Vascular Stiffness and Endothelial Cell Function in Intradialytic Hypertension

透析期间高血压的血管僵硬度和内皮细胞功能

• 批准号: 8198355
• 负责人: Peter Noel Van Buren
• 金额: $ 4.85万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-13 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8198355
• 关键词: Antihypertensive Agents; Arginine; Asses; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Case-Control Studies; Cell physiology; Cessation of life; Chronic; Chronic Kidney Failure; Clinical Research; Clinical Sciences; Clinical Trials; Confounding Factors (Epidemiology); Development; Dialysis procedure; End stage renal failure; Endothelial Cells; Endothelin-1; Endothelium; Enrollment; Functional disorder; Future; General Population; Goals; Health; Hemodialysis; Hospitalization; Hour; Hypertension; Hypotension; Intervention; Kidney Diseases; Knowledge; Laboratories; Learning; Maintenance; Manuscripts; Master' s Degree; Measurement; Measures; Mediating; Mentors; Morbidity - disease rate; Nephrology; Nitric Oxide; Oral Administration; Outcome; Pathogenesis; Patients; Pharmaceutical Preparations; Physiologic pulse; Pilot Projects; Plasma; Population; Randomized Controlled Trials; Reporting; Research; Research Design; Risk; Risk Factors; Role; Side; Techniques; Testing; Therapeutic; Titrations; Training; Translational Research; Treatment Protocols; Vasodilation; Writing; adverse outcome; arm; arterial stiffness; base; cardiovascular risk factor; career; carvedilol; experience; high risk; improved; inhibitor/antagonist; mortality; open label; patient population; prevent; programs; public health relevance; skills

DESCRIPTION (provided by applicant): Patients with end stage renal disease (ESRD) carry a higher risk for cardiovascular morbidity and mortality than the general population. Hemodialysis (HD) patients whose blood pressure increases during a HD session represent a subpopulation with even greater risk for adverse outcomes. When defined as an increase in systolic blood pressure greater than 10 mmHg from pre to post HD treatment, intradialytic hypertension (IH) is an additional independent risk factor for hospitalization and cardiovascular and all cause mortality in HD patients. Endothelial cell dysfunction (ECD) and increased arterial stiffness both are prevalent in HD patients and may be involved in the pathophysiology of IH. The specific aims of the project are to: 1) establish an association with arterial stiffness and IH; 2) demonstrate an association with ECD and IH using more than one variable to asses for ECD; 3) investigate the effects of carvedilol in abolishing IH. For specific aim 1: Pulse wave velocity (PWV) will be obtained from 25 subjects with IH and 25 control HD subjects without IH. Ambulatory blood pressure (ABP) will also be measured in these subjects as a possible confounding variable for PWV. For specific aim 2: Pre and post HD levels of endothelin-1 and asymmetric dimethyl arginine will be measured in addition to mid week non-HD day flow mediated dilation and endothelium independent vasodilation. For specific aim 3: Subjects with IH will be started on carvedilol after all baseline measurements are taken. After 8 weeks of carvedilol therapy, including 4 weeks after titration up to 50 mg twice daily, all measurements from Aims 1 and 2 will be repeated. Establishing an association of IH with ECD and arterial stiffness can prompt efforts to explore the possible causal relationships. Additionally, results from the effects of carvedilol on IH may propagate randomized, controlled trials to determine if improvements in endpoints such as CV or all cause mortality are attainable. The relevance of this information could eventually be extended to more general populations such as pre-HD chronic kidney disease patients or patients without kidney disease, but with elevated arterial stiffness or ECD. The applicant will be supervised by a sponsor and co-sponsor during the program. The applicant will be involved in every step of the project from recruitment to manuscript writing. In addition to gaining clinical research skills, the applicant will be learning the techniques of measuring ABP, PWV, and FMD. Additionally, the applicant will be enrolled in courses in pursuit of a Masters Degree in Clinical Sciences. All activities are aimed towards the applicant gaining knowledge and experience in clinical research to pursue a more independent level of involvement in a research career. PUBLIC HEALTH RELEVANCE: End stage renal disease patients on hemodialysis are at higher risk for cardiovascular disease and death than the general population. Among hemodialysis patients, those whose blood pressure increases during hemodialysis carry a higher risk for poor outcomes. The present study investigates if poor blood vessel health is related to blood pressure increases during dialysis and whether treatment with a specific blood pressure lowering medication helps prevent these blood pressure elevations.

描述（由申请人提供）：终末期肾病（ESRD）患者比一般人群具有更高的心血管发病率和死亡率风险。血液透析 (HD) 期间血压升高的患者是不良后果风险更大的亚群。当定义为 HD 治疗前后收缩压升高超过 10 mmHg 时，透析中高血压 (IH) 是 HD 患者住院以及心血管和全因死亡的另一个独立危险因素。内皮细胞功能障碍 (ECD) 和动脉僵硬度增加在 HD 患者中都很常见，并且可能与 IH 的病理生理学有关。 该项目的具体目标是： 1) 建立动脉僵硬度和 IH 的关联； 2) 使用多个变量来评估 ECD，证明 ECD 和 IH 之间的关联； 3)研究卡维地洛消除IH的作用。 对于具体目标 1：将从 25 名患有 IH 的受试者和 25 名没有 IH 的对照 HD 受试者获得脉搏波速度 (PWV)。还将测量这些受试者的动态血压 (ABP)，作为 PWV 的可能混杂变量。 对于具体目标 2：除了周中非 HD 日流介导的扩张和内皮依赖性血管舒张之外，还将测量 HD 前后内皮素-1 和不对称二甲基精氨酸的水平。 对于具体目标 3：患有 IH 的受试者将在进行所有基线测量后开始服用卡维地洛。卡维地洛治疗 8 周后，包括每日两次滴定至 50 mg 后 4 周，将重复目标 1 和 2 的所有测量。 建立 IH 与 ECD 和动脉僵硬度的关联可以促使人们努力探索可能的因果关系。此外，卡维地洛对 ​​IH 影响的结果可能会传播随机对照试验，以确定是否可以改善心血管或全因死亡率等终点。这些信息的相关性最终可能会扩展到更广泛的人群，例如 HD 前期的慢性肾病患者或没有肾病但动脉僵硬度升高或 ECD 的患者。申请人在项目期间将受到赞助商和共同赞助商的监督。申请人将参与项目从招募到稿件撰写的每一步。除了获得临床研究技能外，申请人还将学习测量 ABP、PWV 和 FMD 的技术。此外，申请人将报名参加攻读临床科学硕士学位的课程。所有活动的目的都是为了让申请人获得临床研究方面的知识和经验，以更独立地参与研究生涯。 公共卫生相关性：接受血液透析的终末期肾病患者患心血管疾病和死亡的风险高于普通人群。在血液透析患者中​​，血液透析期间血压升高的患者预后不良的风险较高。本研究调查血管健康状况不佳是否与透析期间血压升高有关，以及使用特定降压药物治疗是否有助于预防血压升高。