INTRODUCTION
Sarcopenia, characterized by the loss of skeletal muscle mass and strength with age,1) causes health-related adverse outcomes, including physical impairment, falls, fractures, hospitalizations, and mortality.2-4) As Korea is one of the fastest ageing countries worldwide, the prevalence and resulting health burden of sarcopenia among Koreans will increase.5) Thus, sarcopenia diagnosis and treatment guidelines tailored to the Korean circumstance are urgently needed.
As part of this effort, the Korean Working Group on Sarcopenia (KWGS) published a guideline in 2023, developed from Delphi interviews with Korean sarcopenia experts.6) While the KWGS guideline aligns largely with the Asian Working Group on Sarcopenia (AWGS 2019), it introduces some differences.1,6) First, the KWGS guideline recommends a comprehensive geriatric assessment after a diagnosis of sarcopenia because sarcopenia is a phenotype that involves many factors. Second, the KWGS guideline suggests the concept of functional sarcopenia, characterized by low physical performance and muscle strength with normal muscle mass. To date, investigation of the clinical relevance of this, based on the new definition suggested by KWGS, has been limited.
This study, therefore, examined the clinical relevance of sarcopenia in terms of falls, mobility limitations, and mortality as defined by the KWGS in community-dwelling older adults.
MATERIALS AND METHODS
Study Design
This study was performed as a part of the Korean Longitudinal Study on Health and Aging, a community-based study based in Seongnam, Korea. Participants were selected using age- and sex-stratified random sampling from a roster of people aged ≥65 years. Of the 1,000 participants, those who could walk independently, with or without assistance, and who were not experiencing an acute exacerbation of a chronic illness, were re-recruited between 2007 and 2008 for an ancillary study to assess sarcopenia. Finally, 594 participants were included in current study, and details of the methods have been published.7)
All participants were fully informed of the study protocol and gave informed consent. The study protocol was approved by the Institutional Review Board of Seoul National University Bundang Hospital (IRB No. B-0912-089-005).
Sarcopenia Assessment and Definition
Lean mass was measured using dual-energy X-ray absorptiometry (DXA; Lunar, Madison, WI, USA). Appendicular lean mass (ALM) was calculated as the sum of the lean mass of both arms and legs, then divided by height squared to obtain the ALM Index (ALMI). The cutoff points for low ALMI was <7.0 kg/m2 for men and <5.4 kg/m2 for women. Grip strength was assessed using Jamar Hydraulic Dynamometer (Sammons Preston, Bolingbrook, IL, USA) in the sitting position, shoulder adduction, elbow flexion 90°, and forearm in neutral position. The maximum values from two trials were recorded, with low muscle strength defined as grip strength less than 28 kg and 18 kg for men and women, respectively. Physical performance was assessed using the Short Physical Performance Battery (SPPB) test. Balance, usual gait speed, and five sit-to-stand repetitions were tested. Each test was scored from 0 to 4, with a total score ranging from 0 to 12 (worst to best function). Low physical performance was defined as SPPB ≤9 points for both sexes.
Falls and Mobility Limitation
Both falls and mobility limitation were assessed using self-questionnaires. Participants were asked whether they had fallen, and the number of falls during the past year. Falls were defined as having experienced two or more falls in the past 12 months. Regarding mobility limitation, participants were asked “Can you walk more than a kilometer?” The answer was a choice of very limited, somewhat limited, and not limited at all. Mobility limitation was defined as present if participants had any difficulty in task performance.
Mortality
The death of participants were primarily confirmed through a retrospective review of electronic medical records and a search of death certifications in the clinical data warehouse of Seoul National University Bundang Hospital. Additionally, all-cause mortality and the date of death were verified through administrative data from the Korea Ministry of Interior and Safety based on resident registration. The follow-up period was defined as from assessment of sarcopenia until the date of death or the last follow-up in July 2021.
Anthropometric and Geriatric Assessment
Weight and height were measured in centimeters and kilograms, respectively, and reported to the nearest 0.1. Body mass index (BMI) was calculated as weight divided by height squared (kg/m2). Comorbidity data were collected through self-reports, clinical diagnoses, and medication use, and were presented as the Charlson Comorbidity Index (CCI).8) Current smoking, alcohol intake, and regular exercise, defined as exercising more than three or more times at least 30 minutes, were investigated through a self-administered questionnaire. Activities of daily living (ADL) were assessed using the Korean Instrumental Activities of Daily Living (K-IADL). Cognition and severity of depression were assessed using the Korean version of the Mini-Mental State Examination (MMSE) and the Korean version of the Geriatric Depression Scale (GDS), respectively.
Statistical Analyses
Baseline characteristics were compared based on sarcopenia status using the χ2 test for categorical variables and the Kruskal-Wallis test for continuous variables. Logistic regression models were used to analyze the association between falls and mobility limitations and sarcopenia status, reported using odds ratios (ORs) and 95% confidence intervals (CIs). Additionally, Cox proportional hazard models were used to determine the association between mortality and sarcopenia status, reported using hazard ratios (HRs) and 95% CIs. Both the logistic regression and Cox proportional hazard models are presented as unadjusted and adjusted models accounting for age, sex, BMI, regular exercise, GDS, MMSE, K-IADL, current smoking, current alcohol intake and comorbidities. For each model, the non-sarcopenia group was used as the reference category for falls, mobility limitation, and mortality. All analyses were performed using SPSS Statistics 23.0 (IBM, Armonk, NY, USA). p-values <0.05 were considered significant.
RESULTS
Of the 594 participants, 320 (53.9%), 145 (24.4%), and 129 (21.8%) were classified as non-sarcopenia, functional sarcopenia, and sarcopenia, respectively. The prevalence of sarcopenia increased with age, with 33.6% having functional sarcopenia and 24.6% having sarcopenia in the 75–84-year-old group and 41.4% having functional sarcopenia and 39.3% having sarcopenia in those 85 years and older (Table 1).
The characteristics of each group and all participants are shown in Table 2. Age, sex, BMI, GDS score, MMSE scores, K-IADL score, CCI, ALMI, grip strength, and SPPB score differed significantly between groups. In the post-hoc analysis, functional sarcopenia group had a higher proportion of women, weight and BMI, and ALMI, and lower height, MMSE score, proportion of current smoking, alcohol intake, grip strength, and SPPB score than sarcopenia group.
Overall, both functional sarcopenia and sarcopenia were associated with health-related adverse outcomes. Compared with non-sarcopenia group, those with sarcopenia had higher odds of falls (OR=3.934; 95% CI, 1.327–11.713) (Table 3). The risk for mobility limitation was 3.461 (95% CI, 1.956–6.121) and 2.057 (95% CI, 1.172–3.611) times higher in the functional sarcopenia and sarcopenia group, respectively (Table 3). Fig. 2 shows the Kaplan-Meier curves of mortality for non-sarcopenia, functional sarcopenia, and sarcopenia groups (log-rank test, p<0.001). In the multivariate Cox proportional hazards model, the HR of mortality was 1.775 (95% CI, 1.229–2.564) for functional sarcopenia and 1.512 (95% CI, 1.054–2.169) for sarcopenia (Table 3). Comparing functional sarcopenia and sarcopenia, the differences in the risk of falls, mobility limitation, and mortality was not significant (Supplementary Table S1).
DISCUSSION
In a community-based cohort, we investigated the clinical relevance of sarcopenia, defined by the KWGS. Of the participants, 24.4% had functional sarcopenia and 21.8% had sarcopenia, with the prevalence of each increasing with age. We found that both functional sarcopenia and sarcopenia were associated with health-related adverse outcomes.
The KWGS guideline adopted the same cutoff points as the AWGS 2019, while also introducing the concept of functional sarcopenia, defined as low muscle strength and low physical performance without a loss of muscle mass, as subcategories of sarcopenia. In this study, functional sarcopenia was common, affecting one quarter of community-dwelling older adults. Functional sarcopenia was more frequent in women than men, in contrast to previous studies of Koreans in which sarcopenia was found more frequent in men.9,10) Additionally, while functional sarcopenia is characterized by a higher muscle mass and lower muscle function (strength and performance) by definition, compared to sarcopenia, the risk of health-related adverse outcomes for both was comparable (Supplementary Table S1).
Despite the clinical significance of functional sarcopenia demonstrated here, the existing sarcopenia consensuses emphasized low muscle mass as a key component in the diagnosis of sarcopenia; the category of low muscle function despite preserved muscle mass has received little consideration.11) However, previous studies demonstrated that low muscle mass per se was a poor predictor of functional outcomes, and the loss of muscle mass did not fully explain the preceding decline in muscle strength.12-14) Furthermore, changes in muscle mass and strength do not correspond, and an increase in muscle mass did not prevent the loss of strength due to aging, in a longitudinal study by Goodpaster et al.15) This implies that the clinical significance noted in this study, which involved a group with impaired muscle function despite having normal muscle mass, indicates that non-mass plays a role in age-related changes.
The first non-mass factor is muscle quality. In 2014, the concept of skeletal muscle function deficit (SMFD) was suggested, which embraces the evolving concepts of sarcopenia and other ageing-related muscle dysfunction that cause significant mobility impairment.16) SMFD implies deterioration in muscle quality, which determines how well muscle tissue functions. From a pathophysiologic viewpoint, as ageing progresses, ectopic fat infiltration and accumulation of non-contractile tissue within skeletal muscle increase, impending muscle contractility and force production regardless of muscle mass.17,18) The neural component is another contributor to muscle function, reportedly contributing up to 50%.19,20) Changes in the nervous system with ageing affect everything from supraspinal center to the neuromuscular junction. Over the age of 65, the motor cortex atrophies, and neurotrophic damage reduces cortical excitability and plasticity.21-23) At the spinal level, there is a progressive decrease in spinal excitability, maximal compound muscle action potentials, allogenic facilitation, and oligosynaptic reflexes.24,25) With age, the number of motor unit decreases, and changes in recruitment, firing frequency, neuromuscular junction, and intermuscular coordination occur.26,27) Last, the clinical relevance of functional sarcopenia, a concept that does not include a muscle mass factor, may be due to inaccurate measurements of muscle mass. DXA is considered the gold standard for evaluating muscle mass, but it measures muscle mass indirectly through ALM. ALM includes not only muscle but also water, fibrous tissue, and connective tissue.28) The Sarcopenia Definition and Outcomes Consortium has stated that ALM is a poor predictor of health-related adverse outcomes, leading some experts to advocate excluding ALM measured by DXA from the definition of sarcopenia.29)
Issues regarding nomenclature remain: the term of functional sarcopenia is not yet established and is not generally accepted by experts. Some have concerns about adding another type of sarcopenia. “Low muscle mass and physical performance,” “muscle dysfunction with preserved mass,” or “skeletal muscle function deficit without sarcopenia” could be alternative terms for functional sarcopenia. There is a need for a term that embraces the evolving concept of sarcopenia, which includes muscle weakness and reduced physical performance without loss of muscle mass.
This study had several limitations. First, it was performed based on self-administered questionnaires regarding falls and mobility limitation, which may lead to recall bias in older adults. Second, because the study investigated all-cause mortality, unrelated mortalities such as suicidal and accidental deaths could not be excluded. Third, selection bias was possible in this study. Participants who were eventually included in this study may have been relatively healthy enough to measure sarcopenic variables, including physical capacity.
In conclusion, this study investigated the association between health-related adverse outcomes and sarcopenia, defined by KWGS guideline, among community-dwelling older adults. Low muscle strength and physical performance, despite normal muscle mass, was associated with mobility limitation, and mortality, and its risk was comparable with sarcopenia group. The findings suggest that non-mass factors associated with ageing may lead to health-related adverse outcomes and that functional sarcopenia should be considered as part of the diagnosis in sarcopenia.
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