Inflammatory markers, sarcopenia and its diagnostic criteria among the elderly: a systematic review

Margutti, Karen Mello de Mattos; Schuch, Natielen Jacques; Schwanke, Carla Helena Augustin

doi:10.1590/1981-22562017020.160155

Abstract

Objective:

To identify the relationship between inflammatory markers and sarcopenia, and the diagnostic criteria of the condition among the elderly.

Methods:

A systematic review was performed based on the consultation of the PubMed and LILACS databases. Eligible original articles were those involving individuals aged 60 years or more, which investigated sarcopenia [low muscle mass (MM) associated with poor muscle strength and/or reduced physical performance, according to the European Working Group on Sarcopenia in Older People consensus (EWGSOP)] or its diagnostic criteria, published in English or Portuguese, between 2010-2015.

Results:

Four articles were included in the review, the principle results of which were: the growth differentiation factor (GDF-15) exhibited a negative correlation with MM, handgrip strength and gait speed; the insulin-like growth factor-1 (IGF-1) correlated positively with MM; follistatin exhibited a weak correlation with physical performance; activin A and myostatin did not correlate with the diagnostic criteria; the highest tercile of extracellular heat shock protein 72 (eHsp72) was associated with lower median levels of MM, handgrip strength and gait speed; elderly persons with low MM had higher serum ferritin concentrations; women with low MM exhibited lower serum concentration levels of C-reactive protein (CRP).

Conclusion:

the six investigated inflammatory markers (GDF-15, IGF-1, follistatin, eHsp72, ferritin and CRP) were associated with the diagnostic criteria for sarcopenia, but not with sarcopenia itself. As research in this area is still developing, additional studies are required to broaden knowledge and eventually establish the role of these markers in the diagnosis and management of sarcopenia.

Keywords:
Biomarkers; Elderly; Sarcopenia

[1] Correspondence Carla Helena Augustin Schwanke E-mail: schwanke@pucrs.br

Author(s)/year of publication	Quality of articles
Author(s)/year of publication	Score (%)
Hofmann et al., 2015¹⁴	18.5 (84.09)
Ogawa et al., 2012¹⁵	18.4 (83.63)
Chung et al., 2013¹⁶	19.1 (86.81)
Santos et al., 2014¹⁷	18.8 (85.45)

Autor(s)/ Year of publication/Study design	Population (gender, place of recruitment, age/age group, sample size, country) and objective	Methods for measuring diagnostic criteria for sarcopenia	Inflammatory markers evaluated	Synthesis of the main results regarding sarcopenia and conclusion of the study
Study with sarcopenia			Inflammatory markers evaluated
Hofmann et al.¹⁴ Year: 2015 Design: Prospective study	Population: Young women living in the community - N= 17, Age= 22-28 years Elderly residents of long term care facilities - N= 81, Age= 65-92 years - Country= Austria Objective: Investigate whether serum concentrations of transforming growth factor beta (TGF-β) superfamily members such as GDF-15, myostatin, activin A or its follistatin antagonist, as well as IGF-1 differed between young and elderly women in different stages of dynapenia or with sarcopenia.	Muscle mass: - SMI was calculated through the MM/H² equation (kg/m²) Method of measuring MM= BIA Cut-off point SMI= ≤6,75 kg/m² Muscle strength: - HGS= Evaluated by dynamometry Cut-off point HGS= considering best result. - PTE= evaluated knee extensor strength. Cut-off point PTE= ≤61.5 Nm Physical performance: - GS over ten-meter course=the time traveled at maximum speed over course of six meters was timed. Cut-off point= ≤1 m/s - Six Minute Walk Test= the maximum distance possible was travelled in six minutes. Cut-off point= distance in meters travelled in six minutes. - Chair stand test= sit and stand up from a chair as many times as possible in 30 seconds, Cut-off point= adequate when there was more than 50% control of the test. Women with low MM (SMI ≤6,75 kg/m²), combined with low muscle strength (PTE≤61.5 Nm) and/or low physical performance (GS) were considered sarcopenic.	- GDF-15 - IGF-1 - Follistatin - Activin A - Myostatin	GDF-15: the elderly had higher serum concentrations of GDF-15 (p<0.001) than the young women, regardless of the presence or absence of sarcopenia. GDF-15 exhibited a moderate negative correlation with MM (r= -0.320, p<0.01), a weak negative correlation with HGS (r= -0.290, p<0.01) and the 6-minute Walk Test 0.261, p<0.05) and a moderate positive correlation with GS (r=0.333, p<0.01) and age (r=0,388, p<0.01). IGF-1: The elderly had lower serum IGF-1 concentrations (p<0.001) than the young women, regardless of the presence or absence of sarcopenia. IGF-1 exhibited a moderate positive correlation with MM (r=0.365, p<0.01) and a moderate negative correlation with age (r= -0.359, p<0.01). In multiple linear regression analysis with the combination of markers, age and fat mass, IGF-1 was the only moderately predictive inflammatory marker for MM (+2.9%) Follistatin: follistatin presented a weak positive correlation with physical performance evaluated by the Chair Lift Test (r=0.220; p<0.05) among the elderly. No correlation was observed with age, MM, and physical performance. Activin A: there was no difference in serum concentration between elderly and young women, nor in terms of sarcopenia. No significant correlation was found with age and the diagnostic criteria for sarcopenia. Myostatin: There was no difference in serum concentration between elderly and young women, nor in terms of sarcopenia. No significant correlation was found with age and the diagnostic criteria for sarcopenia. Conclusion: the isolated or combined presence of inflammatory markers does not reflect sarcopenia in elderly women.
Studies involving the diagnostic criteria of sarcopenia			- GDF-15 - IGF-1 - Follistatin - Activin A - Myostatin
Ogawa et al.¹⁵ Year: 2012 Design: Cross-sectional study	Population: Elderly persons living in the community - N= 652 - N women= 382, N men= 270, Age= 65-96 years - Country= Japan Objective: evaluate serum concentrations of eHsp72 protein in elderly subjects and investigate their potential interaction with sarcopenia components (muscle strength, physical performance, and skeletal muscle mass).	Muscle mass: - Measurement method= BIA. Muscle strength: - Measurement method=dynamometry to identify HGS. Physical performance: - Measurement method=GS carried out on a flat course of 11 meters (the speed and number of steps were evaluated at the midpoint of 5 meters of the course).	- eHsp72	eHsp72: individuals with higher serum concentrations of eHsp72 (higher tercile) had significantly lower mean MM, HGS and GS levels than individuals with lower serum levels of eHsp72 (p<0.01). In the analysis of multiple logistic regression, adjusted for age, gender and incidence of pathologies, it was observed that the highest tercile of eHsp72 maintained a significant association with the lower terciles of MM (OR 2.72; CI 95%=1.21-6.16; p<0.01), HGS (OR 2.60; CI 95%=1.17-5.81; p<0.01) and low GS (OR 1.82; CI 95%=1.03-3.20; p<0.01). And there was a greater risk for low HGS when there were combined mean and high serum concentrations of IL-6 and eHsp72 adjusted for age and gender (OR 3.31; CI 95%=1.48-7.41). Conclusion: the presence of higher serum concentrations of eHsp72 was associated with changes in the diagnostic criteria for sarcopenia, which is a potential marker of sarcopenia.
Chung et al.¹⁶ Year: 2013 Design: Cross-sectional study	Population: elderly persons in the community - N women= 1693, N men=1250, Age=60 years or older - Country= Korea Objective: to analyze the relationship of body composition with several factors for cardiometabolic risk in an elderly population participating in the Korea National Health and Nutrition Survey (KNHANES)	Muscle mass: - ASMM calculated through ASMM/W (kg) equation Method of measuring ASMM= DEXA Cut-off point= sarcopenia when % ASMM was 32.5% for men and 25.7% for women	- Ferritin	Ferritin: elderly persons with low ASMM had higher serum ferritin concentrations than the elderly with adequate ASMM, but with a statistically significant difference only among men (p<0.001). Conclusion: in relation to body composition, elderly persons with sarcopenic obesity presented greater resistance to insulin and the presence of more cardiometabolic risk factors than with obese or sarcopenic elderly persons.
Santos et al.¹⁷ Year: 2014 Design: Cross-sectional study	Population: Post-menopausal women living in the community - N= 149, Age= mean of 67.17(±6.12) years - Country= Brasil Objective: To examine the association of sarcopenia and sarcopenic obesity with cardiometabolic risk factors in postmenopausal women.	Muscle mass: - FFAM= calculated by FFAM/H(m)² equation Measurement method of FFAM= DEXA Cut-off point: sarcopenia when low FFAM (<5.45 kg/m²)	- CRP	CRP: Elderly patients with low FFAM had lower serum CRP concentrations when compared to the elderly with normal FFAM (p <0.05). There was also a positive and weak correlation between low FFAM and CRP (r=0.27, p<0.01). Conclusion: The criteria used to define sarcopenia were not associated with cardiometabolic risk.