Mechanisms of Increased Ambulatory Blood Pressure in Intradialytic Hypertension

透析期间高血压动态血压升高的机制

• 批准号: 8581493
• 负责人: Peter Noel Van Buren
• 金额: $ 14.46万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8581493
• 关键词: Academic Medical Centers; Adrenergic Antagonists; Adrenergic alpha-Antagonists; Adverse event; Advisory Committees; Affect; Angiotensin II; Award; Blood Pressure; Body Water; Cardiovascular system; Cessation of life; Chronic; Clinical Research; Clinical Sciences; Clinical Trials; Cross-Over Studies; Dialysis procedure; Dietary Sodium; Discipline; End stage renal failure; Endothelial Cells; Endothelin-1; Fellowship; Functional disorder; Funding; Future; Goals; Heart Diseases; Hemodialysis; Hour; Hypertension; Hypotension; Impedance Cardiography; In Vitro; Ingestion; Intervention; Investigation; Learning; Link; Measures; Mediator of activation protein; Medical center; Mentored Patient-Oriented Research Career Development Award; Mentors; Modeling; Morbidity - disease rate; N,N-dimethylarginine; Outcome; Patients; Pattern; Perception; Performance; Pharmaceutical Preparations; Physiological; Plasma; Population; Prazosin; Randomized; Research; Research Activity; Research Personnel; Resources; Risk; Risk Reduction; Sodium Chloride; Spectrum Analysis; Statistical Models; Testing; Texas; Training Programs; Translational Research; Ultrafiltration; United States National Institutes of Health; Universities; Vascular resistance; Vasoconstrictor Agents; Water; beta-adrenergic receptor; blood pressure regulation; career; career development; carvedilol; case control; design; experience; extracellular; hemodynamics; improved; mortality; prospective; public health relevance; randomized trial; research study; skills; trial comparing; vasoconstriction

DESCRIPTION (provided by applicant): This NIH Mentored Patient-Oriented Research Career Development Award proposal describes a 5 year training program with the long-term goal of the candidate developing into an independent academic investigator with a research focus in hypertension in patients with chronic and end-stage kidney disease. The candidate will build on a background in clinical research developed during a comprehensive research fellowship spent studying ambulatory blood pressure and endothelial cell dysfunction in patients with intradialytic hypertension. The career development objectives are to obtain skills in designing and conducting prospective clinical research studies, learn statistical models to analyze ambulatory blood pressure in hemodialysis patients, gain experience in measuring and interpreting cardiovascular physiologic parameters including extracellular water and vascular resistance utilizing bioimpedance analysis, and participate in scholarly activities to facilitate te transition into an independent investigator. These will be applied immediately to investigating how extracellular volume and mediators of vascular resistance affect ambulatory blood pressure in patients with intradialytic hypertension and hemodialysis controls. Aim 1 will use a case control design to compare differences in extracellular water in patients with intradialytic hypertension and hemodialysis controls. Aim 2 will determine how extracellular volume, vasoconstrictor mediators of vascular resistance, and vascular resistance itself modify ambulatory blood pressure and the ambulatory blood pressure slope in these two groups. In aim 3, the candidate will gain experience in designing and conducting a randomized trial by comparing the effects of carvedilol vs. prazosin on ambulatory blood pressure, vascular resistance, and mediators of vascular resistance in patients with intradialytic hypertension. The candidate will develop these skills with the support a primary mentor, 3 co-mentors (including one translational research cardiologist and one biostatistician), and a research advisory committee with extensive experience in multiple research disciplines. The candidate and his advisors are located at the University of Texas Southwestern Medical Center, a leading academic medical center with substantial physical and intellectual resources necessary for the career development of young investigators and the performance of cutting-edge research. The candidate will take advantage of numerous courses and research activities as a Clinical Research Scholar in the Department of Clinical Sciences that will promote the overall development of his career. Consistent with the candidate's long term career goals, the findings from this study can be broadened to studying hypertension in hemodialysis patients in general. Understanding the relationship between extracellular volume, vascular resistance, and ambulatory blood pressure will provide the opportunity to investigate how pharmacologic therapies affect each component and how this can improve cardiovascular outcomes in hemodialysis patients.

描述（由申请人提供）：该NIH指导的以患者为导向的研究职业发展奖提案描述了一项为期5年的培训计划，其长期目标是将候选人发展成为一名独立的学术研究者，研究重点是慢性和终末期肾病患者的高血压。候选人将建立在一个综合研究奖学金期间开发的临床研究背景上，该奖学金用于研究透析中高血压患者的动态血压和内皮细胞功能障碍。职业发展目标是获得设计和进行前瞻性临床研究的技能，学习统计模型来分析血液透析患者的动态血压，获得测量和解释心血管生理参数的经验，包括利用生物阻抗分析细胞外水和血管阻力，并参加学术活动，以促进TE转变为独立研究者。这些将立即应用于研究细胞外容积和血管阻力介质如何影响透析中高血压患者和血液透析对照患者的动态血压。目的1将使用病例对照设计比较透析中高血压患者和血液透析对照患者细胞外水的差异。目的2将确定细胞外容积、血管阻力的血管收缩介质和血管阻力本身如何改变这两组的动态血压和动态血压斜率。在目标3中，候选人将通过比较卡维地洛与哌唑嗪对透析中高血压患者动态血压、血管阻力和血管阻力介质的影响，获得设计和实施随机试验的经验。候选人将在一名主要导师，3名共同导师（包括一名翻译研究心脏病学家和一名生物统计学家）以及一个在多个研究学科拥有丰富经验的研究咨询委员会的支持下发展这些技能。候选人及其顾问位于德克萨斯大学西南医学中心，这是一个领先的学术医学中心，为年轻研究人员的职业发展和尖端研究的表现提供了大量的物质和智力资源。候选人将利用众多的课程和研究活动作为临床科学系的临床研究学者，这将促进他职业生涯的全面发展。与候选人的长期职业目标一致，这项研究的结果可以扩展到研究血液透析患者的高血压。了解细胞外容积、血管阻力和动态血压之间的关系将为研究药物治疗如何影响每个组分以及如何改善血液透析患者的心血管结局提供机会。