Higher Body Mass Index in Hospitalized Older Patients Is Related to Higher Muscle Quality

Abstract

Objectives

This study aimed to examine the relationship between muscle mass, intramuscular adipose tissue, and body mass index (BMI) in older inpatients.

Design

Cross-sectional study.

Setting

Hospital-based study.

Participants

This study included 413 inpatients aged ≥ 65 years (186 men and 227 women).

Measurements

Muscle mass and intramuscular adipose tissue of the quadriceps were assessed by measuring the muscle thickness and echo intensity on ultrasound images. To examine the relationship between quadriceps thickness and echo intensity and BMI in total participants and each sex, the Kendall rank correlation coefficient was used. Multiple regression analysis was performed to examine whether BMI was independently and significantly related to the quadriceps thickness and echo intensity, even after adjusting for other variables for total participants and each sex. The independent variables in multiple regression analyses were BMI, age, disease, days from onset disease.

Results

The results of the correlation analyses showed that BMI was significantly related to the quadriceps thickness (total participants, τ = 0.431; men, τ = 0.491; women, τ = 0.388) and echo intensity (total participants, τ = −0.239; men, τ = −0.318; women, τ = −0.188). In the multiple regression analysis, BMI was independently and significantly associated with the quadriceps thickness (total participants, β = 0.535; men, β = 0.548; women, β = 0.519) and echo intensity (total participants, β = −0.287; men, β = −0.398; women, β = −0.210).

Conclusion

This study indicated that older inpatients with a higher BMI have greater muscle mass and less intramuscular adipose tissue of the quadriceps. These results suggested that a higher BMI in older inpatients is related to higher quadriceps muscle quality.

Abbreviations

ADL

activities of daily living

BMI

body mass index

MRI

magnetic resonance imaging

FILS

Food Intake Level Scale

CRP

C-reactive protein

GNRI

Geriatric Nutritional Risk Index

UCCI

updated Charlson Comorbidity Index

FIM

functional independence measure

Introduction

Loss of muscle mass is related to a decrease in activities of daily living (ADL) (1) and an increase in mortality rate (2). Recently, loss of muscle mass and an increase in intramuscular adipose tissue with age have been reported (3). Furthermore, an increase in intramuscular adipose tissue has been related to a decrease in muscle strength (4), gait ability (5), and ADL (6, 7); hip fracture (8); and an increase in mortality rate (9) compared with loss of muscle mass. In other words, the assessment of intramuscular adipose tissue in addition to muscle mass is important when considering the prognosis of older individuals. In fact, the European Working Group on Sarcopenia in Older People 2 recommended the assessment of muscle quality, including intramuscular adipose tissue, to diagnose sarcopenia (10).

Many studies (11, 12, 13) reported that the prognosis of patients with obesity is better than that of underweight patients, and this phenomenon is known as “obesity paradox.” However, the cause of this paradox remains unclear. A recent study (14) reported that an increase in body mass index (BMI) is related to an increase in muscle mass and a decrease in intramuscular adipose tissue of the quadriceps in chronic stroke survivors. Considering the aforementioned knowledge, an increase in muscle mass and decrease in intramuscular adipose tissue (i.e., high muscle quality) may be observed in older inpatients with higher BMI, and these factors may be one of the causes of the obesity paradox. However, the complex relationship between muscle quality and BMI in older inpatients who experience various conditions affecting their muscle mass and intramuscular adipose tissue, including nutritional deficiencies, inflammatory conditions, decreased ADL, and swallowing problems (5, 6, 7, 15, 16, 17, 18) is unclear. Understanding this relationship will emphasize the importance of weight management in older inpatients, from the perspective of muscle quality. Therefore, this study aimed to examine the relationship between muscle mass, intramuscular adipose tissue, and BMI in older inpatients.

Materials and Methods

Study design and participants

This cross-sectional study included older inpatients referred to the Department of Rehabilitation at Kasei Tamura Hospital. The hospital has post-acute and convalescent rehabilitation wards. Patients aged < 65 years and those who lacked data were excluded from the study. A total of 453 inpatients were recruited for the study. Of these, 40 patients aged < 65 years (n = 34) or those who lacked necessary data (n = 6) were excluded. Consequently, 413 inpatients (186 men and 227 women) participated in the study. All participants underwent rehabilitation performed by a physical, occupational, or speech therapist for 40–60 min/day, 5–6 days/week. All participants provided informed consent prior to their participation in the study. The study was approved by the ethics committee of our institution.

Outcome measures

The primary outcome measures were muscle mass and intramuscular adipose tissue of the quadriceps. The following characteristics were also measured: disease, age, sex, subcutaneous fat mass in the thigh, swallowing ability, inflammatory and nutritional status, comorbidities, number of medications, ADL, and days from onset disease. Most inpatients at our hospital were admitted from another acute-phase hospital. For these patients, the number of days from disease onset was measured as the total length of stay in both hospitals.

BMI measurement

BMI was calculated by dividing the weight (kg) by the height in meters squared (m²). Weight was measured in the standing position or while sitting on a wheelchair in accordance with the participants' condition using a digital scale and was recorded to the nearest 0.1 kg. Height was measured in the standing position using a stadiometer and recorded to the nearest 0.5 cm. Height was measured using a tape measure in the supine position in patients who could not stand on the stadiometer. Weight and height were measured by a trained physical therapist, occupational therapist, nurse, or medical technologist. In addition, the weight and stadiometer scales were regularly calibrated to obtain accurate measurements.

Measurements of muscle mass and intramuscular adipose tissue in the quadriceps and subcutaneous fat mass in the thigh

Transverse ultrasound images were obtained using a B-mode ultrasound system (NanoMaxx; SonoSite Japan, Tokyo, Japan) with a linear-array probe (NanoMaxx). The muscle mass and intramuscular adipose tissue of the rectus femoris and vastus intermedius of all participants were assessed based on the muscle thickness and echo intensity (3, 4, 5, 6, 7, 14, 15, 16, 19), respectively. The validity of muscle mass and intramuscular adipose tissue measurements using ultrasound has been confirmed in recent studies using magnetic resonance imaging (MRI) (20, 21, 22). Images of the rectus femoris and vastus intermedius were obtained at 30% of the distance from the anterior superior iliac spine to the proximal end of the patella (5, 6, 7, 14, 15, 16, 19). The participants lay in the supine position with their lower limbs relaxed, while a water-soluble transmission gel was applied to the skin surface of the thigh. The probe was pressed lightly against the skin to prevent muscle deformation. All ultrasound images were recorded by the same investigator. The thickness of the rectus femoris was determined as the distance between the superficial adipose tissue-muscle interface and the deep muscle-muscle interface (5, 6, 7, 14, 15, 16, 19), while that of the vastus intermedius was determined as the distance between the superficial muscle-muscle interface and the bone-muscle interface (5, 6, 7, 14, 15, 16, 19). Echo intensity was measured in the regions of interest selected to include as much muscle as possible, while avoiding the bone and surrounding fascia (5, 6, 7, 14, 15, 16, 19). Muscle thickness and echo intensity were measured using the ImageJ 1.49 software (National Institutes of Health, Bethesda, MD, USA) (4, 5, 6, 7, 14, 15, 16, 19). Echo intensity was determined by performing a computer-assisted 8-bit gray-scale analysis, and the mean echo intensity of the regions of interest was rated from 0 (black) to 255 (white) (3, 4, 5, 6, 7, 14, 15, 16, 19). A higher echo intensity indicates greater intramuscular adipose tissue (23).

The sum of the thicknesses of the rectus femoris and vastus intermedius was used as a measure of quadriceps thickness. The mean thicknesses of the right and left quadriceps were included in the analysis. The echo intensity of the quadriceps was calculated as the mean echo intensity of the rectus femoris and vastus intermedius. Mean echo intensities of the right and left quadriceps were used in the analysis. Measurements of the rectus femoris and vastus intermedius muscle thicknesses and echo intensities have relatively high reliability (intraclass correlation coefficients [1.1] = 0.857–0.959) (19). Subcutaneous fat mass in the thigh was assessed based on subcutaneous fat thickness. Subcutaneous fat thickness was defined as the distance between the dermis and adipose tissue interface and the muscle-adipose tissue interface (5, 6, 7, 14, 15, 16, 19). The mean subcutaneous fat thickness of the right and left thighs was used in the analysis.

Measures of other characteristics

Swallowing ability was assessed using the Food Intake Level Scale (FILS) (24), a 10-point observer-rated scale. A higher FILS score indicates a higher swallowing ability. The inflammatory status was assessed based on C-reactive protein (CRP) levels. Nutritional status was assessed using the Geriatric Nutritional Risk Index (GNRI) (25). The GNRI score was calculated using the following formula: GNRI = (14.89 × serum albumin [g/dl]) + (41.7 × weight [kg]/ideal body weight) (25). Ideal body weight was defined as a BMI of 22.0 kg/m² (26). If the weight/ideal body weight was ≥ 1.0, the ratio was set to 1 (25). The comorbidities were evaluated using the updated Charlson Comorbidity Index (UCCI) (27). ADL was assessed using the Functional Independence Measure (FIM) (28). This assessment tool consists of 13 motor items and 5 cognitive items. The motor-FIM items were used in this study. Each item was scored from 1 to 7 based on the amount of assistance required. The motor-FIM score ranges from 13 to 91, with higher scores indicating higher ADL.

Statistical analysis

All statistical analyses were performed using SPSS version 24 software (IBM SPSS Japan, Tokyo, Japan). All variables were assessed for normality using the Shapiro-Wilk test. Parametric data are reported as mean ± standard deviation, whereas nonparametric data are presented as median (interquartile range [IQR]).

To examine the relationship between quadriceps thickness and echo intensity and BMI in total participants and each sex, the Kendall rank correlation coefficient was used. Multiple regression analysis (forced entry method) was performed to examine whether BMI was independently and significantly related to quadriceps thickness and echo intensity, even after adjusting for other variables in total participants and each sex. BMI, age, sex (male = 1, female = 0), disease (stroke, fracture, pneumonia, and others, reference = stroke), days from onset disease were set as independent variables in multiple regression analyses for the models including total participants. The independent variables in multiple regression analyses for the models including males and females were BMI, age, disease (stroke, fracture, pneumonia, and others, reference = stroke), and days from onset disease. The variance inflation factor was used to assess multicollinearity. A variance inflation factor value > 10 was considered to indicate the presence of multicollinearity. Statistical significance was set at p < 0.05. In addition, we calculated the effect size (f²) of the multiple regression analysis using the equation R²/(1 − R²), the statistical power of the analysis based on f², an alpha error of 0.05, the total sample size, and the number of predictor variables. Statistical power was calculated using G* Power version 3.1.9.2 (Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany).

Results

In this study, the median (IQR) BMI values of males and females were 19.7 (17.6–22.3) kg/m² and 20.0 (17.4–22.6) kg/m², respectively. Table 1 shows the characteristics of total participants, including men and women.

Table 1.

Characteristics of total participants, including men and women

	Total (n = 413)	Men (n = 186)	Women (n = 227)
Age, years	83 (77–88)	82 (76–87)	84 (78–88)
Height, cm	152 (146–161)	162 (155–165)	148 (144–150)
Body weight, kg	46.5 (39.6–54.0)	51.0 (44.8–57.1)	43.6 (36.5–50.0)
Body mass index, kg/m2	19.9 (17.5–22.6)	19.7 (17.6–22.3)	20.0 (17.4–22.6)
Disease
Stroke, n (%)	61 (14.8)	30 (16.1)	31 (13.7)
Fracture, n (%)	143 (34.6)	34 (18.3)	109 (48.0)
Pneumonia, n (%)	64 (15.5)	40 (21.5)	24 (10.6)
Others, n (%)	145 (35.1)	82 (44.1)	63 (27.8)
Days from onset disease, days	26 (12–39)	26 (14–41)	25 (11–38)
Quadriceps thickness, cm	1.2 ± 0.5	1.3 ± 0.5	1.1 ± 0.4
Quadriceps echo intensity (gray-scale range, 0–255)	84.6 ± 21.7	81.0 ± 20.2	87.6 ± 22.5
Subcutaneous fat thickness of the thigh, cm	0.4 (0.3–0.5)	0.4 (0.2–0.5)	0.4 (0.3–0.6)
Food Intake Level Scale score	8 (7–9)	8 (7–9)	8 (7–9)
C-reactive protein level, mg/dl	0.5 (0.4–1.8)	0.6 (0.4–2.1)	0.4 (0.4–1.5)
Serum albumin level, g/dl	3.4 (3.0–3.7)	3.3 (3.0–3.6)	3.4 (3.1–3.7)
Geriatric Nutritional Risk Index score	87.6 (79.9–93.8)	87.2 (78.4–93.7)	87.9 (81.2–94.4)
Updated Charlson Comorbidity Index score	2(0–3)	2 (1–4)	2 (0–3)
Number of medications	7 (5–10)	7 (4–9)	7 (5–10)
Motor-FIM score	41.0 (20.5–62.0)	41.5 (19.8–63.0)	41.0 (21.0–61.0)

Data are presented as median (interquartile range), n (%), or mean ± standard deviation; FIM, Functional Independence Measure.

Table 2 presents the results of the correlation analysis. BMI was significantly related to quadriceps thickness (total participants, τ = 0.431; men, τ = 0.491; women, τ = 0.388) and echo intensity (total participants, τ = −0.239; men, τ = −0.318; women, τ = −0.188) in total participants and both sexes. Tables 3, 4, and 5 show the results of the multiple regression analysis for quadriceps thickness and echo intensity for total participants, men, and women, respectively. No multicollinearity was observed between the independent variables in any of the multiple regression analyses. In the multiple regression analyses for the models including total participants, BMI, age, sex, disease, and days from onset disease were independently and significantly associated with quadriceps thickness (R² = 0.445, f² = 0.802, statistical power = 1.000) and BMI, age, sex, and days from onset disease were independently and significantly associated with quadriceps echo intensity (R² = 0.256, f² = 0.344, statistical power = 1.000) (Table 3). In the multiple regression analyses for the models including males, BMI, age, disease, and days from onset disease were independently and significantly associated with quadriceps thickness (R² = 0.470, f² = 0.887, statistical power = 1.000) and echo intensity (R² = 0.325, f² = 0.481, statistical power = 1.000) (Table 4). In the multiple regression analyses for the models including females, BMI, age, disease, and days from onset disease were independently and significantly associated with quadriceps thickness (R² = 0.425, f² = 0.739, statistical power = 1.000) and BMI, age, and days from onset disease were independently and significantly associated with quadriceps echo intensity (R² = 0.202, f² = 0.253, statistical power = 1.000) (Table 5).

Table 2.

Relationship between quadriceps thickness and echo intensity and body mass index in total participants (n = 413), men (n = 186), and women (n = 227)

	Body mass index (Kendall rank correlation coefficient)	P value
Total participants
Quadriceps thickness	0.431	< 0.001
Quadriceps echo intensity	−0.239	< 0.001
Men
Quadriceps thickness	0.491	< 0.001
Quadriceps echo intensity	−0.318	< 0.001
Women
Quadriceps thickness	0.388	< 0.001
Quadriceps echo intensity	−0.188	< 0.001

Table 3.

Multiple regression analyses adjusted with age, sex, disease, and days from onset disease for assessing the relationship between quadriceps thickness and echo intensity and body mass index in total participants

	Quadriceps thickness		Quadriceps echo intensity
	β	P value	β	P value
Body mass index	0.535	< 0.001	−0.287	< 0.001
Age	−0.228	< 0.001	0.298	< 0.001
Sex	0.144	< 0.001	−0.127	0.006
Disease
Stroke	(Reference)	-	(Reference)	-
Fracture	−0.107	0.059	0.068	0.302
Pneumonia	−0.141	0.005	0.101	0.082
Others	−0.150	0.008	0.090	0.164
Days from onset disease	−0.149	< 0.001	0.186	< 0.001

β, standardized partial regression coefficient

Table 4.

Multiple regression analyses adjusted with age, disease, and days from onset disease for assessing the relationship between quadriceps thickness and echo intensity and body mass index in men

	Quadriceps thickness		Quadriceps echo intensity
	β	P value	β	P value
Body mass index	0.582	< 0.001	−0.365	< 0.001
Age	−0.178	0.003	0.268	< 0.001
Disease
Stroke	(Reference)	-	(Reference)	-
Fracture	−0.154	0.036	0.184	0.026
Pneumonia	−0.137	0.078	0.156	0.074
Others	−0.184	0.024	0.176	0.057
Days from onset disease	−0.130	0.024	0.223	0.001

β, standardized partial regression coefficient

Table 5.

Multiple regression analyses adjusted with age, disease, and days from onset disease for assessing the relationship between quadriceps thickness and echo intensity and body mass index in women

	Quadriceps thickness		Quadriceps echo intensity
	β	P value	β	P value
Body mass index	0.523	< 0.001	−0.244	< 0.001
Age	−0.277	< 0.001	0.322	< 0.001
Disease
Stroke	(Reference)	-	(Reference)	-
Fracture	−0.055	0.500	−0.027	0.781
Pneumonia	−0.152	0.022	0.074	0.339
Others	−0.089	0.258	0.009	0.922
Days from onset disease	−0.144	0.008	0.142	0.026

β, standardized partial regression coefficient

Discussion

Our findings indicated that older inpatients with a higher BMI have greater muscle mass and less intramuscular adipose tissue of the quadriceps. These results suggested that a higher BMI in older inpatients is related to higher quadriceps muscle quality.

Many studies (11, 12, 13, 29) have reported a good prognosis (i.e., greater improvement in ADL and better survival rate) in patients with obesity. Considering that the loss of muscle mass and increase in intramuscular adipose tissue are related to a decrease in motor function (4, 5, 19) and ADL (6, 7) and an increase in mortality rate (9), higher muscle quality in older inpatients with a higher BMI, suggested by our study, could be related to the cause of the obesity paradox.

Previous studies have reported that weight loss in community-dwelling older people is related to a higher risk of mortality (30) and that weight loss in convalescent older stroke patients is related to a decrease in ADL (31). Therefore, the weight of older persons should be carefully monitored, and weight loss must be avoided. The findings of our study are considered to be contributed to a deeper understanding of the importance of weight management in older inpatients from the perspective of muscle quality.

Weight gain is attributed to changes in body fat and muscle mass (32, 33, 34). However, it is yet to be determined if intramuscular adipose tissue in older inpatients is related to weight changes. The current study showed a negative relationship between BMI and intramuscular adipose tissue, which suggests that weight gain could contribute to decreasing intramuscular adipose tissue in older inpatients. However, our results cannot confirm a causal relationship, because this study had a cross-sectional design.

Muscle mass and intramuscular adipose tissue of the quadriceps in older inpatients are closely related to gait ability (5) and ADL (6, 7) as well as swallowing ability (15) and malnutrition risk (16). In addition, loss of muscle mass with aging and disuse particularly occurs in the quadriceps muscles of the upper and lower extremities (35, 36). More recently, the International Society of Physical and Rehabilitation Medicine's special interest group on sarcopenia (ISarcoPRM) adopted the assessment of quadriceps thickness, using ultrasound imaging, as an indicator of muscle mass in the diagnosis criteria of sarcopenia (37). With this considered, a strength of our study was targeting the quadriceps in examining the muscle quality of older inpatients.

This study had several limitations. Firstly, it was cross-sectional in nature. Thus, we were unable to determine the causal relationship between the changes in weight, muscle mass, and intramuscular adipose tissue. Secondly, although MRI and computed tomography are considered the “gold standard” for assessing muscle quality, ultrasound is preferred because it is easily accessible, easy to use, and inexpensive. In contrast, echo intensity has been shown to show both intramuscular adipose tissue and fibrotic tissue (38). A previous study conducted in golden retrievers (38) reported that echo intensity is more strongly related to fibrotic tissue than intramuscular adipose tissue determined by muscle biopsy. However, muscle biopsy from patients with various neuromuscular diseases indicates that echo intensity is more strongly related to intramuscular adipose tissue than to fibrosis tissue (39); intramuscular adipose tissue in the quadriceps determined by MRI was significantly correlated with echo intensity (21, 22). Thirdly, the days from the onset of disease of the participants in this study were relatively long. In addition, heterogeneity of diseases was also observed. Additional research that targets each disease in an acute setting will be required. Finally, according to the BMI classifications of the World Health Organization (40), the number of participants in the underweight, normal weight, overweight, and obese categories, including men and women, were 64 (34.4%), 105 (56.5%), 15 (8.1%), and 2 (1.1%) and 76 (33.5%), 126 (55.5%), 19 (8.4%), and 6 (2.6%), respectively. This indicates that the majority of participants were in the underweight or normal weight range. BMI is an important indicator of nutrition status (41). In fact, the median (IQR) GNRI value of the total participants in this study was 87.6 (79.9–93.8), and many participants had a malnutrition risk. Therefore, further studies that target participants in the overweight and obese ranges, who may have no malnutrition risk, are required.

Conclusions

This study showed that older inpatients with a higher BMI have greater muscle mass and less intramuscular adipose tissue of the quadriceps. These results suggested that a higher BMI in older inpatients is related to higher quadriceps muscle quality.

Statement of Authorship

(1) Conception and design of the study, acquisition of data, or analysis and interpretation of data; NA, MK, TH, RT, KT, AH, HM. (2) Drafting of the article; NA, MK, TH, RT, KT, AH, HM. (3) Final approval of the version to be submitted; NA, MK, TH, RT, KT, AH, HM.

Disclosure of interest

The authors declare that there is no conflict of interest.

Funding sources

This work was supported by JSPS KAKENHI Grant Number JP17K18294 and JP20K19661.