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The Journal of Nutrition Vol. 129 No. 1 January 1999,
pp. 260S-263S
Department of Medicine, College of Medicine, University of Vermont, Burlington, Vermont 05405
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ABSTRACT |
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Abstract
Introduction
References
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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 VO2 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.
KEY WORDS: body composition · energy expenditure · wasting · cachexia · heart failure
The intent of this short paper is to briefly highlight the importance of accurately measuring energy expenditure, body composition and exercise capacity as important endpoints in the assessment and understanding of wasting and cachexia in elderly persons. It is known that fluctuations in energy balance occur through alterations in energy intake or energy expenditure (Poehlman 1992 We specifically highlight congestive heart failure to examine the physiological basis underlying cachexia and wasting. However, the tools and methodologies involved in the assessment of energy expenditure, body composition and physical activity are applicable and adaptable to the understanding of wasting and loss of physical function in other cachectic diseases such as Alzheimer's Disease (Donaldson et al. 1996 Heart failure is an increasingly important clinical problem, with the highest prevalence being seen in the elderly (Parmley 1989 Although many factors are likely to be involved in the pathogenesis of wasting, weight loss must ultimately be the consequence of a negative energy imbalance. Energy balance is defined as energy intake minus energy expenditure. Daily energy expenditure is comprised of several components which include: (1) resting metabolic rate, (2) the thermic effect of meals, and (3) physical activity (Poehlman 1993
Several important variables have been identified to measure when designing clinical trials for the treatment of secondary wasting and cachexia in the elderly. We used heart failure as a physiological model to stress the importance of measuring energy expenditure, body composition and physical activity. The measurement of these interrelated factors provides insight into the wasting process and a more sophisticated understanding of the significance of energy dysregulation, deleterious changes in body composition and exercise intolerance to the wasting process in healthy and diseased elderly.
INTRODUCTION
Abstract
Introduction
References
). The balance between energy intake and expenditure ultimately determines body energy stores. Thus, unexplained weight loss, the erosion of muscle mass and decline in functional independence ultimately must have a physiological basis rooted in an energy imbalance caused by a low energy intake, an abnormally high level of energy expenditure or a combination of both. Recently, methodological advances to assess energy expenditure, body composition and physical activity have increased our understanding regarding mechanisms related to wasting and cachexia in elderly. A thorough physiological understanding of the causes of wasting is important if successful treatments are to be developed in an attempt to reverse catabolic states in the elderly.
, Poehlman et al. 1997) and Parkinson's disease (Toth et al. 1997a).
HEART FAILURE AND WASTING
). The incidence of heart failure increases 50-fold between the ages of 40 to 60 years. At a time when mortality from coronary disease is decreasing, the incidence and prevalence of heart failure are increasing (Parmley 1989). Heart failure is now the most common hospital discharge diagnosis for those over age of 65, accounting for millions of hospital admissions each year. The unexplained loss of body weight and muscle mass are hallmark clinical features of end-stage congestive heart failure (Pittman and Cohen 1964). Weight loss may lead to cardiac atrophy and further decompensation (Abel et al. 1979). Moreover, weight loss is associated with increased mortality.
). Many factors are likely to be involved in the pathogenesis of cardiac cachexia. For example, reduced blood flow to the limbs may deprive tissues of the necessary substrates for normal protein turnover and growth (Wilson et al. 1984). The immobility of patients who are breathless and have effort intolerance may result in disuse atrophy and deconditioning, which contribute to muscle wasting through reduced skeletal muscle protein synthesis (Gibson et al. 1987). Anorexia as a result of hepatic congestion, hypoxia, or drug toxicity, together with delayed emptying and hypomotility of the gut may cause impaired assimilation of nutrients (Berkowitz et al. 1963), resulting in an energy supply too small to maintain adequate tissue growth.
HEART FAILURE AND ENERGY EXPENDITURE
). The relative importance of these components in the wasting syndrome associated with heart failure is unknown.
) and others (Riley et al. 1991) showed a higher resting metabolic rate (
18%; 283 kcal per day) in class III and IV heart failure patients compared to age-matched healthy individuals. Moreover, we showed that resting metabolic rate increased with severity of symptoms in heart failure (Obisesan et al. 1996). Because resting metabolic rate is a large component of daily energy expenditure (Poehlman 1993), elevations in this component may be associated with the negative energy imbalance and cachexia in heart failure patients. Although the mechanism for the higher resting metabolic rate in heart failure patients is unknown, several metabolic pathways should be considered. Increased myocardial oxygen consumption, as well as the increased metabolic cost of breathing may be contributory (Pittman and Cohen 1964). Circulating levels of tumor necrosis factor are higher in cachectic heart failure patients (Levine et al. 1990), but their relation to alterations in resting metabolic rate remains speculative. A possible explanation is elevated sympathetic nervous system activity, which is typically observed in heart failure patients, especially in the advanced stages (Davis et al. 1988). We have shown that resting metabolic rate increases in relation to increments in the rate of norepinephrine appearance into circulation (Poehlman and Danforth 1991).
). Twelve cachectic patients (age, 73 ± 6 yr; weight loss = 15 ± 6 kg), 13 noncachectic patients (age 67 ± 5 yr) and 50 healthy elderly controls (age = 69 ± 6 yr) were studied. Daily energy expenditure and its components were measured using doubly labeled water and indirect calorimetry and body composition by dual energy x-ray absorptiometry. Table 1 shows the physical characteristics of cachectic, noncachectic and healthy control groups. Body mass index was lower (P < 0.05) in cachectic patients compared with noncachectic patients and healthy controls. Cachectic patients weighed less than the other groups due to a lower quantity of fat mass and fat-free mass (all P < 0.01).
View this table:
Table 1.
Physical characteristics of cachectic and noncachectic heart failure patients and healthy controls
View this table:
Table 2.
Daily energy expenditure, its components and energy intake in cachectic and noncachectic
heart failure patients and healthy controls
; Toth et al. 1997c). Elevated rates of myofibrillar protein breakdown have been identified as a contributing factor to skeletal muscle atrophy in heart failure patients (Morrison et al. 1988). Reduced peak oxygen consumption (peak VO2) is a hallmark of chronic heart failure. Skeletal muscle atrophy may contribute to reduced peak VO2 by reducing the quantity of tissue available to utilize oxygen during exercise. We recently found a strong correlation (r = 0.91; Fig. 1) between peak VO2 and skeletal muscle mass in heart failure patients, suggesting that skeletal muscle atrophy contributes to low peak VO2, whereas this relationship was less robust in healthy elderly (0.34; P < 0.05; Toth et al. 1997c). Reduced skeletal muscle blood flow during exercise (Wilson et al. 1984) may partially explain the strong dependence of peak VO2 on skeletal muscle mass in heart failure patients. Reduced oxygen delivery to exercising skeletal muscles necessitates an increase in oxygen extraction by skeletal muscle to sustain exercise at a given workload. Increased oxygen extraction depends on both the quantity and oxidative capacity of skeletal muscle. Thus, a reduction in skeletal muscle mass or oxidative capacity would decease peak VO2 in heart failure patients. However, the degree of cardiac dysfunction and reduced oxidative capacity of skeletal muscle (Minotti et al. 1991) are also likely contributors. Although it is presently unclear whether alterations in protein kinetics are a consequence of physical inactivity, it is possible that therapeutic interventions designed to increase physical activity, such as exercise training, may preserve skeletal muscle mass by increasing myofibrillar protein synthesis (Yarasheski et al. 1993).
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Fig 1.
Relationship between peak oxygen consumption (VO2) and total skeletal muscle mass in heart failure patients and healthy controls. The correlation between peak VO2 and total skeletal muscle mass was significantly stronger (P < 0.01) in heart failure than in controls, as assessed by Fisher's z test. (From Toth et al. 1997).
) precludes a thorough testing of this hypothesis. Several factors, including abdominal pain and distension, gastrointestinal hypomotility, and delayed gastric emptying, have been suggested to contribute to anorexia in heart failure patients (Pittman and Cohen 1964). Further studies that covertly monitor food intake in heart failure patients in response to perturbations in energy balance are needed to examine the regulation of energy intake.
SUMMARY
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FOOTNOTES |
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LITERATURE CITED |
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Abstract
Introduction
References
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