ULTRASONOGRAPHIC MARKERS OF CARDIOVASCULAR DISEASE RISK IN OBESE CHILDREN

ASTRACT

Objective:

To evaluate whether the obesity alters ultrasonographical markers of metabolic and cardiovascular disease risk in children.

Methods:

A cross-sectional study evaluated 80 children aged between 6 and 10 years, comparing 40 obese with 40 normal children. The following parameters were assessed: weight; height; body mass index; arterial blood pressure; body fat; basal metabolic rate; HDL-cholesterol, LDL-cholesterol and total cholesterol; fasting insulin and glucose; quantitative insulin sensitivity check index (QUICKI); homeostasis model of assessment - insulin resistance (HOMA-IR); basal diameter of the brachial artery; brachial artery flow mediated dilation (FMD) and of pulsatility index change (PI-C).

Results:

Significant differences were observed between obese vs. non-obese children: systolic blood pressure (97.7±8.4 vs. 89.0±5.8 mmHg; p<0.01), diastolic blood pressure (64.3±7.9 vs. 52.9±5.1 mmHg; p<0.01), proportion of body fat (45.1±5.9 vs. 21.3±6.0%; p<0.01), basal metabolic rate (1216.1±102.1 vs. 1072.9±66.4 Kcal; p<0.01), total cholesterol (164.7±25.2 vs. 153.4±15.8 mg/dL; p=0.03), fasting insulin (7.1±5.2 vs. 2.8±1.8 pIU/mL; p<0.01), HOMA-IR (1.5±1.1 vs. 0.6±0.4; p<0.01), basal diameter of the brachial artery (2.5±0.3 vs. 2.1±0.3 mm; p<0.01); PI-C (-15.5±27.2 vs. -31.9±15.5%; p<0.01), decreased QUICKI (0.4±0.05 vs. 0.4±0.03; p<0.01), and FMD (6.6±3.2 vs. 15.6±7.3%; p<0.01).

Conclusions:

Obesity worsens ultrasonographical and laboratorial markers of metabolic and cardiovascular disease risk in children.

Keywords:
Child; Obesity; Cardiovascular disease; Endothelium; Ultrasonography

RESUMO

Objetivo:

Avaliar se a obesidade altera os marcadores ultrassonográficos de risco metabólico e cardiovascular em crianças.

Métodos:

Estudo transversal com 80 crianças entre 6 e 10 anos, comparando 40 crianças obesas com 40 crianças normais. Foram avaliados os seguintes parâmetros: peso; altura; índice de massa corporal; pressão arterial; massa gorda; taxa metabólica basal; HDL-colesterol, LDL-colesterol e colesterol total; insulina de jejum e glicose; índice quantitativo de verificação da sensibilidade à insulina (QUICKI); Homeostase Modell Assessment (HOMA-IR); Diâmetro basal da artéria braquial; Dilatação mediada pelo fluxo da artéria braquial (FMD) e variação do índice de pulsatilidade (PI-C).

Resultados:

Entre obesos e não obesos, observaram-se diferenças significativas na pressão arterial sistólica (97,7±8,4 vs. 89,0±5,8 mmHg; p<0,01), pressão arterial diastólica (64,3±7,9 vs. 52,9±5.1 mmHg; p<0,01), gordura corporal (45,1±5,9 vs. 21,3±6,0%; p<0,01), taxa metabólica basal (1216,1±102,1 vs. 1072,9±66,4 Kcal; p<0,01), colesterol (164,7±25,2 vs. 153,4±15,8 mg/dL; p=0,03), insulina de jejum (7,1±5,2 vs. 2,8±1,8 pIU/mL; p<0,01), HOMA-IR (1,5±1,1 vs. 0,6±0,4; p<0.01), diâmetro basal da artéria braquial (2,5±0,3 vs. 2,1±0,3 mm; p<0,01); PI-C (-15,5±27,2 vs. -31,9±15,5%; p<0,01), redução de QUICKI (0,4±0,05 vs. 0,4±0,03; p<0,01) e FMD (6,6±3,2 vs. 15,6±7,3%; p<0,01).

Conclusões:

A obesidade piora os marcadores ultrassonográficos e laboratoriais de risco metabólico e cardiovascular em crianças.

Palavras-chave:
Criança; Obesidade; Doenças cardiovasculares; Endotélio; Ultrassonografia

INTRODUCTION

Obesity in childhood is an important risk factor to cardiovascular disease (CVD), dyslipidemia, impaired glucose tolerance, hypertension, adult obesity and premature mortality.^1,2 In the last decades, the prevalence of obesity has markedly increased: about 10% of school-aged children worldwide are overweight; inwestern countries, approximately 35% are overweight, and about one fourth of those children are obese.^3,4 Thus, excess weight in children represents a public health issue, and is associated with endothelial damage and metabolic abnormalities.^1,5,6

The injured endothelium plays an important role in the development of many cardiovascular diseases,⁷ such as atherosclerosis and coronary heart disease.⁷ Furthermore, it may be used as a risk predictor for such events.⁸ Endothelial dysfunction is the major event in the development of atherosclerosis, and it may be observed a long time before the appearance of structural atherosclerotic disease.⁹

For the clinician, even considering that he will not make endothelial evaluation of all his patients, the knowledge of the comorbidities linked to obesity is crucial, because it is an opportunity of reinforcing the risks associated with this condition. The non-invasive evaluation of endothelial function shows the potential for cardiovascular risk stratification in children¹⁰ and, among such methods, main flow-mediated dilation (FMD) and pulsatility index change (PI-C) of the brachial artery stand out because they are safe, reproducible, and relatively simple techniques to be performed;⁹ which may be applied in children.^10,11 Nevertheless, there is no previously published study assessing the variation in the pulsatility index of the brachial artery as a marker of endothelial dysfunction, comparing obese and non-obese children. Therefore, in the present study, we aimed to compare ultrasonographic, clinical and metabolic markers of cardiovascular risk between obese and eutrophic children.

METHOD

It is a descriptive cross-sectional study with patients attending in the outpatient pediatric clinics of the primary health care public network in Ribeirão Preto, Brazil. Children aged between 6 and 10 years old were invited to participate if they were either obese [Body Mass Index (BMI) >95 percentile] or eutrophic [BMI >5th percentile and BMI <85th percentile]. The classification of children as obese or eutrophic was based on normality curves of the National Centers for Health Statistics (NCHS), considering BMI for gender and age.¹² This reference was chosen due to its being the curve used at the service where the data was collected. No matching criterion was adopted. The only exclusion criterion adopted was failure to perform all the proposed evaluation. The sample size was estimated based on other studies with flow-mediated dilation. In a parallel-design study, 23 subjects would be required to detect an FMD difference of 60% (two-tailed) (e.g., 5 vs. 8%, at 90% power). To achieve an FMD difference of 40% (e.g., 5 vs. 7%, at 90% power), 46 subjects should be included.¹³ Considering that an absolute difference of 4 to 8% may be due to a personal variation and that a minimum of 2% difference when comparing two groups would be considered as the minimal clinically important,^13,14,15 40 children were evaluated in each group.

All children’s legal guardians were fully informed and had given written informed consent before the children were enrolled in this study. The study was approved by the local ethics committee.

Anthropometric parameters (weight, height, BMI), systolic and diastolic blood pressure, body fat percentage, basal metabolic rate, laboratory markers (fasting insulin, fasting glucose, quantitative index of insulin sensitivity [QUICKI], homeostasis assessment model of insulin resistance [HOMA-IR)], total cholesterol, HDL-cholesterol and LDL- cholesterol were studied. Some sonographic parameters were also evaluated (flow-mediated dilation (FMD), a variation of the pulsatility index (PI- C) and basal diameter of the brachial artery). The examinations were performed in the morning (7-9 am) after 15 minutes of rest in dorsal decubitus, in a room with temperature control (20-23ºC). All individuals were fasting for a minimum of 12 hours and had rested the night before for at least 8 hours. Initially, blood pressure was taken in the left arm with a standard mercury sphygmomanometer, establishing systolic blood pressure (SBP) and diastolic blood pressure (DBP). Weight and height were used to determine the BMI. The percentage of body fat and the basal metabolic rate were assessed by bioelectrical impedance analyzer (BIA), equipment BF-906 (Maltron^®, UK). The sonographic evaluation used a linear probe 6-12 MHz present in the HD7 device (Philips Medical Systems^®, Bothell, WA) attached to an electrocardiogram. All anthropometric, blood pressure and sonographic assessments were performed by a single observer.

The technique for obtaining FMD and PI-C of the brachial artery was performed as follows: after the rest period, an ultrasound image of the right brachial artery in the longitudinal plane was obtained, 5-10 cm proximal to the antecubital fossa, visualizing the intima interface and the vessel lumen in both vascular walls. A clip of 5 seconds was recorded, which would be evaluated at the end of echographic exam. The spectral Doppler mode was adjusted and standardized with a frequency of 5 MHz, 50 Hz filter and sample volume of 1.0 mm. The sample was positioned in the middle of the brachial artery at a maximum angle of 60º. Using the product software, the following variables of three consecutive similar waves were determined: peak systolic velocity (PSV), end-diastolic velocity (EDV), mean velocity (MV) and pulsatility index (PI) [PI = (PSV- DV)/MV].¹⁶

A pneumatic compression (standardized at 200 mmHg) was performed for 5 minutes on the right forearm just below the medial epicondyle of the children. After this period, a rapid sphygmomanometer deflation was performed. One minute after deflation, another 5-second echographic clip of the brachial artery was recorded and stored. Then, the Doppler was held between 70-80 seconds after cuff release to obtain the Doppler parameters to determine new PI values, which were recorded on the apparatus.

After examination, the values of baseline brachial artery diameter (BDpre) and 1 minute after stimulation (BDpost) were determined.¹⁷ For these measures, it was subjectively chosen the best image of the vessel during the end-diastolic (R wave in the electrocardiogram) to perform 3 measures, from intima proximal to intima distal.

Blood samples (20 mL) were collected and stored in conical tubes (Becton Dickinson, Plymouth, UK). The serum was stored at -80ºC for simultaneous determination of the following variables: fasting glucose, determined by the oxidase method using a Konelab 60i analyzer (WienerLab^®, Rosario, Argentina); total cholesterol and HDL-cholesterol, determined by enzymatic method, with BT 3000BTplus analyzer (WienerLab, Rosario, Argentina), LDL cholesterol calculated according to the formula: LDL cholesterol = (Total cholesterol) - ((HDL) + (Triglycerides/5), fasting insulin, measured by chemiluminescence with DPCImmulite 2000 (DiagnosticProductsCorporation^®, LosAngeles, CA). Insulin resistance was evaluated by checking the QUICKI; QUICKI = 1/(log [fasting glucose (mg/dl)] + log [fasting insulin (pIU/mL)]) and the homeostasis model assessment of insulin resistance (HOMA-IR), HOMA-IR = fasting glucose (mg/dL) x fasting insulin (pU / mL)/405.¹⁸

Data were analyzed by the SPSS program 18.0 (SPSS Inc., Chicago, USA). Descriptive statistics were performed to establish mean, standard deviation, minimum and maximum values of the studied parameters. The comparison of quantitative parameters between groups was demonstrated by unpaired t test or Mann-Whitney. The level of statistical significance was set at p<0.05.

RESULTS

A total of 92 children were assessed for eligibility. Of those, 83 agreed to participate in the study: 41 obese children and 42 eutrophic. From those, 3 children did not complete laboratory (1 obese and 2 eutrophic) and were excluded from the final analysis. Weight, BMI, systolic and diastolic blood pressure, body fat percentage, andbasal metabolic rate were significantly different between groups. No significant difference was observed in age (Table 1).

Table 1:
Anthropometric parameters, arterial blood pressure and body composition in obese children and controls.

	Obese (N=40)	Control (N=40)	p-value*
Age (years)	7.8±1.1	7.6±1.1	0.82
Weight (Kg)	45.9±10.45	25.4±4.4	<0.01
BMI (Kg/m2)	24.5±3.4	15.4±1.4	<0.01
Systolic pressure (mmHg)	97.7±8.4	89.0±5.8	<0.01
Diastolic pressure (mmHg)	64.3±7.9	52.9±5.2	<0.01
Body fat (%)	45.1±5.9	21.3±6.0	<0.01
Basal Metabolic Rate (Kcal)	1,216.1±102.1	1,072.9±66.4	<0.01

• Data presented as mean ± standard deviation; *unpaired t test or Mann-Whitney U test were used depending on the distribution of the data.

When comparing the laboratory and sonographic findings of endothelial dysfunction (Table 2) in obese individuals, it was observed higher rates of total cholesterol (164.7±25.2 vs. 15.8±153.4; p=0.03), fasting insulin (7.1±5.2 vs. 2.8±1.8 pIU/mL; p<0.01), HOMA-IR (1.5±1.1 vs. 0.60±0.34; p<0.01), basal diameter of the brachial artery (2.5±0.3 vs. 2.1±0.3 mm; p<0.01). Additionally, obese children showed lower values: QUICKI (0.38±0.05 vs. 0:43±0.03, p<0.01), FMD (6.6±3.2 vs. 15.6±7.3%; p<0.01) and PI-C (-15.5±27.2 vs. -31.9±15.5%; p<0.01). There was no significant difference in fasting glucose, HDL-cholesterol and LDL-cholesterol.

Table 2:
Ultrasonographic and laboratorial parameters in obese children and controls.

	Obese (N=40)	Control (N=40)	p-value*
Fasting insulin (pUI/mL)	7.1±5.2	2.8±1.8	<0.01
Fasting glucose (mg/dL)	82.4±5.9	83.6±6.2	0.38
QUICKI	0.38±0.05	0.43±0.03	<0.01
Total cholesterol (mg/dL)	164.7±25.2	153.4±15.8	0.03
HDL-cholesterol (mg/dL)	59.8±5.9	60.1±4.6	0.46
LDL-cholesterol (mg/dL)	83.1±22.2	77.9±13.7	0.32
HOMA-IR	1.5±1.1	0.6±0.4	p<0.01
BD pre(mm)	2.5±0.3	2.1±0.3	p<0.01
FMD (%)	6.6±3.2	15.6±7.3	p<0.01
PI-C (%)	-15.5±27.2	-31.9±15.5	p<0.01

• Data presented as: mean ± standard deviation; QUICKI: quantitative insulin sensitivity check index; HOMA-IR: homeostasis model of assessment - insulin resistance; BD pre: basal diameter of the brachial artery; FMD: brachial artery flow mediated dilation; PI-C: pulsatility index change. *unpaired t test or Mann-Whitney U test were used depending on the distribution of the data.

DISCUSSION

The present study aimed to improve the evaluation of the endothelial dysfunction in obese children through a noninvasive method, compared to already acknowledged clinical, laboratory and metabolic markers of cardiovascular risks.^19,20 It is an opportunity to introduce the study of the PI-C of the brachial artery, method with good reliability and greater technical facility at sonographic analysis of endothelial dysfunction when compared to FMD.²¹

Regarding metabolic parameters, significant increased values of systolic and diastolic pressure, body fat, and basal metabolic rate among obese children were observed. There was evidence of worsening of insulin resistance markers with significantly increased fasting insulin and HOMA-IR; and decreased QUICKI in the obese group, compared to the eutrophic group. Regarding the study of endothelial function, it was observed significantly lower values of FMD and PI-C in the obese group.

Some previous studies have shown a correlation between obesity in children and changes in laboratory markers, especially total cholesterol,²² LDL-cholesterol, HDL-cholesterol, triglycerides, fasting glucose and basal insulin^20,23,24,25 partially coincident with some results found in the present study. Furthermore, the positive correlation between HOMA-IR with metabolic syndrome, BMI, waist circumference and weight in children was already described;²⁶ as well as lower QUICKI scores in obese adult individuals.^26,27 Those markers showed significant differences in the investigated groups of children, which translates the increased insulin resistance in the obese.

When examining the results of the present study regarding endothelial function, significantly decreased FMD-C and PI in obese children were observed. The main findings of noninvasive markers of cardiovascular risks studied are: decreased FMD of the brachial artery and increased intima medial thickness (IMT) of the carotid artery, both in children^{28,29,30,31,32} and adults.^23,27,33 The evaluation of the variation of PI-C of the brachial artery 1 minute after compression of the forearm for 5 minutes was evaluated for the first time as an endothelial marker for children in this study. Among adults, high correlations to age, BMI, waist circumference, cholesterol, systolic blood pressure, and IMT were already demonstrated.²⁷ Moreover, the technique appears to be easier to learn and it has a good reproducibility when compared to FMD.²¹ The contribution of the present study for clinicians is not the suggestion of evaluating endothelium of all his patients, but the possibility of doing it and the knowledge that the comorbidities linked to obesity are frequent and have an early effect on the cardiovascular system.

The main limitation of the study was the selection bias. Cross sectional studies, using convenient and not randomized samples add a selection bias that could only be eliminated by conducting a cohort study. Another important limitation refers to the inclusion of scholar children without considering their pubertal stage and gender. During this period, the variability of maturation and the differences between boys and girls, may influence the results, because some children under the age of 10, mainly when obesity is present, already started puberty. On the other hand, considering the innovative aspect of the sonographic evaluation, the results presented, even considering the insufficient external and internal validity, may be useful to launch the discussion about the importance of evaluating, through medical images, the evolution of the atherosclerotic process during childhood. Studies of biomarkers and non-invasive markers of endothelial dysfunction have increased in recent years in the search for the best method of clinical applicability as a tool for research in overweight and obese children.³⁴ Hence, in view of the changing lifestyle and increasing childhood obesity, there is a continuing need to advance the prevention and early diagnosis of cardiovascular and metabolic alterations imposed by this pathology, in order to modify the natural history of the disease.³⁵

In conclusion, obesity worsens ultrasonographical and laboratorial markers of metabolic and cardiovascular disease risk in children.

REFERÊNCIAS

• ¹
  Ruminska M, Witkowska-Sedek E, Majcher A, Brzewski M, Czerwonogrodzka-Senczyna A, Demkow U, et al. Carotid intima-media thickness and metabolic syndrome components in obese children and adolescents. Adv Exp Med Biol. Epub 2017 Apr 30.
• ²
  Levy E, Saenger AK, Steffes MW, Delvin E. Pediatric obesity and cardiometabolic disorders: risk factors and biomarkers. EJIFCC. 2017;28:6-24.
• ³
  Jones RE, Jewell J, Saksena R, Ramos Salas X, Breda J. Overweight and obesity in children under 5 years: surveillance opportunities and challenges for the WHO European Region. Front Public Health. 2017;5:58.
• ⁴
  Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA. 2014;311:806-14.
• ⁵
  Ostrem JD, Evanoff N, Kelly AS, Dengel DR. Presence of a high-flow-mediated constriction phenomenon prior to flow-mediated dilation in normal weight, overweight, and obese children and adolescents. J Clin Ultrasound. 2015;43:495-501.
• ⁶
  Williams MJA, Milne BJ, Ambler A, Theodore R, Ramrakha S, Caspi A, et al. Childhood body mass index and endothelial dysfunction evaluated by peripheral arterial tonometry in early midlife. Int J Obes (Lond). 2017.
• ⁷
  Vita JA, Treasure CB, Nabel EG, McLenachan JM, Fish RD, Yeung AC, et al. Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. Circulation. 1990;81:491-7.
• ⁸
  Yeboah J, Sutton-Tyrrell K, McBurnie MA, Burke GL, Herrington DM, Crouse JR. Association between brachial artery reactivity and cardiovascular disease status in an elderly cohort: the cardiovascular health study. Atherosclerosis. 2008;197:768-76.
• ⁹
  Patel S, Celermajer DS. Assessment of vascular disease using arterial flow mediated dilatation. Pharmacol Rep. 2006;58:3-7.
• ¹⁰
  Järvisalo MJ, Raitakari OT. Ultrasound assessment of endothelial function in children. Vasc Health Risk Manag. 2005;1:227-33.
• ¹¹
  Hopkins ND, Stratton G, Tinken TM, McWhannell N, Ridgers ND, Graves LE, et al. Relationships between measures of fitness, physical activity, body composition and vascular function in children. Atherosclerosis. 2009;204:244-9.
• ¹²
  Krebs NF, Himes JH, Jacobson D, Nicklas TA, Guilday P, Styne D. Assessment of child and adolescent overweight and obesity. Pediatrics. 2007;120(Suppl 4):S193-228.
• ¹³
  Moens AL, Goovaerts I, Claeys MJ, Vrints CJ. Flow-mediated vasodilation: A diagnostic instrument, or an experimental tool? Chest. 2005;127:2254-63.
• ¹⁴
  Sorensen KE, Celermajer DS, Spiegelhalter DJ, Georgakopoulos D, Robinson J, Thomas O, et al. Non-invasive measurement of human endothelium dependent arterial responses: accuracy and reproducibility. Br Heart J. 1995;74:247-53.
• ¹⁵
  Welsch MA, Allen JD, Geaghan JP. Stability and reproducibility of brachial artery flow-mediated dilation. Med Sci Sports Exerc. 2002;34:960-5.
• ¹⁶
  Gosling RG, Dunbar G, King DH, Newman DL, Side CD, Woodcock JP, et al. The quantitative analysis of occlusive peripheral arterial disease by a non-intrusive ultrasonic technique. Angiology. 1971;22:52-5.
• ¹⁷
  Nicolau LG, Martins WP, Gallarreta FM, Lima JC, Filho FM. Influence of pregnancy and smoking on brachial artery flow-mediated dilation values and time until maximum response. Arch Gynecol Obstet. 2011;284:313-7.
• ¹⁸
  Martins MP, Santana LF, Nastri CO, Ferriani FA, Sa MF, Reis RM. Agreement among insulin sensitivity indexes on the diagnosis of insulin resistance in polycystic ovary syndrome and ovulatory women. Eur J Obstet Gynecol Reprod Biol. 2007;133:203-7.
• ¹⁹
  Baker JL, Olsen LW, Sorensen TI. Childhood body-mass index and the risk of coronary heart disease in adulthood. N Engl J Med. 2007;357:2329-37.
• ²⁰
  Lloyd LJ, Langley-Evans SC, McMullen S. Childhood obesity and risk of the adult metabolic syndrome: a systematic review. Int J Obes (Lond). 2012;36:1-11.
• ²¹
  Lima JC, Martins WP, Nastri CO, Nicolau LG, Filho FM. Pulsatility index change of brachial artery shows better reproducibility than flow-mediated vasodilation. Ultrasound Med Biol. 2010;36:2036-41.
• ²²
  Hudgins LC, Annavajjhala V, Kovanlikaya A, Frank MD, Solomon A, Parker TS, et al. Non-invasive assessment of endothelial function in children with obesity and lipid disorders. Cardiol Young. 2016;26:532-8.
• ²³
  Raitakari OT, Juonala M, Viikari JS. Obesity in childhood and vascular changes in adulthood: Insights into the cardiovascular risk in young finns study. Int J Obes (Lond). 2005;29(Suppl 2):S101-4.
• ²⁴
  Ryder JR, Dengel DR, Jacobs Jr. DR, Sinaiko AR, Kelly AS, Steinberger J. Relations among adiposity and insulin resistance with flow-mediated dilation, carotid intima-media thickness, and arterial stiffness in children. J Pediatr. 2016;168:205-11.
• ²⁵
  Woo KS, Chook P, Yu CW, Sung RY, Qiao M, Leung SS, et al. Overweight in children is associated with arterial endothelial dysfunction and intima-media thickening. Int J Obes Relat Metab Disord. 2004;28:852-7.
• ²⁶
  Akinci G, Akinci B, Coskun S, Bayindir P, Hekimsoy Z, Ozmen B. Evaluation of markers of inflammation, insulin resistance and endothelial dysfunction in children at risk for overweight. Hormones (Athens). 2008;7:156-62.
• ²⁷
  Martins WP, Nastri CO, Ferriani RA, Filho FM. Brachial artery pulsatility index change 1 minute after 5-minute forearm compression: comparison with flow-mediated dilatation. J Ultrasound Med. 2008;27:693-9.
• ²⁸
  Aggoun Y, Tounian P, Dabbas-Tyan M, Massih TA, Girardet JP, Ricour C, et al. Arterial rigidity and endothelial dysfunction in obese children. Arch Mal Coeur Vaiss. 2002;95:631-5.
• ²⁹
  Karpoff L, Vinet A, Schuster I, Oudot C, Goret L, Dauzat M, et al. Abnormal vascular reactivity at rest and exercise in obese boys. Eur J Clin Invest. 2009;39:94-102.
• ³⁰
  Meyer AA, Kundt G, Steiner M, Schuff-Werner P, Kienast W. Impaired flow-mediated vasodilation, carotid artery intima-media thickening, and elevated endothelial plasma markers in obese children: the impact of cardiovascular risk factors. Pediatrics. 2006;117:1560-7.
• ³¹
  Yilmazer MM, Tavli V, Carti OU, Mese T, Güven B, Aydin B, et al. Cardiovascular risk factors and noninvasive assessment of arterial structure and function in obese Turkish children. Eur J Pediatr. 2010;169:1241-8.
• ³²
  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.
• ³³
  Zueff LF, Martins WP, Vieira CS, Ferriani RA. Ultrasonographic and laboratory markers of metabolic and cardiovascular disease risk in obese women with polycystic ovary syndrome. Ultrasound Obstet Gynecol. 2012;39:341-7.
• ³⁴
  Canas JA, Sweeten S, Balagopal PB. Biomarkers for cardiovascular risk in children. Curr Opin Cardiol. 2013;28:103-14.
• ³⁵
  Dupuy M, Godeau E, Vignes C, Ahluwalia N. Socio-demographic and lifestyle factors associated with overweight in a representative sample of 11-15 year olds in France: results from the WHO-Collaborative Health Behaviour in School-aged Children (HBSC) cross-sectional study. BMC Public Health. 2011;11:442.

• Funding: This study did not receive funding.

• ERRATUM

  In the manuscript “Ultrasonographic markers of cardiovascular disease risk in obese children”, DOI: 10.1590/1984-0462/;2018;36;2;00016, published in the Rev. paul. pediatr. 2018;36:171-5. Where it reads: Carlos Alberto Nogueira-de-Almeida^{a a}Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil. It should read: Carlos Alberto Nogueira de Almeida^{b b}Departamento de Medicina, Universidade Federal de São Carlos, São Carlos, SP, Brazil.

Publication Dates

• Publication in this collection
  29 Mar 2018
• Date of issue
  Apr-Jun 2018

History

• Received
  21 Mar 2017
• Accepted
  28 July 2017