Vol.2, No.9, 1078-1084 (2010) Health
doi:10.4236/health.2010.29158
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
High-sensitivity C-reactive protein as a marker of
cardiovascular risk in obese children and adolescents
Hatem Hamed El-shorbagy1*, Ibraheim Abdel-aziz Ghoname2
1Departments of Pediatrics, Faculty of Medicine, Menoufia University and Clinical Pathology, Shibin el Kom, Egypt
2Departments of Pediatrics, Faculty of Medicine Al-azhar University, Cairo, Egypt; *Corresponding Author: hatem732000@yahoo.com
Received 20 February 2010; revised 19 April 2010; accepted 20 April 2010.
ABSTRACT
Background and aim of the work: High-sensiti-
vity C-reactive protein (hsCRP) is a marker of
low grade inflammatory state, which character-
ises an atherosclerotic process. The metabolic
syndrome is associated with insulin resistance
and a systemic low-grade inflammatory state.
These disorders may arise at a very early age in
obese children. We aimed to assess the utility of
(hsCRP) as a marker of cardiovascular risk in
obese children and adolescents. Patients and
methods: This study was conducted on 100
obese child and adolescents (6-16 years). 50
apparently healthy children of matched age and
sex served as control. All patients and controls
were subjected to: 1-complete history taking.
2-anthropometric measurements and clinical
examination including body height, weight,
waist circumference, body mass index and
blood pressure. 3-laboratory investigations in-
cluding fasting glucose, lipid profile, apolipo-
protiens and (hsCRP) were assessed. Metabolic
syndrome patients had to meet three out of five
criteria: concentration of triglycerides (TG) 110
mg/dL, high density lipoprotein cholesterol (HDL-
C) 40 mg/dL, waist circumference 90th per-
centile, glucose concentration 110 mg/dL, and
systolic or diastolic blood pressure 90th per-
centile. Results, height, weight BMI and blood
pressure were significantly higher in the obese
than the control. Obese group had significantly
higher (hsCRP) levels than control group, (p <
0.01) and significantly higher LDL-C, triglyceride
(TG), and lower HDL-C than the control group.
Log (hsCRP) showed a positive correlation with
BMI (p < 0.001), blood pressure, and TG. The pre-
valence of the metabolic syndrome was 24%.
Mean concentrations of (hsCRP) were higher
among patients who had the metabolic syn-
drome. Among whom, 35% had a concentration
of (hsCRP) > 3.0 mg/L, a concentration consid-
ered to place adults at high risk for cardiovas-
cular disease. In multiple logistic regression
analysis only abdominal obesity was signifi-
cantly associated with (hsCRP). Conclusion: me-
tabolic syndrome and abdominal obesity among
our patients predispose to cardiovascular dis-
ease later in life through early low grade in-
flammation. (hsCRP) is one of the inflammatory
markers that can be easily estimated in these
patients.
Keywords: HsCRP; Cardiovascular Risk; Obesity
1. INTRODUCTION
The prevalence of childhood obesity has more than dou-
bled in the last 15 years in many regions of the world [1].
This phenomenon is associated with a rapidly increasing
trend in cases of type 2 diabetes in childhood. Obesity in
childhood also seems to harbor a number of risk factors
for cardiovascular disease (CVD) in adult life, but is not
yet clear whether these are determined by glycemia, de-
gree of obesity, or other demographic, clinical, or bio-
chemical features of the obese child [2]. Childhood obe-
sity seems to contribute to the development of vascular
inflammation and the progression of arterial wall
changes. (hsCRP) has recently emerged as a useful bio-
marker for vascular inflammation associated with athe-
Rosclerosis [3]. Of novel risk factors for cardiovascular
disease currently under investigation, high-sensitivity
C-reactive protein (hsCRP) is the most promising. To
date, more than 20 prospective epidemiologic studies
have demonstrated that (hsCRP) independently predicts
vascular risk [4]. CRP is a major inflammatory cytokine
that functions as a nonspecific defense mechanism in
Aim of the work: We aimed to assess the utility of the high-sensitivity
C-reactive protein (hsCRP) as a marker of cardiovascular risk in obese
children and adolescents.
H. H. El-shorbagy et al. / HEALTH 2 (2010) 1078-1084
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
1079
response to tissue injury or infection. Synthesized mainly
in the liver, CRP activity is stimulated by other cytokines,
especially interleukin (IL)-6, IL-1β, and tumor necrosis
factor-α (TNF-α). Accumulating evidence suggests that
CRP, which is also found within macrophages of athero-
matous plaques, is causally or mechanistically related to
atherothrombosis [5]. The metabolic syndrome has gen-
erated a great deal of interest in recent years. Comprised
of a constellation of anthropometric, physiologic, and bio-
chemical abnormalities, the metabolic syndrome is a risk
factor for cardiovascular disease and diabetes among
adults. However, research about the metabolic syndrome
among children and adolescents and the implications of
having the metabolic syndrome is limited [6]. The
metabolic syndrome has been defined as a cluster of risk
factors for atherosclerotic cardiovascular disease that
includes insulin resistance, dyslipidemia, abdominal
adiposity, and often hypertension [7].
2. PATIENTS AND METHODS
This study was conducted on 100 obese child and ado-
lescent (simple obesity) their ages ranged from (6-16
years) enrolled from pediatric outpatient clinic, Prince
Sultan Armed Forces Hospital, Saudia Arabia. 50 ap-
parently healthy children of matched age and sex served
as control.
Exclusion Criteria:
1) Smokers.
2) Under any regular medication.
3) Family history of premature vascular disease.
4) Any symptoms of infection during the 2 weeks be-
fore the study.
5) Underlying etiology (secondary obesity).
All patients and controls were subjected to:
1) Complete history taking
2) Anthropometric measurement and clinical examina-
tion: All anthropometric measurements were taken with
stress on body height and weight were measured in light
clothes using a portable standiometer. Body mass index
(BMI) was calculated as weight divided by the square of
the height (kg/m2). In children, > 95th percentile for
BMI growth chart is considered obese (4), so we used
BMI > 30 as our prospectively defined criterion for
obesity, and BMI < 25 was defined as the non-obese
control level [8].
Waist circumference was measured at the high point
of the iliac crest to the nearest 0.1 cm at the end of nor-
mal expiration with a steel measuring tape. Blood pres-
sure measurements were obtained for each participant in
the study. Participants were seated with their right arm
resting at the level of the heart. Blood pressure was mea-
sured with a mercury-gravity sphygmomanometer. Child,
adult, and large arm-cuff sizes were available.All meas-
ures were evaluated according to appropriate centiles.
Characteristics of studied groups was shown in Table 1,
There was found that height, weight and BMI were sig-
nificantly higher in the obesity group than in the control
group. BMI was 27.20 ± 12.30 kg/m2 in the obesity
group and was 16.68 ± 2.00 kg/m2 in the control group.
Obese children had significantly higher systolic blood
pressure (SBP) (115.0 ± 9.95 mmHg vs. 95.0 ± 7.82
mmHg) and diastolic blood pressure (DBP) (75.85 ±
5.03 mmHg vs. 68.28 ± 7.45 mmHg).
3. LABORATORY INVESTIGATIONS
Fasting glucose: concentration was measured using the
glucose hexokinase method [9].
Serum lipids and apolipoprotein: Venous blood
samples were taken in the morning after overnight fast-
ing (10-12 hr). Serum total cholesterol (TC), low density
lipoprotein cholesterol (LDL-C), high density lipopro-
tein cholesterol (HDL-C), and triglyceride (TG) concen-
trations were measured by standard enzymatic methods
with the use of Boehringer Mannheim GmbH and a fully
automatic analyzer. Serum apolipoprotein A-1 (Apo A-1),
apolipoprotein B (Apo B), and apolipoprotein E (Apo E)
were measured by immunonephelometry (Behring Ne-
phelometer II, Dade Behring, Inc., Newark, DE [10].
High-sensitivity C-reactive protein was assessed with
the immunonephelometric assay method using company
reagents (assessments made using high sensitivity method
with a latex intensification). High-sensitivity C-reactive
protein A BN II Nephelometer Analyzer (Dade Behring,
Inc.) was used to measure serum (hsCRP) values using a
high sensitivity latex-enhanced immunonephelometric
assay method. The detection limit of this assay was 0.17
mg/dL. Because the 90th percentile of normal CRP dis-
tribution is 0.3 mg/dL, we included only patients with
Table 1. Comparison of characteristics between obesity and
control groups.
Obesity (N = 100) Control (N = 50)P
Age 11.82 ± 0.6 11 ± 0.2 NS
Height 134.23 ± 4.0 125.13 ± 6.0 < 0.01
Weight 68.05 ± 14.40 31.56 ± 7.28 < 0.01
BMI 27.20 ± 12.30 16.68 ± 2.00 < 0.01
Systolic BP 115.0 ± 9.95 95.0 ± 7.82 < 0.01
Diastolic BP75.85 ± 5.03 68.28 ± 7.45 < 0.01
NS: not significant.
H. H. El-shorbagy et al. / HEALTH 2 (2010) 1078-1084
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
1080
CRP values below 0.3 mg/dL to avoid the influence of
acute infection [11]. Metabolic syndrome, Patients had
to meet three out five criteria: concentration of triglyc-
erides 110 mg/dL, HDL cholesterol 40 mg/dL, waist
circumference 90th percentile (sex specific), glucose
concentration 110 mg/dL, and systolic or diastolic
blood pressure 90th percentile (age, height, and sex
specific) [6].
Statistical analysis: Data was collected and expressed
in tables. SPSS version computer program was used for
all statistical calculations. Results were expressed as
mean ± standard deviation. Geometric mean and stan-
dard error were calculated. Comparisons between two
groups were performed by the independent student-t test.
Univariate and multivariate regression analyses were
used to delineate the relationships between components
of metabolic syndrome and (hsCRP). Due to the skewed
distribution of (hsCRP) levels, (hsCRP) values were lo-
garithmically transformed prior to regression analyses.
For all analyses, probability (p) values below 0.05 were
considered statistically significant tests were performed
to compare mean and log-transformed concentrations of
hsCRP. We examined the independent contribution of the
five components of the metabolisc syndrome to (hsCRP)
concentration in multiple linear regression analyses.
For regression analyses, (hsCRP) concentration was log
transformed to improve the distribution of this variable
[12].
4. RESULTS
Results of our study were expressed in the following
tables:
Table 2 shows comparison of metabolic parameters
between obesity and control groups: Obese group had
significantly higher hs-CRP levels than control group,
hs-CRP levels were 1.40 ± 0.78 mg/dL vs. 0.56 ± 0.47.
mg/dL, p < 0.01 and significantly higher LDL-C, TG,
Apo B and lower HDLC than the control group. TC and
Apo E were higher and Apo A-1 was lower in the obe-
sity group than in the control group, but these differ-
ences were statistically insignificant.
Table 3 shows Correlation of log hs-CRP with BMI,
BP, lipid profile, and apolipoprotein concentrations: Log
[hsCRP] showed a positive correlation with BMI (r =
0.464, p < 0.001), SBP (r = 0.207, p < 0.05), DBP (r =
0.225, p < 0.05), Apo E (r = 0.272, p < 0.01), and TG (r
= 0.298, p < 0.05) by simple regression.
Table 4 shows Unadjusted mean concentrations ± SE,
geometric mean concentrations ± SE, and percentage ±
SE of CRP > 3.0 mg/L by presence or absence of meta-
bolic syndrome or its five components among patients:
Among all patients 50% had no components of meta-
bolic syndrome, 20% had one component, 6% had two
components, 20% had three components, and 4% had
four components. No participants had all five compo-
nents. The prevalence of the metabolic syndrome was
24% (no sex difference was found, P > 0.05). Further-
more, 40% had a large waist circumference, 32% had
Table 2. Comparison of metabolic parameters between obesity
and control groups.
metabolic
parameters Obesity (N = 100) Control (N = 50) P
TC (mg/dL)180.45 ± 25.30 160.23 ± 24.67 NS
HDL-C
(mg/dL) 53.40 ± 11.78 61.45 ± 14.08 < 0.05
LDL-C
(mg/dL) 105.04 ± 22.70 92.62 ± 22.61 < 0.05
TG (mg/dL)130.45 ± 68.37 88.23 ± 45.23 < 0.01
Apo A1
(mg/dL) 65.13 ± 21.67 68.65 ± 22.55 NS
Apo B
(mg/dL) 27.78 ± 30.0 20.00 ± 8.47 < 0.05
Apo E
(mg/dL) 2.89 ± 1.23 2.32 ± 1.35 NS
hs-CRP
(mg/L) 1.40 ± 0.78 0.56 ± 0.47 < 0.01
TC, total cholesterol; HDL-C, high density lipoprotein cholesterol; LDL-C,
low density lipoprotein cholesterol; TG, triglyceride; Apo A-1, apolipopro-
tein A-1; Apo B, apolipoprotein B; Apo E, apolipoprotein E; NS,not sig-
nificant; p, p-value.
Table 3. Correlation of log (hsCRP) with BMI, BP, lipid pro-
file, and apolipoprotein concentrations.
Variables hs-CRP R P
BMI 0.464 < 0.001
SBP 0.207 < 0.05
DBP 0.225 < 0.05
TC 0.087 NS
LDL 0.101 NS
HDL 0.113 NS
TG 0.298 < 0.01
ApoA 0.173 NS
ApoB 0.015 NS
ApoE 0.272 < 0.01
BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood
pressure; PP, pulse pressure; TC, total cholesterol; LDL-C, low density
lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol; TG,
triglyceride; Apo A-1, apolipoprotein A-1; Apo B, apolipoprotein B; Apo E,
apolipoprotein E; r, correlation coefficient; p, p-value.
H. H. El-shorbagy et al. / HEALTH 2 (2010) 1078-1084
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
1081
Table 4. Unadjusted mean concentrations ± SE, geometric mean concentrations ± SE, and percentage ± SE of CRP > 3.0 mg/L by
presence or absence of metabolic syndrome or its five components among patients.
Metabolic syndrome
or components
Sample
Yes Size No Mean Yes +_SE No(mg/l) PGeometric
Yes
mean +_SE
(mg/l)
No
p %_SE of
Yes CRP No> 3 mg/l p
Metabolic syndrome 25 75 3.8 ± 1.2 1.3 ± 0.2< 0.051.9 ± 0.50.4 ± 0.04< 0.00135 ± 7.2 12.7 ± 0.3< 0.05
Abdominal obesity 40 60 3.8 ± 0.3 0.9 ± 0.4< 0.0011.8 ± 0.40.5 ± 0.02< 0.00133.0 ± 5.0 5.4 ± 0.8< 0.001
Hypertriglyceridemia 32 68 1.6 ± 0.4 1.4 ± 0.8> 0.050.6 ± 0.20.4 ± 0.04< 0.0512.6 ± 2.1 10.8 ± 109> 0.05
Low HDL cholesterol 28 72 2.1 ± 0.9 1.6 ± 0.6> 0.050.8 ± 0.30.4 ± 0.03< 0.0512.4 ± 0.3 8.8 ± 0.6> 0.05
High blood pressure 18 82 5.1 ± 0.3 1.7 ± 0.8> 0.050.7 ± 0.40.5 ± 0.07< 0.0520.2 ± 6.5 11.3 ± 0.3< 0.05
0.6 Hyperglycemia
_110 mg/dl 6 94 2.4† 1.7 ± 0.6- 0.9 † 0.5 ± 0.03- 16.4† 11.2 ± 0.7-
P value calculated based on log-transformed concentration of CRP. †Unstable estimates.
Table 5. Results of multiple linear regression analysis with
concentration of log-transformed hsCRP as the dependent va-
riable among patients.
Independent variables Regression
coefficient SE P
Age (years) 0.104 0.129 0.003
Sex (male vs. female)
(ref.) 0.068 0.113 0.524
Abdominal obesity
Yes vs. no (ref.) 1.876 0.123 0.001
Hypertriglyceridemia
Yes vs. no (ref.) 0.061 0.132 0.670
HDL < 40
Yes vs. no (ref.) 0.157 0.120 0.117
High blood pressure
Yes vs. no (ref.) 0.257 0.264 0.134
Glucose_110
Yes vs. no (ref.) 0.038 0.253 0.139
hypertriglyceridemia, 28% had a low concentration of
HDL cholesterol, 18% had high blood pressure and 6%
had a concentration of glucose 110 mg/dL. Mean and
geometric mean concentrations of hs CRP were higher
among patients who had the metabolic syndrome (mean
3.8 mg/L, geometric mean 1.9 mg/L) than among those
who did not (mean 1.3 mg/L, geometric mean 0.4 mg/L).
Among patients with the metabolic syndrome, 35% had a
concentration of hsCRP > 3.0 mg/L, a concentration con-
sidered to place adults at high risk for cardiovascular
disease. In comparison, 12.7% of adolescents without
the syndrome had such a concentration of hsCRP (P <
0.05).
Table 5 shows results of multiple linear regression
analysis with concentration of log-transformed CRP as
the dependent variable among patients.
Of the five components of the metabolic syndrome,
mean concentration of hs CRP was higher only among
those with abdominal obesity. However, mean concen-
trations of log-transformed hsCRP were higher among
patients with abdominal obesity, hypertriglyceridemia,
low HDL cholesterol, and high blood pressure compared
with patients without those conditions. In multiple logis-
tic regression analysis with age, sex, and all five com-
ponents of the metabolic syndrome added as independ-
ent variables, only abdominal obesity was significantly
and independently associated with log-transformed con-
centration of hsCRP. When the same five components
were examined as continuous variables in another linear
regression model, only waist circumference was signifi-
cantly associated with concentrations of log-transformed
hsCRP. Results from an analogous logistic regression
model with dichotomized concentration of hsCRP as the
dependent variable and the five components added as
continuous independent variables yielded similar con-
clusions.
5. DISCUSSION
While there have been many previous studies relating
CRP and cardiovascular risk factors, the association of
CRP with subclinical cardiovascular complication has
been examined primarily in adults, with few studies in
obese children [13]. Traditional risk factors for cardio-
vascular disease include aging, hypertension, dyslipide-
mia, smoking, and diabetes. The contribution of lipid
accumulation to atherosclerotic disease is well known,
but laboratory and experimental evidence indicates that
chronic inflammatory processes also play an important
role in the development of atherosclerosis [14]. In order
to prevent the incidence of cardiovascular events, it is
important to weigh the influence of each risk factor on
the cardiovascular system [15]. In this respect, we inves-
tigated the relationship of inflammatory markers with
other risk factors. In our study, we found that height,
H. H. El-shorbagy et al. / HEALTH 2 (2010) 1078-1084
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
1082
weight and BMI were significantly higher in the obesity
group than in the control group. Also, obese group had
significantly higher hs-CRP, LDL-C, TG and Apo B and
significantly lower HDLC than the control group. These
findings were in concordance with Quijada et al. (2008)
who stated that, Systolic, diastolic, and mean blood
pressures (MBP), low-density lipoprotein cholesterol
(LDL-C), Tg/HDL-C, total cholesterol/HDL-C, LDL-C/
HDL-C ratios, CRP, and leptin were significantly higher
in the obese group [16]. Our study showed elevated se-
rum hsCRP levels were positively associated with ele-
vated BMI, confirming previous observations in both
children [17] and adults [18]. The mechanisms underly-
ing this association with BMI or obesity might be as
follows; the adipose tissue is a source of cytokines such
as tumor necrosis factor-a (TNF-a) and interleukin-6
(IL-6), and these cytokines stimulate the production of
acute-phase proteins such as C-reactive protein in the
liver. Not unexpectedly, then, we found that serum
hsCRP levels were positively associated with BMI [19].
Our results are in agreement of Martos et al. (2009) who
reported that C-reactive protein (CRP) levels were sig-
nificantly (P < 0.001) higher in obese children than in
controls. After 9 months of treatment, obese children
with lowered BMI SD score (SDS-BMI) displayed a
significant decrease CRP (P = .006), levels compared
with obese children with stable SDS-BMI. In addition to
BMI, hsCRP was also found to be closely correlated
with SBP, DBP, and ApoE and TG concentrations. Pre-
vious studies reported that CRP levels are significantly
positively correlated with TG, total ratio of serum cho-
lesterol to serum HDL cholesterol, fibrinogen levels,
heart rate, SBP, smoking, and white blood cell count and
negatively correlated with HDL-C levels [20]. In this
study, the prevalence of the metabolic syndrome was
24%. Mean and geometric mean concentrations of hs
CRP were significantly higher among patients who had
the metabolic syndrome than among those who did not.
Among patients with the metabolic syndrome, 35% had
a concentration of hsCRP > 3.0 mg/L, a concentration
considered to place adults at high risk for cardiovascular
disease. In comparison, 12.5% of adolescents without the
syndrome had such a concentration of hsCRP (P < 0.05).
Soriano-Guillén et al. (2008) carried out his study on
115 obese children, 24% showed signs of metabolic syn-
drome. Those with metabolic syndrome presented higher
levels of hs-CRP in comparison with the obese patients
who did not show signs of metabolic syndrome After a
multivariate analysis, the variables that appeared to in-
fluence the changes in (hsCRP)were BMI, triglycerides
and HDL-cholesterol levels. From his study he con-
cluded that (hsCRP) is a useful tool for early diagnosis
of cardiovascular risk in obese children and teenagers
[21]. Current estimates are that approximately 25% of
American adults, and an increasing percentage of chil-
dren and adolescents, can be classified as having Meta-
bolic Syndrome. The wide prevalence of metabolic Syn-
drome makes this condition a major contributor to car-
diovascular risk [6]. Of the five components of the me-
tabolic syndrome, mean concentration of (hsCRP) was
higher only among those with abdominal obesity. How-
ever, mean concentrations of log-transformed hs CRP
were higher among patients with abdominal obesity,
hypertriglyceridemia, low HDL cholesterol, and high
blood pressure compared with patients without those
conditions. Weiss et al., 2004 agreed that log-transformed
(hsCRP) levels were affected by abdominal obesity, hy-
pertriglyceridemia, hypertension, HDL cholesterol, and
high blood pressure [22]. The metabolic syndrome has
generated a great deal of interest in recent years. Among
adults and adolescents, components of the metabolic
syndrome and the metabolic syndrome itself are associ-
ated with measures of inflammation, such as concentra-
tions of (CRP). This low-grade inflammation, which has
been associated with an increased risk for cardiovascular
disease and diabetes may provide a mechanism for the
increased risk of these conditions experienced by indi-
viduals who have the metabolic syndrome, however,
abdominal obesity was the component that was respon-
sible for much of the difference in concentrations of
(hsCRP) [23]. The present study showed association
between obesity and elevated concentrations of (hsCRP)
in children and adolescents. In univariate analysis, con-
centrations of (hsCRP) have also been significantly as-
sociated with the other four components of the metabolic
syndrome. Our results suggest that the presence of the
metabolic syndrome and abdominal obesity among chil-
dren and adolescents may be laying the foundation for
the emergence of cardiovascular disease and diabetes
later in life through early low-grade inflammation. Un-
fortunately, the sample size was inadequate to provide
results separately for males and females. Similar results
were obtained by Cizmecioglu et al. (2009) as they
found that Waist circumference had the highest sensitiv-
ity and specificity for predicting MS in their patients
[24]. We appreciate the comments of Dr. Kholeif re-
garding the utility of (CRP) measurement in stratifying
cardiovascular disease (CVD) risk as it relates to our
results of patients with the metabolic syndrome catego-
rizing CRP into normal (_1 mg/l), borderline (1-3 mg/L),
and high-risk (_3 mg/l) levels are appropriate for strati-
fying patient risk in combination with other risk factor
[25]. While our data must be interpreted cautiously be-
cause they are of a cross-sectional nature, our findings
are consistent with those of Ridker et al. showing meta-
bolic syndrome patients with elevated (hsCRP) levels to
H. H. El-shorbagy et al. / HEALTH 2 (2010) 1078-1084
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
1083
have a less optimistic prognosis than those with normal
(hsCRP) levels [26]. Although our study relied on a sin-
gle measurement as provided by the National Health and
Nutrition Examination Survey (NHANES) study and
thus did not have duplicate measures over time, Dr.
Kholeif reported that a single CRP measurement, given
its intraindividual biological variability, is not suitable
and that the use of multiple measures would establish the
certainty of a given level [25]. Recently, the Centers for
Disease Control (CDC)/American Heart Association
(AHA) workshop on markers of inflammation and car-
diovascular disease did recommend that the mean of
only two measures taken 2 weeks apart could be aver-
aged to provide a clinically useful value [27]. The stud-
ies above demonstrate that vascular risk prediction and
the prediction of type 2 diabetes can be improved by
knowledge of (hsCRP) levels, even among those with
metabolic syndrome. Recent studies relating (hsCRP) to
incident hypertension serve to reinforce the importance
of blood pressure in the metabolic syndrome complex
[28,29] Investigators have long hypothesized links be-
tween the metabolic derangements of insulin resistance
syndrome/type 2 diabetes and the development and pro-
gression of atherosclerosis. A number of investigators
have similarly concluded that IL-6 and CRP are associ-
ated with hyperglycemia, insulin resistance, and overt
type 2 diabetes, and both are strong predictors of car-
diovascular disease in apparently healthy people [30].
Although ultrasonography allows visualization of early
subclinical stages of atherosclerosis in obese children,
the measurement of the serum (hsCRP) level is simpler
and cheaper than ultrasonography, is highly reproducible,
and well correlates with carotid intima-media wall thi-
ckness (IMT) and brachial flow-mediated dilation in
obese children (FMD). Thus, (hsCRP) would be a useful
screening marker for evaluating and estimating the de-
gree of atherosclerosis in children [31].
6. CONCLUSIONS
Our results suggest that the presence of the metabolic
syndrome and abdominal obesity among children and
adolescents may be laying the foundation for the emer-
gence of cardiovascular disease later in life through early
low grade inflammation. hsCRP is one of the inflamma-
tory markers that can be easily estimated in these pa-
tients.
7. RECOMMENDATION
hsCRP can be used as a useful screening test for predic-
tion of cardiovascular changes in Obese children and
adolescents. More work is needed to establish whether
intervention targeting “highrisk” metabolic syndrome
patients, identified on the basis of elevated (hsCRP),
effectively lowers CVD risk. To reduce adverse effects
of inflammation that accompanies the metabolic syn-
drome, children should avoid excessive energy intake,
limit sedentary behavior, and increase their energy ex-
penditure. In contrast to other biomarkers that also reflect
inflammation, (hsCRP) measurement is inexpensive, stan-
dardized, widely available, and has a decade-to-decade
variation similar to that of cholesterol. Given the consis-
tency of prognostic data for (hsCRP) and the practicality
of its use in outpatient clinical settings, we believe the
time has come for a careful consideration of adding
(hsCRP) as a clinical criterion for metabolic syndrome
and for the creation of an (hsCRP) modified coronary
risk score useful for global risk prediction.
REFERENCES
[1] Chinn S. and Rona, R.J. (2008) Prevalence and trends in
overweight and obesity in three cross sectional studies of
British children, 1974-1994. British Medical Journal,
322(7277), 24-26.
[2] Bruno, G., Fornengo, P., Novelli, G., Panero, F., Perotto,
M., Segre, O., et al. (2009) C-reactive protein and 5-year
survival in type 2 diabetes: The casale monferrato study.
Diabetes, 58(4), 926-933.
[3] Ridker, P.M. (2007) CRP and the prediction of cardio-
vascular events among those at intermediate risk. Journal
of the American College of Cardiology, 49(21), 2129-
2138.
[4] Sinha, R., Fisch, G., Teague, B., Tamborlane, W.V., Ban-
yas, B., Allen, K., et al. (2002) Prevalence of impaired
glucose tolerance among children and adolescents with
marked obesity. The New England Journal of Medicine
346, 802-810.
[5] David, M., Capuzzi, A., Jeffrey, S. and Freeman (2007)
CRP and cardiovascular risk in the Metabolic Syndrome.
Clinical Diabetes, 25(1), 16-22.
[6] Chen, J. (2009) Metabolic syndrome and salt sensitivity
of blood pressure in non-diabetic people in China, a die-
tary intervention study. Lancet, 373(9666), 829-835.
[7] Steinberger, J., Daniels, S.R. and Eckel, R.H. (2009):
Progress and challenges in metabolic syndrome in chil-
dren and adolescents. Circulation, published online.
[8] Ford, E.S., Galuska, D.A., Gillespie, C., Will, J.C., Giles,
W.H. and Dietz, W.H. (2001) CRP and body mass index in
children. Journal of Pediatric Surgery, 138(4), 486-492.
[9] Shea, S., Aymong, E., Zybert, P., Shamoon, H., Tracy,
R.P., Deckelbaum, R.J., et al. (2003) Obesity, fasting
plasma insulin and CRP levels in healthy children. Obe-
sity Research, 11(1), 95-103.
[10] Vikram, N.K., Misra, A., Dwivedi, M., Sharma, R.,
Pandey, R.M., Luthra, K., et al. (2003) Correlations of
CRP levels with anthropometric profile. Ath e rosc l erosi s ,
168(2), 305-313.
[11] Roberts, W.L., Moulton, L. and Law, T.C. (2001) Evalua-
tion of nine automated (hsCRP) methods. Clinical Che-
H. H. El-shorbagy et al. / HEALTH 2 (2010) 1078-1084
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
1084
mistry, 47(5), 979-980.
[12] Goldstone, L.A. (1983) Statistical tests and concepts of
significance. Understanding Medical Statistics, 1st Ed-
tion, William Heinman Medical Books Ltd., London.
[13] Cook, D.G., Mendall, M.A., Whincup, P.H., Carey, I.M.,
Ballam, L., Morris, J.E., et al. (2000) C-reactive protein
concentration in children: relationship to adiposity and
other cardiovascular risk factors. A therosclerosis, 149(1),
139-150.
[14] Ryu, S.Y., Lee, Y.S., Park, J., Kang, M.G. and Kim. K.S.
(2005) Relations of plasma (hsCRP) to various cardio-
vascular risk factors. Journal of Korean Medical Science,
20(3), 379-383.
[15] Caballero, A.E., Bousquet-Santos, K., Robles-Osorio, K.,
Montagnani, V., Soodini, G., Porramatikul, S., et al.
(2008) Overweight latino children and adolescents have
marked endothelial dysfunction and subclinical vascular
inflammation. Diabetes Care, 31(3), 576-582.
[16] Quijada, Z., Paoli, M., Zerpa, Y., Camacho, N., Cichetti,
R., Villarroel, V., et al. (2008) The triglyceride/HDL-
cholesterol ratio as a marker of cardiovascular risk in
obese children; association with traditional and emergent
risk factors. Pediatric Diabetes, 9(5), 464-471.
[17] Lambert, M., Delvin, E.E., Paradis, G., O’Loughlin, J.,
Hanley, J. and Levy, E. (2004) CRP and metabolic syn-
drome children and adolescents. Clinical Chemistry, 50,
1762-1768.
[18] Ruckerl, R., Peters, A., Khuseyinova, T., Andreani, M.,
Koenig, W., Meisinger, C., et al. (2009) Determinants of
the acute-phase protein c-reactive protein in myocardial
infarction survivors. Clinical Chemistry, 55(2), 322-335.
[19] Hiura, M., Kikuchi, T., Nagasaki, K. and Uchiyama, M.
(2003) Elevation of serum CRP levels is associated with
obesity in boys. Hypertension Research, 26(7), 541-546.
[20] Martos, R., Valle, M., Morales, R.M., Cañete, R., Gascón,
F. and Urbano, M.M. (2009) Changes in body mass index
are associated with changes in inflammatory and endo-
thelial dysfunction biomarkers in obese prepubertal chil-
dren after 9 months of body mass index SD score loss.
Metabolism.
[21] Soriano-Guillén, L., Hernández-García, B., Pita, J., Do-
mínguez-Garrido, N., Del Río-Camacho, G., et al. (2008)
HsCRP is a good marker of cardiovascular risk in obese
children and adolescents. European Journal of Endocri-
nology, 159(1), R1-R4.
[22] Weiss, R., Dziura, J., Burgert, T.S., Tamborlane, W.V.,
Taksali, S.E., Yeckel, C.W., et al. (2004) Obesity and the
metabolic syndrome in children and adolescents. The
New England Journal of Medicine, 350(23), 2362-2374.
[23] Danesh, J., Wheeler, J.G., Hirschfield, G.M., Eda, S.,
Eiriksdottir, G., Rumley, A., et al. (2004) CRP and other
circulating markers of inflammation in the prediction of
coronary heart disease. The New England Journal of
Medicine, 350(14), 1387-1397.
[24] Cizmecioglu, F.M., Etiler, N., Ergen, A., Gormus, U.,
Keser, A., Hekim, N., et al. (2009) Association of adi-
ponectin, resistin and hscrp level with the metabolic syn-
drome in childhood and adolescence. Experimental and
Clinical Endocrinology & Diabetes, 117(10), 622-627.
[25] Kholeif, M.A. (2005) CRP for cardiovascular risk assess.
Diabetes Care, 28(7), 1833-1834.
[26] Ridker, P.M., Wilson, P.W.F. and Grundy, S.M. (2004)
Should CRP be added to metabolic syndrome and to as-
sessment of global cardiovascular risk? Circulation, 109
(23), 2818-2825.
[27] Myers, G.L., Rifai, N., Tracy, R.P., Roberts, W.L., Alex-
ander, R.W., Biasucci, L.M., et al. (2005) The Centers for
Disease Control, the American Heart association: CDC/
AHA workshop on markers of inflammation and cardio-
vascular disease. Circulation, 110(6), 22-26.
[28] Reaven, P.D., Traustadottir, T., Brennan, J. and Nader,
P.R. (2005) Cardiovascular risk factors associated with
insulin resistance in children persist into late adolescence.
Diabetes Care, 28(1), 148-150.
[29] Kriketos, A.D., Greenfield, J.R., Peake, P.W., Furler, S. M.,
Denyer, G.S., Charlesworth, J.A. and Campbell, V., et al.
(2004) Inflammation, insulin resistance, and adiposity: A
study of first-degree relatives of type 2 diabetes. Diabe-
tes Care, 27(8), 2033-2040.
[30] Mattsson, N., Rönnemaa, T., Juonala, M., Viikari, J.S.
and Raitakari, O.T. (2008) Childhood predictors of the
metabolic syndrome in adulthood. Annals of Medicine,
40(7), 542-552.
[31] Roh, E.J., Lim, J.W., Kyoung, O.K. and Cheon, E.J.
(2007) A useful predictor of early atherosclerosis in
obese children: hsCRP. Journal of Korean Medical Sci-
ence, 22(2), 192-197.