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 mechanism underlying unexplained weight loss. We examine heart failure as a physiological model to demonstrate the importance of measuring several physiological outcome variables that have increased our understanding of wasting and cachexia in the elderly. These include the assessment of: energy expenditure, body composition, physical activity and exercise tolerance. We review recent data that has assessed energy expenditure in free-living heart failure patients using stable isotope methodology (doubly labeled water). Preliminary results show low levels of daily energy expenditure in heart failure patients due to extremely low levels of physical activity. Thus, a hypermetabolic 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 muscle atrophy. This concept is support by the relationship between peak VO 2 and muscle mass (r = 0.92; P < 0.01), as measured from dual energy x-ray absorptiometry. 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 independence in patients with chronic heart failure.