Endothelial function in pre-pubertal children at risk of developing cardiomyopathy: a new frontier

Tavares, Aline Cristina; Bocchi, Edimar Alcides; Guimarães, Guilherme Veiga

doi:10.6061/clinics/2012(03)12

Abstract

Although it is known that obesity, diabetes, and Kawasaki's disease play important roles in systemic inflammation and in the development of both endothelial dysfunction and cardiomyopathy, there is a lack of data regarding the endothelial function of pre-pubertal children suffering from cardiomyopathy. In this study, we performed a systematic review of the literature on pre-pubertal children at risk of developing cardiomyopathy to assess the endothelial function of pre-pubertal children at risk of developing cardiomyopathy. We searched the published literature indexed in PubMed, Bireme and SciELO using the keywords 'endothelial', 'children', 'pediatric' and 'infant' and then compiled a systematic review. The end points were age, the pubertal stage, sex differences, the method used for the endothelial evaluation and the endothelial values themselves. No studies on children with cardiomyopathy were found. Only 11 papers were selected for our complete analysis, where these included reports on the flow-mediated percentage dilatation, the values of which were 9.80±1.80, 5.90±1.29, 4.50±0.70, and 7.10±1.27 for healthy, obese, diabetic and pre-pubertal children with Kawasaki's disease, respectively. There was no significant difference in the dilatation, independent of the endothelium, either among the groups or between the genders for both of the measurements in children; similar results have been found in adolescents and adults. The endothelial function in cardiomyopathic children remains unclear because of the lack of data; nevertheless, the known dysfunctions in children with obesity, type 1 diabetes and Kawasaki's disease may influence the severity of the cardiovascular symptoms, the prognosis, and the mortality rate. The results of this study encourage future research into the consequences of endothelial dysfunction in pre-pubertal children.

Endothelial Function; Infant; Healthy; Cardiomyopathy; Heart Failure

REVIEW

Endothelial function in pre-pubertal children at risk of developing cardiomyopathy: a new frontier

Aline Cristina Tavares^I; Edimar Alcides Bocchi^I; Guilherme Veiga Guimarães^I,II

^IHospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Heart Institute (InCor), São Paulo/SP, Brazil

^IIUniversidade de São Paulo, Laboratory of Physical Activity and Health (LAtiS), Sport Practice Center, São Paulo/SP, Brazil

ABSTRACT

Although it is known that obesity, diabetes, and Kawasaki's disease play important roles in systemic inflammation and in the development of both endothelial dysfunction and cardiomyopathy, there is a lack of data regarding the endothelial function of pre-pubertal children suffering from cardiomyopathy. In this study, we performed a systematic review of the literature on pre-pubertal children at risk of developing cardiomyopathy to assess the endothelial function of pre-pubertal children at risk of developing cardiomyopathy. We searched the published literature indexed in PubMed, Bireme and SciELO using the keywords 'endothelial', 'children', 'pediatric' and 'infant' and then compiled a systematic review. The end points were age, the pubertal stage, sex differences, the method used for the endothelial evaluation and the endothelial values themselves. No studies on children with cardiomyopathy were found. Only 11 papers were selected for our complete analysis, where these included reports on the flow-mediated percentage dilatation, the values of which were 9.80±1.80, 5.90±1.29, 4.50±0.70, and 7.10±1.27 for healthy, obese, diabetic and pre-pubertal children with Kawasaki's disease, respectively. There was no significant difference in the dilatation, independent of the endothelium, either among the groups or between the genders for both of the measurements in children; similar results have been found in adolescents and adults. The endothelial function in cardiomyopathic children remains unclear because of the lack of data; nevertheless, the known dysfunctions in children with obesity, type 1 diabetes and Kawasaki's disease may influence the severity of the cardiovascular symptoms, the prognosis, and the mortality rate. The results of this study encourage future research into the consequences of endothelial dysfunction in pre-pubertal children.

Keywords: Endothelial Function; Infant; Healthy; Cardiomyopathy; Heart Failure.

INTRODUCTION

There are similarities between children and adults suffering from heart failure (HF), such as the preferred pharmacological treatment (1), the use of pace-makers and heart transplants (2,3), the inability of the patient to reach the predicted heart rate for the patient's age during cardiopulmonary exercise testing (4,5), and the ergoespirometric response under similar clinical conditions (5). In adults, endothelial dysfunction is related to the development of diastolic dysfunction (6,7), Chagas disease, left ventricular hypertro phy (8), ischemic cardiomyopathy, HF (8,9), obesity, type 1 diabetes, hyperlipidemia, arterial hypertension (10), peripher al arterial disease, chronic kidney disease (11) and atherosclerosis (12) because the dysfunction predisposes the vasculature to vasoconstriction, leukocyte adherence, platelet activation, and vascular inflammation (13). Nevertheless, there is a lack of data regarding endothelial function in chil dren with cardiomyopathy.

The severity of endothelial dysfunction is related to the cardiovascular risk (14), the severity of cardiovascular symptoms (15), and the inability to exercise (11) and repre sents a predictor for cardiac transplant and death (16).

It is known that diseases, such as Kawasaki's disease (8), hyperlipidemia (10), obesity, and type 1 diabetes, play important roles in systemic inflammation and endothelial dysfunction (17). These diseases may increase the likelihood of cardiovascular events (18) and may predispose children to the development of cardiomyopathy. Based on these considerations, we reviewed the published literature on endothelial function in pre-pubertal children to evaluate the endothelial function in pre-pubertal children with cardiomyopathy or children at risk of developing cardiomyopathy, and we conducted an analysis of the data from the relevant studies. This analysis was undertaken to help clarify the role of endothelial impairment in children at risk of suffering from cardiomyopathy.

Endothelial function can be analyzed by noninvasive methods, including ultrasonography (US) (19) and peripheral artery tonometry (PAT) (20). During a US examination, the baseline rest image of the subject's brachial artery is acquired, and a 5-min arterial occlusion is performed using cuff inflation to at least 50 mm Hg suprasystolic pressure. The subsequent cuff deflation induces reactive hyperemia that results in an increase in flow or, more precisely, shear stress by dilating the brachial artery; this phenomenon is designated flow-mediated dilatation (FMD). After returning to the baseline, a second brachial artery image is recorded after the administration of nitroglycerine (NTG); this image corresponds to the contribution of the intima muscle relaxation to the dilation and is known as the endothelium-independent vasodilatation (19).

In contrast to US, the PAT evaluation is a method that does not require the administration of drugs, and it combines the assessment of the flow-mediated dilatation after the same 5-min arterial cuff occlusion, with the arterial pulse wave amplitude measurement taken using a pneumatic fingertip probe (20).

Literature search strategy

A search of the PubMed, Bireme, and SciELO databases was conducted to perform a systematic review, according to the recommendations of PRISMA (21). The search was performed using the following keywords: endothelial, child, pediatrics, and infant. The results were limited to human studies published in English, Spanish, and Portuguese. The initial selection was based on the title and abstract, and those deemed relevant were retained for further analysis.

The exclusion criteria included the following: analyses of the endothelial function in animals, cadavers, adolescents or adults; reviews; analyses of either the coronary or pulmonary arteries or the neurological or osteomuscular systems; if the patients had rheumatic, oncohematological, splenic or hepatic diseases; or if the studies were trials related to markers, genetics and interventions.

The list of potential trials to include was verified by the authors of the present study. We note that there may be a risk of bias across the studies because not all of the trials published have been indexed in the selected databases.

Collected data

The following data were collected for analysis: the number of patients enrolled in the study; the patient's age; whether sexual maturity had been reached; any diseases involved; the protocol used for the endothelial function evaluation and the FMD, NTG, and PAT values. Collected data in all tables were expressed following disease order, in order to better clarify data presentation and analysis.

Statistical analysis

The values of endothelial function were expressed as the mean ± standard deviation (SD), as collected from the original trials. The data from healthy children were compared with the data for unhealthy children, and the differences were analyzed using the Student t-test. A p-value <0.05 was considered statistically significant.

A total of 559 articles were retrieved after the preliminary search, and 21 articles were considered potentially relevant based on the title and abstract. A careful analysis of these articles was performed, and ten trials were excluded for several reasons. Eleven articles were chosen for the final analysis (Figure 1).

All of the selected studies were dated from 1996 to 2009. Table 1 presents the general descriptions of the included studies and provides information regarding the participants, their ages, their diseases, the endothelial evaluation method used and whether there were differences between genders (Table 1).

Thumbnail

All eleven of the selected studies provided data for healthy children for comparison, and, with the exception of one study (22), all of the studies compared healthy children to ill children. Four of the studies evaluated obese children (23-26), one evaluated children with obesity and type 1 diabetes (27), three studied children with type 1 diabetes (28-30), and two evaluated children with Kawasaki's disease (31-32). No trial involving children with cardiomyopathy was found.

These reviewed studies reported a mean age of 9.8±1.8 years old, and only four articles investigated the sexual maturation of the group of pre-pubertal children (23,25,26,29). Forty-five percent of all of the studies found no difference in the endothelial function between genders, and 55% of the reports did not provide these data (Table 1).

Most of the studies used ultrasound to determine the percent diameter changes for the FMD and NTG assessments (22-29,31,32). Only one study used reactive hyperemiaperipheral artery tonometry (RH-PAT) for the same purpose (30), showing that the endothelial function was impaired in diabetic children relative to that in healthy children (1.63±0.5 vs. 1.95±0.3 for diabetic children vs. healthy children) (30).

The FMD response values from all of the other articles for obese and diabetic children were significantly lower than those for healthy children (5.9±1.29% for obese children, 4.5±0.7% for diabetic children, and 9.8±1.8% for healthy children; p<0.0008). The obese children had a 39% lower FMD response than the healthy children, and the diabetic children had a decrease in their FMD of 25% (Table 2).

Thumbnail

The children with Kawasaki's disease had 27% lower FMD responses than the healthy children (7.1±1.27% vs. 9.8±1.8%, respectively), but this difference was not statistically significant (p = 0.26) . The FMD data for the obese children, diabetic children, and children with Kawasaki's disease exhibited no statistically significant differences (p<0.38) (Table 2).

The NTG response (Table 2) also showed no significant difference among the groups (22.7±7.1% for healthy children, 19.6± 2.0% for obese children and 16.6±5.9% for diabetic children; p<0.19).

Among the excluded studies, one contained no data on endothelial function (33), and most of the excluded studies did not list the data for pre-pubertal children, post-pubertal children (34-39) and adults (40,41) separately. Another study (42) published data for the same patients as used in a previously published study (32).

Ultrasound is the most frequently used method to evaluate endothelial function because it has a low cost, is safe and is sufficiently reproducible. However, some limitations of this method are that the FMD response can be influenced by both temperature and age, and ultrasound requires drug administration and the recording of images for posterior analysis (19).

Another technique for the assessment of endothelial function is the PAT method, which has been proposed to be more practical and precise (20), and PAT results are moderately significantly correlated with US results (43). The PAT method combines the traditional flow-mediated dilatation measurement with pneumatic fingertip probes to measure the arterial pulse wave amplitude (20). One study (31) chose PAT over US and confirmed that diabetic children have endothelial dysfunction, as do adults (44,45).

In five studies (22,24,25,28,32), the gender of the individual did not correlate with the endothelial function, as has been found for adults (60) and adolescents (61). Pre-pubertal children show lower responses to beta-adrenergic receptors and have lower levels of circulating catecholamines (adrenaline and noradrenaline) than adolescents and adults (46). The obese children exhibit accelerated growth and, therefore, earlier puberty (47), which is evidenced by an advancement of menarche by 2.2 years (11.2 vs. 13.4 years, respectively) (48) because fat mass influences the levels of hormones (49,50).

These data reinforce the need for the evaluation of sexual maturation in studies involving children. The extent of sexual maturation is widely accessed using the Tanner-Whitehouse scale, which is based on secondary sexual characteristics, such as breast development and menarche in girls, standards for penis development in boys, and pubic hair development in both sexes (51). This lack of sexual maturity assessment explains why those trials that combined information for children, adolescents (33-39), and adults (40,41) were excluded in the present study and explains the elevated FMD data from one study (24), which included a higher mean age of obese children of 12±4 years old. The evaluation of sexual maturity also explains why three of the included studies (23,25,26) that assessed the pubertal stage by clinical examination yielded similar FMD data.

Diabetic and obese individuals have hyperinsulinemia, and both diabetes and obesity are related to the higher hormone (50) and inflammation levels (52) that contribute to increased arterial stiffness and vascular lesions, which are related to both endothelial function and structural arterial changes (53) and may explain the endothelial dysfunction results for these groups (23-30).

In addition to some methodological disparities, all of the studies showed significantly impaired endothelial function (FMD response) in the obese and diabetic children despite the lack of a difference in the NTG response, a result that was reported for adults (54) when compared with healthy subjects (55). However, FMD impairment seems to be greater in adults than in children (44% in obese adults and 55% in diabetic adults); similarly, adults show no difference in NTG responses (54,56).

The collected FMD values in children with Kawasaki's disease are lower than those in healthy children (31,32), which can indicate a low, but persistent, level of inflammation (57), as evidenced by higher C-reactive protein (CRP) levels (52,53,58). Only one study (32) included NTG data, and this lack of data limits the discussion of the information provided.

The FMD values suggest that the major dysfunctions in these children occur as a result of the local nitric oxide (NO) bioavailability in the endothelium (NO production) because the shear stress induced by reactive hyperemia activates endothelial NO production (59).

The NTG response also suggests that the vascular smooth muscle cell function is preserved (19). Yet, one study showed significantly lower GT values in obese children than in healthy children (27), and two other studies did not publish values for the NTG response (22,24). Some reports (20,25,28) did not describe how long the subjects were at rest, according to Corretti et al. (22), >10 min is recom mended, between the collections of the FMD and NTG response images, which might have contributed to the reported outcomes. It is also worth noting that three of the trials (24,27,29) allowed the arteries to return to the basal condition and that two of these studies (24,29) did not yield statistically significant data.

Limitations

In spite of the statistically significant differences in some of the endothelial function responses, the number of trials regarding this subject remains limited. Another limitation of the data search for pre-pubertal children is that the studies list the results for adults, teenagers, and children together, and do not divide the data by group according to the puberty state and age. The small number of studies in children may also be due to the use of the US method because drug administration is required. However, the new method of endothelial function evaluation, the PAT method, might help increase the number of trials using this population.

Although endothelial dysfunction has been identified in adults as a predictor of cardiac transplant and death, the clinical implications of endothelial dysfunction were not presented in the selected trials, nor were they the focus of the current study; however, this correlation should be further evaluated in children. Lastly, even though the number of pre-pubertal children with endothelial dysfunction is unknown, there is a great number of children who suffer from this condition. Thus, the barriers in the pediatric field must be broken, and more studies on this topic should be performed to understand this population better.

In conclusion, endothelial function is an important clinical feature because it may indicate the severity of cardiovascular symptoms, prognosis, and mortality. Children at risk of developing cardiomyopathy exhibit endothelial dysfunction; however, the prevalence of endothelial dysfunction in cardiomyopathic children remains unknown because of the lack of data. We suggest that attention should be paid to the consequences of endothelial function in this group.

ACKNOWLEDGMENTS

Guilherme V Guimarães (CNPq # 304733/2008-3) was supported by Conselho Nacional de Pesquisa.

AUTHOR CONTRIBUTIONS

Tavares AC organized the trials' selection and the records in the tables, performed the analysis, and wrote the manuscript. Guimaraes GV was responsible for the literature search and provided assistance to the literature revision and manuscript writing. Bocchi EA provided assistance to the manuscript writing.

REFERENCES

1. Hechter SJ, Fredriksen PM, Liu P. Angiotensin-converting enzyme inhibitors in adults after the Mustard procedure. Am J Cardiol. 2001;87:660-711, http://dx.doi.org/10.1016/S0002-9149(00)01452-1.

2. Rusconi P, Gomes-Marin O, Rossique-Gonzalvez M, Redha E, MarínJ, Lon-Young M, et al. Carvedilol in children with cardiomyopathy. A 3year experience at a single institution. J Heart Lung Transplant. 2004;23:832-8.

3. Azeka E, Vasconcelos LM, Cippiciani TM, Oliveira AS, Barbosa DF, Leite RMG. Insuficiência cardíaca congestiva em crianças. Do tratamento farmacológico ao transplante cardíaco. Rev Med. 2008;87(2):99-104.

4. Carvalho VO, Bocchi EA, Guimaraes GV. The Carvedilol's Beta-Blockade in Heart Failure and Exercise Training's Sympathetic Blockade in Healthy Athletes during the Rest and Peak Effort. Cardiovascular Therapeutics. 2010;28:8792, http://dx.doi.org/10.1111/j.1755-5922. 2009.00113.x.

5. Guimarães GV, Bellotti G, Mocelin AO, Camargo PR, Bocchi EA. Cardiopulmonary exercise testingin childrenwithheart failure secondary to idiopathic dilated cardiomyopathy. Chest. 2001;120:81624, http://dx.doi.org/10.1378/chest.120.3.816.

6. Mesquita ET, Socrates J, Rassi S, Villacorta H, Mady C. Insuficiência cardíaca com função sistólica preservada. Arquivos Brasileiros de Cardiologia. 2004;82(4):494-500, http://dx.doi.org/10.1590/S0066782X2004000500014.

7. Verma S, Anderson YJ. Fundamentals of endothelial function for the clinical cardiologist. Circulation. 2002;105:546-9, http://dx.doi.org/ 10.1161/hc0502.104540.

8. Davis SF, Yeung AC, Meredith IT, Charbonneau F, Ganz P, Selwyn AP, et al. Early Endothelial Dysfunction Predicts the Development of Transplant Coronary Artery Disease at 1 Year Posttransplant. Circulation. 1996;93:457-62.

9. Chong AY, Blann AD, Patel J, Freestone B, Hughes E, Lip GYH. Endothelial Dysfunction and Damage in Congestive Heart Failure. Relation of Flow-Mediated Dilation to Circulating Endothelial Cells, Plasma Indexes of Endothelial Damage, and Brain Natriuretic Peptide. Circulation. 2004;110:1794-8.

10. Davignon J, Ganz P. Role of Endothelial Dysfunction in Atherosclerosis. Circulation. 2004;109:27-32, http://dx.doi.org/10.1161/01.CIR.0000115644.35804.8B.

11. Widlansky ME, Gokce N, Keaney JF, Vita JA. The Clinical Implications of Endothelial Dysfunction. J Am Coll Cardiol. 2003;42:114960, http://dx.doi.org/10.1016/S0735-1097(03)00994-X.

12. Conway DSG, Pearce LA, Chin BSP, Hart RG, Lip GYH. Plasma von Willebrand Factor and Soluble P-Selectin as Indices of Endothelial Damage and Platelet Activation in 1321 Patients With Nonvalvular Atrial Fibrillation Relationship to Stroke Risk Factors. Circulation. 2002;106:1962-7, http://dx.doi.org/10.1161/01.CIR.0000033220.97592.9A.

13. Carvalho MHC, Colaço AL, Fortes ZB. Citocinas, Disfunção Endotelial e Resistência à Insulina. Arq Bras Endocrinol Metab. 2006;50(2):304-12, http://dx.doi.org/10.1590/S0004-27302006000200016.

14. Anderson TJ, Uehata A, Gerhard MD. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol. 1995;26:1235-41, http://dx.doi.org/10.1016/0735-1097(95)00327-4.

15. Maxwell AJ, Schauble E, Bernstein D, Cooke JP. Limb blood flow during exercise is dependent on nitric oxide. Circulation. 1998;98:36974.

16. Fischer D, Rossa S, Landmesser U, Spiekermann S, Engberding N, Hornig B, et al. Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death. European Heart Journal. 2005;26:659, http://dx.doi.org/10.1093/eurheartj/ehi001.

17. Jimenez M, 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(4):497-502, http://dx.doi.org/10.1530/EJE-06-0662.

18. Isomaa B, Almgren P, Tuomi T, Forsén B, Lahti K, Nissén M, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001;24:683-89, http://dx.doi.org/10.2337/diacare.24.4.683.

19. Laurent S, Cockcroft J. Bortel LV, Boutouyrie P, Giannattasio G, Hayoz D. Expert consensus document on arterial stiffness. Methodological issues and clinical applications. European Heart Journal. 2006;27:2588605.

20. Kuvin JT, Patel AR, Sliney KA, Pandian NG, Sheffy J, Schnall RP. Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. Am Heart J. 2003;146:168-74, http://dx.doi.org/10.1016/S0002-8703(03)00094-2.

21. Moher D, Liberati A, Tetzlaff J, Altman DG, , The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. 2009;6(6).

22. Germain AM, Irribarra VP, Valdés G, Romanik MC, Leighton F, Mardones F. Evaluación ultrasonográfica de la función endotelial en niños y adultos chilenos. Rev Méd Chile. 2004;132:437-44.

23. 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(7-8):631-5.

24. Kapiotis S, Holzer G, Schaller G, Haumer M, Widhalm H, Weghuber D. A proinflammatory state is detectable in obese children and is accompanied by functional and morphological vascular changes. Arterioscler Thromb Vasc Biol. 2006;26(11):2541-6, http://dx.doi.org/10.1161/01.ATV.0000245795.08139.70.

25. Aggoun Y, Farpour-Lambert NJ, Marchand LM, Golay E, Maggio AB, Beghetti M. Impaired endothelial and smooth muscle functions and arterial stiffness appear before puberty in obese children and are associated with elevated ambulatory blood pressure. Eur Heart J. 2008;29(6):792-9, http://dx.doi.org/10.1093/eurheartj/ehm633.

26. Woo KS, Chook P, Yu CW, Sung RY, Qiao M, Leung SS. Overweight in children is associated with arterial endothelial dysfunction and intima-media thickening. Int J Obes Relat Metab Disord. 2004;28(7):852-7, http://dx.doi.org/10.1038/sj.ijo.0802539.

27. Pena AS, Wiltshire E, MacKenzie K, Gent R, Piotto L, Hirte C. Vascular endothelial and smooth muscle function relates to body mass index and glucose in obese and nonobese children. J Clin Endocrinol Metab. 2006;91(11):4467-71, http://dx.doi.org/10.1210/jc.2006-0863.

28. Järvisalo MJ, Raitakari M, Toikka JO, Putto-Laurila A, Rontu R, Laine S, et al. Endothelial dysfunction and increased arterial intima-media thickness in children with type 1 diabetes. Circulation. 2004;109(14): 1750-5, http://dx.doi.org/10.1161/01.CIR.0000124725.46165.2C.

29. Wiltshire EJ, Gent R, Hirte C, Pena A, Thomas DW, Couper JJ. Endothelial dysfunction relates to folate status in children and adolescents with type 1 diabetes. Diabetes. 2002;51(7):2282-6, http://dx.doi.org/10.2337/diabetes.51.7.2282.

30. Haller MJ, Stein J, Shuster J, Theriaque D, Silverstein J, Schatz DA, et al. Peripheral artery tonometry demonstrates altered endothelial function in children with type 1 diabetes. Pediatric Diabetes. 2007;8:1938, http://dx.doi.org/10.1111/j.1399-5448.2007.00246.x.

31. Borzutzky A, Gutiérrez M, Talesnik E, Godoy I, Kraus J, Hoyos R, Arnaiz P, et al. High sensitivity C-reactive protein and endothelial function in Chilean patients with history of Kawasaki disease. Clin Rheumatol. 2008;27:84550, http://dx.doi.org/10.1007/s10067-007-0808-6.

32. Deng YB, Xiang HJ, Chang Q, Li CL. Evaluation by High-Resolution Ultrasonography of Endothelial Function in Brachial Artery After Kawasaki Disease and the Effects of Intravenous Administration of Vitamin C. Circ J. 2002;66:90812, http://dx.doi.org/10.1253/circj.66.908

33. Mimoun E, Aggoun Y, Pousset M, Dubern B, Bougle D, Girardet JP, et al. Association of arterial stiffness and endothelial dysfunction with metabolic syndrome in obese children. J Pediatr. 2008;153(1):65-70.

34. Sorensen KE, Celermajer DS, Georgakopoulos D, Hatcher G. Betteridge DJ, Deanfield JE. Impairment of endothelium-dependent dilation is an early event in children with familial hypercholesterolemia and is related to the lipoprotein(a) level. J Clin Invest. 1994;93(1):50-5.

35. de Jongh S, Lilien MR, Bakker HD, Hutten BA, Kastelein JJ, Stroes ES. Family history of cardiovascular events and endothelial dysfunction in children with familial hypercholesterolemia. Atherosclerosis. 2002; 163(1):193-7, http://dx.doi.org/10.1016/S0021-9150(02)00003-5.

36. Järvisalo MJ, Lehtimaki T, Raitakari OT. Determinants of arterial nitratemediated dilatation in children: role of oxidized low-density lipoprotein, endothelial function, and carotid intima-media thickness. Circulation. 2004; 109(23):2885-9, http://dx.doi.org/10.1161/01.CIR.0000129304.98566.D8.

37. Ladeia AM, Ladeia-Frota C, Pinho L, Stefanelli E, Adan L. Endothelial dysfunction is correlated with microalbuminuria in children with shortduration type 1 diabetes. Diabetes Care. 2005;28(8):2048-50, http://dx.doi.org/10.2337/diacare.28.8.2048.

38. Noto N, Okada T, Karasawa K, Ayusawa M, Sumitomo N,Harada K, et al. Age-related acceleration of endothelial dysfunction and subclinical atherosclerosis in subjects with coronary artery lesions after Kawasaki disease. Pediatr Cardiol. 2009;30(3):262-8, http://dx.doi.org/10.1007/s00246-008-9329-6.

39. Kadono T, Sugiyama H, Hoshiai M, Osada M, Tan T, Naitoh A, et al. Endothelial Function Evaluated by Flow-Mediated Dilatation in Pediatric Vascular Disease. Pediatr Cardiol. 2005;26:38590, http://dx.doi.org/10.1007/s00246-004-0755-9.

40. Dhillon R, Clarkson P, Donald AE, Powe AJ, Nash M, Novelli V, et al. Endothelial Dysfunction Late After Kawasaki Disease. Circulation. 1996;94:2103-6.

41. Järvisalo MJ, Rönnemaa T, Volanen I. Brachial artery dilatation responses in healthy children and adolescents. Am J Physiol Heart Circ Physiol, 2002;282:8792.

42. Deng YB, Li TL, Xiang HJ, Chang Q, Li CL. Impaired endothelial function in the brachial artery after Kawasaki disease and the effects of intravenous administration of vitamin C. Pediatr Infect Dis J. 2003;22(1):349.

43. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, et al. Guidelines for the Ultrasound Assessment of Endothelial-Dependent Flow-Mediated Vasodilation of the Brachial Artery. J Am Coll Cardiol. 2002;39:25765, http://dx.doi.org/10.1016/ S0735-1097(01)01746-6.

44. Evora PRB, Pearson PJ, Seccombe JF, Discigil B, Schaff HV. Métodos Experimentais no Estudo da Função Endotelial. Arq Bras Cardiol. 1996;66(5):291-7.

45. Laurent S, Cockcroft J, Bortel LV, Boutouyrie P, Giannattasio C, Hayoz D. Expert consensus document on arterial stiffness. Methodological issues and clinical applications. European Heart Journal. 2006;27:2588605.

46. Prado DML, Dias RG, Trombetta IC. Cardiovascular, Ventilatory, and Metabolic Parameters during Exercise: Differences between Children and Adults. Arq Bras Cardiol. 2006;87:e92-e97, http://dx.doi.org/10.1590/S0066-782X2006001700035.

47. Dunger DB, Ahmed ML, Ong KK. Early and late weight gain and the timing of puberty. Mol Cell Endocrinol. 2006;254:1405, http://dx.doi.org/10.1016/j.mce.2006.04.003.

48. Juul A, Teilmann G, Scheike T, Hertel NT, Holm K, Laursen LM. Pubertal development in Danish children: comparison of recent European and US data. Iinternational Journal of Andrology. 2006;29:24755.

49. Ahme ML, Ong KK, Dunger DB. Childhood obesity and the timing of puberty. Trends in Endocrinology and Metabolism. 2009;20(5):237-42.

50. Kalme T, Koistinen H, Loukovaara M, Koistinen R, Leinonen P. Comparative studies on the regulation of insulin-like growth factorbinding protein-1 (IGFBP-1) and sex hormonebinding globulin (SHBG) production by insulin and insulin-like growth factors in human hepatoma cells. J Steroid Biochem Mol Biol. 2003;86(2):197200, http://dx.doi.org/10.1016/S0960-0760(03)00268-1.

51. Tanner JM, Whitehouse RH. Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Archives of Disease in Childhood. 1976;51:170-9, http://dx.doi.org/10.1136/ adc.51.3.170.

52. Järvisalo MJ, Harmoinen A, Hakanen M, Paakkunainen U, Hartiala J, Lehtimäki T. Elevated Serum C-Reactive Protein Levels and Early Arterial Changes in Healthy Children. Arterioscler Thromb Vasc Biol. 2002;22:1323-8, http://dx.doi.org/10.1161/01.ATV.0000024222.06463.21.

53. Kapiotis S, Holzer G, Schaller G, Haumer M, Widhalm H, Weghuber D. A Proinflammatory State Is Detectable in Obese Children and Is Accompanied by Functional and Morphological Vascular Changes. Arterioscler Thromb Vasc Biol. 2006;26:2541-6, http://dx.doi.org/ 10.1161/01.ATV.0000245795.08139.70.

54. Perticone F, Ceravolo R, Candigliota M, Ventura G, Iacopino S, Sinopoli F, et al. Obesity and Body Fat Distribution Induce Endothelial Dysfunction by oxidative Stress. Protective Effect of Vitamin C. Diabetes. 2001;50:15965.

55. Gardin JM, Allebban Z, Wong ND, Sklar SK, Bess RL, Spence MA, et al. Endothelial function and urine albumin levels among asymptomatic Mexican-Americans and non-Hispanic whites. Cardiovascular Ultrasound. 2008;6:43-9, http://dx.doi.org/10.1186/1476-7120-6-43.

56. Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G, Baron AD. Obesity/Insulin Resistance Is Associated with Endothelial Dysfunction. Implications for the Syndrome of Insulin Resistance. J Clin Invest. 1996;97(11):2601-10.

57. Castro PA, Urbano LMF, Costa IMC. Doença de Kawasaki. An Bras Dermatol. 2009;84(4):317-31, http://dx.doi.org/10.1590/S036505962009000400002.

58. Borzutzky A, Gutiérrez M, Talesnik E, Godoy I, Kraus J, Hoyos R. High sensitivity C-reactive protein and endothelial function in Chilean patients with history of Kawasaki disease. Clin Rheumatol. 2008;27: 84550, http://dx.doi.org/10.1007/s10067-007-0808-6.

59. Koyanagi H, Yanagawa H, Nakamura Y, Yashiro M. Serum C-reactive protein levels in patients with Kawasaki disease: from the results of Nation-wide surveys of Kawasaki disease in Japan. Acta Pediatr. 1997;86:613-9, http://dx.doi.org/10.1111/j.1651-2227.1997.tb08944.x.

60. Chequer G, Nascimento BR, Navarro TP, Falqueto EB, Alencar MCN, Miranda MCR. Espessamento Médio-Intimal da Carótida e Função Endotelial na Doença Arterial Coronariana. Arq Bras Cardiol. 2006;87(2):84-90, http://dx.doi.org/10.1590/S0066-782X2006001500004.

61. Andrade ZM, Carvalhaes JTA, Taddei JAAC, Christofalo DMJ, Ajzen AS. Função endotelial de adolescentes normotensos sem fatores de risco para hipertensão arterial. J Pediatr. 2005;81(5):395-9.

Received for publication on September 30, 2011; First review completed on November 3, 2011; Accepted for publication on November 22, 2011

No potential conflict of interest was reported.

E-mail: alinet84@gmail.com

Tel.: 55 11 3069-5419

References

1. Hechter SJ, Fredriksen PM, Liu P. Angiotensin-converting enzyme inhibitors in adults after the Mustard procedure. Am J Cardiol. 2001;87:660-711, http://dx.doi.org/10.1016/S0002-9149(00)01452-1
2. Rusconi P, Gomes-Marin O, Rossique-Gonzalvez M, Redha E, MarínJ, Lon-Young M, et al. Carvedilol in children with cardiomyopathy. A 3year experience at a single institution. J Heart Lung Transplant. 2004;23:832-8.
3. Azeka E, Vasconcelos LM, Cippiciani TM, Oliveira AS, Barbosa DF, Leite RMG. Insuficiência cardíaca congestiva em crianças. Do tratamento farmacológico ao transplante cardíaco. Rev Med. 2008;87(2):99-104.
4. Carvalho VO, Bocchi EA, Guimaraes GV. The Carvedilol's Beta-Blockade in Heart Failure and Exercise Training's Sympathetic Blockade in Healthy Athletes during the Rest and Peak Effort. Cardiovascular Therapeutics. 2010;28:8792, http://dx.doi.org/10.1111/j.1755-5922. 2009.00113.x
5. Guimarães GV, Bellotti G, Mocelin AO, Camargo PR, Bocchi EA. Cardiopulmonary exercise testingin childrenwithheart failure secondary to idiopathic dilated cardiomyopathy. Chest. 2001;120:81624, http://dx.doi.org/10.1378/chest.120.3.816
6. Mesquita ET, Socrates J, Rassi S, Villacorta H, Mady C. Insuficiência cardíaca com função sistólica preservada. Arquivos Brasileiros de Cardiologia. 2004;82(4):494-500, http://dx.doi.org/10.1590/S0066782X2004000500014
7. Verma S, Anderson YJ. Fundamentals of endothelial function for the clinical cardiologist. Circulation. 2002;105:546-9, http://dx.doi.org/ 10.1161/hc0502.104540
8. Davis SF, Yeung AC, Meredith IT, Charbonneau F, Ganz P, Selwyn AP, et al. Early Endothelial Dysfunction Predicts the Development of Transplant Coronary Artery Disease at 1 Year Posttransplant. Circulation. 1996;93:457-62.
9. Chong AY, Blann AD, Patel J, Freestone B, Hughes E, Lip GYH. Endothelial Dysfunction and Damage in Congestive Heart Failure. Relation of Flow-Mediated Dilation to Circulating Endothelial Cells, Plasma Indexes of Endothelial Damage, and Brain Natriuretic Peptide. Circulation. 2004;110:1794-8.
10. Davignon J, Ganz P. Role of Endothelial Dysfunction in Atherosclerosis. Circulation. 2004;109:27-32, http://dx.doi.org/10.1161/01.CIR.0000115644.35804.8B
11. Widlansky ME, Gokce N, Keaney JF, Vita JA. The Clinical Implications of Endothelial Dysfunction. J Am Coll Cardiol. 2003;42:114960, http://dx.doi.org/10.1016/S0735-1097(03)00994-X
12. Conway DSG, Pearce LA, Chin BSP, Hart RG, Lip GYH. Plasma von Willebrand Factor and Soluble P-Selectin as Indices of Endothelial Damage and Platelet Activation in 1321 Patients With Nonvalvular Atrial Fibrillation Relationship to Stroke Risk Factors. Circulation. 2002;106:1962-7, http://dx.doi.org/10.1161/01.CIR.0000033220.97592.9A
14. Anderson TJ, Uehata A, Gerhard MD. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol. 1995;26:1235-41, http://dx.doi.org/10.1016/0735-1097(95)00327-4
15. Maxwell AJ, Schauble E, Bernstein D, Cooke JP. Limb blood flow during exercise is dependent on nitric oxide. Circulation. 1998;98:36974.
16. Fischer D, Rossa S, Landmesser U, Spiekermann S, Engberding N, Hornig B, et al. Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death. European Heart Journal. 2005;26:659, http://dx.doi.org/10.1093/eurheartj/ehi001
17. Jimenez M, 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(4):497-502, http://dx.doi.org/10.1530/EJE-06-0662
18. Isomaa B, Almgren P, Tuomi T, Forsén B, Lahti K, Nissén M, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001;24:683-89, http://dx.doi.org/10.2337/diacare.24.4.683
19. Laurent S, Cockcroft J. Bortel LV, Boutouyrie P, Giannattasio G, Hayoz D. Expert consensus document on arterial stiffness. Methodological issues and clinical applications. European Heart Journal. 2006;27:2588605.
20. Kuvin JT, Patel AR, Sliney KA, Pandian NG, Sheffy J, Schnall RP. Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. Am Heart J. 2003;146:168-74, http://dx.doi.org/10.1016/S0002-8703(03)00094-2
22. Germain AM, Irribarra VP, Valdés G, Romanik MC, Leighton F, Mardones F. Evaluación ultrasonográfica de la función endotelial en niños y adultos chilenos. Rev Méd Chile. 2004;132:437-44.
23. 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(7-8):631-5.
24. Kapiotis S, Holzer G, Schaller G, Haumer M, Widhalm H, Weghuber D. A proinflammatory state is detectable in obese children and is accompanied by functional and morphological vascular changes. Arterioscler Thromb Vasc Biol. 2006;26(11):2541-6, http://dx.doi.org/10.1161/01.ATV.0000245795.08139.70
25. Aggoun Y, Farpour-Lambert NJ, Marchand LM, Golay E, Maggio AB, Beghetti M. Impaired endothelial and smooth muscle functions and arterial stiffness appear before puberty in obese children and are associated with elevated ambulatory blood pressure. Eur Heart J. 2008;29(6):792-9, http://dx.doi.org/10.1093/eurheartj/ehm633
26. Woo KS, Chook P, Yu CW, Sung RY, Qiao M, Leung SS. Overweight in children is associated with arterial endothelial dysfunction and intima-media thickening. Int J Obes Relat Metab Disord. 2004;28(7):852-7, http://dx.doi.org/10.1038/sj.ijo.0802539
27. Pena AS, Wiltshire E, MacKenzie K, Gent R, Piotto L, Hirte C. Vascular endothelial and smooth muscle function relates to body mass index and glucose in obese and nonobese children. J Clin Endocrinol Metab. 2006;91(11):4467-71, http://dx.doi.org/10.1210/jc.2006-0863
28. Järvisalo MJ, Raitakari M, Toikka JO, Putto-Laurila A, Rontu R, Laine S, et al. Endothelial dysfunction and increased arterial intima-media thickness in children with type 1 diabetes. Circulation. 2004;109(14): 1750-5, http://dx.doi.org/10.1161/01.CIR.0000124725.46165.2C
29. Wiltshire EJ, Gent R, Hirte C, Pena A, Thomas DW, Couper JJ. Endothelial dysfunction relates to folate status in children and adolescents with type 1 diabetes. Diabetes. 2002;51(7):2282-6, http://dx.doi.org/10.2337/diabetes.51.7.2282
30. Haller MJ, Stein J, Shuster J, Theriaque D, Silverstein J, Schatz DA, et al. Peripheral artery tonometry demonstrates altered endothelial function in children with type 1 diabetes. Pediatric Diabetes. 2007;8:1938, http://dx.doi.org/10.1111/j.1399-5448.2007.00246.x
31. Borzutzky A, Gutiérrez M, Talesnik E, Godoy I, Kraus J, Hoyos R, Arnaiz P, et al. High sensitivity C-reactive protein and endothelial function in Chilean patients with history of Kawasaki disease. Clin Rheumatol. 2008;27:84550, http://dx.doi.org/10.1007/s10067-007-0808-6
32. Deng YB, Xiang HJ, Chang Q, Li CL. Evaluation by High-Resolution Ultrasonography of Endothelial Function in Brachial Artery After Kawasaki Disease and the Effects of Intravenous Administration of Vitamin C. Circ J. 2002;66:90812, http://dx.doi.org/10.1253/circj.66.908
33. Mimoun E, Aggoun Y, Pousset M, Dubern B, Bougle D, Girardet JP, et al. Association of arterial stiffness and endothelial dysfunction with metabolic syndrome in obese children. J Pediatr. 2008;153(1):65-70.
34. Sorensen KE, Celermajer DS, Georgakopoulos D, Hatcher G. Betteridge DJ, Deanfield JE. Impairment of endothelium-dependent dilation is an early event in children with familial hypercholesterolemia and is related to the lipoprotein(a) level. J Clin Invest. 1994;93(1):50-5.
35. de Jongh S, Lilien MR, Bakker HD, Hutten BA, Kastelein JJ, Stroes ES. Family history of cardiovascular events and endothelial dysfunction in children with familial hypercholesterolemia. Atherosclerosis. 2002; 163(1):193-7, http://dx.doi.org/10.1016/S0021-9150(02)00003-5
36. Järvisalo MJ, Lehtimaki T, Raitakari OT. Determinants of arterial nitratemediated dilatation in children: role of oxidized low-density lipoprotein, endothelial function, and carotid intima-media thickness. Circulation. 2004; 109(23):2885-9, http://dx.doi.org/10.1161/01.CIR.0000129304.98566.D8
37. Ladeia AM, Ladeia-Frota C, Pinho L, Stefanelli E, Adan L. Endothelial dysfunction is correlated with microalbuminuria in children with shortduration type 1 diabetes. Diabetes Care. 2005;28(8):2048-50, http://dx.doi.org/10.2337/diacare.28.8.2048
38. Noto N, Okada T, Karasawa K, Ayusawa M, Sumitomo N,Harada K, et al. Age-related acceleration of endothelial dysfunction and subclinical atherosclerosis in subjects with coronary artery lesions after Kawasaki disease. Pediatr Cardiol. 2009;30(3):262-8, http://dx.doi.org/10.1007/s00246-008-9329-6
39. Kadono T, Sugiyama H, Hoshiai M, Osada M, Tan T, Naitoh A, et al. Endothelial Function Evaluated by Flow-Mediated Dilatation in Pediatric Vascular Disease. Pediatr Cardiol. 2005;26:38590, http://dx.doi.org/10.1007/s00246-004-0755-9
40. Dhillon R, Clarkson P, Donald AE, Powe AJ, Nash M, Novelli V, et al. Endothelial Dysfunction Late After Kawasaki Disease. Circulation. 1996;94:2103-6.
41. Järvisalo MJ, Rönnemaa T, Volanen I. Brachial artery dilatation responses in healthy children and adolescents. Am J Physiol Heart Circ Physiol, 2002;282:8792.
42. Deng YB, Li TL, Xiang HJ, Chang Q, Li CL. Impaired endothelial function in the brachial artery after Kawasaki disease and the effects of intravenous administration of vitamin C. Pediatr Infect Dis J. 2003;22(1):349.
43. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, et al. Guidelines for the Ultrasound Assessment of Endothelial-Dependent Flow-Mediated Vasodilation of the Brachial Artery. J Am Coll Cardiol. 2002;39:25765, http://dx.doi.org/10.1016/ S0735-1097(01)01746-6
44. Evora PRB, Pearson PJ, Seccombe JF, Discigil B, Schaff HV. Métodos Experimentais no Estudo da Função Endotelial. Arq Bras Cardiol. 1996;66(5):291-7.
45. Laurent S, Cockcroft J, Bortel LV, Boutouyrie P, Giannattasio C, Hayoz D. Expert consensus document on arterial stiffness. Methodological issues and clinical applications. European Heart Journal. 2006;27:2588605.
46. Prado DML, Dias RG, Trombetta IC. Cardiovascular, Ventilatory, and Metabolic Parameters during Exercise: Differences between Children and Adults. Arq Bras Cardiol. 2006;87:e92-e97, http://dx.doi.org/10.1590/S0066-782X2006001700035
47. Dunger DB, Ahmed ML, Ong KK. Early and late weight gain and the timing of puberty. Mol Cell Endocrinol. 2006;254:1405, http://dx.doi.org/10.1016/j.mce.2006.04.003
48. Juul A, Teilmann G, Scheike T, Hertel NT, Holm K, Laursen LM. Pubertal development in Danish children: comparison of recent European and US data. Iinternational Journal of Andrology. 2006;29:24755.
49. Ahme ML, Ong KK, Dunger DB. Childhood obesity and the timing of puberty. Trends in Endocrinology and Metabolism. 2009;20(5):237-42.
50. Kalme T, Koistinen H, Loukovaara M, Koistinen R, Leinonen P. Comparative studies on the regulation of insulin-like growth factorbinding protein-1 (IGFBP-1) and sex hormonebinding globulin (SHBG) production by insulin and insulin-like growth factors in human hepatoma cells. J Steroid Biochem Mol Biol. 2003;86(2):197200, http://dx.doi.org/10.1016/S0960-0760(03)00268-1
51. Tanner JM, Whitehouse RH. Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Archives of Disease in Childhood. 1976;51:170-9, http://dx.doi.org/10.1136/ adc.51.3.170
52. Järvisalo MJ, Harmoinen A, Hakanen M, Paakkunainen U, Hartiala J, Lehtimäki T. Elevated Serum C-Reactive Protein Levels and Early Arterial Changes in Healthy Children. Arterioscler Thromb Vasc Biol. 2002;22:1323-8, http://dx.doi.org/10.1161/01.ATV.0000024222.06463.21
53. Kapiotis S, Holzer G, Schaller G, Haumer M, Widhalm H, Weghuber D. A Proinflammatory State Is Detectable in Obese Children and Is Accompanied by Functional and Morphological Vascular Changes. Arterioscler Thromb Vasc Biol. 2006;26:2541-6, http://dx.doi.org/ 10.1161/01.ATV.0000245795.08139.70
54. Perticone F, Ceravolo R, Candigliota M, Ventura G, Iacopino S, Sinopoli F, et al. Obesity and Body Fat Distribution Induce Endothelial Dysfunction by oxidative Stress. Protective Effect of Vitamin C. Diabetes. 2001;50:15965.
55. Gardin JM, Allebban Z, Wong ND, Sklar SK, Bess RL, Spence MA, et al. Endothelial function and urine albumin levels among asymptomatic Mexican-Americans and non-Hispanic whites. Cardiovascular Ultrasound. 2008;6:43-9, http://dx.doi.org/10.1186/1476-7120-6-43
56. Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G, Baron AD. Obesity/Insulin Resistance Is Associated with Endothelial Dysfunction. Implications for the Syndrome of Insulin Resistance. J Clin Invest. 1996;97(11):2601-10.
57. Castro PA, Urbano LMF, Costa IMC. Doença de Kawasaki. An Bras Dermatol. 2009;84(4):317-31, http://dx.doi.org/10.1590/S036505962009000400002
58. Borzutzky A, Gutiérrez M, Talesnik E, Godoy I, Kraus J, Hoyos R. High sensitivity C-reactive protein and endothelial function in Chilean patients with history of Kawasaki disease. Clin Rheumatol. 2008;27: 84550, http://dx.doi.org/10.1007/s10067-007-0808-6
59. Koyanagi H, Yanagawa H, Nakamura Y, Yashiro M. Serum C-reactive protein levels in patients with Kawasaki disease: from the results of Nation-wide surveys of Kawasaki disease in Japan. Acta Pediatr. 1997;86:613-9, http://dx.doi.org/10.1111/j.1651-2227.1997.tb08944.x
60. Chequer G, Nascimento BR, Navarro TP, Falqueto EB, Alencar MCN, Miranda MCR. Espessamento Médio-Intimal da Carótida e Função Endotelial na Doença Arterial Coronariana. Arq Bras Cardiol. 2006;87(2):84-90, http://dx.doi.org/10.1590/S0066-782X2006001500004
61. Andrade ZM, Carvalhaes JTA, Taddei JAAC, Christofalo DMJ, Ajzen AS. Função endotelial de adolescentes normotensos sem fatores de risco para hipertensão arterial. J Pediatr. 2005;81(5):395-9.

Publication Dates

Publication in this collection
27 Mar 2012
Date of issue
2012

History

Received
30 Sept 2011
Accepted
22 Nov 2011
Reviewed
03 Nov 2011

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Hechter SJ, Fredriksen PM, Liu P. Angiotensin-converting enzyme inhibitors in adults after the Mustard procedure. Am J Cardiol. 2001;87:660-711, http://dx.doi.org/10.1016/S0002-9149(00)01452-1

[2] 2. Rusconi P, Gomes-Marin O, Rossique-Gonzalvez M, Redha E, MarínJ, Lon-Young M, et al. Carvedilol in children with cardiomyopathy. A 3year experience at a single institution. J Heart Lung Transplant. 2004;23:832-8.

[3] 3. Azeka E, Vasconcelos LM, Cippiciani TM, Oliveira AS, Barbosa DF, Leite RMG. Insuficiência cardíaca congestiva em crianças. Do tratamento farmacológico ao transplante cardíaco. Rev Med. 2008;87(2):99-104.

[4] 4. Carvalho VO, Bocchi EA, Guimaraes GV. The Carvedilol's Beta-Blockade in Heart Failure and Exercise Training's Sympathetic Blockade in Healthy Athletes during the Rest and Peak Effort. Cardiovascular Therapeutics. 2010;28:8792, http://dx.doi.org/10.1111/j.1755-5922. 2009.00113.x

[5] 5. Guimarães GV, Bellotti G, Mocelin AO, Camargo PR, Bocchi EA. Cardiopulmonary exercise testingin childrenwithheart failure secondary to idiopathic dilated cardiomyopathy. Chest. 2001;120:81624, http://dx.doi.org/10.1378/chest.120.3.816

[6] 6. Mesquita ET, Socrates J, Rassi S, Villacorta H, Mady C. Insuficiência cardíaca com função sistólica preservada. Arquivos Brasileiros de Cardiologia. 2004;82(4):494-500, http://dx.doi.org/10.1590/S0066782X2004000500014

[7] 7. Verma S, Anderson YJ. Fundamentals of endothelial function for the clinical cardiologist. Circulation. 2002;105:546-9, http://dx.doi.org/ 10.1161/hc0502.104540

[8] 8. Davis SF, Yeung AC, Meredith IT, Charbonneau F, Ganz P, Selwyn AP, et al. Early Endothelial Dysfunction Predicts the Development of Transplant Coronary Artery Disease at 1 Year Posttransplant. Circulation. 1996;93:457-62.

[9] 9. Chong AY, Blann AD, Patel J, Freestone B, Hughes E, Lip GYH. Endothelial Dysfunction and Damage in Congestive Heart Failure. Relation of Flow-Mediated Dilation to Circulating Endothelial Cells, Plasma Indexes of Endothelial Damage, and Brain Natriuretic Peptide. Circulation. 2004;110:1794-8.

[10] 10. Davignon J, Ganz P. Role of Endothelial Dysfunction in Atherosclerosis. Circulation. 2004;109:27-32, http://dx.doi.org/10.1161/01.CIR.0000115644.35804.8B

[11] 11. Widlansky ME, Gokce N, Keaney JF, Vita JA. The Clinical Implications of Endothelial Dysfunction. J Am Coll Cardiol. 2003;42:114960, http://dx.doi.org/10.1016/S0735-1097(03)00994-X

[12] 12. Conway DSG, Pearce LA, Chin BSP, Hart RG, Lip GYH. Plasma von Willebrand Factor and Soluble P-Selectin as Indices of Endothelial Damage and Platelet Activation in 1321 Patients With Nonvalvular Atrial Fibrillation Relationship to Stroke Risk Factors. Circulation. 2002;106:1962-7, http://dx.doi.org/10.1161/01.CIR.0000033220.97592.9A

[14] 14. Anderson TJ, Uehata A, Gerhard MD. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol. 1995;26:1235-41, http://dx.doi.org/10.1016/0735-1097(95)00327-4

[15] 15. Maxwell AJ, Schauble E, Bernstein D, Cooke JP. Limb blood flow during exercise is dependent on nitric oxide. Circulation. 1998;98:36974.

[16] 16. Fischer D, Rossa S, Landmesser U, Spiekermann S, Engberding N, Hornig B, et al. Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death. European Heart Journal. 2005;26:659, http://dx.doi.org/10.1093/eurheartj/ehi001

[17] 17. Jimenez M, 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(4):497-502, http://dx.doi.org/10.1530/EJE-06-0662

[18] 18. Isomaa B, Almgren P, Tuomi T, Forsén B, Lahti K, Nissén M, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001;24:683-89, http://dx.doi.org/10.2337/diacare.24.4.683

[19] 19. Laurent S, Cockcroft J. Bortel LV, Boutouyrie P, Giannattasio G, Hayoz D. Expert consensus document on arterial stiffness. Methodological issues and clinical applications. European Heart Journal. 2006;27:2588605.

[20] 20. Kuvin JT, Patel AR, Sliney KA, Pandian NG, Sheffy J, Schnall RP. Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. Am Heart J. 2003;146:168-74, http://dx.doi.org/10.1016/S0002-8703(03)00094-2

[22] 22. Germain AM, Irribarra VP, Valdés G, Romanik MC, Leighton F, Mardones F. Evaluación ultrasonográfica de la función endotelial en niños y adultos chilenos. Rev Méd Chile. 2004;132:437-44.

[23] 23. 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(7-8):631-5.

[24] 24. Kapiotis S, Holzer G, Schaller G, Haumer M, Widhalm H, Weghuber D. A proinflammatory state is detectable in obese children and is accompanied by functional and morphological vascular changes. Arterioscler Thromb Vasc Biol. 2006;26(11):2541-6, http://dx.doi.org/10.1161/01.ATV.0000245795.08139.70

[25] 25. Aggoun Y, Farpour-Lambert NJ, Marchand LM, Golay E, Maggio AB, Beghetti M. Impaired endothelial and smooth muscle functions and arterial stiffness appear before puberty in obese children and are associated with elevated ambulatory blood pressure. Eur Heart J. 2008;29(6):792-9, http://dx.doi.org/10.1093/eurheartj/ehm633

[26] 26. Woo KS, Chook P, Yu CW, Sung RY, Qiao M, Leung SS. Overweight in children is associated with arterial endothelial dysfunction and intima-media thickening. Int J Obes Relat Metab Disord. 2004;28(7):852-7, http://dx.doi.org/10.1038/sj.ijo.0802539

[27] 27. Pena AS, Wiltshire E, MacKenzie K, Gent R, Piotto L, Hirte C. Vascular endothelial and smooth muscle function relates to body mass index and glucose in obese and nonobese children. J Clin Endocrinol Metab. 2006;91(11):4467-71, http://dx.doi.org/10.1210/jc.2006-0863

[28] 28. Järvisalo MJ, Raitakari M, Toikka JO, Putto-Laurila A, Rontu R, Laine S, et al. Endothelial dysfunction and increased arterial intima-media thickness in children with type 1 diabetes. Circulation. 2004;109(14): 1750-5, http://dx.doi.org/10.1161/01.CIR.0000124725.46165.2C

[29] 29. Wiltshire EJ, Gent R, Hirte C, Pena A, Thomas DW, Couper JJ. Endothelial dysfunction relates to folate status in children and adolescents with type 1 diabetes. Diabetes. 2002;51(7):2282-6, http://dx.doi.org/10.2337/diabetes.51.7.2282

[30] 30. Haller MJ, Stein J, Shuster J, Theriaque D, Silverstein J, Schatz DA, et al. Peripheral artery tonometry demonstrates altered endothelial function in children with type 1 diabetes. Pediatric Diabetes. 2007;8:1938, http://dx.doi.org/10.1111/j.1399-5448.2007.00246.x

[31] 31. Borzutzky A, Gutiérrez M, Talesnik E, Godoy I, Kraus J, Hoyos R, Arnaiz P, et al. High sensitivity C-reactive protein and endothelial function in Chilean patients with history of Kawasaki disease. Clin Rheumatol. 2008;27:84550, http://dx.doi.org/10.1007/s10067-007-0808-6

[32] 32. Deng YB, Xiang HJ, Chang Q, Li CL. Evaluation by High-Resolution Ultrasonography of Endothelial Function in Brachial Artery After Kawasaki Disease and the Effects of Intravenous Administration of Vitamin C. Circ J. 2002;66:90812, http://dx.doi.org/10.1253/circj.66.908

[33] 33. Mimoun E, Aggoun Y, Pousset M, Dubern B, Bougle D, Girardet JP, et al. Association of arterial stiffness and endothelial dysfunction with metabolic syndrome in obese children. J Pediatr. 2008;153(1):65-70.

[34] 34. Sorensen KE, Celermajer DS, Georgakopoulos D, Hatcher G. Betteridge DJ, Deanfield JE. Impairment of endothelium-dependent dilation is an early event in children with familial hypercholesterolemia and is related to the lipoprotein(a) level. J Clin Invest. 1994;93(1):50-5.

[35] 35. de Jongh S, Lilien MR, Bakker HD, Hutten BA, Kastelein JJ, Stroes ES. Family history of cardiovascular events and endothelial dysfunction in children with familial hypercholesterolemia. Atherosclerosis. 2002; 163(1):193-7, http://dx.doi.org/10.1016/S0021-9150(02)00003-5

[36] 36. Järvisalo MJ, Lehtimaki T, Raitakari OT. Determinants of arterial nitratemediated dilatation in children: role of oxidized low-density lipoprotein, endothelial function, and carotid intima-media thickness. Circulation. 2004; 109(23):2885-9, http://dx.doi.org/10.1161/01.CIR.0000129304.98566.D8

[37] 37. Ladeia AM, Ladeia-Frota C, Pinho L, Stefanelli E, Adan L. Endothelial dysfunction is correlated with microalbuminuria in children with shortduration type 1 diabetes. Diabetes Care. 2005;28(8):2048-50, http://dx.doi.org/10.2337/diacare.28.8.2048

[38] 38. Noto N, Okada T, Karasawa K, Ayusawa M, Sumitomo N,Harada K, et al. Age-related acceleration of endothelial dysfunction and subclinical atherosclerosis in subjects with coronary artery lesions after Kawasaki disease. Pediatr Cardiol. 2009;30(3):262-8, http://dx.doi.org/10.1007/s00246-008-9329-6

[39] 39. Kadono T, Sugiyama H, Hoshiai M, Osada M, Tan T, Naitoh A, et al. Endothelial Function Evaluated by Flow-Mediated Dilatation in Pediatric Vascular Disease. Pediatr Cardiol. 2005;26:38590, http://dx.doi.org/10.1007/s00246-004-0755-9

[40] 40. Dhillon R, Clarkson P, Donald AE, Powe AJ, Nash M, Novelli V, et al. Endothelial Dysfunction Late After Kawasaki Disease. Circulation. 1996;94:2103-6.

[41] 41. Järvisalo MJ, Rönnemaa T, Volanen I. Brachial artery dilatation responses in healthy children and adolescents. Am J Physiol Heart Circ Physiol, 2002;282:8792.

[42] 42. Deng YB, Li TL, Xiang HJ, Chang Q, Li CL. Impaired endothelial function in the brachial artery after Kawasaki disease and the effects of intravenous administration of vitamin C. Pediatr Infect Dis J. 2003;22(1):349.

[43] 43. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, et al. Guidelines for the Ultrasound Assessment of Endothelial-Dependent Flow-Mediated Vasodilation of the Brachial Artery. J Am Coll Cardiol. 2002;39:25765, http://dx.doi.org/10.1016/ S0735-1097(01)01746-6

[44] 44. Evora PRB, Pearson PJ, Seccombe JF, Discigil B, Schaff HV. Métodos Experimentais no Estudo da Função Endotelial. Arq Bras Cardiol. 1996;66(5):291-7.

[45] 45. Laurent S, Cockcroft J, Bortel LV, Boutouyrie P, Giannattasio C, Hayoz D. Expert consensus document on arterial stiffness. Methodological issues and clinical applications. European Heart Journal. 2006;27:2588605.

[46] 46. Prado DML, Dias RG, Trombetta IC. Cardiovascular, Ventilatory, and Metabolic Parameters during Exercise: Differences between Children and Adults. Arq Bras Cardiol. 2006;87:e92-e97, http://dx.doi.org/10.1590/S0066-782X2006001700035

[47] 47. Dunger DB, Ahmed ML, Ong KK. Early and late weight gain and the timing of puberty. Mol Cell Endocrinol. 2006;254:1405, http://dx.doi.org/10.1016/j.mce.2006.04.003

[48] 48. Juul A, Teilmann G, Scheike T, Hertel NT, Holm K, Laursen LM. Pubertal development in Danish children: comparison of recent European and US data. Iinternational Journal of Andrology. 2006;29:24755.

[49] 49. Ahme ML, Ong KK, Dunger DB. Childhood obesity and the timing of puberty. Trends in Endocrinology and Metabolism. 2009;20(5):237-42.

[50] 50. Kalme T, Koistinen H, Loukovaara M, Koistinen R, Leinonen P. Comparative studies on the regulation of insulin-like growth factorbinding protein-1 (IGFBP-1) and sex hormonebinding globulin (SHBG) production by insulin and insulin-like growth factors in human hepatoma cells. J Steroid Biochem Mol Biol. 2003;86(2):197200, http://dx.doi.org/10.1016/S0960-0760(03)00268-1

[51] 51. Tanner JM, Whitehouse RH. Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Archives of Disease in Childhood. 1976;51:170-9, http://dx.doi.org/10.1136/ adc.51.3.170

[52] 52. Järvisalo MJ, Harmoinen A, Hakanen M, Paakkunainen U, Hartiala J, Lehtimäki T. Elevated Serum C-Reactive Protein Levels and Early Arterial Changes in Healthy Children. Arterioscler Thromb Vasc Biol. 2002;22:1323-8, http://dx.doi.org/10.1161/01.ATV.0000024222.06463.21

[53] 53. Kapiotis S, Holzer G, Schaller G, Haumer M, Widhalm H, Weghuber D. A Proinflammatory State Is Detectable in Obese Children and Is Accompanied by Functional and Morphological Vascular Changes. Arterioscler Thromb Vasc Biol. 2006;26:2541-6, http://dx.doi.org/ 10.1161/01.ATV.0000245795.08139.70

[54] 54. Perticone F, Ceravolo R, Candigliota M, Ventura G, Iacopino S, Sinopoli F, et al. Obesity and Body Fat Distribution Induce Endothelial Dysfunction by oxidative Stress. Protective Effect of Vitamin C. Diabetes. 2001;50:15965.

[55] 55. Gardin JM, Allebban Z, Wong ND, Sklar SK, Bess RL, Spence MA, et al. Endothelial function and urine albumin levels among asymptomatic Mexican-Americans and non-Hispanic whites. Cardiovascular Ultrasound. 2008;6:43-9, http://dx.doi.org/10.1186/1476-7120-6-43

[56] 56. Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G, Baron AD. Obesity/Insulin Resistance Is Associated with Endothelial Dysfunction. Implications for the Syndrome of Insulin Resistance. J Clin Invest. 1996;97(11):2601-10.

[57] 57. Castro PA, Urbano LMF, Costa IMC. Doença de Kawasaki. An Bras Dermatol. 2009;84(4):317-31, http://dx.doi.org/10.1590/S036505962009000400002

[58] 58. Borzutzky A, Gutiérrez M, Talesnik E, Godoy I, Kraus J, Hoyos R. High sensitivity C-reactive protein and endothelial function in Chilean patients with history of Kawasaki disease. Clin Rheumatol. 2008;27: 84550, http://dx.doi.org/10.1007/s10067-007-0808-6

[59] 59. Koyanagi H, Yanagawa H, Nakamura Y, Yashiro M. Serum C-reactive protein levels in patients with Kawasaki disease: from the results of Nation-wide surveys of Kawasaki disease in Japan. Acta Pediatr. 1997;86:613-9, http://dx.doi.org/10.1111/j.1651-2227.1997.tb08944.x

[60] 60. Chequer G, Nascimento BR, Navarro TP, Falqueto EB, Alencar MCN, Miranda MCR. Espessamento Médio-Intimal da Carótida e Função Endotelial na Doença Arterial Coronariana. Arq Bras Cardiol. 2006;87(2):84-90, http://dx.doi.org/10.1590/S0066-782X2006001500004

[61] 61. Andrade ZM, Carvalhaes JTA, Taddei JAAC, Christofalo DMJ, Ajzen AS. Função endotelial de adolescentes normotensos sem fatores de risco para hipertensão arterial. J Pediatr. 2005;81(5):395-9.