High prevalence of cardiovascular risk factors in children and adolescents with Williams-Beuren syndrome

BMC Pediatrics

Rumiko Matsuoka³  Toshio Nakanishi²  Kei Inai¹  Yoshiyuki Furutani²  Yuriko Harada²  Michiko Furutani²  Daiji Takeuchi¹ 

[1] Department of Pediatric Cardiology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku 162-8666, Tokyo, Japan;The International Research and Educational Institute for Integrated Medical Sciences (IREIIMS), Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku 162-8666, Tokyo, Japan;International Center for Molecular, Cellular, and Immunological Research (IMCIR), Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku 162-8666, Tokyo, Japan

关键词: Elastin;    Adolescent;    Child;    Cardiovascular risk;    Williams-Beuren syndrome;   

Others  :  1225222
DOI  :  10.1186/s12887-015-0445-1

 received in 2014-07-10, accepted in 2015-09-09,  发布年份 2015

【 摘 要 】

Background

A high incidence of cardiovascular (CV) risk factors has been reported in adults with Williams-Beuren syndrome (WS). However, the prevalence of these factors in children and adolescents with WS is unknown. Therefore, the purpose of this study was to evaluate the prevalence of CV risk factors in these patients.

Methods

Thirty-two WS patients aged <18 years were enrolled in the study. Oxidized low-density lipoprotein levels (n = 32), oral glucose tolerance test results (n = 20), plasma renin and aldosterone levels (n = 31), 24-h ambulatory blood pressure (ABP; n = 24), carotid artery intima-media thickness (IMT; n = 15), and brachial artery flow-mediated dilatation (FMD; n = 15) were measured and analyzed.

Results

The lipid profile revealed hypercholesterolemia in 22 % and elevated oxidized low-density lipoprotein levels in 94 % of the patients. Glucose metabolism abnormalities were found in 70 % of the patients. Insulin resistance was observed in 40 % of the patients. High plasma renin and aldosterone levels were detected in 45 and 39 % of the patients, respectively. A mean systolic blood pressure above the 90th percentile was noted in 29 % of patients. High IMT (>0.65 mm) and low FMD (<9 %) were detected in 80 and 73 % of patients, respectively.

Conclusion

In patients with WS, CV risk factors are frequently present from childhood. In children with WS, screening tests for the early detection of CV risk factors and long-term follow-up are required to determine whether long-term exposure to these factors increases the risk for CV events in adulthood.

【 授权许可】

   
2015 Takeuchi et al.

【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

【 参考文献 】

• [1]Williams JC, Barratt-Boyes BG, Lowe JB. Supravalvular aortic stenosis. Circulation. 1961; 24:1311-1318.
• [2]Ji C, Yao D, Chen W, Li M, Zhao Z. Adaptive behavior in Chinese children with Williams syndrome. BMC Pediatr. 2014; 14:90. BioMed Central Full Text
• [3]Ewart AK, Morris CA, Atkinson D, Jin W, Sternes K, Spallone P, Stock AD, Leppert M, Keating MT. Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome. Nat Genet. 1993; 5(1):11-16.
• [4]Kotzot D, Bernasconi F, Brecevic L, Robinson WP, Kiss P, Kosztolanyi G, Lurie IW, Superti-Furga A, Schinzel A. Phenotype of the Williams-Beuren syndrome associated with hemizygosity at the elastin locus. Eur J Pediatr. 1995; 154(6):477-482.
• [5]Pober BR, Morris CA. Diagnosis and management of medical problems in adults with Williams-Beuren syndrome. Am J Med Genet C Semin Med Genet. 2007; 145(3):280-290.
• [6]Kimura K, Hirota H, Nishikawa T, Ishiyama S, Imamura S, Korenberg JR, Mizuno K, Nakayama T, Akagawa K, Shimizu N et al.. Chromosomal deletion and Phenotype correlation in patients with Williams syndrome. In: Etiology and morphogenesis of congenital heart disease: twenty years of progress in genetics and developmental biology. edn. Edward B, Clark M, Makoto Nakazawa MD, Atsuyoshi Takao MD, editors. Futura Publishing, Armonk, NY; 2000: p.381-384.
• [7]Screening for type 2 diabetes. Diabetes Care. 2004; 27 Suppl 1:S11-14.
• [8]The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004; 114(2 Suppl 4th Report):555-576.
• [9]Sadler LS, Gingell R, Martin DJ. Carotid ultrasound examination in Williams syndrome. J Pediatr. 1998; 132(2):354-356.
• [10]Rein AJ, Preminger TJ, Perry SB, Lock JE, Sanders SP. Generalized arteriopathy in Williams syndrome: an intravascular ultrasound study. J Am Coll Cardiol. 1993; 21(7):1727-1730.
• [11]Bohm B, Hartmann K, Buck M, Oberhoffer R. Sex differences of carotid intima-media thickness in healthy children and adolescents. Atherosclerosis. 2009; 206(2):458-463.
• [12]Juonala M, Viikari JS, Laitinen T, Marniemi J, Helenius H, Ronnemaa T, Raitakari OT. Interrelations between brachial endothelial function and carotid intima-media thickness in young adults: the cardiovascular risk in young Finns study. Circulation. 2004; 110(18):2918-2923.
• [13]Collins RT, Kaplan P, Somes GW, Rome JJ. Long-term outcomes of patients with cardiovascular abnormalities and williams syndrome. Am J Cardiol. 2010; 105(6):874-878.
• [14]Dridi SM, Foucault Bertaud A, Igondjo Tchen S, Senni K, Ejeil AL, Pellat B, Lyonnet S, Bonnet D, Charpiot P, Godeau G. Vascular wall remodeling in patients with supravalvular aortic stenosis and Williams Beuren syndrome. J Vasc Res. 2005; 42(3):190-201.
• [15]Ingelfinger JR, Newburger JW. Spectrum of renal anomalies in patients with Williams syndrome. J Pediatr. 1991; 119(5):771-773.
• [16]Pober BR, Johnson M, Urban Z. Mechanisms and treatment of cardiovascular disease in Williams-Beuren syndrome. J Clin Invest. 2008; 118(5):1606-1615.
• [17]Cherniske EM, Carpenter TO, Klaiman C, Young E, Bregman J, Insogna K, Schultz RT, Pober BR. Multisystem study of 20 older adults with Williams syndrome. Am J Med Genet A. 2004; 131 A(3):255-264.
• [18]Bedeschi MF, Bianchi V, Colli AM, Natacci F, Cereda A, Milani D, Maitz S, Lalatta F, Selicorni A. Clinical follow-up of young adults affected by Williams syndrome: Experience of 45 Italian patients. Am J Med Genet A. 2011; 155(2):353-359.
• [19]Amenta S, Sofocleous C, Kolialexi A, Thomaidis L, Giouroukos S, Karavitakis E, Mavrou A, Kitsiou S, Kanavakis E, Fryssira H. Clinical manifestations and molecular investigation of 50 patients with Williams syndrome in the Greek population. Pediatr Res. 2005; 57(6):789-795.
• [20]Juonala M, Magnussen CG, Venn A, Dwyer T, Burns TL, Davis PH, Chen W, Srinivasan SR, Daniels SR, Kahonen M et al.. Influence of age on associations between childhood risk factors and carotid intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study, the Childhood Determinants of Adult Health Study, the Bogalusa Heart Study, and the Muscatine Study for the International Childhood Cardiovascular Cohort (i3C) Consortium. Circulation. 2010; 122(24):2514-2520.
• [21]Nadal-Ginard BTK. Prevalence of risk factors of cardiovascular events, and the effects of a natural food diet, ascorbate and vitamine E to prevent the progression of arteriopathy in Williams syndrome. International Research and Educational instutute for Integrated medical Sciences (IREIMS) Tokyo Women’s Medical University, Tokyo; 2007.
• [22]Esterbauer H, Schmidt R, Hayn M. Relationships among oxidation of low-density lipoprotein, antioxidant protection, and atherosclerosis. Adv Pharmacol. 1997; 38:425-456.
• [23]Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989; 320(14):915-924.
• [24]Pober BR, Wang E, Caprio S, Petersen KF, Brandt C, Stanley T, Osborne LR, Dzuria J, Gulanski B. High prevalence of diabetes and pre-diabetes in adults with Williams syndrome. Am J Med Genet C Semin Med Genet. 2010; 154C(2):291-298.
• [25]Fulop T, Larbi A, Fortun A, Robert L, Khalil A. Elastin peptides induced oxidation of LDL by phagocytic cells. Pathol Biol (Paris). 2005; 53(7):416-423.
• [26]Vantrimpont P, Rouleau JL, Ciampi A, Harel F, de Champlain J, Bichet D, Moye LA, Pfeffer M. Two-year time course and significance of neurohumoral activation in the Survival and Ventricular Enlargement (SAVE) Study. Eur Heart J. 1998; 19(10):1552-1563.
• [27]Del Campo M, Antonell A, Magano LF, Munoz FJ, Flores R, Bayes M, Perez Jurado LA. Hemizygosity at the NCF1 gene in patients with Williams-Beuren syndrome decreases their risk of hypertension. Am J Hum Genet. 2006; 78(4):533-542.
• [28]Campuzano V, Segura-Puimedon M, Terrado V, Sanchez-Rodriguez C, Coustets M, Menacho-Marquez M, Nevado J, Bustelo XR, Francke U, Perez-Jurado LA. Reduction of NADPH-oxidase activity ameliorates the cardiovascular phenotype in a mouse model of Williams-Beuren Syndrome. PLoS Genet. 2012; 8(2):e1002458.
• [29]Kawai M, Nishikawa T, Tanaka M, Ando A, Kasajima T, Higa T, Tanikawa T, Kagawa M, Momma K. An autopsied case of Williams syndrome complicated by moyamoya disease. Acta Paediatr Jpn. 1993; 35(1):63-67.
• [30]Raitakari OT, Juonala M, Kahonen M, Taittonen L, Laitinen T, Maki-Torkko N, Jarvisalo MJ, Uhari M, Jokinen E, Ronnemaa T et al.. Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study. JAMA. 2003; 290(17):2277-2283.
• [31]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):792-799.
• [32]Babar GS, Zidan H, Widlansky ME, Das E, Hoffmann RG, Daoud M, Alemzadeh R. Impaired endothelial function in preadolescent children with type 1 diabetes. Diabetes Care. 2011; 34(3):681-685.
• [33]Yilmazer MM, Tavli V, Carti OU, Mese T, Guven B, Aydin B, Devrim I, Tavli T. Cardiovascular risk factors and noninvasive assessment of arterial structure and function in obese Turkish children. Eur J Pediatr. 2010; 169(10):1241-1248.
• [34]Jarvisalo MJ, Raitakari M, Toikka JO, Putto-Laurila A, Rontu R, Laine S, Lehtimaki T, Ronnemaa T, Viikari J, Raitakari OT. Endothelial dysfunction and increased arterial intima-media thickness in children with type 1 diabetes. Circulation. 2004; 109(14):1750-1755.
• [35]Yanagi H, Hamaguchi H, Shimakura Y, Hirano C, Takita H, Tsuchiya S, Yoshiwara C. Cardiovascular risk factors among Japanese school-age children: a screening system for children with high risk for atherosclerosis in Ibaraki, Japan. Nihon Koshu Eisei Zasshi. 1993; 40(12):1120-1128.
• [36]Kelishadi R, Hashemi M, Mohammadifard N, Asgary S, Khavarian N. Association of changes in oxidative and proinflammatory states with changes in vascular function after a lifestyle modification trial among obese children. Clin Chem. 2007; 54(1):147-153.
• [37]McGowan SE, Doro MM, Jackson SK. Endogenous retinoids increase perinatal elastin gene expression in rat lung fibroblasts and fetal explants. Am J Physiol. 1997; 273(2 Pt 1):L410-416.
• [38]Pierce RA, Mariencheck WI, Sandefur S, Crouch EC, Parks WC. Glucocorticoids upregulate tropoelastin expression during late stages of fetal lung development. Am J Physiol. 1995; 268(3 Pt 1):L491-500.
• [39]Tsoporis J, Keeley FW, Lee RM, Leenen FH. Arterial vasodilation and vascular connective tissue changes in spontaneously hypertensive rats. J Cardiovasc Pharmacol. 1998; 31(6):960-962.
• [40]Sluijter JP, de Kleijn DP, Pasterkamp G. Vascular remodeling and protease inhibition--bench to bedside. Cardiovasc Res. 2006; 69(3):595-603.
• [41]Tinker D, Rucker RB. Role of selected nutrients in synthesis, accumulation, and chemical modification of connective tissue proteins. Physiol Rev. 1985; 65(3):607-657.
• [42]Jimenez F, Mitts TF, Liu K, Wang Y, Hinek A. Ellagic and tannic acids protect newly synthesized elastic fibers from premature enzymatic degradation in dermal fibroblast cultures. J Invest Dermatol. 2006; 126(6):1272-1280.
• [43]American Academy of Pediatrics: Health care supervision for children with Williams syndrome. Pediatrics. 2001; 107(5):1192-1204.