Risk Factors for Sudden Cardiac Death in Patients with Chronic Kidney Disease

慢性肾病患者心源性猝死的危险因素

• 批准号: 8699443
• 负责人: PATRICK H PUN
• 金额: $ 15.87万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8699443
• 关键词: Academic Medical Centers; Accounting; Affect; American; Arrhythmia; Award; Calcium; Cardiac; Cardiovascular Diseases; Cardiovascular system; Chronic Kidney Failure; Clinical; Clinical Data; Clinical Research; Computerized Medical Record; Coronary Arteriosclerosis; Databases; Development; Development Plans; Dialysis patients; Disease; Disease Outcome; Disease Pathway; Electrocardiogram; Electrolytes; Event; Faculty; General Population; Genes; Genetic; Goals; Human Genetics; Hypertension; Individual; Institution; Intervention; Investigation; Ion Channel; Lead; Link; Magnesium; Malignant - descriptor; Measurement; Medical Records; Medicine; Mentors; Monitor; Mutation; Nature; Nephrology; Outcome; Pathway interactions; Patients; Play; Population; Potassium; Prevention; Prevention strategy; Quantitative Genetics; Renal function; Research; Research Personnel; Resources; Rest; Risk; Risk Factors; Role; Serum; Staging; Stratification; Structure; Sudden Death; Testing; Therapeutic Intervention; Time; Training; United States National Institutes of Health; Variant; Ventricular; Ventricular Arrhythmia; Work; base; biobank; cardiovascular risk factor; career development; experience; genetic epidemiology; high risk; improved; neglect; novel; patient oriented; patient population; prevent; professor; prospective; public health relevance; risk variant; skills; sudden cardiac death; tool

This is an application for a K23 for Dr. Patrick Pun, who is a nephrologist and Assistant Professor at Duke University Medical Center. Dr. Pun is establishing himself as a young investigator in patient- oriented clinical research on sudden cardiac death (SCD) in chronic kidney disease (CKD) patients. Through a structured career development plan including formal didactic training in genetic epidemiology and quantitative genetics, mentoring by a dedicated group of accomplished senior investigators and collaborators, and the conduct original research examining unique risk factors for SCD among a large population of patients with moderate CKD, this award will provide Dr. Pun the resources, training and protected time to become a an independent clinical researcher in the field of cardiorenal disease. Dr. Pun's mentoring team includes his primary mentor, Dr. Laura Svetkey (Director of the Duke Hypertension Center and the Vice Chair for Faculty development in the Duke Department of Medicine), and two co-mentors, Dr. John Middleton (Director of Clinical Research in the Duke Division of Nephrology) and Dr. Svati Shah (Associate Professor of Medicine, Center for Human Genetics). CKD affects more than 29 million Americans; compared the general population, these patients have a markedly increased risk of SCD. The precise nature of how CKD promotes SCD risk is not well understood, and traditional cardiovascular risk factors do not adequately explain SCD risk. The overall objective of this application is to identify CKD patients at high risk of malignant arrhythmias and SCD, so that these patients might be targeted for intervention. The central hypothesis of this proposal is that cardiac conduction problems related to serum electrolyte disturbances, genetic influences and resting ECG abnormalities play an important role in determining SCD risk in patients with moderate CKD (CKD stage 3-4). Combining and linking a large prospective longitudinal research database containing clinical data and outcomes from more than 35,000 patients with cardiovascular disease, a genetic biorepository, and extensive medical records, the application contains the following specific aims: (1) To evaluate associations between serum electrolyte levels (potassium, calcium and magnesium) and SCD risk in moderate CKD patients; (2) To evaluate associations between common variants in pro-arrhythmic genes and risk of significant ventricular arrhythmias and SCD in moderate CKD patients; and (3) To evaluate associations between resting ECG measurements of ventricular conduction (QRS duration, QTc interval) and SCD risk in the setting of CKD. Since SCD mechanisms in high-risk CKD patients are poorly understood, this contribution will be significant because it may elucidate mechanisms of disease, provide novel tools for risk stratification and monitoring, and identify specific potential targets for SCD prevention.

这是帕特里克·潘 (Patrick Pun) 博士的 K23 申请，他是一名肾脏病学家兼助理教授 杜克大学医学中心。潘博士正在将自己打造成一名年轻的患者研究研究者—— 慢性肾脏病（CKD）患者心源性猝死（SCD）的定向临床研究。 通过结构化的职业发展计划，包括遗传方面的正式教学培训 流行病学和定量遗传学，由一群资深资深人士提供专业指导 研究人员和合作者，以及进行原始研究，检查独特的风险因素 大量中度 CKD 患者中的 SCD，该奖项将为 Pun 博士提供 资源、培训和受保护的时间，成为该领域的独立临床研究员 心肾疾病。 Pun 博士的指导团队包括他的主要导师 Laura Svetkey 博士 （杜克大学高血压中心主任兼杜克大学教师发展副主席 医学系）和两位共同导师约翰·米德尔顿博士（临床研究主任） 杜克大学肾脏病学部）和 Svati Shah 博士（医学中心副教授） 人类遗传学）。 CKD 影响着超过 2900 万美国人；与一般人群相比， 这些患者发生 SCD 的风险显着增加。 CKD 促进的确切性质 SCD 风险尚未被充分了解，传统心血管危险因素无法充分解释 心脏骤停风险。该应用程序的总体目标是识别具有高恶性风险的 CKD 患者。 心律失常和 SCD，因此这些患者可能成为干预的目标。中央 该提案的假设是心脏传导问题与血清电解质有关 紊乱、遗传影响和静息心电图异常在确定 中度 CKD（CKD 3-4 期）患者的 SCD 风险。组合和链接大前景 纵向研究数据库包含超过 35,000 名患者的临床数据和结果 与心血管疾病、遗传生物存储库和大量医疗记录相关的应用程序 包含以下具体目标：（1）评估血清电解质水平之间的关联 中度 CKD 患者的（钾、钙和镁）和 SCD 风险； (2) 评价 促心律失常基因的常见变异与严重心室风险之间的关联 中度 CKD 患者的心律失常和 SCD； (3) 评估休息之间的关联 心电图测量心室传导（QRS 时限、QTc 间期）和 SCD 风险 CKD 的设置。由于对高危 CKD 患者的 SCD 机制知之甚少，因此 贡献将是巨大的，因为它可以阐明疾病机制，提供新的工具 进行风险分层和监测，并确定预防 SCD 的具体潜在目标。