ПОРАЖЕНИЯ СЕРДЕЧНО-СОСУДИСТОЙ СИСТЕМЫ У ДЕТЕЙ С ОЖИРЕНИЕМ

Доминирующая доля сердечно-сосудистых заболеваний в структуре смертности и инвалидизации населения развитых стран, рост сердечно-сосудистой патологии привели к формированию представления о сердечно-сосудистом континууме, основанном на клинической оценке факторов, влияющих на риск развития сердечно-сосудистых осложнений. В связи с этим актуальным является изучение начальных этапов этого процесса, а именно — детства и подросткового периода. В настоящее время стало очевидным, что ожирение у детей может рассматриваться как фактор сердечно-сосудистого риска в последующие зрелые годы. Такому взгляду способствуют накопившиеся сведения о поражении сердечно-сосудистой системы у детей и подростков с ожирением и их созвучность изменениям, обнаруживаемым у взрослых. Актуальности этого вопроса способствует и тот факт, что во всем мире наблюдается неуклонный рост доли детей с избытком массы тела, что может означать возможное увеличение сердечно-сосудистой патологии в недалеком будущем. В обзоре освещены ранние проявления поражения сердечно-сосудистой системы у детей с ожирением. Обсуждаются развитие эндотелиальной дисфункции, процессы ремоделирования артериальной стенки, возникновение атеросклеротических повреждений в аорте и периферических сосудах. Также уделено внимание особенностям развития и течения артериальной гипертензии, рассмотрены признаки ремоделирования сердца и критерии диагностики гипертрофии миокарда левого желудочка. Приведены направления профилактики и лечения кардиоваскулярных изменений у детей и подростков с ожирением.

1. Эдлеева А. Г., Хомич М. М., Волков Н. Ю., Леонова И. А., Юрьев В. В. Оценка состава тела как способ выявления предикторов развития метаболического синдрома. Профилактическая и клиническая медицина. 2010;3–4(36–37):183–186. [Edleeva AG, Khomich MM, Volkov NY, Leonova IA, Yuryev VV. Estimation of body composition as a way to identify predictors of the development of the metabolic syndrome in children. Preventive and Clinical Medicine. 2010;3–4(36–37):183–186. In Russian].

2. Gokce N, Keaney JF Jr, Hunter LM, Watkins MT, Nedeljkovic ZS, Menzoian JO et al. Predictive value of noninvasivelydetermined endothelial dysfunction for long-term cardiovascular events inpatients with peripheral vascular disease. J Am Coll Cardiol. 2003;41(10):1769–1775.

3. Yeboah J, Sutton-Tyrrell K, Mcburnie MA, Burke GL, Herrington DM. Crouse JR. Association between brachial artery reactivity and cardiovascular disease status in an elderly cohort: The cardiovascular health study. Atherosclerosis. 2008;197:768–776.

4. Shechter M, Issachar A, Marai I, Koren-Morag N, Freinark D, Shahar Y et al. Long-term association of brachial artery flow-mediated vasodilation and cardiovascular events in middle-aged subjects with no apparent heart disease. Int J Cardiol. 2009;134(1):52–58.

5. Järvisalo MJ, Rönnemaa T, Volanen I, Kaitosaari T, Kallio K, Hartiala JJ et al. Brachial artery dilatation responses in healthy children and adolescents. Am J Physiol Heart Circ Physiol. 2002;282 (1):H87-H92.

6. Perticone F, Ceravolo R, Pujia A, Ventura G, Iacopino S, Scozzafava A et al. Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation. 2001;104 (2):191–196.

7. Aggoun Y, Farpour-Lambert NJ, Marchand LM, Golay E, Maggio ABR, 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;29:792–799.

8. Peña AS, Wiltshire E, MacKenzie K, Gent R, Piotto L, Hirte C et al. 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):4467–4471.

9. Meyer AA, Kundt G, Steiner M, Schuff-Werner P, Kienast W. Impaired flow-mediated vasodilation, carotid artery intima-media thickening, and elevated endothelial plasma markers in obese children: the impact of cardiovascular risk factors. Pediatrics. 2006;117:1560–1567.

10. Skilton MR, Celermajer DS. Endothelial dysfunction and arterial abnormalities in childhood obesity. Int J Obes. 2006;30 (7):1041–1049.

11. Woo KS, Chook P, Yu CW, Sung RY, Qiao M, Leung SS et al. Effects of diet and exercise on obesity related vascular dysfunction in children. Circulation. 2004;109(16):1981–1986.

12. Tounian P, Aggoun Y, Dubem B, Varille V, Guy-Grand B, Sidi D et al. Presence of increased stiffness of the common carotid artery and endothelial dysfunction in severely obese children: a prospective study. Lancet. 2001;358(9291):1400–1404.

13. Meyer AA, Kundt G, Lenschow U, Schuff-Werner P, K i e n a s t W. I m p r o v e m e n t o f e a r l y v a s c u l a r c h a n g e s a n d cardiovascular risk factors in obese children after a six-month exercise program. J Am Coll Cardiol. 2006;48(9):1865–1870.

14. Singhal A. Endothelial dysfunction: role in obesity-related disorders and the early origins of CVD. Proc Nutr Soc. 2005;64 (1):15–22.

15. Aggoun Y, Szezepanski I, Bonnet D. Noninvasive assessment of arterial stiffness and risk of atherosclerotic events in children. Pediatr Res. 2005;58(2):173–178.

16. Bonithon-Kopp C, Touboul PJ, Berr C, Leroux C, Mainard F, Courbon D et al. Relation of intima-media thickness to atherosclerotic plaques in the carotid arteries: the Vascular Aging (EVA) Study. Arterioscler Thromb Vasc Biol. 1996;16 (2):310–316.

17. O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. N Engl J Med. 1999;340(1):14–22.

18. Chambless LE, Heiss G, Folsom AR, Rosamond W, Szklo M, Sharrett AR et al. Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC). Study. Am J Epidemiol. 1997;146(6):483–494.

19. 9 . L o r e n z M W, M a r k u s H S , B o t s M L , R o s v a l l M , Sitzer M. Predictionof clinical cardiovascular events with carotid intima-media thickness: a systematic review and metaanalysis. Circulation. 2007;115(4):459–467.

20. Raghuveer G. Lifetime cardiovascular risk of childhood obesity. Am J Clin Nutr. 2010;91(5):1514S-1519S.

21. Kapiotis S, Holzer G, Schaller G, Haumer M, Widhalm H, Weghuber D et al. A proinflammatory state Isdetectable in o b e s e c h i l d r e n a n d i s a c c o m p a n i e d b y f u n c t i o n a l a n d morphological vascular changes. Arterioscler Thromb Vasc Biol. 2006;26(11):2541–2546.

22. Reinehr T, Kiess W, de Sousa G, Stoffel-Wagner B, Wunsch R. Intima media thickness in childhood obesity: Relations to inflammatory marker, glucose metabolism, and blood pressure. Metabolism. 2006;55,(1):113–118.

23. Karpoff L, Vinet A, Schuster I, Oudot C, Goret L, Dauzat M et al. Abnormal vascular reactivity at rest and exercise in obese boys. Eur J Clin Invest. 2009;39(2):94–102.

24. Urbina EM, Kimball TR, McCoy CE, Khoury PR, Daniels SR, Dolan LM. Youth With obesity and obesity-related type 2 diabetes mellitus demonstrate abnormalities in carotid structure and function. Circulation. 2009;119(22):2913–2919.

25. Dangardt F, Osika W, Volkmann R, Gan LM, Friberg P. Obese children show increased intimal wall thickness and decreased pulse wave velocity. Clin Physiol Funct Imaging. 2008;28(5):287–293.

26. Toledo-Corral C, Ventura E, Weigenberg M, Hodis H, Li Y, Goran M. Persistence of the metabolic syndrome and its influence on carotid artery intima media thickness in overweight Latino children. Atherosclerosis. 2009;206(2):594–598.

27. Davis PH, Dawson JD, Riley WA, Lauer RM. Carotid IntimalMedial Thickness Is Related to Cardiovascular Risk Factors Measured. From Childhood Through Middle Age: The Muscatine Study. Circulation. 2001;104(23):2815–2819.

28. McGill HC Jr, McMahan CA, Malcom GT, Oalmann MC, Strong JP. Relation of glycohemoglobin and adiposity to atherosclerosis in youth. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb Vasc Biol. 1995;15(4):431–440.

29. McGill HC Jr, McMahan CA, Malcom GT, Oalmann MC, Strong JP. Relation of glycohemoglobin and adiposity to atherosclerosis in youth: Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb Vasc Biol. 1995;15(4):431–440.

30. Berenson GS, Srinivasan SR, Bao W, Newman WP, Tracy RE, Wattigney WA. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N Engl J Med. 1998;338:1650–1656.

31. Haynes WG. Role of leptin in obesity-related hypertension. Exp Physiol. 2005;90(5):683–688.

32. Lуpez-Jaramillo P, Herrera E, Garcia RG, Camacho PA, Castillo VR. Inter-relationships between body mass index, C-reactive protein and blood pressure in a Hispanic pediatric population. Am J Hypertens. 2008;21:527–532.

33. Głowińska-Olszewska B, Tołwińska J, Urban M.Relationship between endothelial dysfunction, carotid artery intima media thickness and circulating markers of vascular inflammation in obese hypertensive children and adolescents. J Pediatr Endocrinol Metab. 2007;20:1125–1136.

34. Stumpf C, Jukic J, Yilmaz A, Raaz D, Schmieder RE, Daniel WG et al. Elevated VEGF-plasma levels in young patients with mild essential hypertension. Eur J Clin Invest. 2009;39:31–36.

35. Syrenicz A, Garanty-Bogacka B, Syrenicz M, Gebala A, Dawid G, Walczak M. Relation of low-grade inflammation and endothelial activation to blood pressure in obese children and adolescents. Neurol Endocrinol Lett. 2006;27(4):459–464.

36. Cottone S, Mulu G, Nardi E, Vadalа A, Guarneri M, Briolotta C et al. Relation of C-reactive protein to oxidative stress and to endothelial activation in essential hypertension. Am J Hypertens. 2006;19(3):313–318.

37. Reinehr T, Kiess W, de Sousa G, Stoffel-Wagner B, Wunsch R. Intima media thickness in childhood obesity: relations to inflammatory marker, glucose metabolism, and blood pressure. Metab Clin Exp 2006;55 (1):113–118.

38. Kampus P, Muda P, Kals J, Ristimae T, Fischer K, Teesalu R et al. The relationship between inflammation and arterial stiffness in patients with essential hypertension. Int J Cardiol. 2006;112(1):46–51.

39. Assadi F. C-reactive protein and incident left ventricular hypertrophy in essential hypertension. Pediatr Cardiol. 2007;28 (4):280–285.

40. Noronha JAF, CCM, Cardoso AdS, Gonzaga NC, Ramos AT, Ramos ALC. C-reactive protein and its relation to high blood pressure in overweight or obese children and adolescents. Rev Paul Pediatr. 2013;31(3):331–337.

41. Makni E, Moalla W, Benezzeddine-Boussaidi L, Lac G, Tabka Z, Elloumi M. Correlation of resistin with inflammatory and cardiometabolic markers in obese adolescents with and without metabolic syndrome. Obes Facts. 2013;6(4):393–404.

42. Howe LD, Chaturvedi N, Lawlor DA, Ferreira DL, Fraser A, Davey Smith G et al. Rapid increases in infant adiposity and overweight/obesity in childhood are associated with higher central and brachial blood pressure in early adulthood. J Hypertens. 2014;32(9):1789–1796.

43. Filler G, Rayar MS, da Silva O, Buffo I, Pepelassis D, Sharma AP. Should prevention of chronic kidney disease start before pregnancy? Int. Urol. Nephrol. 2008;40(2):483–488.

44. Clarke WR, Woolson RF, Lauer RM. Changes in ponderosity and blood pressure in childhood: the Muscatine Study. Am J Epidemiol. 1986;124(2):195–206.

45. Voors AW, Webber LS, Frerichs RR, Berenson GS. Body height and body mass as determinants of basal blood pressure in children — The Bogalusa Heart Study. Am J Epidemiol. 1977;106 (2):101–108.

46. Aristimuño GG, Foster TA, Voors AW, Srinivasan SR, Berenson GS. Influence of persistent obesity in children on cardiovascular risk factors: the Bogalusa Heart Study. Circulation. 1984;69(5):895–904.

47. Jiang X, Srinivasan SR, Urbina E, Berenson GS. Hyperdynamic circulation and cardiovascular risk in children and adolescents. The Bogalusa Heart Study. Circulation. 1995;91 (4):1101–1106.

48. Madrevica I, Ligere R, Krikis J. Determinant factors of arterial hypertension in school-age boys in Latvia. Endocrine Abstracts. 2002;4:DP9.

49. Muntner P, He J, Cutler JA, Wildman RP, Whelton PK. Trends in blood pressure among children and adolescents. J Am Med Assoc. 2004;291(17):2107–2113.

50. Weiss R, Dziura J, Burgert TS, Tamborlane WV, Taksali SE, Yeckel CW et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med. 2004;350(23):2362–2374.

51. Falkner B, Gidding SS, Ramirez-Garnica G, Wiltrout SA, West D, Rappaport EB. The relationship of body mass index and blood pressure in primary care pediatric patients. J Pediatr. 2006;148 (2):195–200.

52. Sorof JM, Lai D, Turner J, Poffenbarger T, Portman RJ. Overweight, ethnicity, and the prevalence of hypertension in schoolaged children. Pediatrics. 2004;113(3):475–481.

53. Lo JC, Chandra M, Sinaiko A, Daniels SR, Prineas RJ, Maring BInt J et al. Severe obesity in children: prevalence, persistence and relation to hypertension. Pediatr Endocrinol. 2014;2014(1):3.

54. Kim YK, Kim HU, Song JY. Ambulatory blood pressure monitoring and blood pressure load in obese children. Korean Circ J.

55. ;39(11):482–487.

56. Tekın N, Ersoy B, Coskun S, Tekın G, Polat M. Ambulatory blood pressure parameters in office normotensive obese and non-obese children: relationship with insulin resistance and atherosclerotic markers. Med Princ Pract. 2014;23(2):154–159.

57. Образцова Г. И., Гуркина Е. Ю. Артериальная гипертензия у детей с ожирением. Трансляционная медицина. 2012;1 (12):32–37. [Obraztsova GI, Gurkina EY. Arterial hypertension in children with obesity. Translyatsionnaya Medicina = Translational Medicine. 2012;1(12):32–37. In Russian].

58. Ben-Dov IZ, Bursztyn M. Ambulatory blood pressure monitoring in childhood and adult obesity. Curr Hypertens Rep. 2009;11(2):133–142.

59. Бекезин В. В., Козлова Л. В., Козлова И. С., Иголкина М. В. Особенности кардиоваскулярного синдрома у детей и подростков с ожирением в зависимости от уровня инсулинорезистентности. Кардиология. 2008;3:69–74. [Bekezin VV, Kozlova LV, Kozlova IS, Igolkina MV. Peculiarities cardiovascular syndrome in children and adolescents with obesity depending on level of insulin resistance. Cardiology. 2008;3:69–74. In Russian].

60. Александров А. А. Высокое артериальное давление у детей и подростков. Российский медицинский журнал. 1997;9:59–65. [Aleksandrov AA. High blood pressure in childhood and adolescence. Russian medical journal. 1997;9:59–65. In Russian].

61. Автандилов А. Г. Артериальная гипертензия у подростков мужского пола. Москва, Российская медицинская академия последипломного образования. 1997:285. [Avtandilov AG. Arterial hypertension in adolescent males. Moscow, Russian academy of postgraduate education. 1997:285. In Russian].

62. Verdecchia P, Schillaci G, Borgioni C, Ciucci A, Gattobigio R, Guerrieri M et al. Altered circadian blood pressure profile and prognosis. Blood Press. Monit. 1997;2(6):347–452.

63. Lanfranchi P, Somers VK. Obstructive sleep apnea and vascular disease. Respir Res. 2001;2(6):315–319.

64. Verhulst SL, van Gaal L, de Backer W, Desager K. The prevalence, anatomical correlates and treatment of sleep-disordered breathing in obese children and adolescents. Sleep Medicine Reviews. 2008;12(5):339–346.

65. Marcus L, Curtis S, Koerner CB, Joffe A, Serwint JR, Loughlin GM. Evaluation of pulmonary function and polysomnography in obese children and adolescents. Pediatr Pulmonol. 1996;21(3):176–183.

66. Silvestri JM, Weese-Mayer DE, Bass MT, Kenny AS, Hauptman SA, Pearsall SM. Polysomnography in obese children with a history of sleep-associated breathing disorders. Pediatric Pulmonology. 1993;16(2):124–129.

67. Leung L, Ng D, Lau M, Kwok K, Chow P, Cheung J. Twentyfour-hour ambulatory BP in snoring children with obstructive sleep apnea syndrome. Chest. 2006;130(4):1009–1017.

68. Laurer M, Anderson K, Kannel W, Levy D. The impact of obesity on left ventricle mass and geometry: the Framingham Heart Study. J Am Med Assoc. 1991;266(2):231–236.

69. Levy D, Murabito JM, Anderson KM. Echocardiographic left ventricular hypertrophy — clinical characteristics — the Framinghan Heart Study. Clin Exp Hypertens. 1992;14(1–2):85–97.

70. Vasan RS. Cardiac function and obesity. Heart. 2003; 89:1127–1129.

71. Daniels SR, Kimball TR, Morrison JA, Khoury P, Witt S, Meyer RA. Effect of lean body mass, fat mass, blood pressure, and sexual maturation on left ventricular mass in children and adolescents. Statistical, biological, and clinical significance. Circulation. 1995;92(11):3249–3254.

72. Kibar AE, Pac FA, Ballı S, Oflaz MB, Ece I, Bas VN et al. Early subclinical left-ventricular dysfunction in obese nonhypertensive children: a tissue Doppler imaging study. Pediatr Cardiol. 2013;34(6):1482–1490.

73. Ting Fei Ho. Cardiovascular risks associated with obesity in children and adolescents. Ann Acad Med Singapore. 2009;38 (1):48–49.

74. Di Salvo G, Pacileo G, Del Giudice EM, Natale F, Limongelli G, Verrengia M et al. Abnormal myocardial deformation properties in obese, non-hypertensive children: an ambulatory blood pressure monitoring, standard echocardiographic, and strain rate imaging study. Eur Heart J. 2006;27:2689–2695.

75. Villa MP, Ianniello F, Tocci G, Evangelisti M, Miano S, Ferrucci A et al. Early cardiac abnormalities and increased C-reactive protein levels in a cohort of children with sleep disordered breathing. Sleep Breath. 2012;16(1):101–110.

76. Attia G, Ahmad MA, Saleh AB, Elsharkawy A. Impact of obstructive sleep apnea on global myocardial performance in children assessed by tissue Doppler imaging. Pediatr Cardiol. 2010;31(7):1025–1036.

77. Hedvall Kallerman P, Hagman E, Edstedt Bonamy AK, Zemack H, Marcus C, Norman M et al. Obese children without comorbidities have impaired microvascular endothelial function. Acta Paediatr. 2014;103(4):411–417.

78. Joo Turoni C, Maraсуn RO, Felipe V, Bruno ME, Negrete A, Salas N et al. Arterial stiffness and endothelial function in obese children and adolescents and its relationship with cardiovascular risk factors. Horm Res Paediatr. 2013;80(4):281–286.

79. Khoury PR, Mitsnefes M, Daniels SR, Kimball TR. Agespecific reference intervals for indexed left ventricular mass in children. J Am Soc Echocardiogr. 2009;22(6):709–714.

80. Daniels SR, Meyer RA, Liang YC, Bove KE. Echocardiographically determined left ventricular mass index in normal children, adolescents and young adults. J Am Coll Cardiol. 1988;12(3):703–708.

81. Tudor-Locke C, Craig C, Beets M, Belton S, Cardon G, Duncan S et al. How many steps/day are enough? For children and adolescents. IJBNPA. 2011;8:78.

82. Национальные рекомендации по диагностике, лечению и профилактике гипертонии у детей и подростков (второй пересмотр). Обзор 2009. Сердечно-сосудистая терапия и профилактика. 2009;8(4). [National guidelines for diagnosis, treatment and prevention of hypertension in children and adolescents (second revision). Review of 2009. Cardiovascular therapy and prevention. 2009;8(4). In Russian].

83. Farpour-Lambert NJ, Aggoun Y, Marchand LM, Martin XE, Herrmann FR, Beghetti M. Physical activity reduces systemic blood pressure and improves early markers of atherosclerosis in pre-pubertal obese children. J Am Coll Cardiol. 2009;54(25):2396–2406.

84. Maggio AB, Aggoun Y, Martin XE, Marchand LM, Beghetti M, Farpour-Lambert NJ. Long-term follow-up of cardiovascular risk factors after exercise training in obese children. J Pediatr Obes. 2011;6(2–2): e603-e610.

85. Hopkins ND, Stratton G, Tinken TM, McWhannell N, Ridges ND, Graves LE et al. Relationships between measures of fitness, physical activity, body composition and vascular function in children. Atherosclerosis. 2009;204(1):244–249.

86. Meyer AA, Kundt G, Lenschow U, Schuff-Werner P, K i e n a s t W. I m p r o v e m e n t o f e a r l y v a s c u l a r c h a n g e s a n d cardiovascular risk factors in obese children after a six-month exercise program. J Am Coll Cardiol. 2006;48(9):1865–1870.

87. Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003;348 (7):593–600.

88. Park JH, Miyashita M, Kwon YC, Park HT, Kim EH, Park JK et al. A 12-week after-school physical activity programme improves endothelial cell function in overweight and obese children: a randomised controlled study. BMC Pediatr. 2012;12:111.

89. Barnes VA, Orme-Johnson DW. Clinical and Pre-clinical Applications of the Transcendental Meditation Program in the Prevention and Treatment of Essential Hypertension and Cardiovascular Disease in Youth and Adults. Curr Hypertens Rev.2006;2(3):207–218.

90. Трушкина И.В., Филиппов Г.П., Леонтьева И.В. Прогнозирование развития метаболического синдрома в подростковом возрасте. Педиатрия. Журнал им. Г.Н. Сперанского. 2010;89(5):33–36. [Trushkina IV, Filippov GP, Leontievа IV. Forecasting the development of the metabolicsyndrome in adolescence. Pediatrics. 2010:33–36. In Russian]. Pediatriia. Zhurnal imeni G.N. Speranskogo = Pediatrics. Journal n.a. G.N. Speranskii. 2010;89(5):33–36. In Russian].