Blood pressure variability and cardiovascular disease in hemodialysis patients

描述(由申请人提供)： 这一综合性的五年职业发展计划有两个目的：1)通过正规的教学课程、指导指导和本申请中详细介绍的研究项目的实施，使候选人发展成为一名独立的临床研究人员；2)在接受血液透析(HD)的患者中传授血压变异性(BPV)和心血管(CV)疾病之间的关联知识。 鉴于HD患者的心血管病死率极高，识别新的和潜在可逆的心血管危险因素至关重要。动物模型和非尿毒症患者的数据表明，BPV和心血管疾病之间存在潜在的因果关联。考虑到接受HD治疗的患者巨大的心血管负担和血压波动特性，对这种联系的研究是令人信服的。 这一系列研究的长期目标是：确定在HD患者中是否存在BPV和心血管疾病之间的因果关系，并开发有针对性的干预措施，旨在通过减少BPV来降低HD患者的心血管发病率和死亡率。这一研究领域将成为候选人发展为独立调查员的理想平台。 这项研究的具体目的是：1)描述具有代表性的费城HD患者样本中血压变异性的分布；2)确定预测BPV的临床因素；3)确定血压变异性与心血管死亡率和心血管疾病住院之间是否存在因果关系。 考虑到对不同水平的BPV进行随机化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，这使得识别这一人群中的危险因素至关重要。这项研究旨在研究一个潜在的危险因素，即血压随时间的变化，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.