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。这些额外的死亡率大部分是由于心源性猝死（SCD）。令人惊讶的是，很少有前瞻性研究检查ESRD患者SCD的危险因素，而且这些研究没有测量许多已知在普通人群中重要的危险因素。在CHOICE队列研究中，我们发现随访4年的SCD发病率为18%。我们的总体假设是，在普通人群中增加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的独立预测因素。我们建议对1000例接受血液透析治疗的ESRD患者进行前瞻性、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%的队列将是非裔美国人，50%将患有糖尿病。调查小组在其他成功的ESRD研究中开发的技术将用于招募和跟踪参与者。冠状动脉钙化、血管狭窄、左心室结构和功能将在基线时使用计算机断层扫描（CT）和CT血管造影进行评估；将在基线和每年收集心电图、问卷和生物标本。心率变异性、QT持续时间的测量和心室晚电位的存在将通过分析年度心电图记录来评估。死因将根据标准标准进行裁决。该研究还将确定透析相关的SCD风险因素及其ESRD特有的中间产物，为临床试验奠定基础，以测试在这一高危人群中预防SCD的治疗方法。此外，拟议的工作将提供基础设施，以便在未来的研究中回答与ESRD人群发病率和死亡率发病机制有关的许多问题。

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.