Epidemiology and pathophysiology of elevated nighttime blood pressure in CKD

描述（由申请人提供）：这个为期五年的职业发展奖的总体目标是：1）通过先进的教学课程，结构化的指导和临床研究的进行/分析，使候选人的职业发展成为独立的临床研究人员;和2）更好地了解动态血压（BP）的流行病学和病理生理学，特别是夜间血压升高，慢性肾病（CKD）受试者。高血压非常普遍，是心血管疾病、肾脏疾病和死亡的主要危险因素。BP传统上是在临床上测量的，但对动态BP监测的兴趣越来越大。最好的动态血压预测似乎是夜间血压。CKD已被证明是夜间血压升高的危险因素。心脏自主神经病变与CKD患者和非CKD患者夜间血压升高相关。CKD、心脏自主神经病变和夜间血压升高之间的关系尚未得到充分研究。候选人将对入组慢性肾功能不全队列（CRIC）研究的受试者进行动态血压的横断面和纵向研究，并收集额外数据，作为已批准的CKD辅助研究中夜间血压升高的流行病学和病理生理学的一部分。候选人拟定研究的具体目的是：1）确定CKD患者中隐性高血压、白大衣高血压和真实高血压的患病率; 2）评价CKD患者中与夜间血压升高相关的临床特征，包括心脏自主神经病变; 3）评价CKD患者中与夜间血压随时间变化相关的临床特征。数据将包括详细的病史、实验室评价、心电图、综合心血管评价和临床结局的确定。统计分析将包括多重线性和逻辑回归。候选人将接受由Mahboob Rahman博士领导的多学科团队的指导，Mahboob Rahman博士是CRIC的首席研究员，也是一位在高血压和CKD方面具有专业知识的经验丰富的研究人员。候选人通过临床研究学者的工作表现出对研究事业的奉献精神，并将通过参加统计学和流行病学的高级课程来增强这种研究经验和正式培训。除了先进的教学课程和指导研究经验，候选人将参加研究和职业发展研讨会和会议作为医学系和临床研究中心的教员。该职业发展奖将为候选人提供基础，以追求独立的研究生涯，致力于更好地了解慢性肾脏疾病和高血压的病理生理学，并降低随后的发病率和死亡率。 公共卫生相关性：高血压是常见的，是心血管疾病，肾脏疾病和死亡的主要危险因素。夜间血压可能是不良临床事件的最佳预测因子，但尚未得到很好的研究。更好地了解导致夜间血压升高的机制将为未来专门针对夜间血压升高的临床试验提供见解，以降低发病率和死亡率。

DESCRIPTION (provided by applicant): The overall aims of this five-year Career Development Award are to: 1) enable the candidate's career development as an independent clinical researcher through advanced didactic coursework, structured mentoring, and conduct/analysis of a clinical research study; and 2) better understand the epidemiology and pathophysiology of ambulatory blood pressure (BP), specifically elevated nighttime BP, in subjects with chronic kidney disease (CKD). Hypertension is highly prevalent and is a major risk factor for cardiovascular disease, kidney disease, and death. BP is traditionally measured in the clinic, but there is increasing interest in ambulatory BP monitoring. The best ambulatory BP predictor appears to be nighttime BP. CKD has been shown to be a risk factor for elevated nighttime BP. Cardiac autonomic neuropathy is associated with elevated nighttime BP in patients with and without CKD. The relationship between CKD, cardiac autonomic neuropathy, and elevated nighttime BP is not well studied. The candidate will conduct a cross-sectional and longitudinal study of ambulatory BP in subjects enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study, and collect additional data as part of the approved Epidemiology and Pathophysiology of Elevated Nighttime Blood Pressure in CKD Ancillary Study. The specific aims of the candidate's proposed study are: 1) determine the prevalence of masked hypertension, white-coat hypertension, and true hypertension in patients with CKD; 2) evaluate the clinical characteristics, including cardiac autonomic neuropathy, associated with elevated nighttime BP in patients with CKD; and 3) evaluate the clinical characteristics associated with a change in nighttime BP over time in patients with CKD. Data will include detailed medical history, laboratory evaluation, electrocardiograms, comprehensive cardiovascular evaluation, and ascertainment of clinical outcomes. Statistical analysis will include multiple linear and logistic regressions. The candidate will be mentored by a multidisciplinary team led by Dr Mahboob Rahman, a principal investigator in CRIC and an experienced researcher with expertise in hypertension and CKD. The candidate has shown a dedication to a career in research through work as a Clinical Research Scholar and will enhance this research experience and formal training by taking advanced coursework in statistics and epidemiology. In addition to the advanced didactic coursework and mentored research experience, the candidate will participate in research and career development seminars and conferences as a faculty member in the Department of Medicine and the Center for Clinical Investigation. This Career Development Award will provide the foundation for the candidate to pursue an independent research career dedicated to better understanding the pathophysiology of and reducing the subsequent morbidity and mortality associated with chronic kidney disease and hypertension. PUBLIC HEALTH RELEVANCE: High blood pressure is common and is a major risk factor for cardiovascular disease, kidney disease, and death. Nighttime blood pressure may be the best predictor for adverse clinical events but is not well sudied. A better understanding of the mechanisms that lead to elevated nighttime BP will provide insight for future clinical trials that specifically target elevated nighttime BP with the goal of reducing morbidity and mortality.