Original article
Vol. 147 No. 2122 (2017)
Markers of subclinical atherosclerosis in schoolchildren with obesity and metabolic syndrome
Summary
BACKGROUND
Although increased carotid intima-media thickness (cIMT), soluble adhesion molecules and proinflammatory biomarkers are strongly implicated in the development of atherosclerotic lesions, the role of obesity and metabolic syndrome (MetS) in atherogenicity and inflammation among schoolchildren is not well investigated.
AIM
To determine the levels of cIMT, endothelial dysfunction and inflammatory biomarkers in a group of schoolchildren with obesity and MetS.
METHODS
Eighty-seven schoolchildren (age 10–15 years) were categorised into three groups: normal bodyweight group, obese group and severely obese with MetS group (17 boys and 12 girls in each group). Levels of cIMT were measured with high-resolution B-mode ultrasound. Serum proinflammatory cytokines interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), and soluble adhesion molecules E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1(ICAM-1) were measured.
RESULTS
Mean cIMT levels were significantly higher (p ≤0.05) among severely obese schoolchildren with MetS (0.49 ± 0.02 mm) compared with both the obese (0.43 ± 0.03 mm) and the normal bodyweight counterparts (0.36 ± 0.03 mm). Serum levels of IL-6, TNF-α, IL-1β, E-selectin, VCAM-1 and ICAM-1 were significantly higher (p ≤0.05) in severely obese with MetS and obese children compared with the normal bodyweight group. However, no significant differences (p >0.05) were found between the severely obese schoolchildren with MetS and the obese without MetS.
CONCLUSIONS
Severely obese schoolchildren having MetS exhibited higher cIMT levels than obese and normal bodyweight counterparts. Biomarkers of inflammation and endothelial dysfunction were higher in obese schoolchildren, but biomarkers were not increased any further by the degree of obesity nor the MetS cluster.
References
- Elkiran O, Yilmaz E, Koc M, Kamanli A, Ustundag B, Ilhan N. The association between intima media thickness, central obesity and diastolic blood pressure in obese and overweight children: a cross-sectional school-based study. Int J Cardiol. 2013;165(3):528–32. https://doi.org/10.1016/j.ijcard.2011.09.080
- Iannuzzi A, Licenziati MR, Acampora C, Salvatore V, Auriemma L, Romano ML, et al. Increased carotid intima-media thickness and stiffness in obese children. Diabetes Care. 2004;27(10):2506–8. https://doi.org/10.2337/diacare.27.10.2506
- Zimmet P, Alberti KGM, Kaufman F, Tajima N, Silink M, Arslanian S, et al.; IDF Consensus Group. The metabolic syndrome in children and adolescents - an IDF consensus report. Pediatr Diabetes. 2007;8(5):299–306. https://doi.org/10.1111/j.1399-5448.2007.00271.x
- Juonala M, Singh GR, Davison B, van Schilfgaarde K, Skilton MR, Sabin MA, et al. Childhood metabolic syndrome, inflammation and carotid intima-media thickness. The Aboriginal Birth Cohort Study. Int J Cardiol. 2016;203:32–6. https://doi.org/10.1016/j.ijcard.2015.10.073
- Novo S, Peritore A, Guarneri FP, Corrado E, Macaione F, Evola S, et al. Metabolic syndrome (MetS) predicts cardio and cerebrovascular events in a twenty years follow-up. A prospective study. Atherosclerosis. 2012;223(2):468–72. https://doi.org/10.1016/j.atherosclerosis.2012.05.018
- Esser N, Legrand-Poels S, Piette J, Scheen AJ, Paquot N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract. 2014;105(2):141–50. https://doi.org/10.1016/j.diabres.2014.04.006
- Vanlancker T, Schaubroeck E, Vyncke K, Cadenas-Sanchez C, Breidenassel C, González-Gross M, et al.; HELENA project group. Comparison of definitions for the metabolic syndrome in adolescents. The HELENA study. Eur J Pediatr. 2017;176(2):241–52. https://doi.org/10.1007/s00431-016-2831-6
- Morrison JA, Friedman LA, Gray-McGuire C. Metabolic syndrome in childhood predicts adult cardiovascular disease 25 years later: the Princeton Lipid Research Clinics Follow-up Study. Pediatrics. 2007;120(2):340–5. https://doi.org/10.1542/peds.2006-1699
- McGill HC, Jr, McMahan CA, Herderick EE, Malcom GT, Tracy RE, Strong JP, Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Origin of atherosclerosis in childhood and adolescence. Am J Clin Nutr. 2000;72(5, Suppl):1307S–15S.
- Civilibal M, Duru NS, Elevli M. Subclinical atherosclerosis and ambulatory blood pressure in children with metabolic syndrome. Pediatr Nephrol. 2014;29(11):2197–204. https://doi.org/10.1007/s00467-014-2836-1
- Caballero AE, Bousquet-Santos K, Robles-Osorio L, Montagnani V, Soodini G, Porramatikul S, et al. Overweight Latino children and adolescents have marked endothelial dysfunction and subclinical vascular inflammation in association with excess body fat and insulin resistance. Diabetes Care. 2008;31(3):576–82. https://doi.org/10.2337/dc07-1540
- Dalla Pozza R, Ehringer-Schetitska D, Fritsch P, Jokinen E, Petropoulos A, Oberhoffer R ; Association for European Paediatric Cardiology Working Group Cardiovascular Prevention. Intima media thickness measurement in children: A statement from the Association for European Paediatric Cardiology (AEPC) Working Group on Cardiovascular Prevention endorsed by the Association for European Paediatric Cardiology. Atherosclerosis. 2015;238(2):380–7. https://doi.org/10.1016/j.atherosclerosis.2014.12.029
- Desideri G, De Simone M, Iughetti L, Rosato T, Iezzi ML, Marinucci MC, et al. Early activation of vascular endothelial cells and platelets in obese children. J Clin Endocrinol Metab. 2005;90(6):3145–52. https://doi.org/10.1210/jc.2004-1741
- Montero D, Walther G, Perez-Martin A, Roche E, Vinet A. Endothelial dysfunction, inflammation, and oxidative stress in obese children and adolescents: markers and effect of lifestyle intervention. Obes Rev. 2012;13(5):441–55. https://doi.org/10.1111/j.1467-789X.2011.00956.x
- Landgraf K, Rockstroh D, Wagner IV, Weise S, Tauscher R, Schwartze JT, et al. Evidence of early alterations in adipose tissue biology and function and its association with obesity-related inflammation and insulin resistance in children. Diabetes. 2015;64(4):1249–61. https://doi.org/10.2337/db14-0744
- Jacobs M, van Greevenbroek MM, van der Kallen CJH, Ferreira I, Blaak EE, Feskens EJ, et al. Low-grade inflammation can partly explain the association between the metabolic syndrome and either coronary artery disease or severity of peripheral arterial disease: the CODAM study. Eur J Clin Invest. 2009;39(6):437–44. https://doi.org/10.1111/j.1365-2362.2009.02129.x
- Ritchie SA, Connell JM. The link between abdominal obesity, metabolic syndrome and cardiovascular disease. Nutr Metab Cardiovasc Dis. 2007;17(4):319–26. https://doi.org/10.1016/j.numecd.2006.07.005
- World health organization (WHO). (2007). Growth reference 5-19 years. URL http://www.who.int/growthref/who2007_bmi_for_age/en/.
- Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, Flegal KM, Guo SS, Wei R, et al. CDC growth charts: United States. Adv Data. 2000;314(314):1–27.
- Fryar CD, Gu Q, Ogden CL. Anthropometric reference data for children and adults: United States, 2007-2010. Vital Health Stat 11. 2012;252(252):1–48.
- Park MH, Skow Á, De Matteis S, Kessel AS, Saxena S, Viner RM, et al. Adiposity and carotid-intima media thickness in children and adolescents: a systematic review. BMC Pediatr. 2015;15(1):161. https://doi.org/10.1186/s12887-015-0478-5
- Cruickshank JK, Mzayek F, Liu L, Kieltyka L, Sherwin R, Webber LS, et al. Origins of the “black/white” difference in blood pressure: roles of birth weight, postnatal growth, early blood pressure, and adolescent body size: the Bogalusa heart study. Circulation. 2005;111(15):1932–7. https://doi.org/10.1161/01.CIR.0000161960.78745.33
- Chowdhury SM, Henshaw MH, Friedman B, Saul JP, Shirali GS, Carter J, et al. Lean body mass may explain apparent racial differences in carotid intima-media thickness in obese children. J Am Soc Echocardiogr. 2014;27(5):561–7. https://doi.org/10.1016/j.echo.2014.01.007
- Tzou WS, Douglas PS, Srinivasan SR, Bond MG, Tang R, Chen W, et al. Increased subclinical atherosclerosis in young adults with metabolic syndrome: the Bogalusa Heart Study. J Am Coll Cardiol. 2005;46(3):457–63. https://doi.org/10.1016/j.jacc.2005.04.046
- Gøbel RJ, Jensen SM, Frøkiaer H, Mølgaard C, Michaelsen KF. Obesity, inflammation and metabolic syndrome in Danish adolescents. Acta Paediatr. 2012;101(2):192–200. https://doi.org/10.1111/j.1651-2227.2011.02493.x
- Muniyappa R, Sowers JR. Role of insulin resistance in endothelial dysfunction. Rev Endocr Metab Disord. 2013;14(1):5–12. https://doi.org/10.1007/s11154-012-9229-1
- Okazaki S, Sakaguchi M, Miwa K, Furukado S, Yamagami H, Yagita Y, et al. Association of interleukin-6 with the progression of carotid atherosclerosis: a 9-year follow-up study. Stroke. 2014;45(10):2924–9. https://doi.org/10.1161/STROKEAHA.114.005991
- Wild RA, Wu C, Curb JD, Martin LW, Phillips L, Stefanick M, et al. Coronary heart disease events in the Women’s Health Initiative hormone trials: effect modification by metabolic syndrome: a nested case-control study within the Women’s Health Initiative randomized clinical trials. Menopause. 2013;20(3):254–60.
- Maggio AB, Wacker J, Montecucco F, Galan K, Pelli G, Mach F, et al. Serum resistin and inflammatory and endothelial activation markers in obese adolescents. J Pediatr. 2012;161(6):1022–7 e1. https://doi.org/10.1016/j.jpeds.2012.05.063
- Ritchie SA, Connell JMC. The link between abdominal obesity, metabolic syndrome and cardiovascular disease. Nutr Metab Cardiovasc Dis. 2007;17(4):319–26. https://doi.org/10.1016/j.numecd.2006.07.005
- Libby P. Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol. 2012;32(9):2045–51. https://doi.org/10.1161/ATVBAHA.108.179705
- Kapiotis S, Holzer G, Schaller G, Haumer M, Widhalm H, Weghuber D, et al. 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. https://doi.org/10.1161/01.ATV.0000245795.08139.70
- Olza J, Aguilera CM, Gil-Campos M, Leis R, Bueno G, Valle M, et al. A continuous metabolic syndrome score is associated with specific biomarkers of inflammation and CVD risk in prepubertal children. Ann Nutr Metab. 2015;66(2-3):72–9. https://doi.org/10.1159/000369981
- Magnussen CG, Koskinen J, Chen W, Thomson R, Schmidt MD, Srinivasan SR, et al. Pediatric metabolic syndrome predicts adulthood metabolic syndrome, subclinical atherosclerosis, and type 2 diabetes mellitus but is no better than body mass index alone: the Bogalusa Heart Study and the Cardiovascular Risk in Young Finns Study. Circulation. 2010;122(16):1604–11. https://doi.org/10.1161/CIRCULATIONAHA.110.940809
- Kassi E, Pervanidou P, Kaltsas G, Chrousos G. Metabolic syndrome: definitions and controversies. BMC Med. 2011;9(1):48. https://doi.org/10.1186/1741-7015-9-48