Blood pressure variability and cardiovascular disease in hemodialysis patients

描述（由申请人提供）： 这一全面的五年职业发展计划有两个目的：1）通过正式的教学课程，指导和本申请中详细介绍的研究项目的实施，将候选人发展成为独立的临床研究者，2）了解血液透析（HD）患者血压变异性（BPV）与心血管（CV）疾病之间的关系。 鉴于HD患者的CV死亡率极高，因此在该人群中识别新的和潜在可逆的CV风险因素至关重要。动物模型和非尿毒症患者的数据表明，BPV和CV疾病之间存在潜在的因果关系。考虑到HD治疗患者的显著CV负担和血压的波动性，对该相关性的研究是令人信服的。 这一系列研究的长期目标是：确定血液透析患者中BPV和CV疾病之间是否存在因果关系，并制定针对性干预措施，旨在通过降低BPV降低血液透析患者的CV发病率和死亡率。这一研究领域将成为候选人发展成为独立调查员的理想平台。 本研究的具体目的是：1）描述费城HD患者代表性样本中血压变异性的分布，2）定义预测BPV的临床因素，3）确定血压变异性与心血管死亡率和因CV疾病住院治疗之间是否存在因果关系。 鉴于随机分配至不同水平的BPV既不可能也不符合伦理，因此选择了前瞻性队列设计。 公共卫生相关性：接受透析的患者死于心血管疾病的比率非常高，因此确定这一人群的风险因素至关重要。本研究旨在检查一个潜在的风险因素，血压随时间的变化，是否会导致或促成透析患者的心血管疾病。

DESCRIPTION (provided by applicant): This comprehensive five-year career development plan has a two-fold purpose: 1) to bring about the candidate's development into an independent clinical investigator through a combination of formal didactic coursework, directed mentoring and the conduct of the research project detailed within this application, 2) to render knowledge of the association between blood pressure variability (BPV) and cardiovascular (CV) disease in patients treated with hemodialysis (HD). Identification of novel and potentially reversible CV risk factors in HD patients is of paramount importance given the exceedingly high CV mortality rate in this population. Data in animal models and in non-uremic patients suggest that a potentially causal assocaiton between BPV and CV disease exists. Given both the dramatic CV burden and volatile nature of blood pressure in patients treated with HD, study of this association is compelling. The long-term goals of this line of research are: to determine if a causal association between BPV and CV disease exists in HD patients, and to develop targeted interventions aimed at reducing CV morbidity and mortality in HD patients via reductions in BPV. This line of research will serve as an ideal platform for the candidate's development into an independent investigator. The specific aims of this study are: 1) to describe the distribution of blood pressure variability in a representative sample of Philadelphia HD patients, 2) to define clinical factors that predict BPV and 3) to determine whether a causal association exists between blood pressure variability and cardiovascular mortality and hospitalization for CV disease. Given that randomization to various levels of BPV is neither possible nor ethical, a prospective cohort design was chosen. PUBLIC HEALTH RELEVANCE: Patients undergoing dialysis die from cardiovascular disease at very high rates, making identification of risk factors in this population critically important. This study is designed to examine whether one potential risk factor, variability in blood pressure over time, causes or contributes to cardiovascular disease in dialysis patients.