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.
