Longitudinal Study of Dialysis

描述(申请人提供)：在美国，终末期肾病(ESRD)患者的年死亡率超过20%，心脑血管疾病的年龄别死亡率比普通人群高10-100倍。这种额外的死亡率很大程度上是由于心脏性猝死(SCD)。令人惊讶的是，很少有前瞻性研究研究ESRD患者SCD的危险因素，这些研究也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，我们发现在4年的随访中，SCD的发病率为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名接受血液透析的ESRD患者进行前瞻性的纵向研究，以确定导致自主神经张力改变、心室传导障碍和SCD的心血管、透析相关和遗传危险因素。18岁及以上的参与者将从巴尔的摩地区招募。我们预计，队列中60%的人将是非裔美国人，50%的人将患有糖尿病。调查小组在对ESRD的其他成功研究中开发的技术将用于招募和跟踪参与者。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化、血管狭窄和左心室结构和功能；在基线和每年收集心电图、问卷和生物标本。心率变异性、QT间期的测量和心室晚电位的存在将通过分析年度心电记录来评估。死因将使用标准标准进行判定。这项研究还将有助于确定终末期肾病独有的SCD及其中间体的透析相关风险因素，为在这一高危人群中测试预防SCD的治疗方法奠定基础。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终末期肾病人群发病率和死亡率的发病机制有关的一系列问题。

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.