Abstract
The objective of this study was to test the hypothesis that accelerated endothelial dysfunction and the development of premature atherosclerosis are associated with age in subjects with coronary artery lesions after Kawasaki disease (KD). A case-control study was performed at a university hospital that included 35 post-KD subjects across a wide age range (range, 8–42 years) without traditional cardiovascular risk factors and 35 age- and sex-matched healthy control subjects (Cont). Flow-mediated dilatation (FMD) of the brachial artery-induced by reactive hyperemia, intima media thickness (IMT), and elastic modulus (Ep) of the common carotid artery were compared between KD and Cont subjects assessed against age. KD subjects had slightly higher levels of body mass index, lipid profile, and HbA1c than Cont subjects, but the differences were not significant. The mean IMT (p < 0.001), age-adjusted percentage normal IMT (%N IMT; p < 0.0001), and Ep (p < 0.001) were significantly higher in KD than Cont subjects, and the peak FMD% (p < 0.01) was significantly lower in KD than Cont subjects. There were significant correlations between FMD% and age (r = −0.51 p < 0.0001), IMT and age (r = 0.68, p < 0.001), and Ep and age (r = 0.58, p < 0.01) in KD but not Cont subjects. When the difference in FMD% between KD and matched Cont subjects (ΔFMD%) was plotted against age, no significant relationship was found, although significant correlations between ΔIMT and age (r = 0.52, p < 0.01) as well as between ΔEp and age (r = 0.46, p < 0.05) were observed. When we defined values that were +2.0 SD over the mean control values (i.e., %N IMT ≥ 120% and/or Ep ≥ 50 kPa) as markers of subclinical atherosclerosis, 15 subjects met the criteria. Subjects over the age of 22 years were more likely to have (OR = 16.54, p = 0.0001) subclinical atherosclerosis in this cohort. Our results suggest that endothelial dysfunction and the development of premature atherosclerosis were accelerated in adult post-KD compared to Cont subjects.
Similar content being viewed by others
Abbreviations
- CAL:
-
Coronary artery lesion
- CRFs:
-
Cardiovascular risk factors
- Ep:
-
Elastic modulus
- FMD:
-
Flow-mediated dilatation
- IMT:
-
Intima-media thichness
- KD:
-
Kawasaki disease
References
Bhagat K, Moss R, Collier J, Vallance P (1996) Endothelial “stunning” following a brief exposure to endotoxin: a mechanism to link infection and infarction? Cardiovasc Res 32:822–829
Cabana VG, Gidding SS, Getz GS, Chapman J, Shulman ST (1997) Serum amyloid A and high density lipoprotein participate in the acute phase response of Kawasaki disease. Pediatr Res 42:651–655
Cheung YF, Ho MH, Tam SC, Young TC (2004) Increased high sensitivity C reactive protein concentrations and increased arterial stiffness in children with a history of Kawasaki disease. Heart 90:1281–1285
Cheung YF, Wong SJ, Ho MH (2007) Relationship between carotid intima-media thickness and arterial stiffness in children after Kawasaki disease. Arch Dis Child 92:43–47
Cheung YF, Young TC, Ho MH, Chau AK (2004) Novel and traditional cardiovascular risk factors in children after Kawasaki disease. J Am Coll Cardiol 43:120–124
Della Pozza R, Bechtold S, Urshel S, Kozlik-Feldmann R, Netz H (2007) Subclinical atherosclerosis, but normalautonomic function after Kawasaki disease. J Pediatr 151:239–243
Dhillon R, Clarkson P, Donald AE, Powe AJ, Nash M, Novelli V, Dillon MJ, Deanfield JE (1996) Endothelial dysfunction late after Kawasaki disease. Circulation 94:2103–2106
Heiss G, Sharrett AR, Barnes R, Chambless LE, Szklo M, Alzola C (1991) Carotid atherosclerosis measured by B-mode ultrasound in populations: association with cardiovascular risk factors in the ARIC study. Am J Epidemiol 134:250–256
Herrington DM, Fan L, Drum M, Riley WA, Pusser BE, Crouse JR, Burke GL, McBurnie MA, Morgan TM, Espeland MA (2001) Brachial flow-mediated vasodilatator responses in population-based research: methods, reproducibility and effects of age, gender and baseline diameter. J Cardiovasc Risk 8:319–328
Ikemoto Y, Ogini H, Teraguchi M, Kobayashi Y (2005) Evaluation of preclinical atherosclerosis by flow-mediated dilatation of the brachial artery and carotid artery analysis in patients with a history Kawasaki disease. Pediatr Cardiol 26:782–786
Imanaga I, Hara H, Koyanagi S, Tanaka K (1998) Correlation between wave components of the second derivative of plethysmogram and arterial distensibility. Jpn Heart J 39:775–784
Juonala M, Kähönen M, Laitinen T, Hutri- Kähönen N, Jokinen E, Taittonen L, Pietikäinen M, Helenius H, Viikari JSA, Raitakari OT (2008) Effect of age and sex on carotid intima-media thickness, elasticity and brachial endothelial function in healthy adults: the cardiovascular risk in young Finns study. Eur Heart J 29:1198–1206
Kato H, Ichinose E, Yoshioka F, Takechi T, Matsunaga S, Suzuki K, Rikitake N (1982) Fate of coronary aneurysms in Kawasaki disease: serial coronary angiography and long-term follow-up study. Am J Cardiol 49:1758–1766
McCrindle BW, McIntyre S, Kim C, Lin T, Adeli K (2007) Are patients after Kawasaki disease at increased risk for accelerated atherosclerosis? J Pediatr 151:244–248
McGill HC Jr, McMahan CA, Herderick EE, Tracy RE, Malcom GT, Zieske AW, Strong JP (2000) Effects of coronary heart disease risk factors on atherosclerosis of selected regions the aorta and right coronary artery: PDAY Research Group: pathobiological determinants of atherosclerosis in youth. Arterioscler Thromb Vasc Biol 20:836–845
Mitani Y, Sawada H, Hayakawa H, Aoki K, Ohashi H, Matsumura M, Kuroe K, Shimpo H, Nakano M, Komada Y (2005) Elevated levels of hight-sensitivity C-reactive protein and serum amyloid-A late after Kawasaki disease: association between inflammation and coronary sequelae in Kawasaki disease. Circulation 111:38–43
Newberger JW, Burns JC, Beiser AS, Loscalzo J (1991) Alterd lipid profile after Kawasaki syndrome. Circulation 84:625–631
Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, Shulman ST, Bolger AF, Ferrieri P, Baltimore RS, Wilson WR, Baddour LM, Levison ME, Pallasch TJ, Falace DA, Taubert KA (2004) Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the committee on rheumatic fever, endocardiitis, and Kawasaki disease, council on cardiovascular disease in the young, American Heart Association. Pediatrics 114:1708–1733
Noto N, Okada T, Yamasuge M, Taniguchi K, Karasawa K, Ayusawa M, Sumitomo N, Harada K (2001) Noninvasive assessment of the early progression of atherosclerosis in adolescents with Kawasaki disease and coronary artery lesions. Pediatrics 107:1095–1099
Ooyanagi R, Fuse S, Tomita H, Takamuro M, Horita N, Mori M, Tsutsumi H (2004) Pulse wave velocity and ankle brachial index in patients with Kawasaki disease. Peditr Int 46:398–402
Peterson LH, Jensen RE, Parnell J (1960) Mechanical properties of arteries in vivo. Circ Res 8:622–639
Silva AA, Maeno Y, Hashimi A, Smallhorn JF, Silverman ED, McCrindle BW (2001) Cardiovascular risk factors after Kawasaki disease: a case–control study. J Pediatr 138:400–405
Strong WB, Deckelbaum RJ, Gidding SS, Kavey RE, Washington R, Wilmore JH, Perry CL (1992) Integrated cardiovascular health promotion in childhood. A statement for health professionals from the subcommittee on atherosclerosis and hypertension in childhood of the council on cardiovascular disease in the young, American Heart Association. Circulation 85:1638–1650
Suzuki A, Miyagawa-Tomita S, Komatsu K, Nishikawa T, Sakomura Y, Horie T, Nakazawa M (2000) Active remodeling of the coronary arterial lesions in the late phase of Kawasaki disease: immunohistochemical study. Circulation 27:2935–2941
Takahashi K, Oharaseki T, Naoe S (2001) Pathological study of postcoronary arteritis in adolescents and young adults: with reference to the relationship between sequelae of Kawasaki disease and atherosclerosis. Pediatr Cardiol 22:138–142
Tiemey ESS, Newbwerger JW (2007) Are patients with Kawasaki disease at risk for premature atherosclerosis? J Pediatr 151:225–228
Vita JA, Treasure CB, Nabel EG, McLenachan JM, Fish RD, Yeung AC, Vekshtein VI, Selwyn AP, Ganz P (1990) Coronary vasomotor response toacetylcholine relates to risk factors for coronary artery disease. Circulation 81:491–497
Wiegman A, Groot ED, Hutten BA, Rodenberg J, Gort J, Bakker HD, Sijbrands EJ, Kastelein JJ (2004) Arterial intima-media thickness in children heterozygous for familial hypercholesterolaemia. Lancet 363:369–370
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Noto, N., Okada, T., Karasawa, K. et al. Age-Related Acceleration of Endothelial Dysfunction and Subclinical Atherosclerosis in Subjects with Coronary Artery Lesions After Kawasaki Disease. Pediatr Cardiol 30, 262–268 (2009). https://doi.org/10.1007/s00246-008-9329-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00246-008-9329-6