Special considerations in design of trials with elderly subjects: Unexplained weight loss, body composition and energy expenditure

Wasting and cachexia are significant problems in the elderly that increase mortality and morbidity, It is presently unclear as to the physiological me chanism underlying unexplained weight loss. We examine heart failure as a p hysiological model to demonstrate the importance of measuring several physi ological outcome variables that have increased our understanding of wasting and cachexia in the elderly. These include the assessment of: energy expen diture, body composition, physical activity and exercise tolerance. We revi ew recent data that has assessed energy expenditure in free-living heart fa ilure patients using stable isotope methodology (doubly labeled water). Pre liminary results show low levels of daily energy expenditure in heart failu re patients due to extremely low levels of physical activity. Thus, a "hype rmetabolic state" in free-living heart failure patients is not supported by these findings. The low level of physical activity is likely a consequence of their reduced exercise capacity and contributes to their skeletal muscl e atrophy. This concept is support by the relationship between peak VO2 and muscle mass (r = 0.92; P < 0.01), as measured from dual energy x-ray absor ptiometry. An understanding of the physiological factors influencing energy dysregulation and low exercise capacity may help guide future therapeutic interventions to restore energy balance and increase functional independenc e in patients with chronic heart failure.