Blood pressure as a modifiable risk factor for cardiovascular events in liver transplant recipients

项目总结 1/3的肝移植受者会在移植后一年内发生心血管事件。 由于免疫抑制的影响和潜在可改变的心血管危险因素的高发， 比如高血压。然而，早期或强化降压可能会造成潜在的危害。 通过降低肝移植受者的肝移植和肾功能。事实上，对于肝移植接受者来说， 与降压、治疗时机和治疗策略相关的临床结果是 未知。对于这一应用，我们组建了一个肝移植、心血管领域的专家团队 流行病学、高血压和生物统计学，以确定肝脏的血压模式 美国的移植受者；量化血压水平和最佳血压水平之间的关系 肝移植受者的临床结果；并确定与肝移植相关的治疗策略 使用创新的统计学方法，降低血压并最大限度减少心血管事件的高血压 技巧。为了实现这些目标，我们将在办公室和办公室外测量血压(7- 日间家庭血压监测和24小时动态血压监测)方法 从5个三级医院招募的1268名成人肝移植受者的前瞻性、观察性、队列研究 护理移植网络(西北大学、加州大学旧金山分校、贝勒移植 研究所，哥伦比亚大学，宾夕法尼亚大学)超过五年。这些数据将用于评估 主要血压暴露量与心血管事件主要结局的关系 肝移植受者的事件。次要结果将包括肝移植或肾移植标志物的变化。 这一人群的功能和死亡率。然后，我们将把队列数据与其中包含的丰富数据合并 每个参与地点的电子健康记录，包括降压信息 药物处方模式和合并症数据。我们将应用新的统计技术，包括Q- 学习评估肝移植受者的动态治疗方案，以合并数据集进行评估 与(A)降低不同的肝移植相关高血压的治疗策略 肝移植受者的血压和(B)较低的心血管事件。这些数据将填补一个关键的 通过精确量化血压水平和血压之间的关系，我们的知识差距 肝移植受者的心血管事件。我们还将确定最重要的治疗策略 可能有效地降低血压，成为肝脏心血管事件的关键可修改危险因素 移植受者。这些数据是未来血压干预试验的基础工作 在肝移植接受者中。这项提议与NHLBI的研究任务高度相关，目的是减少人类 疾病“，通过”消除高血压相关的心血管疾病“，与四项之一保持一致 2016年NHLBI战略愿景中概述的以使命为导向的目标。

PROJECT SUMMARY One in three liver transplant recipients will experience a cardiovascular event within one year of transplant due to the effects of immunosuppression and a high prevalence of potentially modifiable cardiovascular risk factors, such as high blood pressure. However, early or intensive blood pressure-lowering may potentially cause harm in liver transplant recipients by reducing liver graft and renal function. Indeed, for liver transplant recipients, the clinical outcomes associated with blood pressure-lowering, treatment timing and treatment strategies are unknown. For this application, we assembled a team of experts in liver transplantation, cardiovascular epidemiology, hypertension, and biostatistics, in order to determine patterns of blood pressure in liver transplant recipients in the United States; quantify associations between blood pressure levels and optimal clinical outcomes in liver transplant recipients; and identify treatment strategies of liver transplant-associated hypertension that lower blood pressure and minimize cardiovascular events, using innovative statistical techniques. To achieve these goals, we will measure blood pressure using both in-office and out-of-office (7- day home blood pressure monitoring and 24-hour ambulatory blood pressure monitoring) approaches in a prospective, observational, cohort study of 1,268 adult liver transplant recipients, recruited from five tertiary care transplant networks (Northwestern University, University of California San Francisco, Baylor Transplant Institute, Columbia University, University of Pennsylvania) over five years. These data will be used to assess associations between the main exposure of blood pressure and the main outcome of incident cardiovascular events in liver transplant recipients. Secondary outcomes will include changes in markers of liver graft or renal function and mortality in this population. We will then merge the cohort data with the rich data contained within the electronic health record at each participating site including information on blood pressure-lowering medication prescribing patterns and comorbidity data. We will apply novel statistical techniques, including Q- learning to estimate dynamic treatment regimes in liver transplant recipients, to the merged data set to assess treatment strategies of liver transplant-associated hypertension that are differentially associated with (a) lower blood pressure and (b) lower cardiovascular events in liver transplant recipients. These data will fill a critical gap in our knowledge by precisely quantifying the associations between blood pressure levels and cardiovascular events among liver transplant recipients. We will also identify treatment strategies that are most likely to effectively reduce blood pressure as a key modifiable risk factor for cardiovascular events in liver transplant recipients. These data are essential as the ground work for future blood pressure intervention trials in liver transplant recipients. This proposal is highly relevant to NHLBI’s research mission “to reduce human disease”, through “eliminating hypertension-related cardiovascular disease,” in alignment with one of the four mission-oriented goals outlined in the 2016 NHLBI’s Strategic Vision.