Cardiovascular Causes of Falls/Syncope in the Elderly

晕厥和跌倒在老年人中会导致严重的发病率和死亡率。这项建议将探索血管僵硬在导致老年人跌倒/晕厥的血压[BP]调节紊乱中的作用。这项研究将重点放在直立性低血压和颈动脉窦过敏[CSH]上，这两种疾病在老年人跌倒/晕厥中占很大比例。随着人口老龄化，了解这些疾病的病理生理学的必要性显而易见。申请者职业生涯的最初阶段表明，他们强烈致力于了解与年龄相关的心血管生理学变化如何导致人口中增长最快的部分跌倒/晕厥。这项以患者为中心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，并追求生物统计学和实验临床设计方面的教学培训，促进申请者作为临床研究员的发展。有待检验的总体假设是，与年龄相关的血管功能变化使老年人容易受到血压调节紊乱的影响。最初，申请者将前瞻性地评估血压的逐次立位变化和疗养院居民跌倒的发生率，以确定血压体位变化的时机和程度是否增加了预后价值，如果SBP和DBP的变化在预测后续跌倒方面是相同的，以便确定BP下降的程度具有最佳预测价值。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，并确定参与未来机械学研究的受试者。随后，我们建议：(1)评估静脉僵硬在长时间立位和餐后进食后症状性低血压发生中的作用；(2)确定动脉僵硬对压力反射控制心率随年龄下降的影响，以评估使用外周和中心动脉压测量压力反射功能是否存在系统性偏差；(3)比较老年CSH患者和年龄、性别匹配的对照组的血管僵硬程度、动脉硬化程度和压力反射对心率的控制程度。这项研究将在欧文临床研究中心的自主神经功能实验室、希伯来养老院和哥伦比亚大学循环生理学分部进行。生物统计学和实验临床设计方面的课程将在哥伦比亚大学公共卫生学院进行。这些课程将是对循环生理学分部指导计划的补充，该计划将包括关于临床试验设计、良好的临床实践和负责任的研究进行的一对一会议和课程。

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.