Nutrition, Metabolism & Cardiovascular Diseases (2014) 24, 737e743

Available online at www.sciencedirect.com

Nutrition, Metabolism & Cardiovascular Diseases

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

Association of serum triglyceride-to-HDL cholesterol ratio with

carotid artery intima-media thickness, insulin resistance and
nonalcoholic fatty liver disease in children and adolescents
L. Pacifico a, E. Bonci b, G. Andreoli a, S. Romaggioli a, R. Di Miscio c, C.V. Lombardo c,
C. Chiesa d,*
a
Department of Pediatrics and Child Neuropsychiatry, Sapienza University of Rome, Italy
b
Department of Experimental Medicine, Sapienza University of Rome, Italy
c
Department of Radiological Sciences, Sapienza University of Rome, Italy
d
Institute of Translational Pharmacology, National Research Council, Via del Fosso del Cavaliere 100, 00133 Rome, Italy

Received 10 October 2013; received in revised form 17 December 2013; accepted 7 January 2014
Available online 29 January 2014

KEYWORDS Abstract Background and aims: The triglyceride (TG)/high-density lipoprotein-cholesterol

Triglyceride-to-HDL (HDL-C) ratio has been reported as a useful marker of atherogenic lipid abnormalities, insulin
cholesterol ratio; resistance, and cardiovascular disease. We evaluated in a large sample of children and adoles-
Carotid artery cents the association of TG/HDL-C ratio with early signs of morphological vascular changes
intima-media and cardiometabolic risk factors including nonalcoholic fatty liver disease (NAFLD).
thickness; Methods and results: The study population, including 548 children (aged 6e16 years), of whom
Insulin resistance; 157 were normal-weight, 118 overweight, and 273 obese, had anthropometric, laboratory, liver
Nonalcoholic fatty and carotid ultrasonography (carotid artery intima-media thickness-cIMT) data collected. Sub-
liver disease; jects were stratified into tertiles of TG/HDL-C. There was a progressive increase in body mass in-
dex (BMI), BMI-SD score (SDS), waist circumference, blood pressure (BP), liver enzymes, glucose,
Children
insulin, homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein
(hsCRP), and cIMT values across TG/HDL-C tertiles. The odds ratios for central obesity, insulin
resistance, high hsCRP, NAFLD, metabolic syndrome, and elevated cIMT increased significantly
with the increasing tertile of TG/HDL-C ratio, after adjustment for age, gender, pubertal status,
and BMI-SDS. In a stepwise multivariate logistic regression analysis, increased cIMT was associ-
ated with high TG/HDL-C ratio [OR, 1.81 (95% CI, 1.08e3.04); P < 0.05], elevated BP [5.13 (95% CI,
1.03e15.08); P < 0.05], insulin resistance [2.16 (95% CI, 1.30e3.39); P < 0.01], and NAFLD [2.70
(95% CI, 1.62e4.56); P < 0.01].
Conclusion: TG/HDL-C ratio may help identify children and adolescents at high risk for structural
vascular changes and metabolic derangement.
ª 2014 Elsevier B.V. All rights reserved.

Introduction Obesity is associated with increased risk of insulin resis-

tance, dyslipidemia, elevated blood pressure (BP), and
Over the last few decades obesity has reached epidemic inflammation, which is linked to an increased risk of type
proportions in children as well as adults in developed 2 diabetes and cardiovascular disease (CVD), among other
countries and more recently in developing countries. diseases [1]. Thus, there is growing interest in the

* Corresponding author. Tel.: þ39 (0) 6 49979215; fax: þ39 (0) 6 49979216.
E-mail addresses: lucia.pacifico@uniroma1.it, claudio.chiesa@ift.cnr.it (C. Chiesa).

0939-4753/$ - see front matter ª 2014 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.numecd.2014.01.010
738
identification of cardiovascular risk factors at an early
stage of life because they might have long-term effects on
arterial health.
In adults, lipoprotein ratios have been recognized as
being more useful than isolated lipid values for cardio-
vascular risk assessment because they better reflect the
interactions between lipid fractions [2]. In particular,
the triglyceride (TG)/high-density lipoprotein-cholesterol
(HDL-C) ratio has been reported as a useful marker of
atherogenic lipid abnormalities, namely small low-density
lipoprotein cholesterol (LDL-C) and small HDL-C, as well as
of insulin resistance, metabolic syndrome (MetS), and high
cardiovascular risk [3,4]. In childhood, the clinical and
prognostic value of lipid ratios has been much less inves-
tigated [5e9]. Quijada et al. showed that the TG/HDL-C
ratio was useful in identifying prepubertal children at
risk for obesity, dyslipidemia, hypertension, and MetS [5].
In a large sample of high school adolescents, Musso et al.
demonstrated that the TG/HDL-C ratio and high-sensitivity
C-reactive protein (hsCRP) positively correlated with body
mass index (BMI) and waist circumference (WC) [6].
Recently, Weiss et al. have demonstrated that the TG/HDL-
C ratio measured in late adolescence predicts a proa-
therogenic lipid profile in adulthood independently of
obesity and weight gain [7]. Giannini et al. demonstrated
that the TG/HDL-C ratio is associated with insulin resis-
tance particularly in white girls and boys but not signifi-
cantly in African Americans or Hispanics [8]. Thus the TG/
HDL-C ratio may vary by ethnicity. Interestingly, Di Bonito
et al. have shown that a TG/HDL-C ratio 2.0 is associated
with several cardiometabolic risk factors and proves to be
useful in identifying children with a high risk of elevated
ALT and left ventricular hypertrophy [9]. However, corre-
lations of the TG/HDL-C ratio with early vascular damage
in children and adolescents are very limited [10,11].
Atherosclerosis begins in childhood. Pre-clinical
vascular changes can be assessed noninvasively and reli-
ably by ultrasound in young subjects. Increased carotid
artery intima-media thickness (cIMT) reflects early struc-
tural abnormalities during atherogenesis. It correlates with
cardiovascular risk factors and the severity of coronary
atherosclerosis, and predicts cardiovascular events [12,13].
Exposure to atherogenic lipid profile in early life might
induce changes in arteries that contribute to the devel-
opment of atherosclerosis. Therefore, the aim of the pre-
sent study was to explore in children and adolescents the
association of TG/HDL-C ratio with early signs of
morphological vascular changes as well as with car-
diometabolic risk factors including nonalcoholic fatty liver
disease (NAFLD).
Methods
Study population
A total of 391 Caucasian overweight/obese children and
adolescents (282 boys) with a median age of 10.10 (range
of 6e16) years were included in the study. Among them,
118 (30.2%) were overweight, and 273 (69.8%) were obese.
L. Pacifico et al.
They were consecutively enrolled at the outpatient clinics
of the Department of Pediatrics, Sapienza University of
Rome, Italy. Exclusion criteria were the presence of renal
disease; type 1 or 2 diabetes; any condition known to in-
fluence body composition, insulin action, or insulin
secretion (e.g. glucocorticoid therapy, hypothyroidism, and
Cushing’s disease); a history of pre-existing heart disease;
familial or secondary dyslipidemia other than that due to
the state of obesity; any laboratory or clinical evidence of
chronic liver disease other than that due to the state of
obesity, including hepatic virus infections (Hepatitis A-E
and G, cytomegalovirus, and EpsteineBarr virus), autoim-
mune hepatitis, metabolic hepatic disease, a-1-antitrypsin
deficiency, cystic fibrosis, Wilson’s disease, hemochroma-
tosis, and celiac disease; and history of alcohol consump-
tion and smoking (where appropriate). The study also
included a random sample of apparently healthy school
students aged 6e16 years drawn from four randomly
selected schools (2 elementary, and 2 middle schools) in
the Rome area. Every student in each of these 4 selected
schools was invited to participate in a pilot study aimed at
preventing CVD in childhood. Eligibility criteria were BMI
appropriate for age and gender, no history of familiar
dyslipidemia, and no history of alcohol consumption and
smoking (where appropriate). The final sample included
157 healthy normal-weight school children (70 boys;
median age, 11.05 years).
All study participants underwent physical examination
including measurements of weight and standing height
[from which BMI was calculated], WC, determination of
the pubertal status, systolic and diastolic BP, as previously
reported in detail [14]. The degree of obesity was quanti-
fied by Cole’s least mean square method, which normal-
izes the skewed distribution of BMI and expresses BMI as
SD score (SDS) [15]. This measure gives age- and gender-
specific estimates of the distribution median, the coeffi-
cient of variation, and the degree of skew by a maximum-
likelihood fitting technique. Systolic and diastolic BP were
measured twice at the right arm after a 10 min rest in the
supine position by using an automated oscillatory system
(Dinamap Vital Signs Monitor, Model 1846 SX; Criticon
Incorporated, Tampa, FL, USA).
The study was approved by the Hospital Ethics Com-
mittee, and informed consent was obtained from subjects’
parents before assessment.
Definitions
Overweight and obesity were defined according to age and
gender specific cut-off points of BMI defined by the In-
ternational Obesity Task Force criteria proposed by Cole
et al. [15]. In all subjects, the diagnosis of NAFLD was
established by the ultrasonographic evidence of liver
steatosis, and the presence of persistently (>6 months)
elevated alanine aminotransferase (ALT) (>25.8 U/L for
boys and >22.1 U/L for girls) [16], after exclusion of in-
fectious and metabolic disorders. Central obesity was
defined as WC  90th percentile for age and gender ac-
cording to Cook et al. reference curves for children aged
Serum triglyceride-to-HDL cholesterol ratio in children and adolescents
2e18 years [17]; elevated BP as systolic or diastolic
BP  90th percentile for age, gender, and height [18]; and
impaired fasting glucose as glucose 5.6 mmol/L. MetS
was diagnosed in the presence of any three of the
following: central obesity, hypertension, low HDL values
[17], elevated TG values [17], and glucose impairment.
Insulin resistance was determined by a homeostasis
model assessment of insulin resistance (HOMA-IR). Scores
were calculated as the product of the fasting serum insulin
level (mU/mL) and the fasting serum glucose level
(mmol/L), divided by 22.5. We considered HOMA-IR values
90th percentile for age and gender of those observed in
our population of healthy normal-weight children as an
indicator of insulin resistance. High hsCRP was defined as
hsCRP 90th percentile of values observed in healthy lean
subjects.
Laboratory methods
Blood samples were taken from each subject, after an
overnight fast, for estimation of glucose, insulin, total
cholesterol, HDL-C, TG, ALT, aspartate aminotransferase,
gamma-glutamyl transferase, creatinine, and hsCRP. All
analyses were conducted by cobas 6000 (Roche Di-
agnostics). We measured serum insulin concentration on
cobas e 601 module using an electrochemiluminescent
immunoassay (ECLIA, Roche Diagnostics). The analytical
reporting range for the assay is 0.2e1000 mU/mL. Accord-
ing to the manufacturer the intraassay imprecision at 5.93
and 399 mU/mL is 1.5% and 0.8%, respectively, while the
intralaboratory imprecision at 6.85 and 425 mU/mL is 4.9%
and 2.4%, respectively. The remaining analytes were
measured on cobas c 501 clinical chemistry module
(Photometric Technology), according to the instructions of
the manufacturer.
Hepatic and carotid ultrasonography
Hepatic and carotid ultrasonography were performed in all
patients by a single experienced radiologist, who was
blinded to the participants’ details. Hepatic steatosis was
diagnosed on the basis of characteristic sonographic fea-
tures, e.g. increased echogenicity (brightness) of the liver
parenchyma in comparison with the renal cortex and
spleen, attenuation of the ultrasound beam by liver, loss of
definition of the diaphragm, and poor delineation of the
intrahepatic architecture.
Measurement of cIMT was performed as previously
described [14,19]. In brief, longitudinal ultrasonographic
scans of the carotid artery included the evaluation of the
right and left common carotid arteries near the bifurcation
during end diastole. We measured four values on each
side, and the maximum and mean cIMT were calculated.
The coefficient of variation was less than 3%.
Statistical analysis
Statistical analyses were performed using the SPSS pack-
age (Version 19). Data are expressed either as frequencies
739
or as median and interquartile range (IQR). The whole
study population, including overweight/obese and
normal-weight children, was stratified into tertiles of the
TG/HDL-C ratio. Differences between groups in quantita-
tive variables were evaluated by one-way analysis of
variance or KruskaleWallis test, as appropriate. Pro-
portions were compared by the chi-square test. To evaluate
the cardiometabolic risk factors, including increased cIMT,
across tertiles of TG/HDL-C ratio, we performed multiple
logistic regression analysis adjusted for age, gender, pu-
bertal status, and BMI-SDS. For this purpose, subjects were
stratified into those having maximum cIMT 90th
percentile of values observed in healthy lean subjects. We
also performed a multiple logistic regression analysis with
a forward stepwise selection procedure to determine the
independent impact of variables including high BP, high
hsCRP, NAFLD, insulin resistance, TG/HDL-C ratio (top ter-
tile) in addition to age, gender, pubertal status and WC (or
BMI-SDS) on increased cIMT. A two-sided P value <0.05
was considered statistically significant.
Results
Baseline characteristics of the entire study population
according to tertiles of TG/HDL-C
Baseline characteristics of all participants according to
tertiles of TG/HDL-C ratio are summarized in Table 1. There
was a progressive increase in BMI, BMI-SDS, WC, systolic
and diastolic BP, liver enzymes, glucose, insulin, HOMA-IR,
and hsCRP, and a progressive decrease in HDL-C from the
lower to the upper tertile of the TG/HDL-C ratio. A statis-
tically significant difference across tertiles was also found
in maximum cIMT (P Z 0.009) and mean cIMT (P Z 0.004)
(Table 1). In contrast, no significant differences were seen
in age, gender, pubertal status, and total cholesterol across
the TG/HDL-C tertiles.
Relationship between high TG/HDL-C ratio and risk
variables
We analyzed the cardiometabolic profile across TG/HDL-C
ratio tertiles in the entire study population. As shown in
Table 2, the prevalence of central obesity, high BP, insulin
resistance, high hsCRP, NAFLD, MetS, and elevated cIMT
increased steadily across tertiles of TG/HDL-C ratio. After
adjustment for age, gender, pubertal status and BMI-SDS,
children with the highest TG/HDL-C ratio showed a 1.8-
to 3.8-fold increased risk of central obesity, insulin resis-
tance, high hsCRP, NAFLD, MetS, and increased cIMT,
(Table 3).
In order to investigate the potential independent
contribution of the TG/HDL-C ratio on cIMT, a multiple
stepwise logistic regression analysis was performed. The
variables included in the model were age, gender, pubertal
status, WC, high BP, TG/HDL-C ratio (top tertile), high
hsCRP, NAFLD, and insulin resistance. Elevated cIMT was
associated with high BP [OR, 5.13 (95% CI, 1.03e15.8);
P Z 0.046], insulin resistance [OR, 2.16 (95% CI, 1.30e3.39);
740 L. Pacifico et al.

Table 1 Characteristics of study population according to tertiles of the TG/HDL-C ratio.a

TG/HDL-C ratio P
Tertile I Tertile II Tertile III
Number of subjects 176 187 185
Age, years 10.1 (8.1e12.5) 10.8 (9.0e13.4) 11.2 (9.3e13.2) 0.028
Male gender, n (%) 95 (54.0) 84 (44.9) 103 (55.7) 0.15
Prepubertal status, n (%) 53 (30.1) 45 (24.1) 41 (22.1) 0.47
BMI, kg/m2 20.9 (18.1e23.7) 22.8 (20.0e26.0) 25.5 (22.8e29.2) <0.0001
BMI-SDS 1.35 (0.42e0.81) 1.55 (0.90e1.97) 1.93 (1.45e2.24) <0.0001
Waist circumference, cm 73 (65e82) 78 (69e88) 88 (78e98) <0.0001
Systolic BP, mm Hg 100 (95e110) 105 (100e110) 110 (100e120) <0.0001
Diastolic BP, mm Hg 60 (60e70) 65 (60e70) 70 (60e70) <0.0001
AST, U/L 24 (21e30) 24 (20e29) 25 (22e34) 0.007
ALT, U/L 17 (13e24) 18 (14e25) 27 (17e49) <0.0001
GGT, U/L 11 (9e13) 12 (10e15) 16 (12e24) <0.0001
Total cholesterol, mg/dL 159 (138e183) 162 (144e190) 172 (144e196) 0.087
HDL-C 60 (54e70) 52 (45e57) 41 (35e47) <0.0001
Triglycerides, mg/dL 48 (40e57) 73 (63e81) 124 (105e167) <0.0001
Glucose, mmol/L 4.61 (4.40e4.89) 4.63 (4.38e4.90) 4.70 (4.49e5.00) 0.039
Insulin, mU/mL 8 (5e12) 10 (6e15) 15 (11e23) <0.0001
HOMA-IR values 1.66 (1.09e2.45) 2.15 (1.35e3.14) 3.24 (2.25e4.839) <0.0001
hsCRP, mg/L 835 (420e1949) 1105 (50e2824) 1500 (728e3400) <0.0001
Maximum cIMT, mm 0.50 (0.46e0.55) 0.50 (0.44e0.56) 0.54 (0.46e0.59) 0.009
Mean cIMT, mm 0.42 (0.39e0.46) 0.43 (0.38e0.47) 0.45 (0.40e0.50) 0.004
TG/HDL-C, triglycerides/high density lipoprotein cholesterol; BMI, body mass index; BMI-SDS, BMI-SD score; BP, blood pressure; AST, aspartate
aminotransferase; ALT, alanine aminotransferase; GGT, g-glutamyl transferase; HOMA-IR, homeostasis model assessment of insulin resistance;
hsCRP, high-sensitivity C-reactive protein; cIMT, carotid artery intima-media thickness.
a
Tertile I, TG/HDL-C: <1.10; tertile II, TG/HDL-C: 1.10e1.98; tertile III, TG/HDL-C: >1.98. Results are expressed as n (%), median (interquartile
range).

P Z 0.003], NAFLD [OR, 2.70 (95% CI, 1.62e4.56);
P Z 0.003], and a high TG/HDL-C ratio [OR, 1.81 (95% CI,
1.08e3.04); P Z 0.025] (Table 4). When BMI-SDS (instead
of WC) was included in the model results were similar. In a
separate model, where age, gender, pubertal status, TG/
HDL-C ratio and MetS (considered as a single clinical en-
tity) were included, the association between cIMT and TG/
HDL-C ratio remained statistically significant [OR, 2.55
(95% CI, 1.71e3.80); P < 0.001].
Discussion
In this study we show that a high TG/HDL-C ratio is
associated with an unfavorable cardiovascular and meta-
bolic profile. In particular, this is the first report showing,
in a large sample of Caucasian children, that a high TG/
HDL-C ratio is significantly associated with an increased
cIMT. This association remains significant after adjustment
for total and visceral adiposity, systemic inflammation,
high blood pressure, insulin resistance, and NAFLD. Our
data suggest that using the TG/HDL-C ratio may be helpful
for identifying obese children requiring prompt and
aggressive intervention to prevent atherosclerotic CVD.
Few studies have examined the relationship between
TG/HDL-C ratio and vascular damage [10,11,20e22]. In a
study investigating relationships between coronary artery
heart disease (CHD) risk markers and progression of cIMT
in men and women at moderate risk of CHD, Maki et al.
showed that TG/HDL-C ratio independently predicted cIMT
progression [20]. Nicholls et al., based on data from the
PERISCOPE (Pioglitazone Effect on Regression of Intravas-
cular Sonographic Coronary Obstruction Prospective
Evaluation) study, reported that the favorable effects of
pioglitazone on the TG/HDL-C ratio correlated with
delayed atheroma progression in diabetic patients [21].
Shimizu et al. found that diabetes, especially associated
with high TG/HDL-C ratio was a significant risk factor for
increased cIMT and arterial stiffness [22]. In a study
involving 893 subjects aged 10e26 years (mean 18.9
years), Urbina et al. found that TG/HDL-C ratio was a sig-
nificant determinant of arterial stiffness in adolescents and
young adults [10]. Finally, in a very recent study involving
a small group of prepubertal children (50 obese, and 37
normal-weight), de Giorgis et al. reported that obese
children had an increased TG/HDL-C ratio compared to
normal weight peers, and that this ratio was associated
with well-known cardiovascular risk factors as well as
with increased cIMT [11]. Thus, our results extend these
observations, by showing that a high TG/HDL-C ratio is
associated with carotid atherosclerosis independently of
other cardiovascular risk factors and MetS.
Many reasons could explain the predictive value of the
TG/HDL-C ratio. First, as the TG/HDL-C ratio increases, LDL
particles are smaller and denser, which correlates strongly
to the initiation and progression of atherosclerosis [23].
Second, higher values of the TG/HDL-C ratio are associated
with a higher risk of cardiovascular events even if LDL-C is
low or lowered by active treatment without decreases in
the TG/HDL-C ratio [24,25]. Third, the TG/HDL-C ratio has
been identified as an accurate marker of insulin resistance
[8,26], and MetS [27], which are independent risk factors
Serum triglyceride-to-HDL cholesterol ratio in children and adolescents 741

Table 2 Prevalence of cardiometabolic risk factors according to TG/HDL-C ratio tertiles among the whole study population.

TG/HDL-C ratio
Tertile I (n Z 176) Tertile II (n Z 187) Tertile III (n Z 185) P for linear trend
Central obesity, 32.9 (20.6e45.2) 42.2 (31.1e53.3) 68.6 (60.4e76.8) <0.0001
% (95% CI)
Elevated blood pressure, 1.1 (e,e) 4.8 (0e19.1) 8.6 (0e22.6) 0.001
% (95% CI)
Glucose  5.6 mmol/L, 1.1 (e,e) 1.6 (e,e) 2.7 (0e17.2) 0.48
% (95% CI)
Insulin resistance, 21.0 (7.6e34.4) 31.0 (18.9e43.1) 63.2 (54.3e72.1) <0.0001
% (95% CI)
High hsCRP, 39.2 (27.4e51.0) 48.1 (37.6e58.6) 61.1 (51.9e70.3) <0.0001
% (95% CI)
NAFLD, 18.5 (5.0e32.0) 29.4 (17.1e41.7) 49.2 (38.7e59.7) <0.0001
% (95% CI)
MetS, 0 2.7 (0e5.1) 21.1 (8.0e34.2) <0.0001
% (95% CI)
cIMT  0.50, 24.4 (11.3e37.5) 29.9 (17.7e42.1) 53.5 (43.5e63.5) <0.0001
% (95% CI)
CIs, confidence intervals; TG/HDL-C, triglycerides/high-density lipoprotein cholesterol; hsCRP, high-sensitivity C-reactive protein; NAFLD,
nonalcoholic fatty liver disease; MetS, metabolic syndrome; cIMT, carotid artery intima-media thickness.

for vascular changes. Indeed, we have demonstrated that
children with a high TG/HDL-C ratio have an increased risk
of insulin resistance in agreement with previous studies
[8,26], but we have also shown an association between
this ratio and NAFLD, a well-known component of MetS,
independently of obesity. These findings may have impli-
cations in terms of cardiovascular risk. Increased visceral
adipose tissue and insulin resistance are the undisputed
major contributors to NAFLD, MetS, and atherosclerosis
[28,29]. The adipose tissue inflammation with consequent
release of multiple proinflammatory molecules is one of
the earliest steps in the chain of events involved in the
development of insulin resistance and atherosclerosis, in
particular in obese and overweight persons. While insulin
resistance promotes fatty acid accumulation in the liver,
the latter causes hepatic insulin resistance characterized
by a lack of suppression of endogenous liver glucose pro-
duction. Therefore, NAFLD might act as a stimulus for
further increased whole-body insulin resistance and dys-
lipidemia, leading to accelerated atherosclerosis [28,29].
There is in fact accumulating evidence that NAFLD is
associated with a significantly greater overall mortality
than in the general population, as well as with increased
prevalence of CVD independently of classical atheroscle-
rotic risk factors [28]. Yet, several studies including the
pediatric population have reported independent associa-
tions between NAFLD and impaired flow-mediated vaso-
dilatation and increased cIMT after adjusting for
cardiovascular risk factors and MetS [14,19,29].
The strength of our study is the large sample size, the
comprehensive analysis of several cardiometabolic risk
factors, and the evaluation of signs of early atherosclerosis.
However, some limitations are acknowledged. First, due to
the cross-sectional design we cannot establish whether a
high TG/HDL-C ratio may be a marker of vascular changes
until adulthood. Follow-up of these children will clarify

Table 3 Adjusteda Odds ratio (95% CIs) of cardiometabolic risk factors according to TG/HDL-C ratio tertiles among the whole study population.

TG/HDL-C ratio P for trendb

Tertile I (n Z 176) Tertile II (n Z 187) Tertile III (n Z 185)
Central obesity 1.0 1.06 (0.54e2.07) 1.83 (1.02e3.33) 0.01
Elevated blood pressure 1.0 4.41 (0.77e25.4) 3.65 (0.55e24.3) 0.12
Glucose  5.6 mmol/L 1.0 0.52 (0.09e2.99) 1.05 (0.21e5.32) 0.11
Insulin resistance 1.0 1.24 (0.75e2.06) 3.76 (2.22e6.36) <0.0001
High hsCRP 1.0 1.15 (0.74e1.80) 2.83 (1.75e4.59) 0.02
NAFLD 1.0 1.68 (1.05e2.70) 3.38 (1.86e6.15) 0.001
MetS 1.0 4.35 (0.46e21.2) 17.8 (5.52e57.4) <0.0001
cIMT  0.50 1.0 1.14 (0.71e1.85) 2.02 (1.21e3.35) <0.0001
CIs, confidence intervals; TG/HDL-C, triglycerides/high-density lipoprotein cholesterol; hsCRP, high-sensitivity C-reactive protein; NAFLD,
nonalcoholic fatty liver disease; MetS, metabolic syndrome; cIMT, carotid artery intima-media thickness.
a
Adjusted for age, gender, pubertal status, and BMI-SDS.
b
The significance of the trend has been obtained from the logistic regression analysis in which the tertiles of TG/HDL-C ratios have been
included as an ordinal variable. A similar pattern of results was obtained by entering the median of the tertile categories of TG/HDL-C ratio as a
continuous variable.
742
Table 4 Independent predictors of increased carotid artery intima-
media thickness.
Variable Odds ratio (95% CI)
Elevated blood pressure 5.13 (1.03e15.8)
Insulin resistance 2.16 (1.30e3.39)
NAFLD 2.70 (1.62e4.56)
TG/HDL-C ratio (top tertile) 1.81 (1.08e3.04)
Variables included in the model were: age, gender, pubertal status,
waist circumference, high blood pressure, high hsCRP, NAFLD, and
insulin resistance. When BMI-SDS (instead of waist circumference)
was included in the model results were similar.
NAFLD, nonalcoholic fatty liver disease; TG/HDL-C, triglycerides/
high-density lipoprotein cholesterol; hsCRP, high-sensitivity C-
reactive protein; BMI-SDS, body mass index-SD score.
this issue. Second, the absence of liver biopsies as the
reference standard for the diagnosis of fatty liver. None-
theless, liver biopsies in a large study collective such as our
cohort are difficult to perform, also for ethical reasons, as
no specific therapy follows histologic diagnosis of NAFLD
apart from recommending lifestyle modification which is
generally advised to all obese children. Conversely, ultra-
sonography is by far the most common way of diagnosing
hepatic steatosis in clinical practice. Third, we have to
acknowledge that data on dietary patterns and physical
activity of the study population were not available. Such
information may be critical for the future development of
sound public health nutrition policies and behavioral in-
terventions for cardiometabolic risk reduction and health
promotion. Indeed, the combination of dietary and phys-
ical activity interventions appears to provide the most
beneficial improvements in components of the MetS
including NAFLD [29,30]. Comprehensive behavioral
modification in overweight children reduces body weight,
improves body composition, and positively modifies many
of the components of the MetS. Similar effects have been
observed for endothelial dysfunction, with the greatest
improvements occurring when combined dietary and ex-
ercise interventions are used in overweight children [31].
In conclusion, our findings support the notion that the
TG/HDL-C ratio may help identify children and adolescents
at high risk for accelerated vascular changes as well as
metabolic derangement who need early and aggressive
therapy to improve long-term cardiovascular and meta-
bolic outcome. TG/HDL-C ratio is easier to perform than
advanced lipid testing including small dense LDL particles,
the measurement of which requires complicated pro-
cedures (e.g., gradient gel electrophoresis), and therefore
may be a simple way for evaluation of cardiovascular risk
in routine clinical examination, and mass screening
examination.
Acknowledgments
This study was supported by a grant from Sapienza
University of Rome (Progetti di Ricerca Universitaria
2011e2012).
L. Pacifico et al.
No potential conflicts of interest relevant to this article
were reported.
We thank professor John Frederick Osborn from
P
Department of Health Sciences and Infectious Diseases,
0.046 Sapienza University of Rome, for his critical review of the
0.003
manuscript and for statistical support.
0.003
0.025
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