Nutrition, Metabolism & Cardiovascular Diseases (2023) 33, 1899e1906

Available online at www.sciencedirect.com

Nutrition, Metabolism & Cardiovascular Diseases

journal homepage: www.elsevier.com/locate/nmcd

Body composition markers from classic anthropometry, bioelectrical

impedance analysis, and magnetic resonance imaging are associated
with inflammatory markers in the general population
Saima Bibi a,*, Muhammad Naeem a,f, Martin Bahls b,c, Marcus Dörr b,c,
Nele Friedrich c,d, Matthias Nauck c,d, Robin Bülow e, Henry Völzke a,c,
Marcello Ricardo Paulista Markus b,c,1, Till Ittermann a,c,1
a
Institute for Community Medicine e Department Clinical-Epidemiological Research, University Medicine Greifswald, Greifswald, Germany
b
Department of Internal Medicine B e Cardiology, Intensive Care, Pulmonary Medicine and Infectious Diseases, University Medicine Greifswald,
Germany
c
DZHK (German Center for Cardiovascular Research), partner site Greifswald, Germany
d
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Germany
e
Institute for Radiology and Neuroradiology, University Medicine Greifswald, Germany
f
Department of Zoology, University of Malakand, 18800, Pakistan

Received 31 January 2023; received in revised form 28 April 2023; accepted 24 May 2023
Handling Editor: A. Siani
Available online 14 June 2023

KEYWORDS Abstract Background and aim: The associations of body composition markers derived from
Obesity; different modalities with inflammatory markers are unclear. The aim of this study was to deter-
Inflammation; mine associations of the body composition markers from different modalities with inflammatory
High-sensitivity C- markers in a population-based study.
reactive protein Methods and results: We analyzed data from 4048 participants (2081 women, 51.4%) aged 20e84
(hsCRP); years. Linear regression models adjusted for confounding were used to analyze the association of
Waist circumference classic anthropometry markers, absolute and relative fat mass, absolute fat-free mass (FFM), and
(WC); body cell mass (BCM) assessed by bioelectrical impedance analysis, subcutaneous, visceral, and
Magnetic resonance liver fat from magnetic resonance imaging (MRI), with markers of inflammation. We found pos-
itive associations of classic anthropometry markers, total body fat, subcutaneous, visceral, and
imaging (MRI)
liver fat, with all inflammatory markers. Waist circumference (WC) showed the strongest asso-
ciation with high-sensitivity C-reactive protein (hsCRP) (b: 1.39; 95% confidence interval [CI]:
1.22 to 1.56) and white blood cell (WBC) (0.39; 0.29 to 0.48), whereas visceral fat showed the
strongest association with ferritin (41.9; 34.7 to 49.0). Relative body fat was strongly associated
with hsCRP (1.39; 1.20 to 1.58), fibrinogen (0.29; 0.27 to 0.32), and WBC (0.35; 0.25 to 0.46).
Conversely, we found inverse associations of body height, FFM, and BCM with hsCRP, fibrinogen,
and WBC.
Conclusions: Our study indicates the importance of WC as an easily measured marker for early
inflammation. MRI-assessed markers of central obesity seem to be most strongly related to
ferritin.
ª 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Ital-
ian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II
University. Published by Elsevier B.V. All rights reserved.

* Corresponding author. Institute for Community Medicine e Department Clinical-Epidemiological Research, University Medicine Greifswald,
Walther Rathenau Str. 48. D-17475, Greifswald, Germany.
E-mail address: saima.bibi@stud.uni-greifswald.de (S. Bibi).
1
equally contribute.

https://doi.org/10.1016/j.numecd.2023.05.026
0939-4753/ª 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical
Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
1900
1. Introduction
Cardiovascular diseases (CVDs) are the leading cause of
mortality worldwide [1]. About 523 million people are
affected by CVDs, resulting in 18.6 million deaths globally
[2]. Inflammation is an important cause of CVD that leads
to adverse clinical events [3]. High-sensitivity C-reactive
protein (hsCRP) is the most frequently used marker of
inflammation in clinical practice. Elevated hsCRP concen-
trations predict an increased CVD risk independent of
other cardiovascular risk factors [4]. Likewise, it is well
established that overweight and obesity and their comor-
bidities increase CVD and overall morbidity and mortality
rates [5e8]. High waist circumference (WC) as an indicator
of abdominal body fat has been associated with car-
diometabolic disease and CVD and has been reported to be
predictive for cardiovascular mortality [9].
Several studies demonstrated elevated hsCRP levels in
obese subjects [10]. A meta-analysis and systematic review
of 51 cross-sectional studies concluded that obesity is
strongly associated with C-reactive protein (CRP) in the
general population [11]. Moreover, various cross-sectional
studies have reported positive associations of body fat,
WC, body mass index (BMI), and weight gain with hsCRP
as well as fibrinogen and white blood cell (WBC) count
[12e16]. Similarly, a longitudinal study also investigated
associations of changes in body weight, BMI, or WC with
changes in CRP in a middle-aged adult population after 11
years of follow-up [17].
Limitations of the above studies are that most of them
considered only hsCRP as an inflammatory marker and
were conducted in relatively small and selected pop-
ulations [12,13,15]. Moreover, these studies used indirect
methods for the measurement of body fat such as BMI or
WC [12,13]. Magnetic resonance imaging (MRI) is the gold
standard method for the estimation of visceral and sub-
cutaneous adipose tissue as well as liver fat and has been
reported to be more sensitive than CT and ultrasound [18].
Similarly, bioelectrical impedance analysis (BIA) is a
cheaper and accurate method for determination of fat
mass (FM) and fat-free mass (FFM) that can be easily
reproduced [19,20].
To the best of our knowledge, there are no population-
based studies that investigated associations of body
composition markers from classic anthropometry, BIA, and
MRI with inflammatory markers in parallel. Against this
background, the aim of our study was to investigate as-
sociations of body composition markers derived from
classic anthropometry, BIA, and MRI with markers of
inflammation (hsCRP, WBC, fibrinogen, ferritin, hsCRP-to-
albumin ratio, and neutrophil-to-lymphocyte ratio) in a
population-based study and to compare their effect sizes.
2. Methods
2.1. Study population
Our analyses were based on data from the second cohort of
the Study of Health in Pomerania (SHIP-TREND), which
S. Bibi et al.
was conducted in the Northeast Germany. For SHIP-
TREND, a random sample of 8826 adults was drawn from
population registries, of which 4420 subjects aged 20e84
years participated between 2008 and 2012 (response
50.1%). From the 4420 adult individuals, we excluded 372
individuals with missing data in inflammatory markers or
body composition markers, resulting in a study population
of 4048 individuals. For MRI data, we include individuals
with available liver fat (n Z 1798) as well as visceral and
subcutaneous fat measurements (n Z 1854) [21].
The study was conducted according to the guidelines
laid down in the Declaration of Helsinki and the Ethical
Review Board of the University of Greifswald approved
protocol. All subjects gave their informed consent to be
included in the study.
2.2. Interview and physical examination
In a standardized computer-assisted personal interview,
information on gender, age, smoking, and physical activity
was collected. Smokers were categorized into three cate-
gories (lifetime non-smokers, former smokers, and current
smokers). Individuals were classified as physically inactive
if they reported less than 1 h of exercise during summer
and/or winter. Participants were asked to bring all medi-
cations taken 7 days before the time of examination.
Medication data were obtained online using the IDOM
program (online drug database-led medication assess-
ment) and categorized according to the Anatomical Ther-
apeutical Chemical (ATC) classification index.
During the anthropometric examination, the subjects
were in light clothing and not wearing shoes. BMI was
calculated as weight in kilograms divided by the square of
height in meters. Standardized measurements of height,
weight, WC, and hip circumference were performed. Body
height was measured to the nearest 0.1 cm and weight to
the nearest 0.1 kg by calibrated scales. Measurements of
WC and hip circumference were performed by using an
inelastic tape with the subject standing comfortably with
weight distributed evenly on both feet. WC was measured
midway between the lower rib margin and the iliac crest
in the horizontal plane. Hip circumference was determined
as the greatest circumference between the highest point of
the iliac crest and the crotch. Waist-to-height ratio (WHtR)
and waist-to-hip ratio (WHR) were calculated. FM, FFM,
and body cell mass (BCM) were measured by BIA using a
multifrequency Nutriguard-M device (Data Input) and the
NUTRI4 software (Data Input) in participants without
pacemakers. The electrodes were placed on hands, wrists,
ankles, and feet. The test frequency was measured at 5, 50,
and 100 kHz following the manufacturer’s instructions (3).
Systolic and diastolic blood pressures were measured
three times after an initial 5-min rest period on the right
arm of seated individuals using a digital blood pressure
monitor. Measurements were separated by 3-min in-
tervals. The mean of the second and third measurements
was calculated and used for the present analyses. Arterial
hypertension was defined as elevated systolic and/or dia-
stolic blood pressures 140/90 mmHg or intake of
The Study of Health in Pomerania (SHIP)
antihypertensive medication (ATC C02, C03, C04, C05, C07,
C08, C09). Participants were classified as having type 2
diabetes if they reported physician’s diagnosis of disease in
the interview, took any glucose-lowering medications (ATC
A10), or had elevated blood glucose or HbA1c levels [22].
2.3. Laboratory measurements
Non-fasting blood samples were taken between 07:00 a.m.
and 04:00 p.m. and analyzed in the central laboratory of
the University Medicine Greifswald. Laboratory bio-
markers were in median analyzed within 90 min after
sampling in the central laboratory of the University Med-
icine Greifswald. For determination of plasma fibrinogen
concentration, BCS XP (Siemens Healthcare Diagnostics)
was used according to Clauss. WBC was determined by
using the Sysmex XE 5000 analyzer (Sysmex) in EDTA
whole blood. hsCRP (nephelometry), ferritin (chemilumi-
nescent assay), low-density lipoprotein cholesterol (LDL-
C), high-density lipoprotein cholesterol (HDL-C), and
creatinine concentrations were determined in serum on
the Dimension VISTA (Siemens Healthcare Diagnostics).
Ferritin concentrations were determined by a chemilumi-
nescent assay (Siemens Vista, TRF Flex reagent cartridge,
Siemens Healthcare Diagnostics Inc). hsCRP-to-albumin
ratio and neutrophil-to-lymphocyte ratio were also
calculated. The estimated glomerular filtration rate (eGFR)
was estimated according to the CKD-EPI equation and
expressed in mL/min/1.73 m2 [23].
2.4. MRI examinations
For the determination of visceral abdominal tissue, sub-
cutaneous adipose tissue, and liver fat, MRI was performed
using a 1.5-T system (Magnetom Avanto, Siemens Health-
care AG, software version syngo MR B15). Abdominal fat
was determined by axial 3D datasets using the 2-point
Dixon technique (matrix: 256  176; slice thickness: 4
mm/4 mm/3 mm without gap; 3  64 slices; inphase: TE
4.76 ms, TR 7.48 ms; opp-phase: TE 2.38 ms, TR 7.48 ms).
The quantification of abdominal visceral and subcutaneous
adipose tissue was done using automatic tissue and la-
beling analysis software, an in-house developed software
at the University of Ulm [24].
2.5. Statistical methods
Continuous data are reported as median (with 25th and 75th
percentiles) and categorical data as absolute numbers and
percentages stratified by quartiles of WC. Multivariable linear
regression analyses were used for the association of body
composition markers (exposure) with inflammatory markers
(outcome) by calculating b coefficients and 95% confidence
intervals (95% CI). All models were adjusted for age, sex,
physical activity, and smoking status. Models for the expo-
sures weight, WC, hip circumference, WHR, subcutaneous
fat, visceral fat, and liver fat were further adjusted for body
height, whereas models for FFM and BCM were adjusted
additionally for absolute FM. To make the regression models
1901
comparable, anthropometric markers were used as stan-
dardized variables. A p-value of p < 0.05 was considered to be
statistically significant. All statistical analyses were per-
formed using Stata 14.2 (Stata Corporation).
3. Results
Table 1 shows the descriptive data of the study population
stratified by quartiles of WC and sex. In both men and
women, the median values of age and body composition
markers such as BMI, body weight, body height, hip
circumference, WHR, WHtR, absolute body fat, absolute
FFM, BCM, visceral fat, subcutaneous fat, and liver fat
increased from the first to the fourth quartile of WC. Men
and women in the fourth quartile of WC had higher me-
dian levels of inflammatory markers like hsCRP, fibrinogen,
WBC, ferritin, hsCRP-to-albumin ratio, and neutrophil-to-
lymphocyte ratio, were more likely former smokers, and
had more often arterial hypertension and type 2 diabetes
compared to individuals in the other quartiles. The lipid
profile was more unfavorable in both men and women
with high WC compared to those with low WC. The eGFR
was lowest in both groups of individuals within the
highest quartile of WC.
We also stratified quartiles of WC by pre- and post-
menopausal women. In pre- and post-menopausal women,
the median values of age and body composition markers
increased from the first to the fourth quartile of WC.
Moreover, both pre- and post-menopausal women in the
first quartiles were more likely to be current smokers. Pre-
and post-menopausal women in the fourth quartile of WC
had higher median levels of inflammatory markers and had
more often type 2 diabetes (Supplementary Table 1).
Multivariable linear regression adjusted for age, sex,
smoking, and physical activity showed associations of
body composition markers with inflammatory markers
(Table 2). Positive associations of BMI, body weight, hip
circumference, WHR, WHtR, total body fat, visceral fat,
subcutaneous fat, and liver fat were found with all in-
flammatory markers. We found inverse associations of
body height, BCM, and absolute FFM with hsCRP, fibrin-
ogen, WBC, and hsCRP-to-albumin ratio. BCM was
inversely associated with serum levels of hsCRP, fibrin-
ogen, and WBC, whereas BCM was positively associated
with serum ferritin. Additionally, relative body fat, BCM,
visceral fat, and liver fat were inversely associated with
neutrophil-to-lymphocyte ratio.
Among all body composition markers, WC, WHtR, and
relative body fat showed the strongest associations with
hsCRP (Fig. 1), whereas relative body fat was most strongly
associated with fibrinogen. WC was the anthropometric
marker that was most strongly associated with WBC,
whereas liver fat and visceral fat were most strongly
associated with ferritin (Fig. 2).
4. Discussion
The objective of the present study was to compare asso-
ciations of various body composition markers derived from
1902 S. Bibi et al.

Table 1 Characteristics of the study population stratified by waist circumference and sex.

Parameter First quartile Second quartile Third quartile Fourth quartile Total
n Z 1016 n Z 1012 n Z 1036 n Z 984 n Z 4048
Age in years Men 38.0 (29.0; 49.0) 52.0 (41.0; 63.0) 58.0 (47.0; 68.0) 60.0 (51.0; 69.0) 53.0 (40.0; 65.0)
Women 39 (31; 50) 48 (39.5; 59.5) 58 (44; 67) 59.5 (59; 68) 52 (39; 63)
Smoking in % Men 29.3 26.2 27.1 18.4 25.3
Never 29.9 40.9 49.7 59.3 44.9
Former 40.8 33.0 23.2 22.3 29.9
Current
Never Women 39.2 44.6 51.2 51.9 46.7
Former 29.0 28.1 26.1 31.4 28.6
Current 31.9 27.4 22.8 16.7 24.7
Body mass index Men 24.0 (21.4; 25.5) 26.7 (25.5.; 28.0) 29.5 (28.3; 31.0) 33.4 (31.3; 35.8) 28.2 (25.4; 31.1)
in kg
Women 21.8 (20.7; 23.2) 25.1 (23.7; 26.5) 28.5 (26.9; 30.4) 34.0 (31.3; 37.3) 26.7 (23.4; 30.9)
Body weight in kg Men 75.4 (69.6; 80.8)) 82.7 (77.6; 88.7) 91.7 (86.0; 97.9) 102 (95.5; 112) 87.2 (78.3; 97.5)
Women 59.1 (55.2; 64.1) 67.8 (63.2; 72.6) 75.6 (70.7; 81.8) 89.6 (81.5; 98.7) 71.7 (63.3; 81.9)
Body height in cm Men 178 (172; 182) 176 (171; 181) 176 (172; 180) 176 (171; 180) 176 (172; 181)
Women 165 (160; 169) 165 (160; 169) 164 (158; 168) 162 (158; 168) 162 (158; 167)
Hip Men 94.0 (90.9; 97.5) 90.0 (96.0; 101) 103 (100; 106) 110 (105; 115) 101 (96.2; 106)
circumference
in cm
Women 91.0 (87.7; 94.1) 97.5 (94.0; 101) 105 (101; 109) 116 (110; 123) 101 (94; 110)
Waist-to-hip Men 0.87 (0.84; 0.90) 0.93 (0.91; 0.96) 0.97 (0.95; 1.00) 1.02 (0.99; 1.06) 0.95 (0.90; 1.00)
ratio
Women 0.78 (0.74; 0.80) 0.81 (0.79; 0.84) 0.84 (0.81; 0.87) 0.89 (0.85; 0.92) 0.88 (0.85; 0.92)
Waist-to-height Men 0.47 (0.44; 0.49) 0.52 (0.50; 0.54) 0.57 (0.56; 0.60) 0.64 (0.61; 0.68) 0.55 (0.50; 0.60)
ratio
Women 0.43 (0.41; 0.44) 0.48 (0.46; 0.50) 0.54 (0.52; 0.56) 0.63 (0.60; 0.68) 0.51 (0.45; 0.59)
Absolute body fat Men 14.3 (11.3; 17.3) 18.7 (16.0; 21.3) 23.2 (20.1; 26.0) 29.8 (5.7; 34.1) 20.8 (16.2; 26.0)
in kg
Women 15.7 (13.5; 18.3) 21.6 (19.0; 24.8) 27.8 (24.2; 31.7) 37.0 (32.3; 42.9) 24.5 (18.8; 32.1)
Absolute fat-free Men 60.8 (56.8; 65.2) 64.3 (59.7; 69.5) 68.3 (64.3; 72.8) 73.5 (68.3; 78.3) 66.6 (60.9; 72.5)
mass in kg
Women 43.6 (40.7; 46.3) 46.1 (43.6; 48.9) 48.2 (45.1; 51.5) 52.6 (48.9; 56.4) 47.1 (43.6; 51.3)
Relative body fat Men 19.0 (16.1; 21.9) 22.6 (20.2; 24.9) 25.5 (22.8; 27.5) 29.1 (26.1; 31.9) 24.0 (20.3; 27.5)
in %
Women 26.7 (23.9; 29.4) 32.1 (29.3; 34.8) 36.7 (33.9; 39.2) 41.5 (38.8; 44.2) 34.4 (29.1; 39.1)
Body cell mass Men 33.3 (30.9; 36.9) 34.7 (31.3; 38.4) 36.9 (32.9; 39.6) 38.8 (35.1; 42.6) 35.9 (32.2; 39.5)
(BCM) in kg
Women 22.4 (20.6; 24.1) 23.7 (21.9; 25.6) 24.4 (22.4; 26.8) 26.3 (24.1; 28.9) 24.1 (22.0; 28.9)
Visceral fat in L Men 2.48 (1.57; 3.18) 4.55 (3.50; 5.49) 6.48 (5.52; 7.67) 8.60 (7.14; 10.0) 5.18 (3.12; 7.13)
Women 0.89 (0.61; 1.27) 2.10 (1.47; 2.79) 3.47 (2.65; 4.16) 5.05 (4.26; 6.29 2.48 (1.26; 3.92)
Subcutaneous fat Men 4.17 (3.25; 5.10) 5.94 (5.08; 7.16) 7.68 (6.57; 8.96) 10.1 (8.44; 12.1) 6.46 (4.83; 8.47)
in L
Women 5.15 (4.10; 6.17) 7.50 (6.57; 8.51) 10.3 (8.74; 11.5) 13.2 (11.6; 15.8) 8.24 (6.17; 11.1)
Liver fat in % Men 2.62 (1.95; 3.71) 4.29 (2.75; 6.59) 6.84 (4.00; 11.3) 10.2 (6.12; 17.2) 4.82 (2.78; 9.05)
Women 2.11 (1.79; 2.65) 2.81 (2.05; 4.82) 4.14 (2.72; 8.19) 9.56 (5.32; 17.7) 3.22 (2.13; 6.83)
hsCRP in mg/L Men 0.64 (0.33; 1.23) 0.97 (0.56; 1.90) 1.29 (0.74; 2.37) 2.18 (1.21; 4.24) 1.14 (0.60; 2.47)
Women 0.74 (0.40; 1.62) 1.12 (0.61; 2.39) 1.16 (0.87; 3.23) 3.34 (1.54; 5.61) 1.42 (0.71; 3.37)
Fibrinogen in g/L Men 2.50 (2.20; 3.00) 2.80 (2.40; 3.30) 3.00 (2.45; 3.40) 3.20 (2.60; 3.60) 2.80 (2.4; 3.40)
Women 2.70 (2.30; 3.20) 3.00 (2.50; 3.40) 3.20 (2.80; 3.60) 3.50 (3.10; 4.00) 3.10 (2.60; 3.60)
WBC count in Gpt/ Men 5.52 (4.69; 6.58) 5.72 (4.75; 6.82) 5.80 (4.93;7.10) 6.37 (5.25; 7.52) 5.80 (4.89; 7.03)
L
Women 5.60 (4.73; 6.79) 5.59 (4.71; 6.76) 5.86 (5.01; 6.98) 6.35 (5.36; 7.43) 5.85 (4.92; 7.02)
Ferritin in mg/L Men 101 (62.0; 170) 129 (79.0; 209) 163 (91.0; 263) 186 (108; 304) 141 (82.0; 235)
Women 35.0 (18.0; 64.0) 53.0 (29.0; 94.5) 68.0 (32.0; 117) 85.5 (41.5; 147) 57.0 (28.0; 104)
hsCRP-to- Men 0.02 (0.01; 0.03) 0.02 (0.01; 0.05) 0.03 (0.02; 0.06) 0.06 (0.03; 0.11) 0.03 (0.01; 0.06)
albumin ratio
Women 0.02 (0.01; 0.04) 0.03 (0.02; 0.06) 0.04 (0.02; 0.08) 0.09 (0.04; 0.15) 0.04 (0.02; 0.09)
Neutrophil-to- Men 1.93 (1.54; 2.53) 2.01 (1.54; 2.71) 2.06 (1.61; 2.66) 2.10 (1.69; 2.79) 2.02 (1.60; 2.68)
lymphocyte
ratio
Women 1.93 (1.50; 2.55) 1.94 (1.53; 2.54) 1.99 (1.51; 2.64) 1.98 (1.61; 2.50) 1.96 (1.54; 2.55)
HDL-cholesterol Men 1.34 (1.15; 1.55) 1.28 (1.09; 1.52) 1.21 (1.03; 1.42) 1.13 (0.98; 1.31) 1.24 (1.05; 1.46)
in mmol/L
Women 1.72 (1.50; 1.98) 1.67 (1.44; 1.90) 1.50 (1.29; 1.76) 1.39 (1.17; 1.59) 1.57 (1.32; 1.82)
The Study of Health in Pomerania (SHIP) 1903

Table 1 (continued )
Parameter First quartile Second quartile Third quartile Fourth quartile Total
n Z 1016 n Z 1012 n Z 1036 n Z 984 n Z 4048
LDL-cholesterol Men 3.13 (2.52; 3.77) 3.38 (2.69; 4.00) 3.38 (2.73; 4.01) 3.33 (2.67; 3.91) 3.30 (2.65; 3.93)
in mmol/L
Women 2.88 (2.39; 3.55) 3.23 (2.69; 3.85) 3.49 (2.96; 4.19) 3.51 (2.87; 4.16) 3.29 (2.70; 3.98)
Glomerular Men 99.7 (89.1; 111) 92.3 (78.5; 105) 84.3 (71.9; 95.8) 82.7 (71.8; 95.0) 90.8 (76.5; 102)
filtration rate
in ml/min
Women 99.4 (86.8; 110) 92.4 (78.5; 103) 86.4 (71.7; 98.0) 79.8 (64.7; 94.0) 89.6 (75.4; 102)
Hypertension in Men 26.2 47.4 69.2 80.2 55.6
%
Women 14.0 28.4 50.5 70.3 40.6
Type 2 diabetes in Men 3.27 6.44 13.3 25.6 12.1
%
Women 0.96 4.14 7.30 22.9 8.80
Data are expressed as median, 25th, and 75th percentile (continuous data) or as percentage (categorical data).
HDL (high-density lipoprotein); LDL (low-density lipoprotein); hsCRP (high-sensitivity C-reactive protein).

different modalities/methods with markers of inflamma-
tion. After adjustment for confounding, we found positive
associations of BMI, body weight, hip circumference, WHR,
WHtR, total body fat, visceral fat, subcutaneous fat, liver
fat, and hsCRP-to-albumin ratio with all inflammatory
markers. Inverse associations were found between body
height, BCM, and absolute FFM with hsCRP, fibrinogen, and
WBC. Markers of central obesity were most strongly
associated with hsCRP, WBC, and ferritin.
In partial agreement with our results, a previous cross-
sectional study found strong associations of CT-derived
visceral adipose tissue with hsCRP and WBC, while there
were no such associations for subcutaneous adipose tissue
[25]. A similar study found a positive association of MRI-
derived liver fat with ferritin in male adolescents, but in
contrast to our study, no such association for visceral ad-
ipose tissue was found [26]. In a random sample of 1000
healthy Qatari adults, positive associations of WC and
visceral obesity with ferritin were observed [27]. In our
study, visceral fat and liver fat were anthropometric
markers, which showed the strongest associations with
ferritin, while WC was most strongly associated with
hsCRP and WBC. The differences in the previous results
[25,26] might be due to the inclusion of overweight/obese
individuals only instead of the general population.
A potential mechanism for our observed associations
can be explained from the role of adipose tissue in the
production of low-grade inflammation [28]. Adipose tissue
produces various types of hormones and cytokines that
can lead to increased levels of inflammatory markers [29].
In obese patients, the production of free fatty acid,
ceramides, and diacylglycerol is increased, which results in
activation of different types of pro-inflammatory serine
kinase reactions [30]. These cascade reactions lead to se-
cretions of cytokines like interleukin-6, which stimulates
the production of CRP in liver [31].
In our study, the inverse associations of body height,
BCM, and FFM with inflammatory markers indicate a
protective effect against inflammation. Similar to our
study, a previous study also found inverse associations of
body height with WBC in middle-aged men with a BMI
23 kg/m2 [32]. Evidence indicates that body height is
positively associated with bone marrow activity and
inversely associated with incidence of mortality from CVDs
[33]. BCM, which is the active part of FFM, has a protective
effect on overall body function [34]. Likewise, results from
seven prospective cohort studies showed that FFM has a
protective effect against mortality [35]. The probable
mechanism might be the activation of myokines in skel-
eton muscles that induce anti-inflammatory activity and
fat oxidation [36].
Importantly, while most of previous studies investi-
gated effects of anthropometric markers on inflammation,
there are also mechanisms that may explain the opposite
direction. Several previous studies reported positive as-
sociations of CRP with BMI, WC, body fat, and visceral
adipose tissue [16,37]. Results from an experimental study
in rats suggest that increased levels of CRP result in
changes to the innate immunity system, thyroid hor-
mones, and gut flora, which are responsible for adult onset
obesity [38]. On the other hand, a Mendelian randomiza-
tion study showed that greater adiposity can increase
circulating levels of CRP with no reverse causation [39,40].
Our study has some limitations. Due to the cross-
sectional design, causal inference cannot be drawn. Lon-
gitudinal studies are needed to investigate the direction of
the observed associations. Furthermore, even though we
included several confounders in our multivariable regres-
sion models, there is still a possibility of residual con-
founding. Assessment for FM, FFM, and BCM was done by
BIA rather than dual-energy X-ray absorptiometry (DXA),
which is the most accurate method. However, the DXA
measurement is not radiation-free and is, therefore, not
feasible in general population samples.
One strength of our study is the large sample size.
Another one is the use of MRI for the assessment of liver
fat content and visceral adipose tissue, which is a more
reliable and sophisticated method than ultrasound and CT
[41]. Furthermore, our study included several body
composition markers derived from BIA.
 1904
Table 2 Associations between body composition markers and inflammatory markers.

Body hsCRP Fibrinogen WBC count Ferritin hsCRP-to-albumin Neutrophil-to-lymphocyte

composition in mg/L in g/L in Gpt/L in mg/L ratio ratio
marker
b (95% CI) b (95% CI) b (95% CI) b (95% CI) b (95% CI) b (95% CI)
Anthropometry
markers
Body mass index 1.22 (1.08; 1.38)a 0.20 (0.18; 0.22)a 0.31 (0.23; 0.39)a 17.6 (12.9; 22.2)a 0.03 (0.03; 0.04)a 0.02 ( 0.06; 0.01)
in kg/m2
Body height in 0.26 ( 0.48; 0.04)a 0.06 ( 0.09; 0.02)a 0.27 ( 0.39; 0.16)a 0.62 ( 7.33; 6.08) 0.01 ( 0.01; 0.00)a 0.05 (-0.10; 0.00)
cm
Body weight in 1.33 (1.16; 1.50)a 0.22 (0.20; 0.25)a 0.33 (0.24; 0.43)a 21.0 (15.8; 26.3)a 0.04 (0.03; 0.04)a 0.03 ( 0.07; 0.01)
kg
Waist 1.39 (1.22; 1.56)a 0.23 (0.20; 0.25)a 0.39 (0.29; 0.48)a 26.1 (20.8; 31.5)a 0.04 (0.03; 0.04)a 0.02 ( 0.06; 0.02)
circumference
in cm
Hip 1.16 (1.00; 1.31)a 0.19 (0.17; 0.21)a 0.30 (0.21; 0.38)a 13.9 (9.20; 18.7)a 0.03 (0.03; 0.04)a 0.01 ( 0.05; 0.02)
circumference
in cm
Waist-to-hip 0.98 (0.77; 1.20)a 0.15 (0.13; 0.19)a 0.32 (0.20; 0.44)a 32.1 (25.6; 38.6)a 0.03 (0.02; 0.03)a 0.03 ( 0.08; 0.02)
ratio
Waist-to-height 1.38 (1.21; 1.54)a 0.23 (0.20; 0.25)a 0.41 (0.32; 0.50)a 24.4 (19.2; 29.5)a 0.04 (0.03; 0.04)a 0.01 ( 0.05; 0.02)
ratio
Bioelectrical
impedance
analysis
Absolute body 1.19 (1.04; 1.33)a 0.22 (0.20; 0.24)a 0.27 (0.19; 0.35)a 18.3 (13.7; 22.9)a 0.00 (0.00; 0.00)a 0.00 ( 0.01; 0.00)
fat in kg
Relative body fat 1.39 (1.20; 1.58)a 0.29 (0.27; 0.32)a 0.35 (0.25; 0.46)a 24.4 (18.5; 30.3)a 0.04 (0.03; 0.04)a 0.01 ( 0.01; 0.00)a
in %
Absolute fat- 0.34 ( 0.64; 0.04)a 0.17 ( 0.21; 0.12)a 0.21 ( 0.38; 0.04)a 1.68 ( 7.73; 11.1) 0.01 ( 0.02; 0.00)a 0.05 ( 0.12; 0.02)
free mass in
kg
Body cell mass 0.49 ( 0.78; 0.20)a 0.13 ( 0.17; 0.09)a 0.18 ( 0.33; 0.02)a 10.6 (1.69; 19.5)a 0.01 ( 0.02; 0.01)a 0.11 ( 0.18; 0.04)a
(BCM) in kg
Magnetic
resonance
imaging
Visceral fat in L 1.02 (0.71; 1.34)a 0.17 (0.13; 0.21)a 0.37 (0.25; 0.49)a 41.9 (34.7; 49.0)a 0.03 (0.02; 0.04)a 0.08 (-0-15; 0.02)a
Subcutaneous 0.96 (0.70; 1.21)a 0.20 (0.17; 0.23)a 0.29 (0.19; 0.39)a 21.8 (15.9; 27.7)a 0.03 (0.02; 0.03)a 0.05 ( 0.11; 0.00)
fat in L
Liver fat in % 0.50 (0.25; 0.76)a 0.06 (0.02; 0.09)a 0.17 (0.08; 0.27)a 33.5 (27.7; 39.2)a 0.01 (0.01; 0.02)a 0.12 ( 0.17; 0.07)a
Linear regression models adjusted for age, sex, smoking status, and physical activity. Models with FFM, ECM, and BCM are further adjusted for absolute FM. Exposures were standardizeddcoefficients
can be interpreted as a difference in the inflammatory marker by 1 standard deviation of the respective body composition markers.

S. Bibi et al.
a
p < 0.05; CI confidence interval.
The Study of Health in Pomerania (SHIP)
Figure 1 Associations of body composition markers with hsCRP levels
adjusted for age, sex, smoking status, and physical activity. Data are
expressed as standardized beta coefficient and 95% confidence interval.
Figure 2 Associations of body composition markers with ferritin
levels adjusted for age, sex, smoking status, and physical activity. Data
are expressed as standardized beta coefficient and 95% confidence
interval.
5. Conclusions
In this study, we examined associations of a broad range of
body composition markers with inflammatory markers. WC
and relative body FM showed the strongest associations
with hsCRP, fibrinogen, and WBC, while visceral fat and
liver fat content were most strongly associated with ferritin.
Our study indicates the importance of WC as a cheap
marker for early inflammation. MRI-assessed markers of
central obesity seem to be most strongly related to ferritin.
This study indicates the role of body composition markers
in the setup of early inflammation. It is important to stop
the obesity pandemic in order to prevent inflammatory-
related severe clinical conditions. This study argues for the
longitudinal studies with large data sets to clarify the
possible mechanism between inflammatory markers, fat
distribution, and chronic inflammation-related diseases.
Declaration of competing interest
The authors do not have any disclosures to report.
1905
Acknowledgement and funding
SHIP is part of the Community Medicine Research Network
of the University Medicine Greifswald, which is supported
by the German Federal State of Mecklenburg-West Pomer-
ania, the Ministry of Cultural Affairs, and the Social Ministry
of the Federal State of Mecklenburg-West Pomerania. The
CMR encompasses several research projects that are sharing
data of the population-based Study of Health in Pomerania
(SHIP; http://ship.community-medicine.de).
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.numecd.2023.05.026.
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