Skip to main content Accesibility Help

Long-term evaluation of endothelial function in Kawasaki disease patients

  • Fátima F. Pinto (a1), Sérgio Laranjo (a1), Filipa Paramés (a1), Isabel Freitas (a1) and Miguel Mota-Carmo (a2)...

Kawasaki disease is an acute systemic vasculitis. Cardiac complications are frequent and include endothelial dysfunction in patients with coronary anomalies. So far, the presence of endothelial dysfunction in patients with no coronary lesions has not been demonstrated. Peripheral arterial tonometry (Endo-PAT) measures the microvascular function in response to local ischaemia and has been validated in adult population, but its use in children is scarce.


To evaluate endothelial dysfunction in children as a long-term complication after Kawasaki disease using Endo-PAT.


We evaluated two groups of subjects: (1) Kawasaki disease patients over 11 years of age, diagnosed for >5 years, with no coronary lesions, or any other risk factors for cardiovascular disease; (2) control group of individuals without cardiovascular risk factors. Patients and controls were clinically accessed. Endo-PAT was performed to determine reactive hyperaemia index and augmentation index.


A total of 35 individuals (21 males, age 21 ± 6 years) were evaluated (group 1: 19; controls: 16). Kawasaki disease patients presented significant lower reactive hyperaemia index (1.68 ± 0.49 versus 2.31 ± 0.53; p = 0.001). Augmentation index was similar in both groups (−10 ± 7 versus −11 ± 5; p > 0.005). Most patients with Kawasaki disease disclosed endothelial dysfunction (68%) compared with only 12% in controls.


Endo-PAT is feasible and reproducible in the child population. Endothelial dysfunction is a frequent long-term complication in patients after Kawasaki disease with normal appearing coronary arteries. However, these results need validation in a larger population.

Corresponding author
Correspondence to: Fátima F. Pinto, MD, Serviço de Cardiologia Pediátrica, Hospital de Santa Marta, Centro Hospitalar de Lisboa Central, EPE, Rua de Santa Marta, 1169-024 Lisboa, Portugal. Tel: +213594332; Fax: +213594034; E-mail:
Hide All
1. Taubert, KA, Rowley, AH, Shulman, ST. Nationwide survey of Kawasaki disease and acute reactive hyperaemia rheumatic fever. J Pediatr 1991; 119: 279282.
2. Newburger, JW, Takahashi, M, Gerber, MA, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Circulation 2004; 110: 27472771.
3. Kawasaki, T, Kosaki, F, Okawa, S, Shigematsu, I, Yanagawa, H. A new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan. Pediatrics 1974; 54: 271276.
4. Iemura, M, Ishii, M, Sugimura, T, Akagi, T, Kato, H. Long term consequences of regressed coronary aneurysms after Kawasaki disease: vascular wall morphology and function. Heart 2000; 83: 307311.
5. Noto, N, Okada, T, Yamasuge, M, et al. Noninvasive assessment of the early progression of atherosclerosis in adolescents with Kawasaki disease and coronary artery lesions. Pediatrics 2001; 107: 10951099.
6. Cheung, YF, Wong, SJ, Ho, MH. Relationship between carotid intima-media thickness and arterial stiffness in children after Kawasaki disease. Arch Dis Child 2007; 92: 4347.
7. Cheung, YF, Yung, TC, Tam, SC, Ho, MH, Chau, AK. Novel and traditional cardiovascular risk factors in children after Kawasaki disease: implications for premature atherosclerosis. J Am Coll Cardiol 2004; 43: 120124.
8. Amano, S, Hazama, F, Hamashima, Y. Pathology of Kawasaki disease: II. Distribution and incidence of the vascular lesions. Jpn Circ J 1979; 43: 741748.
9. Singh, S, Bansal, A, Gupta, A, Kumar, RM, Mittal, BR. Kawasaki disease: a decade of experience from North India. Int Heart J 2005; 46: 679689.
10. Suzuki, A, Yamagishi, M, Kimura, K, et al. Functional behaviour and morphology of the coronary artery wall in patients with Kawasaki disease assessed by intravascular ultrasound. J Am Coll Cardiol 1996; 27: 291296.
11. Sugimura, T, Kato, H, Inoue, O, Takagi, J, Fukuda, T, Sato, N. Vasodilatory response of the coronary arteries after Kawasaki disease: evaluation by intracoronary injection of isosorbide dinitrate. J Pediatr 1992; 121: 684688.
12. Yamakawa, R, Ishii, M, Sugimura, T, et al. Coronary endothelial dysfunction after Kawasaki disease: evaluation by intracoronary injection of acetylcholine. J Am Coll Cardiol 1998; 31: 10741080.
13. Hamaoka, K, Onouchi, Z, Ohmochi, Y. Coronary flow reserve in children with Kawasaki disease without angiographic evidence of coronary stenosis. Am J Cardiol 1992; 69: 691692.
14. Hamaoka, K, Onouchi, Z, Kamiya, Y, Sakata, K. Evaluation of coronary flow velocity dynamics and flow reserve in patients with Kawasaki disease by means of a Doppler guide wire. J Am Coll Cardiol 1998; 31: 833840.
15. Mitani, Y, Okuda, Y, Shimpo, H, et al. Impaired endothelial function in epicardial coronary arteries after Kawasaki disease. Circulation 1997; 96: 454461.
16. Hauser, M, Bengel, F, Kuehn, A, et al. Myocardial blood flow and coronary flow reserve in children with “normal” epicardial coronary arteries after the onset of Kawasaki disease assessed by positron emission tomography. Pediatr Cardiol 2004; 25: 108112.
17. Muzik, O, Paridon, SM, Singh, TP, Morrow, WR, Dayanikli, F, Di Carli, MF. Quantification of myocardial blood flow and flow reserve in children with a history of Kawasaki disease and normal coronary arteries using positron emission tomography. J Am Coll Cardiol 1996; 28: 757762.
18. Cicala, S, Galderisi, M, Grieco, M, et al. Transthoracic echo-Doppler assessment of coronary microvascular function late after Kawasaki disease. Pediatr Cardiol 2008; 29: 321327.
19. Ghelani, SJ, Singh, S, Manojkumar, R. Endothelial dysfunction in a cohort of North Indian children with Kawasaki disease without overt coronary artery involvement. J Cardiol 2009; 53: 226231.
20. Patvardhan, EA, Heffernan, KS, Ruan, JM, Soffler, MI, Karas, RHI, Kuvin, JT. Assessment of vascular endothelial function with peripheral arterial tonometry: information at your fingertips? Cardiol Rev 2010; 18: 2028.
21. Nohria, A, Gerhard-Herman, M, Creager, MA, Hurley, S, Mitra, D, Ganz, P. Role of nitric oxide in the regulation of digital pulse volume amplitude in humans. J Appl Physiol 2006; 101: 545548.
22. Kuvin, JT, Karas, RH. Clinical utility of endothelial function testing: ready for prime time? Circulation 2003; 107: 32433247.
23. Kuvin, JT, Patel, AR, Sliney, KA, et al. Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. Am Heart J 2003; 146: 168174.
24. Selamet Tierney, ES, Newburger, JW, Gauvreau, K, et al. Endothelial pulse amplitude testing: feasibility and reproducibility in adolescents. J Pediatr 2009; 154: 901905.
25. Haller, MJ, Stein, J, Shuster, J, et al. Peripheral artery tonometry demonstrates altered endothelial function in children with type 1 diabetes. Pediatr Diabetes 2007; 8: 193198.
26. Ayusawa, M, Sonobe, T, Uemura, S, et al. Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition). Pediatr Int 2005; 47: 232234.
27. Bonetti, PO, Pumper, GM, Higano, ST, et al. Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. JACC 2004; 44: 21372141.
28. Duong, TT, Silverman, ED, Bissessar, MV, Yeung, RS. Superantigenic activity is responsible for induction of coronary arteritis in mice: an animal model of Kawasaki disease. Int Immunol 2003; 15: 7989.
29. Rowley, AH. The etiology of Kawasaki disease: superantigen or conventional antigen? Pediatr Infect Dis J 1999; 18: 6970.
30. Wang, CL, Wu, YT, Liu, CA, Kuo, HC, Yang, KD. Kawasaki disease: infection, immunity and genetics. Pediatr Infect Dis J 2005; 24: 9981004.
31. Leung, DY. Immunologic aspects of Kawasaki syndrome. J Rheumatol Suppl 1990; 24: 1518.
32. Burns, JC, Shike, H, Gordon, JB, Malhotra, A, Schoenwetter, M, Kawasaki, T. Sequelae of Kawasaki disease in adolescents and young adults. J Am Coll Cardiol 1996; 28: 253257.
33. Kato, H, Sugimura, T, Akagi, T, et al. Long-term consequences of Kawasaki disease. A 10- to 21-year follow-up study of 594 patients. Circulation 1996; 94: 13791385.
34. Furuyama, H, Odagawa, Y, Katoh, C, et al. Altered myocardial flow reserve and endothelial function late after Kawasaki disease. J Pediatr 2003; 142: 149154.
35. Dhillon, R, Clarkson, P, Donald, AE, et al. Endothelial dysfunction late after Kawasaki disease. Circulation 1996; 94: 21032106.
36. Deng, YB, Xiang, HJ, Chang, Q, Li, CL. Evaluation by high-resolution ultrasonography of endothelial function in brachial artery after Kawasaki disease and the effects of intravenous administration of vitamin C. Circ J 2002; 66: 908912.
37. Dalla Pozza, R, Bechtold, S, Urschel, S, Kozlik-Feldmann, R, Netz, H. Subclinical atherosclerosis, but normal autonomic function after Kawasaki disease. J Pediatr 2007; 151: 239243.
38. Kadono, T, Sugiyama, H, Hoshiai, M, et al. Endothelial function evaluated by flow-mediated dilatation in pediatric vascular disease. Pediatr Cardiol 2005; 26: 385390.
39. Ikemoto, Y, Ogino, H, Teraguchi, M, Kobayashi, Y. Evaluation of preclinical atherosclerosis by flow-mediated dilatation of the brachial artery and carotid artery analysis in patients with a history of Kawasaki disease. Pediatr Cardiol 2005; 26: 782786.
40. McCrindle, BW, McIntyre, S, Kim, C, Lin, T, Adeli, K. Are patients after Kawasaki disease at increased risk for accelerated atherosclerosis? J Pediatr 2007; 151: 244248.
41. 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 2006; 30: 262268.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Cardiology in the Young
  • ISSN: 1047-9511
  • EISSN: 1467-1107
  • URL: /core/journals/cardiology-in-the-young
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed