Cardiovascular Causes of Falls/Syncope in the Elderly

晕厥和跌倒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在导致老年人跌倒/晕厥的血压调节障碍中的作用。该研究将重点关注直立性低血压和颈动脉窦超敏[CSH]，这两种疾病在老年人跌倒/晕厥中占很大比例。随着人口的老龄化，了解这些疾病的病理生理学的必要性是显而易见的。申请人职业生涯的初始阶段已经证明了对理解年龄相关的心血管生理变化如何导致最快速增长的人群中跌倒/晕厥的强烈承诺。这项以患者为导向的指导研究职业发展奖将允许获得测量血管硬度的新技能，并在生物统计学和实验临床设计方面进行教学培训，促进申请人作为临床研究者的发展。要验证的总体假设是，与年龄相关的血管功能变化使老年人易患血压调节紊乱。首先，申请人将前瞻性地评估养老院居民的心跳对心跳的直立性血压变化和跌倒的发生率，以确定血压的姿势变化的时间和程度是否增加了预后价值，如果收缩压和舒张压的变化在预测随后的跌倒方面是等效的，以确定血压下降的程度具有最佳的预测价值。这项研究将提高我们识别有跌倒风险的老年受试者的能力，并确定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直立期间和进餐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，以评估使用外周主动脉压与中央主动脉压相比，在测量压力反射功能时是否存在系统性偏差；(3)比较血管僵硬度；老年CSH患者的动脉粥样硬化程度和心率的压力反射控制，以及年龄和性别匹配的对照组。这项研究将在欧文临床研究中心的自主功能实验室、希伯来老人之家和哥伦比亚大学循环生理学部门进行。哥伦比亚大学公共卫生学院将开设生物统计学和临床实验设计课程。这些课程将补充参与循环生理学部门的指导计划，包括一对一的会议和关于临床试验设计，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.