recent Surgeon General's Call to Action identified the "reasons for the persistent occurrence of VTE" as critical barriers to progress in the field. This project will address this question at the population level and shift clinical practice paradigms for primary and secondary VTE prevention by development and validating risk prediction tools to target specific subsets of high VTE-risk individuals. Our specific aims will address current gaps in knowledge by: (Aim 1) estimating (1a) secular trends in (i) VTE incidence and attack (incident and recurrent VTE) rates, (ii) prevalence and (iii) population attributable risk for each VTE risk factor, and (1b) estimating (i) transition probabilities in a multi-state model for incident and recurrent VTE and death after VTE and (ii) trends in survival after VTE to help inform public policy; (Aim 2) derivin and validating an overall VTE recurrence prediction score, including germline genetic variation (F5 rs6025, F2 rs1799963, ABO rs8176719); and (Aim 3) deriving and validating risk and prediction scores for (a) incident and (b) recurrent VTE among active cancer patients, respectively, including plasma biomarkers, germline genetic variation, and cancer tissue procoagulant (tissue factor) antigen expression for both scores. We will use data from previously completed case-control and case-cohort studies to derive the risk and prediction scores, and the longitudinal resources of the Rochester Epidemiology Project and the Mayo Clinic Cancer Registry to perform cohort studies of the entire population of Olmsted County and a large cohort of active cancer patients, respectively, for validation of the scores. The ability t identify high-risk subsets of individuals within: a) the general population (Aim 1), b) those with an incident VTE (aim 2), and c) those with active cancer (Aim 3) will facilitate targeted primary and secondary VTE prevention in a cost-effective and safe manner.