Download Abnormal body composition phenotypes in Vietnamese women with

RHEUMATOLOGY
Rheumatology 2011;50:1250–1258
doi:10.1093/rheumatology/ker004
Advance Access publication 3 February 2011
Original article
Abnormal body composition phenotypes in
Vietnamese women with early rheumatoid arthritis
Hanh-Hung Dao1,2, Quan-Trung Do3 and Junichi Sakamoto1
Abstract
Objectives. To characterize body composition phenotypes using a dual-energy X-ray absorptiometry
(DXA) method and to explore factors potentially contributing to alterations in body composition in
Vietnamese women with early RA.
Methods. A total of 105 women with early RA (disease duration 43 years) and 105 age-matched healthy
women underwent physical examination, total and regional lean mass (LM) and fat mass (FM) with DXA.
The 28-joint DAS (DAS-28) and disability using HAQ score, nutrition, physical activity and medications
were recorded.
Results. Means of weight and BMI were similar in RA patients and controls, but means of total body and
trunk FM in RA patients were higher: 19.1 vs 16.9 kg (P = 0.007) and 10.1 vs 8.1 kg (P = 0.01), respectively,
and appendicular LM was lower: 12.9 vs 14.1 kg (P = 0.02). The proportion of unhealthy body composition
phenotypes (sarcopenia, overfat and sarcopenic obesity) in RA patients was higher (P < 0.001) than in
controls. DAS-28 score was positively correlated with total FM and fat distribution ratio, and HAQ score
was inversely correlated with appendicular LM. These body composition changes were associated with
RF seropositivity, HAQ and DAS-28 scores.
CLINICAL
SCIENCE
Conclusions. Women with early RA had a significantly higher proportion of unhealthy body composition
phenotypes, higher total and truncal FM and lower appendicular LM than controls. Disease activity and
disability scores were associated with unhealthy body composition. These findings suggest that clinicians
should encourage muscle strengthening and fat loss in RA patients to reduce their disability.
Key words: Early rheumatoid arthritis, Body composition, Dual-energy X-ray absorptiometry, Lean mass,
Fat mass, Rheumatoid cachexia, Cardiovascular risk factor, Vietnamese women.
Introduction
RA is a chronic inflammatory autoimmune disease resulting in joint inflammation, eventually irreversible joint
damage and deformity, and increased risk of cardiovascular disease (CVD) mortality [1–3]. The underlying cause
of accelerated mortality, particularly from CVD, may be
partly related to metabolic and vascular effects of systemic inflammation and also to rheumatoid cachexia: the
1
Department of Young Leaders’ Program in HealthCare
Administration, Nagoya University Graduate School of Medicine,
Nagoya, Japan, 2Outpatient Department, Division of Rheumatology
and 3Outpatient Department, Division of Endocrinology, Bach Mai
University Hospital, Hanoi, Vietnam.
Submitted 27 July 2010; revised version accepted 5 January 2011.
Correspondence to: Hanh-Hung Dao, Department of Young Leaders’
Program in HealthCare Administration, Nagoya University Graduate
School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550,
Japan. E-mail: [email protected]
15% reduction in body cell mass (BCM) (mainly skeletal
muscle mass) is over one-third of the maximum survivable
loss of BCM [4]. Rheumatoid cachexia was reported in
two-thirds of RA patients, characterized by muscle wasting and compensatory increase in fat mass (FM) with
stable or slightly decreased weight or BMI [5]. The exact
mechanisms causing rheumatoid cachexia remain
undetermined, but muscle mass loss due to cytokines,
primarily TNF-a-driven hypermetabolism and reduced
physical activity may both contribute [4–6]. The cachetic
state may give rise to a vicious cycle of decreased exercise, increased fatigue and weakness, and increased
FM (rheumatoid cachetic obesity) with implications for
comorbidity and mortality [7, 8].
Although BMI, a method of adjusting body weight for
height, is widely used as a proxy of body fat, its validity
has been questioned, because the body fat can dramatically differ at the same level of BMI [9–11]. There is
! The Author 2011. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected]
Early RA and abnormal body composition
evidence that under a given BMI, body fat percentage is
greater in Asians than Caucasians [10, 12–14], and greater
in RA patients than controls [11]. Therefore, Asian RA
patients may be predisposed towards more unfavourable
body composition characteristics; however, little information on body composition of this group has been reported
[15]. Analysis of body composition is important because
loss of lean mass (LM) in the limbs may result in weakness
and disability [16], and an increase in FM particularly in the
trunk region can lead to arterial thickening and stiffening in
RA patients [15], and lead to negative metabolic consequences such as insulin resistance, diabetes and hypertension in the general population [17, 18]. Dual-energy
X-ray absorptiometry (DXA) has been validated as a tool
to measure total and regional LM and FM [19], and
DXA-derived LM is highly correlated with MRI-derived
skeletal muscle mass [20].
There are few earlier studies of body composition with
DXA, including regional distribution of LM and FM in patients with RA [21–24], and most of the studies have been
conducted in long-standing disease [21–23]. Giles et al.
[23] investigated abnormal body composition phenotypes
in RA patients (disease duration 9 years) and found that
the proportion of patients with abnormalities in body composition (sarcopenia, overfat and sarcopenic obesity)
were greater in women RA patients compared with controls. Only one study [24] has investigated body composition in patients with early RA (disease duration 41 year)
and reported that total and truncal FM were greater in
women RA patients, and appendicular LM was lower in
both men and women RA patients compared with controls; however, body composition phenotypes were
not analysed. Therefore, the present study was designed
to characterize body composition phenotypes with DXA
and to explore factors potentially contributing to alterations in body composition in Vietnamese women with
early RA.
Materials and methods
Study design and subjects
This study was designed as a cross-sectional investigation with two comparison groups. The first comprised
105 Vietnamese women, from 26 to 73 years of age with
RA who visited our Outpatient Department from October
2007 to March 2009; the second was 105 age-matched
(±2 years) healthy women who were selected randomly
from applicants for annual health checks. They were
judged normal on physical examination. All patients met
the ACR 1987 classification criteria for RA [25], with disease duration of 43 years. Written informed consent
based on the Declaration of Helsinki was obtained from
each subject. The study was approved by the Research
and Ethical Review Board of the Bach Mai University
Hospital, Hanoi, Vietnam.
Assessments
The assessments include a clinical examination, comprising swollen joint count (28 joints) and tender joint count
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(28 joints), and a questionnaire identifying risk factors for
rheumatoid cachexia such as lifestyle: smoking, menopausal status, nutrition, physical activity and RA medications. Daily energy and protein intake were determined
by semi-quantitative food frequency questionnaire and
based on a Vietnamese food composition table [26].
Physical activity was defined by the 7-day physical activity
recall questionnaire [27]. Patients were also evaluated in
terms of disease activity and disability using the 28-joint
DAS (DAS-28) (using ESR) [28] and the HAQ [29], respectively. Pain and general health were measured by a visual
analogue scale (VAS). BMI was calculated as body weight
divided by the square of height (kg/m2). In accordance
with World Health Organization (WHO) standards, for an
Asian population. Individuals with BMI <18.5 kg/m2 are
considered underweight; between 18.5 and 22.9 as
normal; between 23 and 27.49 as overweight; and
values >27.5 indicate obesity [14].
In blood, RF and ESR were measured. Immunoglobulin
M (IgM)-RF was assessed by ELISA, with seropositivity
defined as 540 units.
Body composition was assessed by a DXA Hologic
Explorer (Hologic Inc., Waltham, MA, USA). FM, LM and
BMC of the whole body and specific anatomical region
(arms, trunk and legs) were obtained. Daily quality control
of a spine phantom test was performed according to the
manufacturer’s direction [30]. The coefficient of variation
in our laboratory was 0.42%. The term fat-free mass (FFM)
used in this study refers to LM. Fat distribution ratio (FDR)
was calculated as the FM of the trunk divided by the sum
of FM of arms and legs. FM and FFM i (FMI, FFMI) were
calculated as the total FM and FFM divided by the square
of height (kg/m2). The term obesity is commonly used to
refer to a BMI 530 for Caucasian and 27.5 kg/m2 for
Asian populations [14]. To differentiate terms, overfat
was adopted to denote excess body fatness from DXA,
defined by the criteria proposed by Gallagher et al. [13]
using age, sex and race-stratified cut-off points of
body fat percentage from a large cohort of healthy
adults. The term sarcopenia is usually reserved to describe age-related skeletal muscle loss [9]. Sarcopenia
was defined with the criteria proposed by Hull et al. [31]
using age, sex and race-stratified cut-off points of FFMI
(the term FFM used in that study also refers to
DXA-derived LM) from a large cohort of healthy adults.
Subjects were divided into subgroups as proposed by
Giles et al. [23]: healthy body composition (neither sarcopenic nor overfat), overfat but not sarcopenic, sarcopenic
but not overfat and sarcopenic obesity (fulfilling the criteria for both sarcopenic and overfat). To examine the effects of glucocorticoids on body composition, the patients
were divided into two groups: the first group (users)
including 90 patients, among them 18 patients who had
been prescribed glucocorticoids in the past but were no
longer taking them (ex-users) and 72 patients who were
currently taking glucocorticoids (current users), and the
second group including 15 patients who had never
taken glucocorticoids (never users). Cumulative dose
was calculated from the mean daily dose (equivalence
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Hanh-Hung Dao et al.
TABLE 1 Characteristics of RA patients and controls
Factors
Demographics
Age, years
Postmenopausal women, n (%)
Regular intentional exercise, n (%)
Daily television watching, h
Energy intake, kcal/day
Total protein intake, g/day
RA disease characteristics
RA duration, months
RF seropositivity, n (%)
DAS-28 score
HAQ score (range 0–3)
ESR (mm in first h)
RA medications
DMARDs use, n (%)
No DMARDs use, n (%)
Glucocorticoids use
Ex-users, n (%)
Current users, n (%)
Never users, n (%)
Daily dose, mg
Cumulative dose, mg-months
RA patients (n = 105)
Controls (n = 105)
P-value
56.3 (8.7)
52 (49.5)
26 (24.8)
2.4 (0.7)
2057 (384)
65.3 (18.7)
55.7 (8.5)
49 (46.7)
43 (40.9)
1.3 (0.5)
2013 (361)
62.5 (17.9)
0.58
0.39
<0.001
<0.001
0.78
0.69
21.6 (9.7)
73 (69.5)
4.1 (1.3)
0.96 (0.57)
27.5 (13.9)
94 (89.5)
11 (10.5)
18 (17.1)
72 (68.6)
15 (14.3)
8.6 (3.7)
67.3 (14.6)
Values are the mean (S.D.) unless otherwise indicated.
to prednisolone) multiplied by the mean number of months
the therapy was received.
Statistical analyses
Data were presented as mean and 95% CI for normally
distributed continuous variables. Frequency and percentage were used for categorical variables. Comparisons of
the values between RA patients and controls, between
glucocorticoid users and never-users were performed
using the Student’s t-test for continuous variables and
the chi-square test for categorical variables. In bivariate
linear regression models, we evaluated possible associated factors with total FM, FDR and appendicular LM.
To investigate the predictors of body composition phenotypes within the RA group, differences in mean characteristics were compared among the four body composition
subgroups using analysis of variance (for normally distributed continuous variables) or the Kruskal–Wallis test (for
non-parametric continuous variables). Bonferroni correction was used to adjust for the effects of multiple comparisons. Multivariable ordinary logistic regression models
were constructed and odds ratios (ORs) and 95% CI were
calculated to investigate the independent associations
of individual RA-related characteristics (disease activity
and disability and RA therapy) for the group comprising
the combined abnormal body composition subgroups
(overfat, sarcopenic and sarcopenic obesity) compared
with the healthy body composition group. The ORs were
then adjusted for factors with potential confounding
effects on body composition, including demographics
(age and menopausal status) and lifestyle characteristics
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(physical activity). All statistical analyses were done
using the SPSS version 17.0 for Windows (SPSS,
Chicago, IL, USA). Statistical significance was defined
as the two-tailed P < 0.05.
Results
Comparison of general data of RA patients with
controls
Demographic, disease activity and treatment characteristics of RA patients are presented in Table 1. Compared
with the control group, the RA group had lower physical
activity. Daily energy and protein intake were similar between two groups, and in the normal range of recommended dietary allowances [32]. There was no smoker
among the participants. The proportion of RA patients
with low (DAS-28 score <3.2), moderate (DAS-28 score
3.2–5.1) and high (DAS-28 score >5.1) disease activity
were 36.2, 52.5 and 11.3%, respectively. The majority of
RA patients were currently treated with non-biologic
DMARDs (89.5%) and glucocorticoids (68.6%). Since biologic DMARDs are not yet available in Vietnam, none of
the RA patients was treated with those drugs.
Anthropometry and body composition of RA
patients and controls
Anthropometry and body composition characteristics
of RA patients and controls are shown in Table 2.
Means of weight and BMI were similar between the two
groups, but the proportion of RA patients in the normal
weight BMI category was lower (P = 0.006), and in the
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Early RA and abnormal body composition
TABLE 2 Anthropometric and DXA-derived body composition characteristics
Variables
RA patients (n = 105)
Controls (n = 105)
P-value
Weight, kg
BMI, kg/m2
Underweight (BMI < 18.5), n (%)
Normal weight (BMI: 18.5–22.9), n (%)
Overweight (BMI: 23–27.49), n (%)
Obese (BMI 5 27.5), n (%)
Total FM, kg
Percentage body fat
FMI, kg/m2
Trunk FM, kg
Appendicular FM, kg
FDR
Total LM, kg
LMI, kg/m2
LM to FMR
Appendicular LM, kg
Sarcopenia, n (%)
Overfat, n (%)
Sarcopenic obesity, n (%)
Healthy body composition, n (%)
54.7 (53.3–56.1)
23.1 (22.4–23.8)
12 (11.4)
41 (39.1)
37 (35.2)
15 (14.3)
19.1 (17.8–20.4)
34.9 (33.1–35.8)
8.1 (7.5–8.7)
10.1 (9.2–11.1)
8.1 (7.7–8.5)
1.27 (1.22–1.32)
33.8 (32.9–34.7)
14.29 (14.25–14.33)
1.77 (1.73–1.81)
12.9 (12.2–13.6)
19 (18.1)
44 (41.9)
13 (12.4)
29 (27.6)
53.4 (51.9–54.8)
22.5 (21.9–23.2)
9 (8.6)
52 (49.5)
31 (29.5)
13 (12.4)
16.9 (15.7–18.1)
31.6 (30.8–32.4)
7.1 (6.6–7.7)
8.1 (7.3–8.9)
7.9 (7.4–8.4)
1.03 (0.99–1.07)
34.6 (33.8–35.4)
14.61 (14.57–14.65)
2.05 (2.01–2.09)
14.1 (13.4–14.8)
10 (9.5)
33 (31.4)
4 (3.8)
58 (55.3)
0.36
0.47
0.29
0.006
0.04
0.31
0.007
0.005
0.02
0.01
0.34
0.01
0.29
0.41
0.01
0.02
0.007
0.006
0.002
<0.001
Values are the mean (95% CI) unless otherwise indicated.
TABLE 3 Bivariate correlations of RA disease and treatment characteristics with DXA-derived body composition in
RA patients
Total body FM
FDR
Appendicular LM
Factors
r
P-value
r
P-value
Age
Disease duration
DAS-28 score
HAQ score
Cumulative prednisolone
0.35
0.17
0.32
0.14
0.19
0.04
0.23
0.05
0.27
0.21
0.39
0.12
0.37
0.11
0.13
0.02
0.29
0.03
0.39
0.36
r
0.36
0.31
0.21
0.41
0.09
P-value
0.04
0.05
0.11
0.009
0.67
r: Pearson’s correlation coefficient.
overweight category was higher (P = 0.04) compared with
controls. The proportions of underweight and obese BMI
categories were similar between RA patients and controls.
RA patients had significantly higher total FM, trunk FM
and FDR compared with controls. Although total LM and
LMI were not significantly different between the two
groups, LM to FM ratio and appendicular LM were significantly lower in RA patients compared with controls.
Comparisons of body composition phenotypes
The distributions of body composition phenotypes in RA
patients and controls are presented in Table 2. The prevalence of sarcopenia, overfat and sarcopenic obesity was
significantly higher, whereas the prevalence of healthy
body composition was significantly lower in RA patients
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compared with controls. The prevalence of DXA overfat
and sarcopenic obesity was higher in RA patients, whereas the proportion of obesity BMI category was similar
between RA patients and controls.
Correlations between disease-related factors and
DXA-derived body composition in RA patients
Bivariate correlations between disease-related factors
and DXA-derived body composition in RA patients are
presented in Table 3. Age was positively correlated with
total FM and FDR, and inversely correlated with appendicular LM. Disease duration was inversely correlated with
appendicular LM (P = 0.05). DAS-28 score was positively
correlated with total FM (P = 0.05) and FDR (P = 0.03).
HAQ score was inversely correlated with appendicular
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Hanh-Hung Dao et al.
TABLE 4 Body composition data and phenotypes in RA patients according to glucocorticoid use
Variables
Glucocorticoid users (n = 90)
Glucocorticoid never
users (n = 15)
P-value
Total FM, kg
Percentage body fat
Trunk FM, kg
Appendicular FM, kg
FDR
Total LM, kg
Appendicular LM, kg
Sarcopenia, n (%)
Overfat, n (%)
Sarcopenic obesity, n (%)
Healthy body composition, n (%)
19.2 (18.4–20.9)
35.1 (34.3–37.5)
10.4 (8.9–12.1)
8.1 (7.2–8.9)
1.28 (1.24–1.39)
33.7 (31.4–34.9)
12.8 (11.7–13.4)
16 (17.4)
38 (42.2)
11 (12.2)
25 (27.8)
19.0 (18.1–20.6)
34.7 (33.8–36.9)
9.7 (8.2–11.4)
8.3 (7.7–9.5)
1.19 (1.09–1.28)
34.3 (32.7–35.4)
13.3 (12.5–14.2)
3 (20.0)
6 (40.0)
2 (13.3)
4 (26.7)
0.76
0.64
0.08
0.69
0.06
0.71
0.57
0.36
0.29
0.24
0.54
Values are the mean (95% CI) unless otherwise indicated.
TABLE 5 Characteristics of RA patients according to body composition phenotype
Factors
Demographics
Age, years
Post-menopausal women, n (%)
Regular intentional exercise, n (%)
Daily television watching, h
RA disease characteristics
RA duration, months
RF seropositivity, n (%)
DAS-28 score
HAQ score
ESR (mm in first h)
RA therapy
DMARDs use, n (%)
No DMARDs use, n (%)
Glucocorticoid use, n (%)
Healthy body
composition
(n = 29)
Overfat
(n = 44)
Sarcopenic
(n = 19)
Sarcopenic
obesity
(n = 13)
P-value*
55.7 (8.3)
15 (51.7)
12 (41.4)
1.7 (0.4)
55.9 (7.9)
22 (50.0)
8 (18.2)
2.2 (1.1)
56.6 (8.5)
9 (47.3)
3 (15.8)*
2.6 (1.3)
57.1 (9.1)
6 (46.2)
3 (23.1)*,**
2.9 (1.6)**
0.83
0.19
0.026
0.017
21.7 (10.2)
18 (62.1)
3.4 (1.1)
0.82 (0.53)
21.5 (11.4)
20.9 (9.6)
31 (70.5)
4.3 (1.5)
1.03 (0.73)
31.4 (12.8)
21.3 (9.2)
14 (73.7)
4.1 (1.4)
0.93 (0.59)
24.3 (10.7)
22.5 (10.7)
10 (76.9)**
4.6 (1.6)**
1.09 (0.64)**
32.6 (14.7)**
0.25
0.036
0.071
0.018
0.023
27 (93.1)
2 (6.9)
20 (68.9)
40 (90.9)
5 (11.4)
30 (68.2)
17 (89.5)
2 (10.5)
13 (68.4)
10 (76.9)**
2 (15.4)**
9 (69.2)
0.028
0.012
0.76
Values are the mean (S.D.) unless otherwise indicated. *From global test of all four groups (analysis of variance). **P < 0.05 for
pairwise comparison with the healthy body composition group (adjusted for multiple comparisons using Bonferroni correction).
LM (P = 0.04). Cumulative prednisolone was not correlated
with any DXA-derived body composition.
Associations between glucocorticoid use and body
composition characteristics
There were no significant differences regarding LM, FM
variables and body composition phenotypes between
the two groups, except for trunk FM and FDR, which
tended to be higher in glucocorticoid users than in never
users (P = 0.08 and 0.06, respectively) (Table 4).
Predictors of body composition in RA patients
Comparisons of characteristics of RA patients according to
body composition phenotypes are presented in Table 5.
Among demographic characteristics, the differences
between RA patients with abnormal body composition vs
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those with healthy body composition were observed for a
lower frequency of regular intentional exercise in sarcopenic subjects and more television watching in sarcopenic
obesity subjects. Among RA characteristics, RF positivity,
DAS, HAQ scores and ESR were significantly associated
with sarcopenic obesity. Among RA therapeutics, a significantly higher proportion of healthy body composition was
found in patients being treated with DMARDs and a higher
proportion of sarcopenic obesity was found in patients not
being treated with DMARDs.
Associations of RA disease-related factors with
abnormal vs healthy DXA-derived body composition
in RA patients
Associations of RA disease-related factors with abnormal
vs healthy DXA-derived body composition in RA patients
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Early RA and abnormal body composition
TABLE 6 OR for having abnormal body composition phenotypes compared with healthy
DXA-derived body composition according to RA disease and therapy characteristics
Factors
Disease duration
DAS-28 score
HAQ score
RF seropositivity
DMARDs use
Cumulative prednisolone
Crude ORs (95% CI)
1.11
1.49
1.91
1.98
0.97
1.17
(0.86–1.27)
(0.99–2.18)
(1.03–3.12)
(1.15–3.47)
(0.73–1.92)
(0.96–1.31)
Adjusted ORs (95% CI)
1.07
1.46
1.85
1.97
0.92
1.13
(0.83–1.31)
(0.97–2.14)
(1.09–3.17)
(1.17–3.45)
(0.75–1.89)
(0.94–1.26)
P-value
0.65
0.04
0.009
0.006
0.83
0.71
Analyses are adjusted for age, menopausal status and physical activity.
are shown in Table 6. In multivariate analyses comparing
RA patients with any of the abnormal body composition
phenotypes as a combined group with those with healthy
body composition, RF seropositivity, DAS-28 score and
HAQ score, but not DMARD and glucocorticoid use,
were associated with abnormal body composition.
After adjusting for age, menopausal status and physical
activity, they remained the predictors of abnormal
body composition although with slight attenuation in
their associations: for RF seropositivity (OR 1.97; 95%
CI 1.17, 3.45; P = 0.006), HAQ score (OR 1.85; 95% CI
1.09, 3.17; P = 0.009) and DAS-28 score (OR 1.46; 95%
CI 0.97, 2.14; P = 0.04). To evaluate the differential associations of DMARD therapy on abnormal body composition, we compared clinical characteristics of subjects
treated and untreated with DMARDs. Mean age, disease
duration, DAS-28 score and HAQ score did not significantly differ between groups treated and untreated with
DMARDs (data not shown).
Discussion
This study was carried out in Vietnamese women with RA
and found that: (i) although means of body weight and
BMI were similar in both groups, total and truncal FM
were higher, and appendicular LM was lower in RA patients compared with controls. The proportion of unhealthy body composition phenotypes was higher in RA
patients than in controls. (ii) In RA patients, DAS-28 score
was positively correlated with total FM and FDR, and HAQ
score was inversely correlated with appendicular LM.
These body composition changes were associated with
RF seropositivity, HAQ and DAS-28 scores, not with
DMARD and glucocorticoid use.
This study, to our knowledge, is the first to characterize
body composition phenotypes with DXA in early RA. An
alteration in body composition with higher total FM and
truncal FM, and lower appendicular LM in RA patients
compared with controls in early RA (<1 year) has been
reported [24]. However, in that study, means of weight
and BMI were higher in RA patients than in controls.
Patients with RA had a higher proportion of unhealthy
body composition phenotypes and a lower proportion of
abnormal body composition phenotypes compared with
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controls was also reported by Giles et al. [23] in older
patients and longer disease duration. The proportion of
rheumatoid cachexia varies considerably, largely depends
upon what degree of reduction of muscle mass is considered to be significant, and which method estimating
muscle mass is used [8]. In this study, we categorized
the patients as rheumatoid cachexia if they fulfilled the
criteria for both sarcopenic and overfat, as reported in
an earlier study using DXA [23]. Proportion of rheumatoid
cachexia in our study (12.4%) was similar to the earlier
study (11.1% in women and 15.3% in men) in older patients and longer disease duration [23]. Recently, Elkan
et al. [33] categorized patients as rheumatoid cachexia if
FFMI is below the 25th percentile and FMI is above the
50th percentile of the reference population and found that
18% of women and 26% of men had rheumatoid cachexia. Using the 50th percentile of the reference population
as the ideal for arm muscle area or circumference,
Roubenoff et al. [5] found that 67% of patients had
values below this level, and could therefore be diagnosed
as having rheumatoid cachexia. Using the more stringent
10th percentile of the reference population as a cut-off,
24–50% of RA patients were diagnosed as having
rheumatoid cachexia [34, 35].
We found that a lower frequency of regular intentional
exercise was observed in sarcopenic subjects, whereas
more television watching was observed in sarcopenic
obesity subjects. Furthermore, RF positivity, DAS, HAQ
scores and ESR were significantly associated with sarcopenic obesity. Similar findings were also reported [23],
and these findings further support the role of reduced
physical activity and systemic inflammation in the pathogenesis of rheumatoid cachexia.
RA patients tend to refrain from physical activity due to
joint pain and fear of aggravating their disease [7, 8].
Nevertheless, intensive physical training is well tolerated
and patients consistently report improvement in pain and
fatigue as well as increase in muscle strength and aerobic
capacity with no adverse effect on disease activity [8, 36].
RA patients in our study did not have deficiency in protein
or energy intake; similar findings were also reported in
previous studies [4–8].
Patients with RA had a higher body fat percentage compared with controls as shown in ours and the earlier study
1255
Hanh-Hung Dao et al.
using a bio-impedance analysis (BIA) method [11]. High
FDR seen in our RA patients is a well-known risk factor for
CVD morbidity in the general population [17, 18] and in RA
patients [15], partly explaining the well-known increase in
CVD in RA patients [1–3]. Increased arterial thickening and
stiffening were independently associated with a higher
FDR, but not with BMI [15]. A difference between the
prevalence of DXA overfat and sarcopenic obesity with
the obesity BMI category in our study suggests the limitation of BMI comparing DXA in evaluating body composition as shown previously [23]. FM is known as a producer
of pro-inflammatory cytokines such as TNF-a, IL-6 and
other adipocytokines (adiponectin and leptin), which are
to some extent responsible for the development of insulin
resistance and CVD [37].
Although total LM and LMI were not significantly different between RA patients and controls, LM to FM ratio and
appendicular LM were significantly lower in RA patients,
suggesting that LM was selectively reduced in RA patients. These findings are supported by the results in
early [24] and late state of disease [21]. Several studies
documented a decrease in total DXA-derived LM in RA
patients compared with controls [21, 22, 38, 39], but
others did not [23, 24, 40]. We found that HAQ score was
inversely correlated with appendicular LM, as shown in
previous studies [16, 24]. A decrease in LM increased
risk for joint destruction and disability, as well as an
increased risk of falls and fractures [16, 41]. A decrease
in LM is also associated with a decreased level of exercise
due to sarcopenia and may lead to increased insulin resistance and CVD cormorbidity in RA patients [42].
Associations between abnormal body composition
phenotypes and RF seropositivity, HAQ and DAS-28
scores found in this study were also reported in the earlier
study [23]. Furthermore, patients being treated with
glucocorticoids tended to have a higher trunk FM and
FDR compared with those not being treated with glucocorticoids. However, in multivariate regression model, no
significant relationship (unexpectedly) between abnormal
body composition phenotypes and cumulative glucocorticoids use was observed. These findings further
support the results of earlier study [23]. Due to the
cross-sectional design, it is unable to know whether this
lack of association is due to a true lack of effect or alternatively whether any weight-promoting effect of glucocorticoids was counter-balanced by an ability to
suppress the catabolic effects of inflammation that
reduced RA disease activity and increased physical activity. Due to their potent anti-inflammatory effects, DMARDs
could be expected to reduce the catabolic effect of hypercytokinaemia on muscle. In this study, in multivariate
regression analysis, DMARD treatment was not associated with a decreased risk of abnormal body composition. A similar finding was also reported previously [23]. A
recent trial [43] reported that treatment with etanercept
was associated with gain in LM in a subset of patients
with early RA. This interesting finding deserves confirmation in larger cohorts and raises the question as to
whether anti-TNF therapy has a direct anabolic effect on
1256
muscle or exerts its effects indirectly by reducing RA disease activity and pain, thus enabling increased physical
functioning and activity [8, 23].
Mean BMIs in this study were similar in RA patients and
controls. These finding agree with the results of many
studies [4, 5, 21, 22, 35, 36, 38–40, 44], but disagree
with others [23, 24]. In both groups, the proportion of
underweight was lower but overweight and obesity were
higher than those in an earlier population-based study in
Hanoi [45], suggesting that although underweight remains
the main concern, overweight and obesity is an emerging
burden in Vietnam. The proportion of underweight was
similar to studies from Scotland and Minnesota (USA)
[34, 46], but higher than those from Maryland, Sweden,
German and Texas cohorts [23, 33, 47, 48]. There are
strong positive associations between BMI and adverse
CVD risk factors in RA patients [49], and weight reduction
in obese RA patients has been demonstrated to preserve
BCM and improve physical fitness [44]. However, there is
also evidence that a low BMI is an independent predictor
of poor radiological outcome [47, 50]. Furthermore, a
lower BMI is associated with an increase in CVD mortality
[46] and all-cause mortality [48] in RA patients. This paradoxical effect of BMI on survival in RA is partly mediated
by systemic inflammation, and partly due to the increase
in cachetic-related comorbidities in leaner patients [48].
However, the implications of this paradoxical relationship
need further investigation.
The strengths and limitations of this study require comment. To our knowledge, this is the first study to characterize body composition phenotypes using the DXA
method and to examine the relationship of body composition variables with RA characteristics in patients with early
RA. Further studies using DXA or other methods such as
BIA with larger patient cohorts would be useful. Since the
study design was cross-sectional, it was not possible
to make any cause–effect inference on the relationship
between RA characteristics and body composition
phenotypes. Prospective studies should prove valuable
in determining these causal relationships.
In summary, we observed greater than expected abnormal body fat and lean composition in patients with early
RA compared with age-matched healthy controls, with
significantly higher FM, especially in the trunk region,
and lower appendicular LM in RA patients. Disease activity and disability scores were associated with abnormal
body composition. These findings suggest that clinicians
should encourage muscle strengthening and fat loss in RA
patients to reduce their disability.
Rheumatology key messages
Early RA patients had higher total and truncal fat,
lower appendicular LM than controls.
. The proportion of unhealthy body composition
phenotypes in RA patients was higher than
controls.
. Body composition changes were significantly associated with RF seropositivity, disease activity and
disability scores.
.
www.rheumatology.oxfordjournals.org
Early RA and abnormal body composition
Acknowledgements
The authors would like to thank the cooperation of all
participants and the assistance of the staff of the Out
Patient Department at Bach Mai University Hospital who
helped to conduct this study.
Funding: This work was supported in part by a non-profit
organization—Epidemiology and Clinical Research
Information Network (ECRIN).
Disclosure statement: The authors have declared no
conflicts of interest.
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