Introduction
Sarcopenia, frailty, cachexia and malnutrition are widespread syndromes in older people and associated with an increased risk of poor outcome like mobility limitation, fracture, increased length of hospital stay, hospital readmission, morbidity and mortality [
1‐
4]. In hospital patients the hazard of these syndromes is particularly high due to acute illness, immobility and anorexia. Prevalence rates up to 50% or more have been reported in older patients for all syndromes [
5‐
8], however, with great variation between studies, not least due to of different diagnostic criteria.
One central aspect of all syndromes is the loss of body tissue [
9], which however affects different tissues to a varying extent. Whereas in sarcopenia, frailty and cachexia the loss of fat-free mass, especially skeletal muscle mass, is crucial [
10‐
12], in malnutrition fat free mass as well as fat mass are reduced [
13]. Besides these changes in body composition, all syndromes except malnutrition are characterized by specific additional features: sarcopenia and frailty by reduced strength and function [
10,
11], frailty in addition by exhaustion and low physical activity [
11], and cachexia by reduced strength, fatigue, anorexia and inflammation [
12]. All syndromes also share similar etiological factors which are differently pronounced, i. e. reduced food intake, inflammation, hormonal changes, increased energy requirements and reduced physical activity [
9].
Due to these similarities in etiology and definitions, the syndromes partly overlap and can be present in the same patient. This concurrent occurrence might have implications for adequate treatment but also for outcome. Plenty of studies are available focusing on one specific syndrome, but until now only few studies looked at more than one syndrome in the same population. In geriatric patients, simultaneous occurrence of sarcopenia and malnutrition [
5,
14] and of sarcopenia and cachexia [
15] was described. In community-dwelling older adults, significant overlaps between sarcopenia and frailty [
16‐
18] and between malnutrition and frailty [
19] are reported.
To our knowledge, prevalence and concurrent occurrence of all four aforesaid syndromes in older inpatients have not been investigated before. Thus, the aim of the present study was to assess the prevalence and overlap of sarcopenia, cachexia, frailty and malnutrition in a group of older medical inpatients.
Discussion
To the best of our knowledge this is the first study covering the four tissue loss syndromes (sarcopenia, frailty, cachexia and malnutrition) simultaneously in one patient group. Sarcopenia was the most prevalent syndrome in 42% of older medical inpatients and malnutrition the least prevalent in only 15%. Frailty and cachexia were prevalent in about one third respectively. Almost two thirds of the patients were affected by at least one of these syndromes and considerable overlap was observed (Fig.
1). Eight percent had all four syndromes.
The patients were in rather good physical and mental condition, reflected in complete independence in ADLs in almost all patients, only few cognitive impairment, only occasional depressive symptoms and very low comorbidity (Table
2). Consequently, we experienced no difficulties measuring handgrip strength and gait speed which are reported by others in geriatric populations [
14]. This positive selection is at least partly due to the inclusion criteria and demands for more comprehensive data assessment in the future.
Prevalence rates of a specific syndrome are generally dependent on the applied definition. In recent years, consensus definitions have been developed for all four syndromes which are widely used in research and were also used in the present study. For the assessment of sarcopenia, the EWGSOP definition [
10] was applied because it combines measures of muscle mass and function and its relation to poor clinical outcome is well documented [
33]. This definition is well established, and has previously been used in several studies in older hospitalized patients with reported prevalence rates between 10 and 50% [
34‐
38]. A closer look at the methods used in these studies reveals that despite using the same general definition, different operational procedures were used, i.e. different methods to determine muscle mass, and different cut-off values to define reduced muscle mass and function. Using the same diagnostic criteria as in our study, Perez-Zepeda et al. [
34] reported sarcopenia in 40% and Sousa et al. [
35] in 37% of older patients, which is similar to our results.
Frailty was assessed using the definition of Fried et al. [
11], as this definition is most widely used, is focused on the physical phenotype of frailty and relatively straightforward to assess. In our study one third of the patients were found to be frail. This proportion is in the same range as reported earlier by others using the same definition in older patient populations [
39‐
41]. Frailty was observed less often than sarcopenia and only 58% of frail patients were also sarcopenic (Table
4). This phenomenon, i.e. much lower prevalence of frailty than of sarcopenia, is also reported in community-dwelling older adults [
16,
18], although not consistently [
17]. The frailty definition includes reduced functionality – low grip strength as well as slow gait speed – but is, in contrast to all other syndromes, not necessarily characterized by reduced muscle mass [
11] which is confirmed in our results. The most prevalent features of frail patients were exhaustion and low physical activity in 85 and 88% of patients, respectively (Table
3).
Cachexia is widely acknowledged as a complex metabolic syndrome observed in chronic diseases associated with systemic inflammation, but difficult to assess due to the lack of a clear definition for clinical application. We operationalized cachexia according to Evans et al. [
12] who included biochemical measures which are regarded as important parameters of the cachexia syndrome and found a prevalence of 32% which is almost exactly the same as reported from palliative care cancer patients (age 68 ± 11 years) using the same definition (33%) [
42]. No other studies reporting the prevalence of cachexia in older hospitalized patients were found. This is in accordance with a recent systematic review on the prevalence of cachexia and malnutrition in older cancer patients scheduled for chemotherapy, where 24 studies were identified reporting the prevalence of malnutrition but no study specifically assessed cachexia [
43]. Although cachexia is typically attributed to cancer [
3], it was not significantly more often observed in patients with a primary diagnosis of cancer (Table
1). Several components of the cachexia definition were also present in patients with other syndromes, e.g. anorexia and low hemoglobin levels in frail patients and reduced body mass, fat-free mass and albumin levels in malnourished patients. Besides the necessary criterion loss of weight, the most prevalent features in cachectic patients were increased CRP values and anorexia in more than three quarters of patients (Table
3).
Malnutrition was assessed according to the ESPEN definition [
13], the first consensus definition with age-specific cut off values for a low BMI. Since its publication in 2015, the ESPEN definition was used in a number of studies [
5,
44‐
46] providing a good basis for comparison of our own results. Surprisingly, malnutrition, which is acknowledged as a widespread syndrome in older patients [
4], was by far the least prevalent syndrome in only 15% of our patients, less than half as frequent as the other syndromes. This prevalence is, however, in accordance with previous studies using the ESPEN definition, reporting malnutrition in 11 to 15% of somewhat younger hospitalized patients (mean ages between 57 and 62 years) [
44‐
46]. A slightly higher prevalence of 19% was observed in markedly older patients (85 ± 6 years) in a post-acute geriatric rehabilitation care unit [
5]. In the above mentioned review on malnutrition and cachexia in older cancer patients, a wide variation in the prevalence of malnutrition was reported when using weight loss (8–40%) as well as MNA (3–42%) as criteria for malnutrition [
43]. In our study, the prevalence of malnutrition according to MNA-SF was 11%, thus in the lower part of this range and even lower than found by using the ESPEN definition. This may be explained by the close relation of the MNA to functionality and level of dependence [
47] and the low level of dependence in our patient group (Table
1).
Interestingly, malnutrition according to MNA was significantly more prevalent not only in patients with malnutrition according to ESPEN but also in all other syndromes (Table
3). This might also be due to the functional nature of the MNA. Whereas malnutrition according to MNA was related to frailty as reported earlier by others [
47], malnutrition according to ESPEN was not (Table
4). This is again explainable by the fact that functional aspects are included in the MNA whereas the ESPEN definition is restricted to weight loss and reduced body mass or fat-free mass. Despite this lacking significance in the association between malnutrition and frailty, malnutrition according to ESPEN showed the largest overlap with the other syndromes (Table
4, Fig.
1). All malnourished patients except one were also cachectic, which may be due to the fact that two of the three malnutrition criteria – weight loss and low fat-free mass – are also components of the cachexia definition. Despite completely different diagnostic criteria, however, 80% of the malnourished patients were also sarcopenic. Interestingly, all malnourished patients had a low SMI, probably as a consequence of the experienced weight loss. Thus, the large overlap of malnutrition with the other syndromes is probably caused by the fact that malnutrition is mainly characterized by wasting which is a central symptom also of the other syndromes. Half of all patients reported a weight loss of more than 5% within the last 12 months, and this proportion was significantly higher in all syndromes (Table
3) – also in sarcopenia even though weight loss is not part of the sarcopenia definition.
Interestingly, many more patients in our study had a reduced muscle mass (78%) than reported a weight loss, indicating that muscle mass is often reduced also in persons who did not experience a significant weight loss.
Even though every other patient experienced weight loss, more than one quarter of the patients was obese, and obesity did not preclude the presence of sarcopenia, frailty or cachexia. In these patients, tissue loss is hidden behind high body (fat) mass and may easily be overlooked if no special attention is paid. Obese patients with one or more of the four syndromes might have higher risks for cardio-metabolic diseases and physical disability compared to patients with normal BMI and these syndromes [
48] and thus deserve special attention. In order to identify these patients, body composition needs to be measured.
The major strength of the present study is the application of consensus definitions and complete information on all four syndromes in the same patients. Moreover, all measurements were highly standardized. One limitation of the study is the rather small sample size, which is however, comparable to previous studies investigating the overlap of tissue loss syndromes in hospital settings [
5,
14]. Due to hospital equipment, we were forced to select patients who were able to stand which limits the generalizability of our results. In addition, 13% of the initially admitted or 58% of eligible patients had to be excluded due to their unwillingness to participate, further restraining generalizability. As these patients did not consent to any data collection, it is unfortunately not possible to describe potential differences between these patients and the study sample. It may be assumed that a selective participation of less severely impaired patients also contributed to the high physical and mental performance of the study sample. Another limitation is that weight loss was assessed based on participant’s self-reported body weight 12 months ago and not measured. In addition, the original definition of weight loss in the ESPEN malnutrition definition (> 10% of habitual weight indefinite of time, or > 5% over 3 months [
13]) had to be adapted to > 10% weight loss in the previous year. This might have led to a slight underestimation of the malnutrition prevalence. Furthermore, the accuracy of BIA measurements is limited in case of changes in the amount and distribution of body water.
Conclusion
In the present cross-sectional study, the tissue loss syndromes sarcopenia, frailty, cachexia and malnutrition and their constituting components were widespread among older medical inpatients, even though patients were physically and mentally rather unimpaired. The syndromes occurred concurrently and were interrelated.
In the light of well-known serious health consequences of each syndrome, in clinical routine attention should be paid to the presence of each syndrome, also in obese patients. In addition, each component of the syndromes needs particular attention as weight loss, reduced muscle mass, reduced physical performance and inflammation are treatable by nutritional support, physical exercise or anti-inflammatory treatment.
Future studies with larger patient groups and longitudinal design are required to clarify the significance of single and concurrent occurrence of these syndromes for clinical outcome and successful therapy. In this context, specific attention should be paid to diagnostic tools and cut-off values, since prevalence as well as overlap of the syndromes is largely dependent on the applied diagnostic criteria.