ORIGINAL ARTICLE

Low body mass index is associated with impaired qualityof life in patients with rheumatoid arthritis

Wataru FUKUDA,1 Atsushi OMOTO,1 Tamaki OHTA,1 Saori MAJIMA,1 Toshihiro KIMURA,1

Toru TANAKA,1 Masataka KOHNO2 and Yutaka KAWAHITO2

1Department of Diabetes, Endocrinology and Rheumatology, Japanese Red Cross Kyoto Daiichi Hospital, and 2Inflammation andImmunology, Kyoto Prefectural University of Medicine, Kyoto, Japan

AbstractAim: To investigate the relationship between quality of life (QOL) and rheumatoid chachesia, malnutrition in

patients with rheumatoid arthritis (RA).

Methods: EuroQol Group 5-Dimension Self-Report Questionnaire (EQ5D) and Japanese Health Assessment

Questionnaire (JHAQ) scores, body mass index (BMI), arm muscle area (AMA) and clinical indicators were mea-

sured in 385 RA patients. One-way analysis of variance for obtained data was conducted among three groups:

131 with low BMI (< 20), 163 with moderate (20–25) and 91 with high BMI (�25). Then multiple regression

analyses for JHAQ and EQ5D scores with nutritional and clinical indicators as independent variables were

performed.

Results: EQ5D and JHAQ scores were significantly lower and higher, respectively, in the low BMI group than

those in the moderate BMI group. Clinical indicators including doses of corticosteroid were similar among the

three groups except for disease duration. Disease activity score (DAS) 28, disease duration, C-reactive protein

and AMA were significant variables in the regression model for EQ5D.

Conclusion: Low BMI deteriorates the QOL of RA patients. Muscle protein loss apparently leads to a reduction

in BMI and QOL.

Key words: arm muscle area (AMA), body mass index (BMI), muscle protein, quality of life (QOL),

rheumatoid arthritis (RA), rheumatoid chachexia.

INTRODUCTION

It is a known fact that low body mass index (BMI) is

more common in patients with rheumatoid arthritis

(RA) when compared to that in the healthy popula-

tion.1 Using anthropometric measurements, we have

previously reported that RA patients have a characteris-

tic malnutrition profile with mild obesity in the early

period of illness. In addition, BMI and visceral and

skeletal muscle protein levels decrease as the disease

progresses.2 Apparently, the low BMI in RA patients is

primarily due to rheumatoid cachexia, loss of lean body

mass, and metabolic disorders caused by an increase in

the levels of proinflammatory cytokines such as tumor

necrosis factor (TNF)-a and interleukin (IL)-1b.3,4 The

reduction of BMI in RA patients is reportedly a predic-

tor of poor functional and life prognosis, particularly in

relation to cardiovascular mortality.5–7

Numerous studies have demonstrated that quality of

life (QOL) is lower in RA patients compared to that in

the healthy population. Sustained arthralgia and general

fatigue due to active inflammation are believed to play a

role in deterioration of QOL in RA patients; physical

disability and psychological disorders that result from

Correspondence: Dr Wataru Fukuda, Department of Diabetes,Endocrinology and Rheumatology, Japanese Red Cross KyotoDaiichi Hospital, 15-749 Honmachi, Higashiyama-ku, KyotoCity, Kyoto 605-0981, Japan.Email: wataru-fukuda@kyoto1-jrc.org

© 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd

International Journal of Rheumatic Diseases 2013; 16: 297–302

continuous inflammation may also contribute.8,9

Although the adverse effects of malnutrition on QOL

and prognosis have been investigated for certain disor-

ders such as infectious diseases10 and renal diseases,11 to

our knowledge, reports that investigated a relationship

between QOL and low BMI in RA patients have not been

published. A relationship between QOL and BMI in

arthritis patients has been discussed with a focus on high

BMI, obesity and deterioration of QOL.12,13 The present

cross-sectional study investigated the QOL of RA patients

from the perspective of malnutrition. Thus, we studied

the influence of BMIs of RA patients with the Japanese

Health Assessment Questionnaire (JHAQ),14 which indi-

cates functional disability, and the EuroQol Group

5-Dimension Self-Report Questionnaire (EQ5D).15–17

SUBJECTS AND METHODS

We studied 385 RA patients who regularly visited the

outpatient clinic at the Department of Diabetes, Endo-

crinology and Rheumatology at the Japanese Red Cross

Kyoto Daiichi Hospital, Japan. Written informed con-

sent for study participation was obtained from all

patients. All patients had a diagnosis of RA as per the

1987 American Rheumatism Association criteria.18

The following assessments were performed for all

patients: EQ5D, JHAQ, nutritional indices, and clinical

indicators; namely, age, sex, duration from RA onset

(years and months/12), C-reactive protein (CRP) levels

(mg/L), disease activity score 28 (DAS28)19 and dosages

of prednisolone (PSL) and methotrexate (MTX). The

EQ5D has been validated as an appropriate tool for the

evaluation of QOL in Japanese individuals.16,17

Nutritional status was assessed by measuring anthro-

pometric and biochemical parameters. Anthropometric

parameters included height (H), weight (W), mid-upper

arm circumference (AC), and triceps skinfold thickness

(TSF), which was measured at the mid-point between

the acromion process and the tip of the olecranon with

a Harpenden caliper. AC measurements were performed

at the same level with an insertion tape. Based on these

measurements, BMI and arm muscle area (AMA) were

calculated as follows20:

BMI ¼ W ðkgÞ=H ðmÞ2

AMA ¼ ðAC ðcmÞ � p� TSF ðcmÞÞ2=4p:

As body composition is influenced by gender and

age, we calculated the percentages of AMA (%AMA)

and TSF (%TSF) to age- and sex-adjusted mean val-

ues, which were obtained from the Japanese Anthro-

pometric Reference Data21 for comparative analysis.

Nutritional status was biochemically evaluated on

the basis of serum albumin and total cholesterol

levels.

The study was divided into two parts as follows. (i)

The aforementioned data were compared among three

groups formed on the basis of their BMI values: low

(< 20; n = 131), moderate (20–25; n = 163), and high

BMI groups (� 25; n = 91). Stratification of BMI was

defined according to previous reports.1,6,7 (ii) Stepwise

multivariate regression analyses for the JHAQ and

EQ5D scores were conducted using the nutritional and

clinical indicators of RA. Age, sex, disease duration,

DAS28, %TSF, %AMA, and CRP, serum albumin, total

cholesterol levels and dosages of PSL and MTX were

selected as independent variables, and ln (1 + JHAQ

score) and ln (2 � EQ5D score) were calculated as

dependent variables.

Statistical analysisIn comparisons among the three groups stratified as per

BMI values, a one-way analysis of variance (ANOVA) was

conducted first for continuous variables with normal

distributions. When the P-value for this overall compar-

ison was significant (< 0.05), post hoc pairwise compari-

sons were made using Tukey’s honestly significant

differences test. Kruskal–Wallis one-way ANOVA and Wil-

coxon tests for post hoc comparisons were performed for

nonparametric variables. All statistical analyses were

performed using JMP software version 8.0.1 (2009, SAS

Institute, Cary, NC, USA).

RESULTSComparisons among the three groupsstratified as per BMI valuesThe average age was not significantly different among

the three groups, but the proportion of males was

higher in the high BMI group (P = 0.002 vs. moderate

BMI, P = 0.013 vs. high BMI group). Both %AMA and

%TSF increased significantly with increase in BMI (each

P < 0.001 vs. other two groups). In patients with mod-

erate BMI values, the average value of AMA was

decreased to 91.21% of the normal value, but that of

TSF equaled 104.11% of the normal value. In the high

BMI group, the average value of AMA was close to the

standard at 102.50%, and TSF was significantly elevated

at 142.90% (Table 1). No significant differences were

found in DAS28 and CRP serum albumin levels and

298 International Journal of Rheumatic Diseases 2013; 16: 297–302

W. Fukuda et al.

average dose of PSL and MTX between the three groups,

but disease duration (mean, 11.37 years) was signifi-

cantly longer in the low BMI group than that in the

other two groups (P = 0.010 vs. moderate BMI,

P < 0.001 vs. high BMI group) (Fig. 1c,d). The average

EQ5D and JHAQ scores in the low, moderate and high

BMI groups were 0.67, 0.73 and 0.71, and 0.78, 0.53

and 0.61, respectively. This indicated that the EQ5D

score and JHAQ score were significantly lower and

higher, respectively, in the low BMI patients than those

in the moderate BMI patients (P = 0.013, P < 0.001,

respectively) (Fig. 1a,b).

Multiple regression analysis: dependentvariables of ln (1 + JHAQ score) and ln(2 � EQ5D score); independent variables ofnutritional and clinical indicatorsFive independent variables were selected by forward

stepwise regression analysis for each dependent variable

(Table 2). The significant variables in the regression

models of ln (2 � EQ5D score) were DAS28

(b = 0.5600), RA duration (b = 0.1510), %AMA

(b = �0.1383), and CRP levels (b = �0.1145). Disease

duration (b = �0.2457) and DAS28 (b = 0.4828)

strongly contributed to ln (JHAQ + 1). The age of

patients (b = 0.1897) and %AMA (b = 0.1036) were

also significant factors in the regression model for the

JHAQ score. %TSF, dose of prednisolone and other

variables exhibited no significant contribution to both

the EQ5D and JHAQ scores.

DISCUSSION

In the present study, the EQ5D score was significantly

lower in the low BMI group than that in the moderate

BMI group, which exhibited the highest score among

the three groups. Similarly, the JHAQ score was signifi-

cantly lower in the low BMI group than that in the

moderate BMI group. This means that low BMI, which

is an indicator of malnutrition, is associated with the

deterioration of QOL in RA patients. Conversely, the

indices for disease activity were not significantly differ-

ent among the three groups. The disease duration of RA

was significantly longer in the low BMI group than that

in the other two groups. These findings suggest that

arthralgia and fatigue accompanying severe inflamma-

tion in RA are not major factors contributing to the

worsening of QOL in RA patients with low BMI. How-

ever, joint destruction and muscle weakness caused by

persistent inflammation do appear to be possible causa-

tive factors for the deterioration of QOL in the low BMI

group. However, vascular risk6 and comorbidity scores7

are believed to be high in RA patients with low BMI,

suggesting that comorbidities, including cardiovascular

diseases, may impair QOL.

Multiple regression analysis revealed that the quantity

of muscle protein is an independent contributing factor

for QOL in RA patients. Among the elements constitut-

ing the human body, muscle protein (4.3–9.3%) and

subcutaneous fat (4.4–9.0%) correlate well with

BMI.20,22 In the present study, we observed that the

Table 1 Demographic and clinical characteristics of the RA patients

Low BMI Normal BMI High BMI Average [total]

Number 131 191 63 [385]

Male/female 109/22 146/45 39/24 [294/91]

Age (SD) 62.06 (13.90) 63.63 (12.25) 62.33 (9.87) 62.89 (12.49)

BMI (SD) 8.46 (1.10) 22.23 (1.38) 27.23 (1.95) 21.77 (3.27)

%AMA (SD) 79.6 (13.3) 91.2 (16.0) 102.5 (18.1) 88.80 (17.6)

%TSF (SD) 69.3 (31.4) 104.1 (41.4) 142.9 (55.8) 98.61 (48.1)

Disease duration (SD) 11.3 (9.2) 8.4 (8.9) 8.1 (8.2) 9.4 (9.2)

DAS28 (SD) 3.66 (1.16) 3.42 (1.23) 3.61 (1.13) 3.53 (1.19)

CRP (SD) 8.8 (1.22) 11.4 (2.01) 9.8 (1.15) 10.2 (1.65)

Albumin (SD) 4.05 (0.43) 4.07 (0.36) 4.17 (1.13) 4.077 (1.19)

Prednisolone (mg/day) 1.75 (2.48) 2.10 (2.71) 2.50 (3.03) 2.05 (2.70)

Methotrexate (mg/week) 3.70 (3.47) 3.62 (3.52) 3.59 (3.56) 3.64 (3.50)

Average age, DAS28, CRP and serum albumin levels, dose of prednisolone and methotrexate are not significantly different among the three groupsstratified as per BMI, although the ratio of males is higher in the high BMI group. Both %AMA and %TSF increase significantly with increase in BMI.In patients with normal BMI, the mean %AMA is 91.2% of the normal value, but mean %TSF is 104.1% of the normal value. Although the averagevalue of %AMA (102.5%) is close to the standard, that of %TSF (142.9%) is significantly elevated in the high BMI group. BMI, body mass index; %AMA, age- and sex-adjusted mean value of the percentage of arm muscle area; %TSF, age- and sex-adjusted mean value of the percentage of tricepsskinfold thickness; DAS28, disease activity score 28; CRP, C-reactive protein; SD, standard deviation.

International Journal of Rheumatic Diseases 2013; 16: 297–302 299

Low body mass and quality of life in RA

quantities of both muscle protein, that is, %AMA, and

subcutaneous fat, that is, %TSF, were decreased in the

RA patients with low BMI. Consequently, we needed to

clarify which of these factors was the major contributor

to the reduced QOL observed in the low BMI group.

The results of multivariate regression analysis indicated

(a) (b)

(c) (d) (e)

Figure 1 Comparison of indicatorsrelated to QOL and disease activityamong the three groups stratified as perbody mass index (BMI). The averageEQ5D score and JHAQ score are signifi-cantly lower (a) and higher (b), respec-tively, in the low BMI group than thosein the normal BMI group. The diseaseduration of RA is significantly longer inthe low BMI group than that in the othertwo groups (c), although DAS28 andserum albumin levels are not differentamong the three groups (d–e). QOL,quality of life; BMI, body mass index;EQ5D, the EuroQol Group 5-DimensionSelf-Report Questionnaire; JHAQ, theJapanese Health Assessment Question-naire; DAS28, disease activity score 28.

Table 2 Multiple regression analysis: dependent variables are EQ5D and JHAQ scores, and independent variables are nutritional

and clinical indicators

Analysis Independent

variable

Estimate b P-value

ln (2 � EQ5D score)

r2 = 0.356

P < 0.0001

DAS28 0.0795 0.5601 <0.0001RA duration 0.0028 0.1510 0.0005

%AMA �0.1332 �0.1383 0.0016

CRP �0.00117 �0.1145 0.0170

%TSF �0.0269 �0.0767 0.0664

ln (1 + JHAQ score)

r2 = 0.377

P < 0.0001

DAS28 0.1537 0.4828 <0.0001RA duration 0.0102 0.2457 <0.0001Age 0.0058 0.1897 <0.0001%AMA �0.2237 �0.1036 0.0159

CRP �0.00189 �0.0824 0.0795

Independent variables selected by a forward stepwise method are listed in the table. The significant variables in the regression models of ln(2 � EQ5D score) are DAS28, RA duration, CRP levels and %AMA. Disease duration, DAS28 and %AMA strongly contribute to ln (JHAQ + 1). Patientage is a significant factor in the regression model for the JHAQ but not for the EQ5D score. %TSF and other variables exhibit no significant contributionto both the EQ5D and JHAQ scores. %AMA, age- and sex-adjusted mean value of the percentage of arm muscle area; %TSF, age- and sex-adjustedmean value of the percentage of triceps skinfold thickness; DAS28, disease activity score 28; CRP, C-reactive protein; SD, standard deviation.

300 International Journal of Rheumatic Diseases 2013; 16: 297–302

W. Fukuda et al.

that the quantity of muscle protein was significantly

correlated with QOL independently of disease activity,

which was represented by DAS28 and CRP levels and

disease duration. In other words, decreased subcutane-

ous fat was not a contributing factor to the deteriora-

tion of QOL in RA patients with low BMI; however,

decreased muscle protein is likely to be a contributing

factor. Various factors appear to contribute to the mech-

anism that decreases muscle protein and aggravates

QOL in RA patients. Loss of muscle protein can cause

physical disability and interfere with daily activities and

ambulation, which was reflected in the increased JHAQ

and decreased EQ5D scores of our RA patients. Consid-

ering that the loss of muscle protein is thought to be a

result of increased pro-inflammatory cytokine levels,

metabolic disturbances caused by such cytokines may

be related to the impairment of QOL.

With the knowledge that maintaining the quantity of

muscle protein is essential in minimizing the decrease

in BMI and deterioration of QOL in RA patients, treat-

ments should aim to recover and prevent further loss of

muscle protein. As disease duration appears to be asso-

ciated with a decrease in muscle protein quantity or

BMI, early therapeutic intervention and long-term con-

trol of disease activity are likely to be important.

Although corticosteroids are known to bring catabolism

of protein and accumulation of fat to the body, the

dose of prednisolone does not show significant influ-

ence on either BMI or QOL in our study. This may be

the result of anti-inflammatory effects of corticosteroid

offsetting its less preferable metabolic effects. In addi-

tion, biologic agents that suppress TNF directly may be

more effective than synthetic anti-rheumatic drugs,

although this has not been demonstrated in short-term

studies.23,24 In addition, exercise and diet therapy

should be considered to maintain the quantity of mus-

cle protein, although further studies on the method and

effect of such interventions are warranted. We suppose

that a diet for preventing lipid accumulation and mus-

cle protein loss should be high-protein and low-lipid

with a controlled carbohydrate content, and speculate

that this diet could lead to an improvement in QOL in

RA patients by preventing the loss of muscle protein

and maintaining BMI within the normal range.

A limitation of our study is that it was conducted

using Japanese patients without considering sex, race,

social circumstances and RA treatments except medica-

tion. It is known that the evaluation of BMI is influ-

enced by sex, age, race and social circumstances. In

addition, we did not consider how RA treatments,

except corticosteroid and methotrexate, including

exercise diet and surgical intervention, affect the nutri-

tional state. These topics should be clarified in future

studies.

CONCLUSIONS

Quality of life (QOL) was deteriorated in RA patients

with low BMI, which was evident from the calculated

EQ5D and JHAQ scores, when compared with that in

patients with moderate BMI, although there was no dif-

ference in disease activity indicators between the

groups.

Loss of muscle protein, but not of subcutaneous fat,

plays an important role in the deterioration of QOL in

RA patients independently of disease activity and

duration.

ACKNOWLEDGEMENTS

This study was supported by a research grant from the

Ministry of Health, Labour and Welfare of Japan.

CONFLICT OF INTERESTS

None.

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