Abstract
Background:
Increased carotid intima-media thickness (c-IMT) is considered a marker of early-onset atherosclerosis and it has been found in obese children and adolescents, but the risk factors associated with this population remain to be elucidated.
Objective
: To compare and verify the relationship between c-IMT, metabolic profile, inflammatory markers, and cardiorespiratory fitness in obese and non-obese children and adolescents.
Method
: Thirty-five obese subjects (19 boys) and 18 non-obese subjects (9 boys), aged 10-16 years, were included. Anthropometry, body composition, blood pressure, maximal oxygen consumption (VO2max), and basal metabolic rate were evaluated. Serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), blood lipids, C-reactive protein (CRP), and adiponectin were assessed. c-IMT was measured by ultrasound.
Results:
The results showed that c-IMT, triglycerides, insulin, HOMA-IR, and CRP values were significantly higher in the obese group than in the non-obese group, and high-density lipoprotein cholesterol (HDL-c), adiponectin, and VO2max values were significantly lower in the obese group than in the non-obese group. The c-IMT was directly correlated with body weight, waist circumference, % body fat, and HOMA-IR and inversely correlated with % free fat mass, HDL-c, and VO2max.
Conclusions
: Our findings show that c-IMT correlates not only with body composition, lipids, insulin resistance, and inflammation but also with low VO2max values in children and adolescents.
obesity; inflammation; atherosclerosis; adolescents; fitness; physical therapy
Introduction
Obesity is independently associated with coronary atherosclerosis in young adults11. McGill HC Jr, Herderick EE, McMahan CA, Zieske AW, Malcolm GT, Tracy
RE, et al. Atherosclerosis in youth. Minerva Pediatr. 2002;54:437-47.
PMid:12244281.. Inflammation, obesity, and insulin resistance usually occur together, as they
are part of the atherosclerotic process and contribute to the development of
cardiovascular diseases22. Zhu W, Huang X, He J, Li M, Neubauer H. Arterial intima-media
thickening and endothelial dysfunction in obese Chinese children. Eur J Pediatr.
2005;164:337-44. PMid:15750804. http://dx.doi.org/10.1007/s00431-005-1642-y
http://dx.doi.org/10.1007/s00431-005-164...
. Research in the juvenile population shows a relationship between inflammatory
markers and endothelial dysfunction33. Giannini C, De Giorgis T, Scarinci A, Ciampani M, Marcovecchio ML,
Chiarelli F, et al. Obese related effects of inflammatory markers and insulin
resistance on increased carotid intima media thickness in pre-pubertal children.
Atherosclerosis. 2008;197:448-56. PMid:17681348.
http://dx.doi.org/10.1016/j.atherosclerosis.2007.06.023
http://dx.doi.org/10.1016/j.atherosclero...
,
44. Beauloye V, Zech F, Tran HT, Clapuyt P, Maes M, Brichard SM.
Determinants of early atherosclerosis in obese children and adolescents. J Clin
Endocrinol Metab. 2007;92:3025-32. PMid:17519311.
http://dx.doi.org/10.1210/jc.2007-0619
http://dx.doi.org/10.1210/jc.2007-0619...
. The elevation of C-reactive protein (CRP) is considered an indicator of
inflammation and a predictor of cardiovascular diseases and diabetes55. Brasil AR, Norton RC, Rossetti MB, Leao E, Mendes RP. C-reactive
protein as an indicator of low intensity inflammation in children and adolescents
with and without obesity. J Pediatr (Rio J). 2007;83:477-80.. Low concentrations of adiponectin are associated with obesity66. Asayama K, Hayashibe H, Dobashi K, Uchida N, Nakane T, Kodera K, et
al. Decrease in serum adiponectin level due to obesity and visceral fat accumulation
in children. Obes Res. 2003;11:1072-9. PMid:12972677.
http://dx.doi.org/10.1038/oby.2003.147
http://dx.doi.org/10.1038/oby.2003.147...
,
77. Nishimura R, Sano H, Matsudaira T, Morimoto A, Miyashita Y, Shirasawa
T, et al. Changes in body mass index, leptin and adiponectin in Japanese children
during a three-year follow-up period: a population-based cohort study. Cardiovasc
Diabetol. 2009;8:30. PMid:19490650 PMCid:PMC2701411.
http://dx.doi.org/10.1186/1475-2840-8-30
http://dx.doi.org/10.1186/1475-2840-8-30...
, vasculopathy, and diabetes88. Bouassida A, Chamari K, Zaouali M, Feki Y, Zbidi A, Tabka Z. Review
on leptin and adiponectin responses and adaptations to acute and chronic exercise. Br
J Sports Med. 2010;44:620-30. PMid:18927166.
http://dx.doi.org/10.1136/bjsm.2008.046151
http://dx.doi.org/10.1136/bjsm.2008.0461...
.
Recently, non-invasive techniques have been used in order to evaluate early markers of
atherogenesis, including ultrasound assessment of the wall thickness of the
endothelium99. Kumar V, Sachdev HP, Khalil A. Noninvasive evaluation of endothelial
function and arterial mechanics in overweight adolescents. Indian Pediatr.
2004;41:1105-14. PMid:15591660.
,
1010. Kapuku GK, Harshfield GA, Davis HC, Treiber FA. Early markers of
cardiovascular disease. Vascul Pharmacol. 2006;45:277-80. PMid:17011834.
http://dx.doi.org/10.1016/j.vph.2006.08.009
http://dx.doi.org/10.1016/j.vph.2006.08....
. This evaluation consists in measuring, by means of ultrasound imaging, the
thickness of the tunica intima and tunica media of the artery99. Kumar V, Sachdev HP, Khalil A. Noninvasive evaluation of endothelial
function and arterial mechanics in overweight adolescents. Indian Pediatr.
2004;41:1105-14. PMid:15591660., known as intima-media thickness (IMT). The increase in this value is considered
a risk factor for coronary artery disease1010. Kapuku GK, Harshfield GA, Davis HC, Treiber FA. Early markers of
cardiovascular disease. Vascul Pharmacol. 2006;45:277-80. PMid:17011834.
http://dx.doi.org/10.1016/j.vph.2006.08.009
http://dx.doi.org/10.1016/j.vph.2006.08....
and current data shows that obese children have greater carotid intima-media
thickness (c-IMT) than healthy children, thus suggesting that they are more susceptible
to cardiovascular events in adulthood22. Zhu W, Huang X, He J, Li M, Neubauer H. Arterial intima-media
thickening and endothelial dysfunction in obese Chinese children. Eur J Pediatr.
2005;164:337-44. PMid:15750804. http://dx.doi.org/10.1007/s00431-005-1642-y
http://dx.doi.org/10.1007/s00431-005-164...
,
33. Giannini C, De Giorgis T, Scarinci A, Ciampani M, Marcovecchio ML,
Chiarelli F, et al. Obese related effects of inflammatory markers and insulin
resistance on increased carotid intima media thickness in pre-pubertal children.
Atherosclerosis. 2008;197:448-56. PMid:17681348.
http://dx.doi.org/10.1016/j.atherosclerosis.2007.06.023
http://dx.doi.org/10.1016/j.atherosclero...
,
99. Kumar V, Sachdev HP, Khalil A. Noninvasive evaluation of endothelial
function and arterial mechanics in overweight adolescents. Indian Pediatr.
2004;41:1105-14. PMid:15591660..
Some studies have examined the c-IMT in children and adolescents22. Zhu W, Huang X, He J, Li M, Neubauer H. Arterial intima-media
thickening and endothelial dysfunction in obese Chinese children. Eur J Pediatr.
2005;164:337-44. PMid:15750804. http://dx.doi.org/10.1007/s00431-005-1642-y
http://dx.doi.org/10.1007/s00431-005-164...
,
33. Giannini C, De Giorgis T, Scarinci A, Ciampani M, Marcovecchio ML,
Chiarelli F, et al. Obese related effects of inflammatory markers and insulin
resistance on increased carotid intima media thickness in pre-pubertal children.
Atherosclerosis. 2008;197:448-56. PMid:17681348.
http://dx.doi.org/10.1016/j.atherosclerosis.2007.06.023
http://dx.doi.org/10.1016/j.atherosclero...
, but few studies also verified cardiorespiratory fitness1111. Farpour-Lambert NJ, Aggoun Y, Marchand LM, Martin XE, Herrmann FR,
Beghetti M. Physical activity reduces systemic blood pressure and improves early
markers of atherosclerosis in pre-pubertal obese children. J Am Coll Cardiol.
2009;54:2396-2406. PMid:20082930. http://dx.doi.org/10.1016/j.jacc.2009.08.030
http://dx.doi.org/10.1016/j.jacc.2009.08...
. The diagnosis and prevention of these risk factors in childhood are important
public health issues, as they allow early intervention in individuals at a higher risk
of developing cardiovascular diseases during the juvenile or adult phase. Therefore, the
objective of this paper was to investigate the relationships among endothelial
dysfunction, dyslipidemia, level of cardiorespiratory fitness, and inflammatory markers
in obese and non-obese subjects.
Method
Participants
The sample included 53 subjects, aged 10-16 years of age, from the city of Curitiba, PR, Brazil. Participants were divided into two groups, the obese group (n=35) and the non-obese group (n=18). Inclusion criteria were: a) informed consent signed by parents or guardians, b) meeting the criteria for obesity and non-obesity described below, and c) no history of regular physical activity outside of physical education classes at school. Based on body mass index (BMI) and U.S. growth charts1212. Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, Flegal KM, Guo SS, Wei R, et al. CDC growth charts: United States. Adv Data. 2000;(314)1-27. PMid:11183293., participants were classified as obese (n=35, BMI>P95%) and non-obese (n=18, BMI<85%). The obese group was selected among participants from an intervention project conducted at Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil. The non-obese group consisted of volunteers from public schools matched by sex and age. Exclusion criteria consisted of: a) musculoskeletal problems or physical disability, b) subjects who did not undergo all assessments, c) subjects with abnormal thyroid-stimulating hormone (TSH) function. All of the adolescents and their legal guardians gave written informed consent. The study complied with Resolution 196/96 of the National Health Council and was previously approved by the Human Research Ethics Committee of the UFPR Health Sciences Faculty (CEP/SD: 945.070.10.06).
Variables
Clinical evaluation
Chronological age (CA) was recorded to the nearest 0.1 year by subtracting the birth
date from the date of the mid-testing period. Sexual maturation was given by stages
of pubic hair (PH) and was individually assessed following the criteria described by
Tanner1313. Tanner JM. Normal growth and techniques of growth assessment. Clin
Endocrinol Metab. 1986;15:411-51. http://dx.doi.org/10.1016/S0300-595X(86)80005-6
http://dx.doi.org/10.1016/S0300-595X(86)...
. Resting heart rate (HRres) and systolic (SBP) and diastolic blood pressure
(DBP) were measured with the subjects in the sitting position after 10 minutes of
rest. HRres was obtained using a heart rate monitor (Polar A2) followed by blood
pressure (BP), which was always measured by a single clinician in the right arm
supported at heart level, using a mercury sphygmomanometer (Wan Med(r), São Paulo,
SP, Brazil). Two measurements were taken, with an interval of 2 minutes between them.
The lowest value was considered for the analysis. BP measurements were considered as
borderline or increased if the values were equal to or above the 90th percentile for
age and sex1414. National High Blood Pressure Education Program Working Group on High
Blood Pressure in Children and Adolescents. The fourth report on the diagnosis,
evaluation, and treatment of high blood pressure in children and adolescents.
Pediatrics. 2004;114:555-76. PMid:15286277.
http://dx.doi.org/10.1542/peds.114.2.S2.555
http://dx.doi.org/10.1542/peds.114.2.S2....
.
Anthropometry
Height was measured with a portable stadiometer (Harpenden, Holtain Ltd, Crosswell,
Crymych, Pembs., UK) to the nearest 0.1 cm. Body mass was measured with a portable
scale (Seca 770, Hanover, MD, USA) to the nearest 0.1 kg. Anthropometry was performed
by a single individual following standardized procedures1515. Lohman TG, Roche AF, Martorell R. Anthropometric standardization
reference manual. Champaign: Human Kinetics; 1988.. The BMI was derived and BMI Z-score was obtained using U.S. data tables1212. Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, Flegal KM, Guo SS, Wei
R, et al. CDC growth charts: United States. Adv Data. 2000;(314)1-27.
PMid:11183293.. Waist circumference (WC) was also measured by the same single observer and
was measured in centimeters, using a non-stretch flexible tape measure, to the
nearest 0.1 cm. The tape was placed above the iliac crest, parallel to the ground,
with the individual standing with the abdomen relaxed, arms to the side, and feet
together. The cut-off was taken as the 75th percentile or greater, according to age
and ethnicity1616. Fernandez JR, Redden DT, Pietrobelli A, Allison DB. Waist
circumference percentiles in nationally representative samples of African-American,
European-American, and Mexican-American children and adolescents. J Pediatr.
2004;145:439-44. PMid:15480363. http://dx.doi.org/10.1016/j.jpeds.2004.06.044
http://dx.doi.org/10.1016/j.jpeds.2004.0...
.
Body fat mass assessment
The two-compartment model of body composition was assessed by bioelectrical impedance analysis (BIA), using a standardized body composition analyzer (Biodynamics Corporation, Seattle, WA, USA). Measurements were performed in the morning, without performing any prior vigorous physical activity and before breakfast, after a 10 to 12-hour overnight fast. The procedure required subjects to be in the supine position. Fat free mass (FFM), Fat Mass (FM), and the percentage of body fat mass (%BF) were calculated using validated equations1717. Houtkooper LB, Going SB, Lohman TG, Roche AF, Van Loan M. Bioelectrical impedance estimation of fat-free body mass in children and youth: a cross-validation study. J Appl Physiol. 1992;72:366-73. PMid:1537738. and in accordance with National Institutes of Health guidelines1818. Bioelectrical impedance analysis in body composition measurement: National Institutes of Health Technology Assessment Conference Statement. Am J Clin Nutr. 1996;64(3 Suppl):524S-32. PMid:8780375..
Cardiorespiratory fitness
Cardiorespiratory fitness was assessed on a treadmill (X-Fit 7 Power Treadmill),
using protocols in accordance with age and progressive intensities. The ramp protocol
was used, which consists of 8 to 12 minutes of exercise with small and constant
increments in speed and gradient based on the expected maximum oxygen
consumption1919. American College of Sports Medicine - ACSM. ACSM'S Guidelines for
exercise testing and prescription. Philadelphia: Lippincott Williams & Wilkins;
2006.. Criteria for the maximum test were: a) exhaustion or inability to maintain
the required speed, b) HR equal to or above 200 bpm, c) respiratory exchange ratio
(RER) equal to or greater than one. VO2max was determined by the average
of the three highest consecutive values obtained during the maximum test2020. Leite N, Milano GE, Cieslak F, Lopes WA, Rodacki A, Radominski RB.
Effects of physical exercise and nutritional guidance on metabolic syndrome in obese
adolescents. Rev Bras Fisioter. 2009;13:73-81.
http://dx.doi.org/10.1590/S1413-35552009005000009
http://dx.doi.org/10.1590/S1413-35552009...
.
Oxygen consumption (VO2), volume of expired carbon dioxide (VCO2), and ventilation (VE) were measured in a gas analyzer using open-circuit ergospirometry (Parvo Medics TrueOne(r) 2400 Metabolic Measurement System, Sandy, UT, USA), and the respiratory exchange ratio (RER) was calculated.
Measurement of biochemical markers
Participants were instructed to visit the hospital after 12 hours of fasting. All visits occurred in the morning, before any vigorous physical activity. Blood samples were collected to obtain a hemogram and levels of glucose, insulin, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triacylglycerol (TAG), human adiponectin, and C-reactive protein (CRP). Data were collected by venipuncture and the blood samples were stored in dry tubes for biochemical measurements. The colorimetric enzymatic method was used to measure TC, HDL-c, and TAG. The cutoff points were those proposed to Brazilian children and adolescents2121. Back Giuliano Ide C, Caramelli B, Pellanda L, Duncan B, Mattos S, Fonseca FH. [I guidelines of prevention of atherosclerosis in childhood and adolescence]. Arq Bras Cardiol. 2005;85 Suppl 6:4-36. PMid:16597097.. LDL-c was calculated using the Friedewald et al.2222. Friedewald WT, Levy R, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499-502. PMid:4337382. formula. The ultra-sensitive CRP was measured by the turbidimetric assay and adiponectin, by the ELISA method (Adiponectin DuoSet, R&D Systems, Inc., Minneapolis, MN, USA).
Intima-media thickness (IMT) assessment
The IMT of the common carotid artery (1-2 cm proximal to the carotid bifurcation) was assessed bilaterally in the posterior wall of the vessel with the aid of an ultrasound device (Philips SONOS 5500 with 8 MHz linear transduction). The procedure required subjects to be in the supine position and resting their back on a pillow. The average of three values of the right-side c-IMT (c-IMTr) and left-side c-IMT (c-IMTl) was retained for analysis. c-IMT corresponds to the mean of c-IMTr and c-IMTl. All measurements were performed by the same experienced observer (clinician at Hospital das Clínicas - UFPR). The intraobserver coefficient was 8% for c-IMTl and 2% for c-IMTr.
Statistical analysis
The initial analysis was descriptive in nature to determine the means and standard deviations for anthropometry, metabolic markers, and IMT. The normality of data was assessed by the Shapiro-Wilk test. When necessary, values were transformed into natural logarithm (logn) for normalization. As for the proportion and prevalence, we used the chi-square test and Fisher's exact test. The independent T test was used for parametric data and the Mann-Whitney U test was used for nonparametric data in order to compare variables between groups. Pearson's correlation for parametric data and Spearman's correlation for non-parametric data were used to analyze the possible relationship among BMI, VO2max, inflammatory markers, lipid profile, and c-IMT. For proper analysis, the classification of the magnitude of the correlations was used: r=0.10 to 0.30 (weak), r=0.40 to 0.60 (moderate), r=0.70 to 1.0 (strong). The level of significance was p<0.05. Statistical tests were performed with the SPSS Statistics 18.0 software (SPSS Inc.).
Results
Fifty-three adolescents participated in this study and were divided into two groups according to the presence or absence of obesity. The sample consisted of 35 subjects in the obese group (19 boys and 16 girls) and 18 subjects in the non-obese group (9 boys and 9 girls).
The clinical and anthropometric characteristics are presented in Table 1. The mean age was similar between the obese (12.3± 1.7 years) and non-obese subjects (12.7± 1.4 years). The mean height values did not differ between groups. The obese group showed higher values for weight, BMI, BMI Z-score, and WC than the non-obese group (p<0.001) as a result of the initial group allocation. The mean SBP was higher in the obese group than in the non-obese group (p<0.005) and DBP did not differ between groups. As for the maturation stage, the groups were similar (p<0.59).
For WC, all subjects in the obese group showed increased abdominal adiposity, with 29
subjects (93%) above the 90th percentile. None of the non-obese subjects showed
adiposity above the 75th percentile. In the total sample, there were eight (15.7%)
subjects with systolic hypertensive measurements and 17 (33.3%) with diastolic
hypertensive measurements. The obese group had a higher frequency of hypertensive
measures in SBP (8 vs. 0, χ22. Zhu W, Huang X, He J, Li M, Neubauer H. Arterial intima-media
thickening and endothelial dysfunction in obese Chinese children. Eur J Pediatr.
2005;164:337-44. PMid:15750804. http://dx.doi.org/10.1007/s00431-005-1642-y
http://dx.doi.org/10.1007/s00431-005-164...
=4.74; p<0.029). The frequencies of DBP were similar between groups. The mean
values of FM, fat percentage (%Body Fat), fat-free mass (FFM), and percentage of
fat-free mass (%FFM) were higher in the obese group than in the non-obese group
(p<0.01). As for cardiorespiratory variables, the obese group had lower levels of
VO2max and higher levels of HRrest than the non-obese group
(p<0.001).
The obese group showed higher frequencies of VO2max, lower than the expected for age and sex, than the non-obese group (34 vs. 14; p<0.006). In the non-obese group, three (22.3%) subjects had normal values of VO2max, while none of the subjects in the obese group reached this classification.
The clinical and laboratory variables are presented in Table 2. The obese subjects showed higher TAG and insulin values and lower HDL values than the non-obese ones (p<0.001). The TC, LDL, and glycemia (GL) variables were similar between groups.
The obese subjects had a higher number of occurrences of high TAG (13 vs. 1, χ2=7.50; p<0.007) and low HDL (18 vs. 0, χ2=17.21; p<0.00) than the non-obese ones. TC (10 vs. 5, χ2=0.12; p<0.733) and LDL (2 vs. 0, p<0.27) did not differ between groups. Figure 1 shows the distributions of percentage values of changes in lipid profiles of both groups. The obese subjects had higher CRP, c-IMTr, and c-IMT values than the non-obese subjects (p<0.05) and lower adiponectin values (p<0.001). c-IMTl values were similar between the two groups.
Correlation between maximal oxygen consumption (VO2max) and left-side carotid intima-media thickness (c-IMTl), right-side carotid intima-media thickness (c-IMTr), and carotid intima-media thickness (c-IMT).
BMI showed a strong positive correlation with weight (r=0.93; p<0.01), WC (r=0.95; p<0.01), Fat Mass (FM) (r=0.95; p<0.01), and %Body Fat (r=0.87; p<0.01) and an inverse correlation with %FFM(r=-0.88; p<0.01) and VO2max (r=-0.68; p<0.01). It was also moderately and directly correlated with SBP(r=0.45; p<0.01), HRrest (r=0.42; p<0.01), TAG (r=0.42; p<0.01), GL (r=0.40; p<0.01), and insulin (r=0.44; p<0.01) and inversely correlated with FFM (r=0.65; p<0.01), adiponectin (r=-0.51; p<0.01), and HDL (r=0.61; p<0.01).
The three measures of c-IMT showed a moderate direct correlation with weight, WC, BMI, FM, %Body Fat, and FFM and an inverse correlation with %FFM and VO2max. Figure 1 shows the correlation between VO2max and c-IMT. Only c-IMTr and c-IMT were moderately correlated with the BMI Z-score. As for laboratory variables, c-IMTr showed a weak positive correlation with LDL and GL, and a negative correlation with HDL. It was also moderately correlated with CRP. For c-IMT, we found only a weak inverse correlation with HDL. For c-IMTl, we did not find any correlations with any of the evaluated clinical and laboratory variables.
Adiponectin showed a moderate inverse correlation with weight, WC, FM, %Body Fat, and FFM and a positive correlation with %FFM. It was weakly and directly correlated with VO2max. As for CRP, we found a weak direct correlation with WC and %Body Fat and an inverse correlation with %FFM. CRP and VO2max were moderately and inversely correlated. As for laboratory variables, adiponectin showed moderate inverse correlation with insulinemia (INS). It was also weakly correlated with HDL and inversely correlated with TAG. CRP was moderately correlated with TAG and inversely correlated with HDL. Table 3 shows the correlations among the variables.
Discussion
In our study, we found that obese children and adolescents presented higher c-IMT values
than non-obese ones, corroborating previous studies that reported the contribution of
obesity to the development of early atherosclerosis2323. Lamotte C, Iliescu C, Libersa CFG. Increased intima-media thickness
of the carotid artery in childhood: a systematic review of observational studies. Eur
J Pediatr. 2011;170:719-29. PMid:20978785.
http://dx.doi.org/10.1007/s00431-010-1328-y
http://dx.doi.org/10.1007/s00431-010-132...
,
2424. Silva LR, Stefanello JMF, Pizzi J, Timossi LS, Leite N.
Atherosclerosis subclinical and inflammatory markers in obese and nonobese Children
and adolescents. Rev Bras Epidemiol. 2012;15(4):13. PMid:22450489.. The risk factors for atherosclerosis, such as hypertension, dyslipidemia,
diabetes, and insulin resistance, have been demonstrated in adults2525. Di Pino A, Alagona C, Piro S, Calanna S, Spadaro L, Palermo F, et
al. Separate impact of metabolic syndrome and altered glucose tolerance on early
markers of vascular injuries. Atherosclerosis. 2012;223(2):458-62. PMid:22742860.
http://dx.doi.org/10.1016/j.atherosclerosis.2012.05.008
http://dx.doi.org/10.1016/j.atherosclero...
26. Recio-Rodriguez JI, Gomez-Marcos MA, Patino-Alonso MC, Agudo-Conde
C, Rodriguez-Sanchez E, Garcia-Ortiz L, et al. Abdominal obesity vs general obesity
for identifying arterial stiffness, subclinical atherosclerosis and wave reflection
in healthy, diabetics and hypertensive. BMC Cardiovasc Disord. 2012;12:3.
PMid:22292502 PMCid:PMC3395841. http://dx.doi.org/10.1186/1471-2261-12-3
http://dx.doi.org/10.1186/1471-2261-12-3...
27. Wang Y, Ma X, Zhou M, Zong W, Zhang LYH, Zhu J, et al. Contribution
of visceral fat accumulation to carotid intima-media thickness in a Chinese
population. Int J Obes (Lond). 2012;36(9):51203-8. PMid:22124446 PMCid:PMC3448043.
http://dx.doi.org/10.1038/ijo.2011.222
http://dx.doi.org/10.1038/ijo.2011.222...
-
2828. Manios E, Michas F, Tsivgoulis G, Stamatelopoulos K, Tsagalis G,
Koroboki E, et al. Impact of prehypertension on carotid artery intima-media
thickening: Actual or masked?. Atherosclerosis. 2011;214:215-9. PMid:21122854.
http://dx.doi.org/10.1016/j.atherosclerosis.2010.10.032
http://dx.doi.org/10.1016/j.atherosclero...
, however information on the association of c-IMT with different risk factors
measured in childhood and adolescence is limited and contradictory. In a study conducted
by Mangge et al.2929. Mangge H, Schauenstein K, Stroedter L, Griesl A, Maerz W,
Borkenstein M. Low grade inflammation in juvenile obesity and type 1 diabetes
associated with early signs of atherosclerosis. Exper Clin Endocrinol Diabetes.
2004;112(7):378-82. PMid:15239023. http://dx.doi.org/10.1055/s-2004-821023
http://dx.doi.org/10.1055/s-2004-821023...
, BMI was positively correlated with c-IMT. Additionally, Beauloye et al.44. Beauloye V, Zech F, Tran HT, Clapuyt P, Maes M, Brichard SM.
Determinants of early atherosclerosis in obese children and adolescents. J Clin
Endocrinol Metab. 2007;92:3025-32. PMid:17519311.
http://dx.doi.org/10.1210/jc.2007-0619
http://dx.doi.org/10.1210/jc.2007-0619...
found that SBP, insulin, and HOMA-IR were correlated with c-IMT. In contrast,
some authors did not find any correlation between c-IMT and cardiovascular risk
factors33. Giannini C, De Giorgis T, Scarinci A, Ciampani M, Marcovecchio ML,
Chiarelli F, et al. Obese related effects of inflammatory markers and insulin
resistance on increased carotid intima media thickness in pre-pubertal children.
Atherosclerosis. 2008;197:448-56. PMid:17681348.
http://dx.doi.org/10.1016/j.atherosclerosis.2007.06.023
http://dx.doi.org/10.1016/j.atherosclero...
,
3030. Arnaiz P, Acevedo M, Barja S, Aglony M, Guzmán B, Cassis B, et al.
Adiponectin levels, cardiometabolic risk fators and markers of subclinical
atherosclerosis in children. Int J Cardiol. 2008;138:138-44. PMid:18774612.
http://dx.doi.org/10.1016/j.ijcard.2008.08.007
http://dx.doi.org/10.1016/j.ijcard.2008....
31. Mangge H, Almer G, Haj-Yahya S, Grandits N, Gasser R, Pilz S, et al.
Nuchal thickness of subcutaneous adipose tissue is tightly associated with an
increased LMW/total adiponectin ratio in obese juveniles. Atherosclerosis.
2009;203(1):277-83. PMid:18656877.
http://dx.doi.org/10.1016/j.atherosclerosis.2008.06.013
http://dx.doi.org/10.1016/j.atherosclero...
-
3232. Kelishadi R, Cook SR, Amrac B, Adibi A. Factors associated with
insulin resistance and non-alcoholic fatty liver disease among youths.
Atherosclerosis. 2009;204:538-43. PMid:19013572.
http://dx.doi.org/10.1016/j.atherosclerosis.2008.09.034
http://dx.doi.org/10.1016/j.atherosclero...
. In the present study, we found that c-IMT was positively correlated with BMI,
WC, %BF, and HOMA-IR and inversely correlated with HDL. These findings are in line with
studies demonstrating that obesity, insulin resistance, and dyslipidemia can be
associated with an increase in c-IMT in this population3333. Herouvi D, Karanasios E, Karayianni C, Karavanaki K. Cardiovascular
disease in childhood: the role of obesity. Eur J Pediatr. 2013;172:721-32.
PMid:23340698. http://dx.doi.org/10.1007/s00431-013-1932-8
http://dx.doi.org/10.1007/s00431-013-193...
.
Recently, inflammation biomarkers have been considered a risk factor for early
atherosclerosis44. Beauloye V, Zech F, Tran HT, Clapuyt P, Maes M, Brichard SM.
Determinants of early atherosclerosis in obese children and adolescents. J Clin
Endocrinol Metab. 2007;92:3025-32. PMid:17519311.
http://dx.doi.org/10.1210/jc.2007-0619
http://dx.doi.org/10.1210/jc.2007-0619...
,
3434. Higashi Y, Noma K, Yoshizumi M, Kihara Y. Endothelial function and
oxidative stress in cardiovascular diseases. Circ J. 2009;73(3):411-8. PMid:19194043.
http://dx.doi.org/10.1253/circj.CJ-08-1102
http://dx.doi.org/10.1253/circj.CJ-08-11...
,
3535. Jimenez MV, Estepa RM, Camacho RM, Estrada RC, Luna FG, Guitarte FB.
Endothelial dysfunction is related to insulin resistance and inflammatory biomarker
levels in obese prepubertal children. Eur J Endocrinol. 2007;156:497-502.
PMid:17389466. http://dx.doi.org/10.1530/EJE-06-0662
http://dx.doi.org/10.1530/EJE-06-0662...
. Elevated PCR and reduced adiponectin levels are known to be more frequent in
obese individuals77. Nishimura R, Sano H, Matsudaira T, Morimoto A, Miyashita Y, Shirasawa
T, et al. Changes in body mass index, leptin and adiponectin in Japanese children
during a three-year follow-up period: a population-based cohort study. Cardiovasc
Diabetol. 2009;8:30. PMid:19490650 PMCid:PMC2701411.
http://dx.doi.org/10.1186/1475-2840-8-30
http://dx.doi.org/10.1186/1475-2840-8-30...
. We found that obese children and adolescents had higher PCR and lower
adiponectin levels than non-obese ones. Also, we found that c-IMT was significantly
correlated with PCR, but not with adiponectin. CRP is known to affect endothelial
function via either direct or indirect mechanisms, such as reducing NO (nitric oxide)
production and stimulating inflammation-oxidative stress pathways3434. Higashi Y, Noma K, Yoshizumi M, Kihara Y. Endothelial function and
oxidative stress in cardiovascular diseases. Circ J. 2009;73(3):411-8. PMid:19194043.
http://dx.doi.org/10.1253/circj.CJ-08-1102
http://dx.doi.org/10.1253/circj.CJ-08-11...
. Moreover, adiponectin promotes the production of NO in endothelial cells, and
hypoadiponectinaemia is associated with blunted endothelial function3030. Arnaiz P, Acevedo M, Barja S, Aglony M, Guzmán B, Cassis B, et al.
Adiponectin levels, cardiometabolic risk fators and markers of subclinical
atherosclerosis in children. Int J Cardiol. 2008;138:138-44. PMid:18774612.
http://dx.doi.org/10.1016/j.ijcard.2008.08.007
http://dx.doi.org/10.1016/j.ijcard.2008....
. The lack of NO production induces vasoconstriction, leucocyte adherence,
platelet activation, oxidative stress, and thrombosis, leading to endothelial
dysfunction3434. Higashi Y, Noma K, Yoshizumi M, Kihara Y. Endothelial function and
oxidative stress in cardiovascular diseases. Circ J. 2009;73(3):411-8. PMid:19194043.
http://dx.doi.org/10.1253/circj.CJ-08-1102
http://dx.doi.org/10.1253/circj.CJ-08-11...
,
3636. Vanhoutte PM. Endothelial dysfunction: the first step toward
coronary arteriosclerosis. Circ J. 2009;73:7.
http://dx.doi.org/10.1253/circj.CJ-08-1169
http://dx.doi.org/10.1253/circj.CJ-08-11...
. The lack of correlation between adiponectin and endothelial dysfunction in
obese children and adolescents may be due to different signaling pathways in children
and in adults, especially as regards phosphatidylinositol 3-kinase for adiponectin
stimulation of NO production in endothelial cells3737. Han SH, Sakuma I, Shin EK, Koh KK. Antiatherosclerotic and
anti-insulin resistance effects of adiponectin: basic and clinical studies. Prog
Cardiovasc Dis. 2009;52(2):126-40. PMid:19732605.
http://dx.doi.org/10.1016/j.pcad.2009.06.004
http://dx.doi.org/10.1016/j.pcad.2009.06...
. In addition, the presence of multimetric forms of adiponectin and
high-molecular-weight adiponectin is thought to be superior to total adiponectin level
in predicting the c-IMT3737. Han SH, Sakuma I, Shin EK, Koh KK. Antiatherosclerotic and
anti-insulin resistance effects of adiponectin: basic and clinical studies. Prog
Cardiovasc Dis. 2009;52(2):126-40. PMid:19732605.
http://dx.doi.org/10.1016/j.pcad.2009.06.004
http://dx.doi.org/10.1016/j.pcad.2009.06...
. This was shown by Mangge et al.3131. Mangge H, Almer G, Haj-Yahya S, Grandits N, Gasser R, Pilz S, et al.
Nuchal thickness of subcutaneous adipose tissue is tightly associated with an
increased LMW/total adiponectin ratio in obese juveniles. Atherosclerosis.
2009;203(1):277-83. PMid:18656877.
http://dx.doi.org/10.1016/j.atherosclerosis.2008.06.013
http://dx.doi.org/10.1016/j.atherosclero...
, who reported that only high-molecular-weight adiponectin was correlated with
c-IMT in obese and non-obese children.
Our main finding was that cardiorespiratory fitness (VO2max) was inversely
associated with c-IMT. Studies have reported an inverse association between
cardiorespiratory fitness and c-IMT in middle-aged3838. Lee CD, Jae SY, Iribarren C, Pettee KK, Choi H. Physical fitness and
carotid atherosclerosis in men. Int J Sports Med. 2009;30:672-6. PMid:19569012.
http://dx.doi.org/10.1055/s-0029-1224179
http://dx.doi.org/10.1055/s-0029-1224179...
,
3939. Thijssen DH, Cable NT, Green DJ. Impact of exercise training on
arterial wall thickness in humans. Clin Sci (Lond). 2012;122(7):311-22. PMid:22150253
PMCid:3233305. http://dx.doi.org/10.1042/CS20110469
http://dx.doi.org/10.1042/CS20110469...
and elderly3939. Thijssen DH, Cable NT, Green DJ. Impact of exercise training on
arterial wall thickness in humans. Clin Sci (Lond). 2012;122(7):311-22. PMid:22150253
PMCid:3233305. http://dx.doi.org/10.1042/CS20110469
http://dx.doi.org/10.1042/CS20110469...
individuals. In children and adolescents, only two studies investigated this
relationship and the results were contradictory4040. Kim ES, Park J-H, Lee MK, Lee DH, Kang ES, Lee HC, et al.
Associations between Fatness, Fitness, IGF and IMT among Obese Korean Male
Adolescents. Diabetes Metab J. 2011;35(6):610-8. PMid:22247904 PMCid:PMC3253972.
http://dx.doi.org/10.4093/dmj.2011.35.6.610
http://dx.doi.org/10.4093/dmj.2011.35.6....
,
4141. Pahkala K, Laitinen TT, Heinonen OJ, Viikari JS, Ronnemaa T,
Niinikoski H, et al. Association of fitness with vascular intima-media thickness and
elasticity in adolescence. Pediatrics. 2013;132(1):e77-84. PMid:23753102.
http://dx.doi.org/10.1542/peds.2013-0041
http://dx.doi.org/10.1542/peds.2013-0041...
. Kim et al.4040. Kim ES, Park J-H, Lee MK, Lee DH, Kang ES, Lee HC, et al.
Associations between Fatness, Fitness, IGF and IMT among Obese Korean Male
Adolescents. Diabetes Metab J. 2011;35(6):610-8. PMid:22247904 PMCid:PMC3253972.
http://dx.doi.org/10.4093/dmj.2011.35.6.610
http://dx.doi.org/10.4093/dmj.2011.35.6....
found an inverse significant correlation between VO2max and maximum
IMT in Korean male adolescents. On the other hand, Pahkala et al.4141. Pahkala K, Laitinen TT, Heinonen OJ, Viikari JS, Ronnemaa T,
Niinikoski H, et al. Association of fitness with vascular intima-media thickness and
elasticity in adolescence. Pediatrics. 2013;132(1):e77-84. PMid:23753102.
http://dx.doi.org/10.1542/peds.2013-0041
http://dx.doi.org/10.1542/peds.2013-0041...
did not find an association between fitness and c-IMT in Finnish adolescents. It
is interesting to note that both studies estimated VO2max using indirect
methods. The gold-standard measure of cardiorespiratory fitness in humans involves
direct assessment of peak or maximal oxygen consumption in response to an exercise test.
We used the direct method to measure the VO2max.
Cardiorespiratory fitness is strongly associated with reduced risk of cardiovascular
disease and all-cause mortality4242. Eisenmann JC, Welk GJ, Ihmels M, Dollmlan J. Fatness, fitness, and
cardiovascular disease risk factors in children and adolescents. Med Sci Sports
Exerc. 2007;39(8):1251-7. PMid:17762357.
http://dx.doi.org/10.1249/MSS.0b013e318064c8b0
http://dx.doi.org/10.1249/MSS.0b013e3180...
. There are several plausible mechanisms by which cardiorespiratory fitness might
reduce the risk of carotid atherosclerotic vascular disease. Some studies suggest that
the effect of exercise on arterial wall thickness is explained by exercise-mediated
changes in traditional cardiovascular risk factors, such as adiposity, lipid levels, and
blood pressure3939. Thijssen DH, Cable NT, Green DJ. Impact of exercise training on
arterial wall thickness in humans. Clin Sci (Lond). 2012;122(7):311-22. PMid:22150253
PMCid:3233305. http://dx.doi.org/10.1042/CS20110469
http://dx.doi.org/10.1042/CS20110469...
. High levels of physical activity increase nitric oxide production, which
improve vascular function by enhancing vasodilation and vasomotor function in the
vessels. It also prevents platelet aggregation and adhesion in the endothelium, enhances
fibrinolysis, improves lipid profiles, and reduces blood viscosity and fibrinogen
levels, all of which may contribute to slowing the progression of carotid
atherosclerotic vascular disease3939. Thijssen DH, Cable NT, Green DJ. Impact of exercise training on
arterial wall thickness in humans. Clin Sci (Lond). 2012;122(7):311-22. PMid:22150253
PMCid:3233305. http://dx.doi.org/10.1042/CS20110469
http://dx.doi.org/10.1042/CS20110469...
,
4343. Montero D, Walther G, Perez-Martin A, Roche E, Vinet A. Endothelial
dysfunction, inflammation, and oxidative stress in obese children and adolescents:
markers and effect of lifestyle intervention. Obes Rev. 2012;13:441-55.
PMid:22133012. http://dx.doi.org/10.1111/j.1467-789X.2011.00956.x
http://dx.doi.org/10.1111/j.1467-789X.20...
. In contrast, other studies have demonstrated the impact of exercise on c-IMT
regardless of changes in risk factors3939. Thijssen DH, Cable NT, Green DJ. Impact of exercise training on
arterial wall thickness in humans. Clin Sci (Lond). 2012;122(7):311-22. PMid:22150253
PMCid:3233305. http://dx.doi.org/10.1042/CS20110469
http://dx.doi.org/10.1042/CS20110469...
,
4343. Montero D, Walther G, Perez-Martin A, Roche E, Vinet A. Endothelial
dysfunction, inflammation, and oxidative stress in obese children and adolescents:
markers and effect of lifestyle intervention. Obes Rev. 2012;13:441-55.
PMid:22133012. http://dx.doi.org/10.1111/j.1467-789X.2011.00956.x
http://dx.doi.org/10.1111/j.1467-789X.20...
.
The strength of this study is that we assessed values directly by using gas analyzer and ramp protocol. A limitation of our study is that the number of patients was small and we did not analyze boys and girls separately. In order to minimize the possible effects of gender differences on our data, the number of boys and girls was proportional in both groups (around 50% in each group). Another limitation is that we used the HOMA-IR to assess insulin resistance, which is less accurate than hyperinsulinemic euglycemic clamp. Additionally, we did not measure other isoforms of adiponectin, which could be more sensitive to correlation with c-IMT. Finally, the current study did not use a multivariable adjusted model.
The main finding of this study was the inverse correlation between c-IMT and VO2max, which shows that low aerobic fitness in this age group can be a predictor of the development of increased c-IMT in childhood and adolescence. It also shows that regular physical activity may be a protective factor for atherosclerosis, regardless of the presence of other traditional cardiovascular risk factors and inflammation.
Conclusion
Obese children and adolescents had higher values of c-IMT, as well as metabolic and inflammatory profiles. c-IMT correlates not only with body composition, blood lipids, insulin resistance, and inflammation, but also with low VO2max in children and adolescents. This result confirms the importance of regular physical activity to prevent cardiovascular disease. Further longitudinal studies are needed to determine whether the increase in cardiorespiratory fitness is associated with improvement in c-IMT during adolescence.
The authors declared no conflict of interest.
Acknowledgements
The authors wish to thank Fundação para a Ciência e Tecnologia (FCT), Portugal, Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior (CAPES), Brazil, and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil, for their funding.
References
-
1McGill HC Jr, Herderick EE, McMahan CA, Zieske AW, Malcolm GT, Tracy RE, et al. Atherosclerosis in youth. Minerva Pediatr. 2002;54:437-47. PMid:12244281.
-
2Zhu W, Huang X, He J, Li M, Neubauer H. Arterial intima-media thickening and endothelial dysfunction in obese Chinese children. Eur J Pediatr. 2005;164:337-44. PMid:15750804. http://dx.doi.org/10.1007/s00431-005-1642-y
» http://dx.doi.org/10.1007/s00431-005-1642-y -
3Giannini C, De Giorgis T, Scarinci A, Ciampani M, Marcovecchio ML, Chiarelli F, et al. Obese related effects of inflammatory markers and insulin resistance on increased carotid intima media thickness in pre-pubertal children. Atherosclerosis. 2008;197:448-56. PMid:17681348. http://dx.doi.org/10.1016/j.atherosclerosis.2007.06.023
» http://dx.doi.org/10.1016/j.atherosclerosis.2007.06.023 -
4Beauloye V, Zech F, Tran HT, Clapuyt P, Maes M, Brichard SM. Determinants of early atherosclerosis in obese children and adolescents. J Clin Endocrinol Metab. 2007;92:3025-32. PMid:17519311. http://dx.doi.org/10.1210/jc.2007-0619
» http://dx.doi.org/10.1210/jc.2007-0619 -
5Brasil AR, Norton RC, Rossetti MB, Leao E, Mendes RP. C-reactive protein as an indicator of low intensity inflammation in children and adolescents with and without obesity. J Pediatr (Rio J). 2007;83:477-80.
-
6Asayama K, Hayashibe H, Dobashi K, Uchida N, Nakane T, Kodera K, et al. Decrease in serum adiponectin level due to obesity and visceral fat accumulation in children. Obes Res. 2003;11:1072-9. PMid:12972677. http://dx.doi.org/10.1038/oby.2003.147
» http://dx.doi.org/10.1038/oby.2003.147 -
7Nishimura R, Sano H, Matsudaira T, Morimoto A, Miyashita Y, Shirasawa T, et al. Changes in body mass index, leptin and adiponectin in Japanese children during a three-year follow-up period: a population-based cohort study. Cardiovasc Diabetol. 2009;8:30. PMid:19490650 PMCid:PMC2701411. http://dx.doi.org/10.1186/1475-2840-8-30
» http://dx.doi.org/10.1186/1475-2840-8-30 -
8Bouassida A, Chamari K, Zaouali M, Feki Y, Zbidi A, Tabka Z. Review on leptin and adiponectin responses and adaptations to acute and chronic exercise. Br J Sports Med. 2010;44:620-30. PMid:18927166. http://dx.doi.org/10.1136/bjsm.2008.046151
» http://dx.doi.org/10.1136/bjsm.2008.046151 -
9Kumar V, Sachdev HP, Khalil A. Noninvasive evaluation of endothelial function and arterial mechanics in overweight adolescents. Indian Pediatr. 2004;41:1105-14. PMid:15591660.
-
10Kapuku GK, Harshfield GA, Davis HC, Treiber FA. Early markers of cardiovascular disease. Vascul Pharmacol. 2006;45:277-80. PMid:17011834. http://dx.doi.org/10.1016/j.vph.2006.08.009
» http://dx.doi.org/10.1016/j.vph.2006.08.009 -
11Farpour-Lambert NJ, Aggoun Y, Marchand LM, Martin XE, Herrmann FR, Beghetti M. Physical activity reduces systemic blood pressure and improves early markers of atherosclerosis in pre-pubertal obese children. J Am Coll Cardiol. 2009;54:2396-2406. PMid:20082930. http://dx.doi.org/10.1016/j.jacc.2009.08.030
» http://dx.doi.org/10.1016/j.jacc.2009.08.030 -
12Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, Flegal KM, Guo SS, Wei R, et al. CDC growth charts: United States. Adv Data. 2000;(314)1-27. PMid:11183293.
-
13Tanner JM. Normal growth and techniques of growth assessment. Clin Endocrinol Metab. 1986;15:411-51. http://dx.doi.org/10.1016/S0300-595X(86)80005-6
» http://dx.doi.org/10.1016/S0300-595X(86)80005-6 -
14National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004;114:555-76. PMid:15286277. http://dx.doi.org/10.1542/peds.114.2.S2.555
» http://dx.doi.org/10.1542/peds.114.2.S2.555 -
15Lohman TG, Roche AF, Martorell R. Anthropometric standardization reference manual. Champaign: Human Kinetics; 1988.
-
16Fernandez JR, Redden DT, Pietrobelli A, Allison DB. Waist circumference percentiles in nationally representative samples of African-American, European-American, and Mexican-American children and adolescents. J Pediatr. 2004;145:439-44. PMid:15480363. http://dx.doi.org/10.1016/j.jpeds.2004.06.044
» http://dx.doi.org/10.1016/j.jpeds.2004.06.044 -
17Houtkooper LB, Going SB, Lohman TG, Roche AF, Van Loan M. Bioelectrical impedance estimation of fat-free body mass in children and youth: a cross-validation study. J Appl Physiol. 1992;72:366-73. PMid:1537738.
-
18Bioelectrical impedance analysis in body composition measurement: National Institutes of Health Technology Assessment Conference Statement. Am J Clin Nutr. 1996;64(3 Suppl):524S-32. PMid:8780375.
-
19American College of Sports Medicine - ACSM. ACSM'S Guidelines for exercise testing and prescription. Philadelphia: Lippincott Williams & Wilkins; 2006.
-
20Leite N, Milano GE, Cieslak F, Lopes WA, Rodacki A, Radominski RB. Effects of physical exercise and nutritional guidance on metabolic syndrome in obese adolescents. Rev Bras Fisioter. 2009;13:73-81. http://dx.doi.org/10.1590/S1413-35552009005000009
» http://dx.doi.org/10.1590/S1413-35552009005000009 -
21Back Giuliano Ide C, Caramelli B, Pellanda L, Duncan B, Mattos S, Fonseca FH. [I guidelines of prevention of atherosclerosis in childhood and adolescence]. Arq Bras Cardiol. 2005;85 Suppl 6:4-36. PMid:16597097.
-
22Friedewald WT, Levy R, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499-502. PMid:4337382.
-
23Lamotte C, Iliescu C, Libersa CFG. Increased intima-media thickness of the carotid artery in childhood: a systematic review of observational studies. Eur J Pediatr. 2011;170:719-29. PMid:20978785. http://dx.doi.org/10.1007/s00431-010-1328-y
» http://dx.doi.org/10.1007/s00431-010-1328-y -
24Silva LR, Stefanello JMF, Pizzi J, Timossi LS, Leite N. Atherosclerosis subclinical and inflammatory markers in obese and nonobese Children and adolescents. Rev Bras Epidemiol. 2012;15(4):13. PMid:22450489.
-
25Di Pino A, Alagona C, Piro S, Calanna S, Spadaro L, Palermo F, et al. Separate impact of metabolic syndrome and altered glucose tolerance on early markers of vascular injuries. Atherosclerosis. 2012;223(2):458-62. PMid:22742860. http://dx.doi.org/10.1016/j.atherosclerosis.2012.05.008
» http://dx.doi.org/10.1016/j.atherosclerosis.2012.05.008 -
26Recio-Rodriguez JI, Gomez-Marcos MA, Patino-Alonso MC, Agudo-Conde C, Rodriguez-Sanchez E, Garcia-Ortiz L, et al. Abdominal obesity vs general obesity for identifying arterial stiffness, subclinical atherosclerosis and wave reflection in healthy, diabetics and hypertensive. BMC Cardiovasc Disord. 2012;12:3. PMid:22292502 PMCid:PMC3395841. http://dx.doi.org/10.1186/1471-2261-12-3
» http://dx.doi.org/10.1186/1471-2261-12-3 -
27Wang Y, Ma X, Zhou M, Zong W, Zhang LYH, Zhu J, et al. Contribution of visceral fat accumulation to carotid intima-media thickness in a Chinese population. Int J Obes (Lond). 2012;36(9):51203-8. PMid:22124446 PMCid:PMC3448043. http://dx.doi.org/10.1038/ijo.2011.222
» http://dx.doi.org/10.1038/ijo.2011.222 -
28Manios E, Michas F, Tsivgoulis G, Stamatelopoulos K, Tsagalis G, Koroboki E, et al. Impact of prehypertension on carotid artery intima-media thickening: Actual or masked?. Atherosclerosis. 2011;214:215-9. PMid:21122854. http://dx.doi.org/10.1016/j.atherosclerosis.2010.10.032
» http://dx.doi.org/10.1016/j.atherosclerosis.2010.10.032 -
29Mangge H, Schauenstein K, Stroedter L, Griesl A, Maerz W, Borkenstein M. Low grade inflammation in juvenile obesity and type 1 diabetes associated with early signs of atherosclerosis. Exper Clin Endocrinol Diabetes. 2004;112(7):378-82. PMid:15239023. http://dx.doi.org/10.1055/s-2004-821023
» http://dx.doi.org/10.1055/s-2004-821023 -
30Arnaiz P, Acevedo M, Barja S, Aglony M, Guzmán B, Cassis B, et al. Adiponectin levels, cardiometabolic risk fators and markers of subclinical atherosclerosis in children. Int J Cardiol. 2008;138:138-44. PMid:18774612. http://dx.doi.org/10.1016/j.ijcard.2008.08.007
» http://dx.doi.org/10.1016/j.ijcard.2008.08.007 -
31Mangge H, Almer G, Haj-Yahya S, Grandits N, Gasser R, Pilz S, et al. Nuchal thickness of subcutaneous adipose tissue is tightly associated with an increased LMW/total adiponectin ratio in obese juveniles. Atherosclerosis. 2009;203(1):277-83. PMid:18656877. http://dx.doi.org/10.1016/j.atherosclerosis.2008.06.013
» http://dx.doi.org/10.1016/j.atherosclerosis.2008.06.013 -
32Kelishadi R, Cook SR, Amrac B, Adibi A. Factors associated with insulin resistance and non-alcoholic fatty liver disease among youths. Atherosclerosis. 2009;204:538-43. PMid:19013572. http://dx.doi.org/10.1016/j.atherosclerosis.2008.09.034
» http://dx.doi.org/10.1016/j.atherosclerosis.2008.09.034 -
33Herouvi D, Karanasios E, Karayianni C, Karavanaki K. Cardiovascular disease in childhood: the role of obesity. Eur J Pediatr. 2013;172:721-32. PMid:23340698. http://dx.doi.org/10.1007/s00431-013-1932-8
» http://dx.doi.org/10.1007/s00431-013-1932-8 -
34Higashi Y, Noma K, Yoshizumi M, Kihara Y. Endothelial function and oxidative stress in cardiovascular diseases. Circ J. 2009;73(3):411-8. PMid:19194043. http://dx.doi.org/10.1253/circj.CJ-08-1102
» http://dx.doi.org/10.1253/circj.CJ-08-1102 -
35Jimenez MV, Estepa RM, Camacho RM, Estrada RC, Luna FG, Guitarte FB. Endothelial dysfunction is related to insulin resistance and inflammatory biomarker levels in obese prepubertal children. Eur J Endocrinol. 2007;156:497-502. PMid:17389466. http://dx.doi.org/10.1530/EJE-06-0662
» http://dx.doi.org/10.1530/EJE-06-0662 -
36Vanhoutte PM. Endothelial dysfunction: the first step toward coronary arteriosclerosis. Circ J. 2009;73:7. http://dx.doi.org/10.1253/circj.CJ-08-1169
» http://dx.doi.org/10.1253/circj.CJ-08-1169 -
37Han SH, Sakuma I, Shin EK, Koh KK. Antiatherosclerotic and anti-insulin resistance effects of adiponectin: basic and clinical studies. Prog Cardiovasc Dis. 2009;52(2):126-40. PMid:19732605. http://dx.doi.org/10.1016/j.pcad.2009.06.004
» http://dx.doi.org/10.1016/j.pcad.2009.06.004 -
38Lee CD, Jae SY, Iribarren C, Pettee KK, Choi H. Physical fitness and carotid atherosclerosis in men. Int J Sports Med. 2009;30:672-6. PMid:19569012. http://dx.doi.org/10.1055/s-0029-1224179
» http://dx.doi.org/10.1055/s-0029-1224179 -
39Thijssen DH, Cable NT, Green DJ. Impact of exercise training on arterial wall thickness in humans. Clin Sci (Lond). 2012;122(7):311-22. PMid:22150253 PMCid:3233305. http://dx.doi.org/10.1042/CS20110469
» http://dx.doi.org/10.1042/CS20110469 -
40Kim ES, Park J-H, Lee MK, Lee DH, Kang ES, Lee HC, et al. Associations between Fatness, Fitness, IGF and IMT among Obese Korean Male Adolescents. Diabetes Metab J. 2011;35(6):610-8. PMid:22247904 PMCid:PMC3253972. http://dx.doi.org/10.4093/dmj.2011.35.6.610
» http://dx.doi.org/10.4093/dmj.2011.35.6.610 -
41Pahkala K, Laitinen TT, Heinonen OJ, Viikari JS, Ronnemaa T, Niinikoski H, et al. Association of fitness with vascular intima-media thickness and elasticity in adolescence. Pediatrics. 2013;132(1):e77-84. PMid:23753102. http://dx.doi.org/10.1542/peds.2013-0041
» http://dx.doi.org/10.1542/peds.2013-0041 -
42Eisenmann JC, Welk GJ, Ihmels M, Dollmlan J. Fatness, fitness, and cardiovascular disease risk factors in children and adolescents. Med Sci Sports Exerc. 2007;39(8):1251-7. PMid:17762357. http://dx.doi.org/10.1249/MSS.0b013e318064c8b0
» http://dx.doi.org/10.1249/MSS.0b013e318064c8b0 -
43Montero D, Walther G, Perez-Martin A, Roche E, Vinet A. Endothelial dysfunction, inflammation, and oxidative stress in obese children and adolescents: markers and effect of lifestyle intervention. Obes Rev. 2012;13:441-55. PMid:22133012. http://dx.doi.org/10.1111/j.1467-789X.2011.00956.x
» http://dx.doi.org/10.1111/j.1467-789X.2011.00956.x
Publication Dates
-
Publication in this collection
2014 -
Date of issue
Mar 2014
History
-
Received
05 Feb 2013 -
Reviewed
26 June 2013 -
Accepted
06 Sept 2013