Derivation and validation of a cardiac risk index in liver transplantation

描述(由申请人提供)：该博士后奖学金的目标是促进候选人作为移植结果研究的领导者的发展，重点是围手术期心血管(CV)风险评估。基于她在内科、移植肝病和临床研究方面的背景，候选人建议在获奖期间通过(1)旨在扩大她的方法学技能的课程工作；(2)与赞助商和合作者组成的多学科团队进行互动，以发展更多的技能。 包括心血管流行病学、风险评估、移植结果和卫生服务研究；以及(3)有监督的研究项目。这个项目的总体目标是通过两个主要的具体目标来定义和优化原位肝移植(OLT)患者的术前心血管风险评估模型：(1)通过(1.1)利用国家数据库的二级数据分析确定RCRI作为30天心血管事件的模型，确定国家肝移植特异性心血管风险指数(NOLT-CRI)是否改善了常用的修订的心脏风险指数(RCRI)的预测效用；以及(1.2)比较NOLT-CRI和RCRI在对30天心血管风险进行重新分类并在预测的30天心血管风险的连续统一体上对1年生存率进行分层的能力方面的临床表现；(2)通过(2.1)使用具有比当前全国可用的更详细的临床数据的中心专用数据库来确定是否需要在国家数据库中可用的那些之外的额外变量来提高这些模型的预测能力，从而确定局部导出的心脏风险指数(LOLT-CRI)的模型辨别和校准；以及(2.2)将LOLT-CRI的临床表现与国家模型的风险重新分类能力进行比较。该项目将满足美国国立卫生研究院的使命，通过识别肝移植候选患者特有的心血管疾病标记物，然后可用于改善不断增长的患者群体中移植前和移植后的医疗管理。该项目，以及选定的课程和指导，将使候选人精通数据管理和统计方法。在获奖期接近尾声时，候选人计划利用该项目的结果提交一份职业发展奖，以开发供肝移植前使用的心血管风险评估治疗算法。 公共卫生相关性：原位肝移植(OLT)是终末期肝病患者的一种挽救生命的手术，但由于供体器官的稀缺，它并不是普遍适用于公众。心血管疾病是一个日益严重的公共健康问题，也是原位肝移植术后严重并发症的主要原因。该项目将通过评估心血管疾病对原位肝移植术后结局的影响以及确定不良结局的风险预测因素来造福公众健康，以便改善原位肝移植受者的临床管理，以最大限度地提高稀缺供体器官的利益。

DESCRIPTION (provided by applicant): The goal of this postdoctoral fellowship is to facilitate the candidate's development as a leader in transplantation outcomes research, with a focus on perioperative cardiovascular (CV) risk assessment. Building on her background in internal medicine, transplant hepatology, and clinical investigation, the candidate proposes to develop additional skills during the award period through (1) coursework designed to expand her methodological skills; (2) interaction with a multidisciplinary team of sponsors and collaborators, including those in cardiovascular epidemiology, risk assessment, transplantation outcomes, and health services research; and (3) a supervised research project. The overall objective of this project is to define and optimize a preoperative cardiovascular risk assessment model for orthotopic liver transplant (OLT) candidates through two primary specific aims: (1) To determine if a national liver transplant-specific Cardiovascular Risk Index (NOLT-CRI) improves the predictive utility of the commonly used revised cardiac risk index (RCRI) by (1.1) determining the discrimination (C-statistic) and calibration (Hosmer-Lemeshow statistic) of the RCRI as a model of 30-day CV events using secondary data analysis of a national database; and (1.2) comparing the clinical performance of the NOLT-CRI to the RCRI in its ability to reclassify 30-day CV risk and to stratify 1- year survival across the continuum of predicted 30-day CV risk; (2) To determine whether additional variables are needed beyond those available within a national database in order to improve the predictive ability of these models by (2.1) determining the model discrimination and calibration of a locally-derived cardiac risk index (LOLT-CRI) using a center-specific database with more detailed clinical data than are currently available nationally; and (2.2) comparing the clinical performance of the LOLT-CRI to the national models in its ability to reclassify risk. This project will meet the mission of the National Institutes of Healthby identifying cardiovascular disease markers that are unique to the liver transplant candidate, which can then be used to improve pre- and post-transplant medical management in this growing patient population. The project, along with the chosen coursework and mentorship, will allow the candidate to become proficient at data management and statistical methodology. Near the end of the award period, the candidate plans to submit a career development award using the results of the project to develop a cardiovascular risk assessment treatment algorithm for use prior to liver transplantation. PUBLIC HEALTH RELEVANCE: Orthotopic liver transplantation (OLT) is a life-saving procedure for patients with end-stage liver disease, but it is not universally available to the public due to a scarcity of donor organs. Cardiovascular disease is an increasing public health problem and is often responsible for severe complications following OLT. This project will benefit public health by assessing the impact of cardiovascular disease on outcomes after OLT and by determining risk predictors for poor outcomes in order to improve the clinical management of OLT recipients in order to maximize the benefit of scarce donor organs.