European Journal of Pediatrics

, Volume 172, Issue 6, pp 721–732 | Cite as

Cardiovascular disease in childhood: the role of obesity

  • Despina Herouvi
  • Evangelos Karanasios
  • Christina Karayianni
  • Kyriaki Karavanaki
Review

Abstract

In recent years, childhood obesity is becoming an epidemic health problem. It is now evident from many studies that childhood obesity is correlated with adult excess weight status and the development of risk factors for cardiovascular diseases in adulthood, including hypertension, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome. The exposure to obesity and to the above risk factors during childhood subsequently lead to atherosclerotic development, such as altered vascular structure and function, although the mechanisms are still unclear. Several non-invasive, and thus easy-to-obtain measures of arterial structure and function, have been shown to be clinically useful in providing information about vasculature early in the course of atherosclerosis, including measurement of endothelial function, carotid intima media thickness, and arterial stiffness. The early detection of cardiovascular abnormalities is essential because the control of the atherogenic process is more effective during its early stages. The present review focuses on the cardiovascular consequences of obesity, on the mechanisms and the methods of measurement of endothelial dysfunction in obese children and adolescents, and on the ways of intervention for the improvement of vascular health.

Keywords

Cardiovascular endothelial dysfunction Obesity Childhood 

References

  1. 1.
    Aggoun Y, Bonnet D, Sidi D, Girardet JP, Brucker E, Polak M, Safar ME, Levy BI (2000) Arterial mechanical changes in children with familial hyperholesterolemia. ThrombVasc Biol 20:2070–2075Google Scholar
  2. 2.
    Ahimastos AA, Formosa M, Dart AM, Kingwell BA (2003) Gender differences in large artery stiffness pre- and postpuberty. J Clin Endocr Metab 88:5375–5380PubMedGoogle Scholar
  3. 3.
    Arnaiz P, Acevedo M, Barja S, Aglony M, Guzmán B, Cassis B, Carvajal J, Moreno M, Navarrete C, Berríos X (2010) Adiponectin levels, cardio-metabolic risk factors and markers of subclinical atherosclerosis in children. Int J Cardiol 138:138–144PubMedGoogle Scholar
  4. 4.
    Aygun AD, Gungor S, Ustundag B, Gurgoze MK, Sen Y (2005) Proinflammatory cytokines and leptin are increased in serum of prepubertal obese children. Mediators Inflamm 2005:180–183PubMedGoogle Scholar
  5. 5.
    Bacha F, Saad R, Gungor N, Arslanian SA (2006) Are obesity-related metabolic risk factors modulated by the degree of insulin resistance in adolescents? Diabetes Care 29:1599–1604PubMedGoogle Scholar
  6. 6.
    Balagopal P, George D, Patton N, Yarandi H, Roberts WL, Bayne E, Gidding S (2005) Lifestyle-only intervention attenuates the inflammatory state associated with obesity: a randomized controlled study in adolescents. J Pediatr 146:342–348PubMedGoogle Scholar
  7. 7.
    Barker M, Robinson S, Osmond C, Barker DJ (1997) Birth weight and body fat distribution in adolescent girls. Arch Dis Child 77:381–383PubMedGoogle Scholar
  8. 8.
    Barton M (2012) Childhood obesity: a life-long health risk. Acta Pharmacol Sin 33:189–193PubMedGoogle Scholar
  9. 9.
    Bastard JP, Jardel C, Delattre J, Hainque B, Bruckert E, Oberlin F (1999) Evidence for a link between adipose tissue interleukin-6 content and serum c-reactive protein concentrations in obese subjects. Circulation 99:2221–2222PubMedGoogle Scholar
  10. 10.
    Beauloye V, Zech F, Mong HTT, Clapuyt P, Maes M, Brichard SM (2007) Determinants of early atherosclerosis in obese children and adolescents. J Clin Endocrin Metab 92:3025–3032Google Scholar
  11. 11.
    Bell LM, Watts K, Siafarikas A, Thompson A, Ratnam N, Bulsara M, Finn J, O’Driscoll G, Green DJ, Jones TW, Davis EA (2007) Exercise alone reduces insulin resistance in obese children independently of changes in body composition. J Clin Endocrinol Metab 92:4230–4235PubMedGoogle Scholar
  12. 12.
    Berenson GS, Srinivasan SR, Bao W, Newman WP III, Tracy RE, Wattigney WA (1998) Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N Engl J Med 338:1650–1656PubMedGoogle Scholar
  13. 13.
    Bhagat K, Balance P (1997) Inflammatory cytokines impair endothelium dependent dilatation in human veins in vivo. Circulation 96:3042–3047PubMedGoogle Scholar
  14. 14.
    Cambuli VM, Musiu MC, Incani M, Paderi M, Serpe R, Marras V, Cossu E, Cavallo MG, Mariotti S, Loche S, Baroni MG (2008) Assessment of adiponectin and leptin as biomarkers of positive metabolic outcomes after lifestyle intervention in overweight and obese children. J Clin Endocrinol Metab 93:3051–3057PubMedGoogle Scholar
  15. 15.
    Caprio S, Bronson M, Sherwin RS, Rife F, Tamborlane WV (1996) Co-existence of severe insulin resistance and hyperinsulinaemia in pre-adolescent obese children. Diabetologia 39:1489–1497PubMedGoogle Scholar
  16. 16.
    Celik A, Ozçetin M, Yerli Y, Damar IH, Kadı H, Koc F, Ceyhan K (2011) Increased aortic pulse wave velocity in obese children. Turk Kardiyol Dern Ars 39:557–562PubMedGoogle Scholar
  17. 17.
    Chen W, Bao W, Begum S, Elkasabany A, Srinivasan SR, Berenson GS (2000) Age-related patterns of the clustering of cardiovascular risk variables of syndrome X from childhood to young adulthood in a population made up of black and white subjects: the Bogalusa Heart Study. Diabetes 49:1042–1048PubMedGoogle Scholar
  18. 18.
    Cheung YF, Brogan PA, Pilla CB, Dillon MJ, Redington AN (2002) Arterial distensibility in children and teenagers: normal evolution and the effect of childhood vasculitis. Arch Dis Child 87:348–351PubMedGoogle Scholar
  19. 19.
    Cheung YF, Wong KY, Lam BCC, Tsoi NS (2004) Relation of arterial stiffness with gestational age and birth weight. Arch Dis Child 89:217–221PubMedGoogle Scholar
  20. 20.
    Chiolero A, Cachat F, Burnier M, Paccaud F, Bovet P (2007) Prevalence of hypertension in school children based on repeated measurements and association with overweight. J Hypertens 25:2209–2217PubMedGoogle Scholar
  21. 21.
    Chow AY, Chin C, Dahl G, Rosenthal DN (2006) Anthracyclines cause endothelial injury in pediatric cancer patients: a pilot study. J Clin Oncol 24:925–928PubMedGoogle Scholar
  22. 22.
    Cohen MS (2012) Clinical practice: the effect of obesity in children with congenital heart disease. Eur J Pediatr 171:1145–1150PubMedGoogle Scholar
  23. 23.
    Cook DG, Mendall MA, Whincup PH, Carey IM, Ballam L, Morris JE, Miller GJ, Strachan DP (2000) C-reactive protein concentration in children: relationship to adiposity and other cardiovascular risk factors. Atherosclerosis 149:139–150PubMedGoogle Scholar
  24. 24.
    Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH (2003) Prevalence of a metabolic syndrome phenotype in adolescents: findings from NHANES-III, 1988–1994. Arch Pediatr Adolesc Med 157:821–827PubMedGoogle Scholar
  25. 25.
    Dandona P, Aljada A, Mohanty P (2002) The anti-inflammatory and potential anti-atherogenic effect of insulin: a new paradigm. Diabetologia 45:924–930PubMedGoogle Scholar
  26. 26.
    Daniels SR, Arnett DK, Eckel RH, Gidding SS, Hayman LL, Kumanyika S, Robinson TN, Scott BJ, St Jeor S, Williams CL (2005) Overweight in children and adolescents: pathophysiology, consequences, prevention, and treatment. Circulation 111:1999–2012PubMedGoogle Scholar
  27. 27.
    Dangardt F, Osika W, Volkmann R, Gan LM, Friberg P (2008) Obese children show increased intimal wall thickness and decreased pulse wave velocity. Clin Physiol Funct Imaging 28:287–293PubMedGoogle Scholar
  28. 28.
    Davies JI, Struthers AD (2003) Pulse wave analysis and pulse wave velocity: a critical review of their strengths and weaknesses. J Hypertens 21:463–472PubMedGoogle Scholar
  29. 29.
    Davis PH, Dawson JD, Riley WA, Lauer RM (2001) Carotid intima-medial thickness is related to cardiovascular risk factors measured from childhood through middle age: the Muscatine Study. Circulation 104:2815–2819PubMedGoogle Scholar
  30. 30.
    Dietz WH (1994) Critical periods in childhood for the development of obesity. Am J Clin Nutr 59:955–999PubMedGoogle Scholar
  31. 31.
    Dixon D, Goldberg R, Schneiderman N, Delamater A (2004) Gender differences in TNF-α levels among obese vs nonobese latino children. Eur J Clin Nutr 58:696–699PubMedGoogle Scholar
  32. 32.
    Eckel RH, Grundy SM, Zimmet PZ (2005) The metabolic syndrome. Lancet 365:1415–1428PubMedGoogle Scholar
  33. 33.
    Eisenmann JC, Welk GJ, Wickel EE, Blair SN (2004) Stability of variables associated with the metabolic syndrome from adolescence to adulthood: the Aerobics Center Longitudinal Study. Am J Hum Biol 16:690–696PubMedGoogle Scholar
  34. 34.
    Esper RJ, Nordaby RA, Vilarino JO, Paragano A, Cacharrón JL, Machado RA (2006) Endothelial dysfunction: a comprehensive appraisal. Cardiovasc Diabetol 5:4PubMedGoogle Scholar
  35. 35.
    Fagot-Campagna A, Pettitt DJ, Engelgau MM, Burrows NR, Geiss LS, Valdez R, Beckles GL, Saaddine J, Gregg EW, Williamson DF, Narayan KM (2000) Type 2 diabetes among North American children and adolescents: an epidemiologic review and a public health perspective. Pediatr 136:664–672Google Scholar
  36. 36.
    Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW (2004) Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology 145:2273–2282PubMedGoogle Scholar
  37. 37.
    Freedman DS, Dietz WH, Tang R, Mensah GA, Bond MG, Urbina EM, Srinivasan S, Berenson GS (2004) The relation of obesity throughout life to carotid intima-media thickness in adulthood: the Bogalusa Heart Study. Int J Obes Relat Metab Disord 28:159–166PubMedGoogle Scholar
  38. 38.
    Friedland O, Nemet D, Gorodnitsky N, Wolach B, Eliakim A (2002) Obesity and lipid profiles in children and adolescents. J Ped Endocrinol Metab 15:1011–1016Google Scholar
  39. 39.
    Ford ES, Galuska DA, Gillespie C, Will JC, Giles WH, Dietz WH (2001) C-reactive protein and body mass index in children: findings from the Third National Health and Nutrition Examination Survey, 1988–1994. J Pediatr 138:486–492PubMedGoogle Scholar
  40. 40.
    Gallistl S, Sudi KM, Mangge H, Wolfgang E, Borkenstein M (2000) Insulin is an independent correlate of plasma homocysteine levels in obese children and adolescents. Diabetes Care 23:1348–1352PubMedGoogle Scholar
  41. 41.
    Gerber M, Boettner A, Seidel B, Lammert A, Bär J, Schuster E, Thiery J, Kiess W, Kratzsch J (2005) Serum resistin levels of obese and lean children and adolescents: biochemical analysis and clinical relevance. J Clin Endocrinol Metab 90:4503–4509PubMedGoogle Scholar
  42. 42.
    Gil TY, Sung CY, Shim SS, Hong YM (2008) Intima-media thickness and pulse wave velocity in hypertensive adolescents. J Korean Med Sci 23:35–40PubMedGoogle Scholar
  43. 43.
    Giordano P, Delvecchio GC, Cecinati V, Delvecchio M, Altomare M, De Palma F, De Mattia D, Cavallo L, Faienza MF (2011) Metabolic, inflammatory, endothelial and haemostatic markers in a group of Italian obese children and adolescents. Eur J Pediatr 170:845–850PubMedGoogle Scholar
  44. 44.
    Glowinska B, Urban M, Peczynska J, Florys B (2005) Soluble adhesion molecules (sICAM-1, sVCAM-1) and selectins (sEselectin, sPselectin, sLselectin) levels in children and adolescents with obesity, hypertension, and diabetes. Metabolism 54:1020–1026PubMedGoogle Scholar
  45. 45.
    Grulich-Henn J, Lichtenstein S, Hörster F, Hoffmann GF, Nawroth PP, Hamann A (2011) Moderate weight reduction in an outpatient obesity intervention program significantly reduces insulin resistance and risk factors for cardiovascular disease in severely obese adolescents. Int J Endocrinol 2011:541021PubMedGoogle Scholar
  46. 46.
    Gul K, Ahmadi N, Wang Z et al (2009) Digital thermal monitoring of vascular function: a novel tool to improve cardiovascular risk assessment. Vasc Med 14:143–148PubMedGoogle Scholar
  47. 47.
    Hales CN, Barker DJ (2001) The thrifty phenotype hypothesis. Br Med Bull 60:5–20PubMedGoogle Scholar
  48. 48.
    Haller MJ, Stein J, Shuster J, Theriaque D, Silverstein J, Schatz DA, Earing MG, Lerman A, Mahmud FH (2007) Peripheral artery tonometry demonstrates altered endothelial function in children with type 1 diabetes. Pediatr Diabetes 8:193–198PubMedGoogle Scholar
  49. 49.
    Hamburg NM, Benjamin EJ (2009) Assessment of endothelial function using digital pulse amplitude tonometry. Cardiovasc Med 19:6–11Google Scholar
  50. 50.
    Iannuzzi A, Licenziati MR, Acampora C, Renis M, Agrusta M, Romano L, Valerio G, Panico S, Trevisan M (2006) Carotid artery stiffness in obese children with the metabolic syndrome. Am J Cardiol 97:528–531PubMedGoogle Scholar
  51. 51.
    Iannuzzi A, Licenziati MR, Acampora C, Salvatore V, Auriemma L, Romano ML, Panico S, Rubba P, Trevisan M (2004) Increased carotid intima-media thickness and stiffness in obese children. Diabetes Care 27:2506–2508PubMedGoogle Scholar
  52. 52.
    Iannuzzi A, Licenziati MR, Acampora C, Salvatore V, De Marco D, Mayer MC, De Michele M, Russo V (2004) Preclinical changes in the mechanical properties of abdominal aorta in obese children. Metabolism 53:1243–1246PubMedGoogle Scholar
  53. 53.
    Ikeoka D, Mader JK, Pieber TR (2010) Adipose tissue, inflammation and cardiovascular disease. Rev Assoc Med Bras 56:116–121PubMedGoogle Scholar
  54. 54.
    Inokuchi S, Kimura K, Sugaya T (2001) Hyperplastic vascular smooth muscle cells of the internal arteries in angiotensin II type 1a receptor null mutant mice. Kidney Int 60:722–731PubMedGoogle Scholar
  55. 55.
    Ippisch HM, Inge TH, Daniels SR, Wang B, Khoury PR, Witt SA, Glascock BJ, Garcia VF, Kimball TR (2008) Reversibility of cardiac abnormalities in morbidly obese adolescents. J Am Coll Cardiol 51:1342–1348PubMedGoogle Scholar
  56. 56.
    Järvisalo MJ, Rönnemaa T, Volanen I, Kaitosaari T, Kallio K, Hartiala JJ, Irjala K, Viikari JS, Simell O, Raitakari OT (2002) Brachial artery dilatation responses in healthy children and adolescents. Am J Physiol Heart Circ Physiol 282:H87–H92PubMedGoogle Scholar
  57. 57.
    Jarvisalo MJ, Lehtimaki T, Raitakari OT (2004) Determinants of arterial nitrate-mediated dilatation in children: role of oxidized low-density lipoprotein, endothelial function, and carotid intima-media thickness. Circulation 109:2885–2889PubMedGoogle Scholar
  58. 58.
    Jarvisalo MJ, Harmoinen A, Hakanen M, Paakkunainen U, Viikari J, Hartiala J, Lehtimaki T, Simell O, Raitakari OT (2002) Elevated serum C-reactive protein levels and early arterial changes in healthy children. Arterioscler Thromb Vasc Biol 22:1323–1328PubMedGoogle Scholar
  59. 59.
    Jeffery AN, Murphy MJ, Metcalf BS, Hosking J, Voss LD, English P, Sattar N, Wilkin TJ (2008) Adiponectin in childhood. Int J Pediatr Obes 3:130–140PubMedGoogle Scholar
  60. 60.
    Fang J, Zhang JP, Luo CX, Xiao Mei Y, Lv LQ (2010) Carotid intima-media thickness in childhood and adolescent obesity relations to abdominal obesity, high triglyceride level and insulin resistance. Int J Med Sci 7:278–283PubMedGoogle Scholar
  61. 61.
    Jourdan C, Wuhl E, Litwin M, Fahr K, Trelewicz J, Jobs K, Schenk JP, Grenda R, Mehls O, Troger J, Schaefer F (2005) Normative values for intima-media thickness and distensibility of large arteries in healthy adolescents. J Hypertension 23:1707–1715Google Scholar
  62. 62.
    Juonala M, Viikari JSA, Ronnemaa T, Helenius H, Taittonen L, Raitakari OT (2006) Elevated blood pressure in adolescent boys predicts endothelial dysfunction: the cardiovascular risk in young Finns study. Hypertension 48:424–430PubMedGoogle Scholar
  63. 63.
    Juonala M, Magnussen CG, Berenson GS, Venn A, Burns TL, Sabin MA, Srinivasan SR, Daniels SR, Davis PH, Chen W, Sun C, Cheung M, Viikari JSA, Dwyer T, Raitakari OT (2011) Childhood adiposity, adult adiposity, and cardiovascular risk factors. N Engl J Med 365:1876–1885PubMedGoogle Scholar
  64. 64.
    Kapiotis S, Holzer G, Schaller G, Haumer M, Widhalm H, Weghuber D, Jilma B, Röggla G, Wolzt M, Widhalm K, Wagner OF (2006) A proinflammatory state is detectable in obese children and is accompanied by functional and morphological vascular changes. Arterioscler Thromb Vasc Biol 26:2541–2546PubMedGoogle Scholar
  65. 65.
    Karakosta P, Georgiou V, Fthenou E, Margioris A, Castanas E, Kogevinas M, Kampa M, Chatzi L (2012) Gender-specific reference intervals for cord blood leptin in Crete, Greece. Eur J Pediatr 171:1563–1566PubMedGoogle Scholar
  66. 66.
    Kelishadi R, Hashemi M, Mohammadifard N, Asgary S, Khavarian N (2008) Association of changes in oxidative and proinflammatory states with changes in vascular function after a lifestyle modification trial among obese children. Clin Chem 54:147–153PubMedGoogle Scholar
  67. 67.
    Kelly AS, Wetzsteon RJ, Kaiser DR, Steinberger J, Bank AJ, Dengel DR (2004) Inflammation, insulin, and endothelial function in overweight children and adolescents: the role of exercise. J Pediatr 145:731–7368PubMedGoogle Scholar
  68. 68.
    Kim YJ, Shim YH, Yoo JH, Lee K, Hong YM (2005) Measurement of the common carotid artery by ultrasound as a predictor of atherosclerosis in obese adolescents. Korean J Pediatr 48:745–752Google Scholar
  69. 69.
    Kissebah AH, Krakower GR (1994) Regional adiposity and morbidity. Physiol Rev 74:761–811PubMedGoogle Scholar
  70. 70.
    Klok MD, Jakobsdottir S, Drent ML (2007) The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev 8:21–34PubMedGoogle Scholar
  71. 71.
    Lamont D, Parker L, White M, Unwin N, Bennett SMA, Cohen M, Richardson D, Dickinson HO, Adamson A, Alberti KGMM, Craft AW (2000) Risk of cardiovascular disease measured by carotid intima-media thickness at age 49–51: life course study. BMJ 320:273–278PubMedGoogle Scholar
  72. 72.
    Lande MB, Carson NL, Roy J, Meagher CC (2006) Effects of childhood primary hypertension on carotid intima-media thickness: a matched controlled study. Hypertension 48:40–44PubMedGoogle Scholar
  73. 73.
    Lamotte C, Iliescu C, Libersa C, Gottrand F (2011) Increased intima-media thickness of the carotid artery in childhood: a systematic review of observational studies. Eur J Pediatr 170:719–729PubMedGoogle Scholar
  74. 74.
    Lee JM, Okumura MJ, Davis MM, Herman WH, Gurney JG (2006) Prevalence and determinants of insulin resistance among US adolescents: a population-based study. Diabetes Care 29:2427–2432PubMedGoogle Scholar
  75. 75.
    Leeson CPM, Whincup PH, Cook DG, Donald AE, Papacosta O, Lucas A, Deanfield JE (1997) Flow-mediated dilation in 9- to 11-year-old children. Circulation 96:2233–2238PubMedGoogle Scholar
  76. 76.
    Leoni MC, Valsecchi C, Mantelli M, Marastoni L, Tinelli C, Marchi A, Castellazzi A (2010) Impact of child obesity on adipose tissue physiology: assessment of adipocytokines and inflammatory cytokines as biomarkers of obesity. Pediatric Reports 2:e19PubMedGoogle Scholar
  77. 77.
    Lobstein T, Baur L, Uauy R (2004) Obesity in children and young people:a crisis in public health. Obes Rev 1:4–85Google Scholar
  78. 78.
    Lloyd LJ, Langley-Evans SC, McMullen S (2010) Childhood obesity and adult cardiovascular disease risk: a systematic review. Int J Obes (Lond) 34:18–28Google Scholar
  79. 79.
    Lydakis C, Stefanaki E, Stefanaki S, Thalassinos E, Kavousanaki M, Lydaki D (2012) Correlation of blood pressure, obesity, and adherence to the Mediterranean diet with indices of arterial stiffness in children. Eur J Pediatr 171:1373–1382PubMedGoogle Scholar
  80. 80.
    Mangge H, Schauenstein K, Stoedier L, Griesl A, Maetz W, Borkenstein M (2004) Low grade infammation in juvenile obesity and type 1 diabetes associated with early signs in atherosclerosis. Exp Vlin End Diabetes 112:378–382Google Scholar
  81. 81.
    Meyer AA, Kundt G, Lenschow U, Schuff-Werner P, Kienast W (2006) Improvement of early vascular changes and cardiovascular risk factors in obese children after a six-month exercise program. J Am Coll Cardiol 48:1865–1870PubMedGoogle Scholar
  82. 82.
    Mayer-Davis EJ, Rifas-Shiman SL, Zhou L, Hu FB, Colditz GA, Gillman MW (2006) Breast-feeding and risk for childhood obesity: does maternal diabetes or obesity status matter? Diabetes Care 29:2231–2237PubMedGoogle Scholar
  83. 83.
    Murphy EC, Carson L, Neal W (2009) Effects of an exercise intervention using Dance Revolution on endothelial function and other risk factors in overweight children. Int J Pediatr Obes 3:1–10Google Scholar
  84. 84.
    Nawrot TS, Hoppenbrouwers K, Den Hond E, Fagard RH, Staessen JA (2004) Prevalence of hypertension, hypercholesterolemia, smoking and overweight in older Belgian adolescents. Eur J Public Health 14:361–365PubMedGoogle Scholar
  85. 85.
    Nemet D, Wang P, Funahashi T, Matsuzawa Y, Tanaka S, Engelman L, Cooper DM (2003) Adipocytokines, body composition, and fitness in children. Pediatr Res 53:148–152PubMedGoogle Scholar
  86. 86.
    NHBPEP National High Blood Pressure Education Program (2004) The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114:555–576Google Scholar
  87. 87.
    Niboshi A, Hamaoka K, Sakata K, Inoue F (2006) Characteristics of brachial–ankle pulse wave velocity in Japanese children. Eur J Pediatr 165:625–629PubMedGoogle Scholar
  88. 88.
    Oldroyd J, Renzaho A, Skouteris H (2011) Low and high birth weight as risk factors for obesity among 4 to 5-year-old Australian children: dose gender matter. Eur J Pediatr 170:899–906PubMedGoogle Scholar
  89. 89.
    Pasceri V, Willerson JT, Yeh ET (2000) Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 102:2165–2168PubMedGoogle Scholar
  90. 90.
    Peña AS, Wiltshire E, MacKenzie K, Gent R, Piotto L, Hirte C, Couper J (2006) Vascular endothelial and smooth muscle function relates to body mass index and glucose in obese and non-obese children. J Clin Endocrinol Metab 91:4467–4471PubMedGoogle Scholar
  91. 91.
    Pena AS, Wiltshire E, Gent R, Piotto L, Hirte C, Couper J (2007) Folic acid does not improve endothelial function in obese children and adolescents. Diabetes Care 30:2122–2127PubMedGoogle Scholar
  92. 92.
    Pickup JC, Chusney GD, Thomas SM, Burt D (2000) Plasma interleukin-6, tumour necrosis factor alpha and blood cytokine production in type 2 diabetes. Life Sci 67:291–300PubMedGoogle Scholar
  93. 93.
    Raghuveer G (2010) Lifetime cardiovascular risk of childhood obesity. Am J Clin Nutr 91:1514–1519Google Scholar
  94. 94.
    Raitakari OT, Celermajer DS (2000) Flow-mediated dilatation. Br J Clin Pharmacol 50:397–404PubMedGoogle Scholar
  95. 95.
    Ravelli G, Stem ZA, Susser MW (1976) Obesity in young men after famine exposure in utero and early infancy. N Engl J Med 295:349–353PubMedGoogle Scholar
  96. 96.
    Ravelli A, Van Der Meulen J, Osmond C, Barker D, Bleker O (1999) Obesity at the age of 50 y in men and women exposed to famine prenatally. Am J Clin Nutr 70:811–816PubMedGoogle Scholar
  97. 97.
    Reinehr T, Stoffel-Wagner B, Roth CL, Andler W (2005) High-sensitive C-reactive protein, tumor necrosis factor alpha, and cardiovascular risk factors before and after weight loss in obese children. Metabolism 54:1155–1161PubMedGoogle Scholar
  98. 98.
    Reinehr T, Andler W (2004) Changes in the atherogenic risk factor profile according to degree of weight loss. Arch Dis Child 89:419–422PubMedGoogle Scholar
  99. 99.
    Ribeiro MM, Silva AG, Santos NS, Guazzelle I, Matos LN, Trombetta IC, Halpern A, Negrão CE, Villares SM (2005) Diet and exercise training restore blood pressure and vasodilatory responses during physiological maneuvers in obese children. Circulation 111:1915–1923PubMedGoogle Scholar
  100. 100.
    Rosner B, Prineas R, Daniels SR, Loggie J (2000) Blood pressure differences between blacks and whites in relation to body size among US children and adolescents. Am J Epidemiol 151:1007–1019PubMedGoogle Scholar
  101. 101.
    Sakuragi S, Abhayaratna K, Gravenmaker KJ, O'Reilly C, Srikusalanukul W, Budge MM, Telford RD, Abhayaratna WP (2009) Influence of adiposity and physical activity on arterial stiffness in healthy children: the lifestyle of our kids study. Hypertension 53:611–616PubMedGoogle Scholar
  102. 102.
    Sass C, Herbeth B, Chapet O, Siest G, Visvikis S, Zannad F (1998) Intima-media thickness and diameter of carotid and femoral arteries in children, adolescents and adults from the Stanislas cohort: effect of age, sex, anthropometry and blood pressure. J Hypertens 16:1593–1602PubMedGoogle Scholar
  103. 103.
    Schorah CJ, Devitt H, Lucock M, Dowell AC (1998) The responsiveness of plasma homocysteine to small increases in dietary folic acid: a primary care study. Eur J Clin Nutr 52:407–411PubMedGoogle Scholar
  104. 104.
    Siervogel RM, Roche AF, Guo S, Mukherjee D, Chumlea WC (1991) Patterns of change in weight/stature from 2 to 18 years:findings from long term serial data for children in the Fels Longitudinal Growth Study. Int J Obes 15:479–485PubMedGoogle Scholar
  105. 105.
    Sinaiko AR, Steinberger J, Moran A, Hong CP, Prineas RJ, Jr Jacobs DR (2006) Influence of insulin resistance and body mass index at age 13 on systolic blood pressure, triglycerides, and high-density lipoprotein cholesterol at age 19. Hypertension 48:730–736PubMedGoogle Scholar
  106. 106.
    Singhal A, Lucas A (2004) Early origins of cardiovascular disease. Is there a unifying hypothesis. Lancet 363:1642–1645PubMedGoogle Scholar
  107. 107.
    Singhal A, Sadaf Farooqi I, O’Rahilly S, Cole TJ, Fewtrell M, Lucas A (2002) Early nutrition and leptin concentrations in later life. Am J Clin Nutr 75:993–999PubMedGoogle Scholar
  108. 108.
    Sinha R, Fisch G, Teague B, Tamborlane WV, Banyas B, Allen K, Savoye M, Rieger V, Taksali S, Barbetta G, Sherwin RS, Caprio S (2002) Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med 346:802–810PubMedGoogle Scholar
  109. 109.
    Skilton MR, Celermajer DS (2006) Endothelial dysfunction and arterial abnormalities in childhood obesity. Int J Obes 30:1041–1049Google Scholar
  110. 110.
    Srinivasan SR, Bao W, Wattigney WA, Berenson GS (1996) Adolescent overweight is associated with adult overweight and related multiple cardiovascular risk factors: the Bogalusa Heart Study. Metabolism 45:235–240PubMedGoogle Scholar
  111. 111.
    Stabouli S, Papakatsika S, Kotsis V (2011) The role of obesity, salt and exercise on blood pressure in children and adolescents. Expert Rev Cardiovasc Ther 9:753–761PubMedGoogle Scholar
  112. 112.
    Steinberger J, Daniels SR, Eckel RH, Lustig RH, McCrindle B, Mietus-Snyder ML (2009) Progress and challenges in metabolic syndrome in children and adolescents: a scientific statement from the American Heart Association atherosclerosis, hypertension, and obesity in the young committee of the council on cardiovascular disease in the young, council on cardiovascular nursing, and council on nutrition, physical activity and metabolism. Circulation 119:628–647PubMedGoogle Scholar
  113. 113.
    Stettler N, Stallings VA, Troxel AB, Zhao J, Schinnar R, Nelson SE, Ziegler EE, Strom BL (2005) Weight gain in the first week of life and overweight in adulthood: a cohort study of European American subjects fed infant formula. Circulation 111:1897–1903PubMedGoogle Scholar
  114. 114.
    Stylianou C, Galli-Tsinopoulou A, Farmakiotis D, Rousso I, Karamouzis M, Koliakos G, Nousia-Arvanitakis S (2007) Ghrelin and leptin levels in obese adolescents. Relationship with body fat and insulin resistance. Hormones 6:295–303PubMedGoogle Scholar
  115. 115.
    Tambalis KD, Panagiotakos DB, Kavouras SA, Kallistratos AA, Moraiti IP, Douvis SJ, Toutouzas PK, Sidossis LS (2009) Eleven-year prevalence trends of obesity in Greek children: first evidence that prevalence of obesity is leveling off. Obesity 18:161–166PubMedGoogle Scholar
  116. 116.
    Taylor RW, Grant AM, Goulding A, Williams SM (2005) Early adiposity rebound: review of papers linking this to subsequent obesity in children and adults. Curr Opin Clin Nutr Metab Care 8:607–612PubMedGoogle Scholar
  117. 117.
    Tham DM, Martin-McNulty B, Wang YX, Wilson DW, Vergona R, Sullivan ME, Dole W, Rutledge JC (2002) Angiotensin II is associated with activation of NF-B-associated genes and downregulation of PPARs. Physiol Genomics 11:21–30PubMedGoogle Scholar
  118. 118.
    Thivel D, Isacco L, Lazaar N, Aucouturier J, Ratel S, Dore E, Meyer M, Duche P (2011) Effect of a 6-month school-based physical activity program on body composition and physical fitness in lean and obese schoolchildren. Eur J Pediatr 170:1435–1443PubMedGoogle Scholar
  119. 119.
    Tounian P, Aggoun Y, Dubern B, Varille V, Guy-Grand B, Sidi D, Girardet JP, Bonnet D (2001) Presence of increased stiffness of the common carotid artery and endothelial dysfunction in severely obese children: a prospective study. Lancet 358:1400–1404PubMedGoogle Scholar
  120. 120.
    Tracy RE, Newman WP III, Wattigney WA, Berenson GS (1995) Risk factors and atherosclerosis in youth autopsy findings of the Bogalusa Heart Study. Am J Med Sci 310:37–41Google Scholar
  121. 121.
    Upchurch GR Jr, Welch GN, Fabian AJ, Freedman JE, Johnson JL, Keaney JF Jr, Loscalzo J (1997) Homocysteine decreases bioavailable NO by a mechanism involving glutathione peroxidase. J Biol Chem 272:17012–17017PubMedGoogle Scholar
  122. 122.
    Urbina EM, Kimball TR, McCoy CE, Khoury PR, Daniels SR, Dolan LM (2009) Youth with obesity and obesity-related type 2 diabetes mellitus demonstrate abnormalities in carotid structure and function. Circulation 119:2913–2919PubMedGoogle Scholar
  123. 123.
    Wang Y, Lobstein T (2006) Worldwide trends in childhood overweight and obesity. Int J Pediatr Obes 1:11–25PubMedGoogle Scholar
  124. 124.
    Watts K, Beye P, Siafarikas A, Davis EA, Jones TW, O'Driscoll G, Green DJ (2004) Exercise training normalizes vascular dysfunction and improves central adiposity in obese adolescents. J Am Coll Cardiol 43:1823–1827PubMedGoogle Scholar
  125. 125.
    Webber LS, Harsha DW, Phillips GT, Srinivasan SR, Simpson JW, Berenson GS (1991) Cardiovascular risk factors in Hispanic, white, and black children: the Brooks County and Bogalusa Heart studies. Am J Epidemiol 133:704–714PubMedGoogle Scholar
  126. 126.
    Weiss R, Shaw M, Savoye M, Caprio S (2009) Obesity dynamics and cardiovascular risk factor stability in obese adolescents. Pediatr Diabetes 10:360–367PubMedGoogle Scholar
  127. 127.
    Whincup PH, Gilg JA, Donald AE, Katterhorn M, Oliver C, Cook DG, Deanfield JE (2005) Arterial distensibility in adolescents: the influence of adiposity, the metabolic syndrome, and classic risk factors. Circulation 112:1789–1797PubMedGoogle Scholar
  128. 128.
    Wilkin TJ (2008) Diabetes: 1 and 2, or one and the same? Progress with the accelerator hypothesis. Pediatr Diabetes 9:23–32PubMedGoogle Scholar
  129. 129.
    Woo KS, Chook P, Yu CW, Sung RY, Qiao M, Leung SS, Lam CW, Metreweli C, Celermajer DS (2004) Effects of diet and exercise on obesity-related vascular dysfunction in children. Circulation 109:1981–1986PubMedGoogle Scholar
  130. 130.
    Wunsch R, De Sousa G, Toschke AM, Reinehr T (2006) Intima-media thickness in obese children before and after weight loss. Pediatrics 118:2334–2340PubMedGoogle Scholar
  131. 131.
    Yeste D, Vendrell J, Tomasini R, Broch M, Gussinyé M, Megia A, Carrascosa A (2007) Interleukin-6 in obese children and adolescents with and without glucose intolerance. Diabetes Care 30:1892–1894PubMedGoogle Scholar
  132. 132.
    Yoshinaga M, Sameshima K, Tanaka Y, Wada A, Hashiguchi J, Tahara H, Kono Y (2008) Adipokines and the prediction of the accumulation of cardio-vascular risk factors or the presence of metabolic syndrome in elementary school children. Circ J 72:1874–1878PubMedGoogle Scholar
  133. 133.
    Zhu W, Huang X, He J, Li M, Neubauer H (2005) Arterial intima-media thickening and endothelial dysfunction in obese Chinese children. Eur J Pediatr 164:337–344PubMedGoogle Scholar
  134. 134.
    Zieske AW, Malcom GT, Strong JP (2002) Natural history and risk factors of atherosclerosis in children and youth: the PDAY study. Pediatr Pathol Mol Med 21:213–237PubMedGoogle Scholar
  135. 135.
    Zou CC, Liang L, Wang CL, Fu JF, Zhao ZY (2009) The change in ghrelin and obestatin levels in obese children after weight reduction. Acta Paediatr 98:159–165PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Despina Herouvi
    • 1
  • Evangelos Karanasios
    • 2
  • Christina Karayianni
    • 1
  • Kyriaki Karavanaki
    • 1
  1. 1.2nd Department of Pediatrics, Diabetes & Metabolism Clinic, “P&A Kyriakou” Children’s HospitalUniversity of AthensAthensGreece
  2. 2.Department of Pediatric Cardiology“Aghia Sophia” Children’s HospitalAthensGreece

Personalised recommendations