Longitudinal Study of Dialysis

描述（由申请人提供）：美国终末期肾病（ESRD）患者的年死亡率超过20%，心血管疾病的年龄特异性死亡率比一般人群高10-100倍。这种过度死亡的大部分是由于心脏性猝死（SCD）。令人惊讶的是，很少有前瞻性研究检查了ESRD患者SCD的风险因素，这些研究没有测量许多已知在一般人群中重要的风险因素。在CHOICE队列研究中，我们发现4年随访期间SCD发生率为18%。我们的总体假设是，在一般人群中增加SCD风险的因素在透析人群中非常普遍，并且是自主神经张力改变、心室传导受损和SCD的独立预测因子。我们建议对1,000例接受血液透析治疗的ESRD患者进行一项前瞻性纵向研究，以确定导致自主神经张力改变、心室传导受损和SCD的心血管、透析相关和遗传风险因素。18岁及以上的参与者将从巴尔的摩地区招募。我们预计，60%的队列将是非洲裔美国人，50%将患有糖尿病。研究小组在其他成功的ESRD研究中开发的技术将用于招募和随访参与者。将在基线时使用计算机断层扫描（CT）和CT血管造影术评估冠状动脉钙、血管狭窄以及左心室结构和功能;将在基线时和每年收集ECG、问卷和生物标本。将通过分析年度ECG记录评估心率变异性、QT间期测量值和心室晚电位的存在。将使用标准标准判定死亡原因。本研究还将允许识别SCD及其中间体的透析相关风险因素，这些风险因素是ESRD特有的，为临床试验奠定基础，以测试在该高风险人群中预防SCD的治疗方法。此外，拟议的工作将提供一个基础设施，以回答，在未来的研究中，一系列问题的发病机制和死亡率在ESRD人口。

DESCRIPTION (provided by applicant): Persons in the US with end stage renal disease (ESRD) have an annual mortality rate of over 20% and an age-specific death rate from cardiovascular disease that is 10-100 times higher than the general population. Much of this excess mortality is due to sudden cardiac death (SCD). Surprisingly, few prospective studies have examined risk factors for SCD in ESRD patients and these studies did not measure many risk factors known to be important in the general population. In the CHOICE cohort study, we found an SCD incidence of 18% over 4 years of follow up. Our overall hypothesis is that factors that increase risk for SCD in the general population are highly prevalent in the dialysis population and are independent predictors of altered autonomic tone, impaired ventricular conduction, and SCD. We propose a prospective, longitudinal study of 1,000 incident ESRD patients treated with hemodialysis to determine the cardiovascular, dialysis-related, and genetic risk factors leading to altered autonomic tone, impaired ventricular conduction, and SCD. Participants aged 18 and older will be recruited from the Baltimore area. We anticipate that 60% of the cohort will be African American and 50% will have diabetes. Techniques developed in other successful studies of ESRD by the investigative team will be used to recruit and follow participants. Coronary calcium, vessel stenosis, and left ventricular structure and function will be assessed using computed tomography (CT) and CT angiography at baseline; ECGs, questionnaires and biological specimens will be collected at baseline and annually. Heart rate variability, measures of QT duration, and presence of ventricular late potentials will be assessed by analysis of annual ECG recordings. Cause of death will be adjudicated using standard criteria. This study will also allow identification of dialysis-related risk factors for SCD and its intermediates that are unique to ESRD, setting the stage for clinical trials to test therapies to prevent SCD in this high risk population. In addition, the proposed work will provide an infrastructure to answer, in future studies, a host of questions related to the pathogenesis of morbidity and mortality in the ESRD population.