Cardiovascular Causes of Falls/Syncope in the Elderly

晕厥和福尔斯在老年人中引起显著的发病率和死亡率。本研究将探讨血管僵硬度在老年人血压[BP]调节障碍导致福尔斯/晕厥中的作用。本研究将重点关注直立性低血压和颈动脉窦超敏反应[CSH]，这两种疾病在老年人福尔斯/晕厥中占很大比例。随着人口老龄化，需要了解这些疾病的病理生理学是显而易见的。申请人职业生涯的初始阶段已经证明了对了解年龄相关的心血管生理学变化如何导致人口增长最快的部分中的福尔斯/晕厥的强烈承诺。这个指导病人为导向的研究职业发展奖将允许测量血管硬度和追求生物统计学和实验临床设计促进申请人的发展作为一个临床研究者的教学培训的新技能的收购。有待检验的总体假设是，与年龄相关的血管功能变化易使老年人血压调节紊乱。最初，申请方将前瞻性评价疗养院居民的血压逐搏直立性变化和福尔斯发生率，以确定血压姿势变化的时间和程度是否增加了预后价值，SBP和DBP的变化是否等同于预测随后的福尔斯，以确定何种程度的血压下降具有最佳预测价值。本研究将提高我们识别有福尔斯跌倒风险的老年受试者的能力，并识别参与未来机制研究的受试者。因此，我们建议：（1）评估静脉僵硬度在长时间体位性和进食后症状性低血压发展中的作用，（2）确定动脉僵硬度对心率的压力反射控制随年龄下降的影响，以评估与中心主动脉压相比，当使用外周压力时，在压力反射功能的测量中是否存在系统偏差，（3）比较老年CSH患者与年龄、性别相匹配的对照组的血管僵硬度、运动强度及压力反射对心率的控制。这项研究将在欧文临床研究中心的自主神经功能实验室、希伯来老人院和哥伦比亚大学循环生理学系进行。生物统计学和实验临床设计课程将在哥伦比亚大学公共卫生学院进行。这些课程将补充参与循环生理学部门的导师计划，其中包括一对一会议和临床试验设计，良好临床实践和负责任的研究行为的课程。

Syncope and falls cause significant morbidity and mortality in the elderly. This proposal will explore the role of vascular stiffness in disorders of blood pressure [BP] regulation that result in falls/syncope in the elderly. The research will focus on orthostatic hypotension and carotid sinus hypersensitivity [CSH], which account for a significant percentage of falls/syncope in the elderly. With the aging of the population, the need to understand the pathophysiology of these disorders is evident. The initial stages of the applicant's professional career have demonstrated a strong commitment to understanding how age related changes in cardiovascular physiology result in falls/syncope in the most rapidly growing segment of the population. This Mentored Patient Oriented Research Career Development Award will permit the acquisition of new skills for measuring vascular stiffness and pursuit of didactic training in biostatistics and experimental clinical design facilitating the applicant's development as a clinical investigator. The overall hypothesis to be tested is that age-related changes in vascular function predispose the elderly to disorded BP regulation. Initially, the applicant will prospectively evaluate beat-to-beat orthostatic changes in BP and the incidence of falls in nursing home residents to determine if the timing and degree of postural changes in BP adds prognostic value, if changes in SBP and DBP are equivalent in predicting subsequent falls in order to determine what degree of decline in BP has the best predictive value. This study will improve our ability to identify elderly subjects at risk for falls and identify subjects for participation in future mechanistic studies. Subsequently, we propose to: (1) evaluate the role of venous stiffness in the development of symptomatic hypotension during prolonged orthostatis and after meal ingestion, (2) determine the impact of arterial stiffness on the decline in baroreflex control of heart rate with age to evaluate if there is a systematic bias in the measurement of baroreflex function when using peripheral as compared with central aortic pressure, (3) compare the degree of vascular stiffness, extent of athlerosclerosis and baroreflex control of heart rate in elderly patients with CSH and age and sex-matched controls. This research will take place in the Autonomic Function Laboratory in the Irving Center for Clinical Research, the Hebrew Home for the Aged and the Division of Circulatory Physiology of Columbia University. Coursework in biostatistics and experimental clinical design will be pursued in the Columbia University School of Public Health. These courses will compliment participation in the Mentoring Program in the Division of Circulatory Physiology that will include one-on-one meetings and courses on the design of clinical trials, good clinical practice and responsible conduct of research.