Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
권호 표지

Changes of Lipid and Lipoprotein Compositions in Kawasaki Disease and its Impact on Cardiac Complications

가와사끼병에서 혈중 지질과 지단백의 변화와 심장 합병증에 미치는 영향에 관한 연구

  • Yun, Sin Weon (Department of Pediatrics, College of Medicine, Chung-Ang University) ;
  • Lee, Ho Seok (Department of Pediatrics, College of Medicine, Chung-Ang University) ;
  • Kim, Dong Woon (Department of Pediatrics, College of Medicine, Chung-Ang University) ;
  • Rhee, Kang Won (Department of Pediatrics, College of Medicine, Chung-Ang University) ;
  • Jung, Young Soo (Department of Pediatrics, College of Medicine, Chung-Ang University)
  • 윤신원 (중앙대학교 의과대학 소아과학교실) ;
  • 이호석 (중앙대학교 의과대학 소아과학교실) ;
  • 김동운 (중앙대학교 의과대학 소아과학교실) ;
  • 이강원 (중앙대학교 의과대학 소아과학교실) ;
  • 정영수 (중앙대학교 의과대학 소아과학교실)
  • Received : 2005.05.13
  • Accepted : 2005.08.18
  • Published : 2005.12.15
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose : Delineation of serum lipid and lipoprotein values in children after Kawasaki disease(KD) is important because of the predilection of this disease for the coronary arteries. Methods : The KD group was composed of 51 patients who were hospitalized from Jan. 2002 to Dec. 2003. Control was 25 patients with non-KD febrile illness. The levels of total lipid, phospholipid, triglyceride, HDL-cholesterol(HDL-C), LDL-cholesterol, total cholesterol, apolipoprotein A1(apo A1), apolipoprotein B, and Lipoprotein(a) were measured and compared with Echocardiographic findings. Measurements were obtained in four time periods: acute febrile, subacute, convalescent phase and 1 year after KD. Results : HDL-C($33.64{\pm}7.49mg/dL$ vs $50.43{\pm}14.41mg/dL$, P<0.01) and apo A1($99.75{\pm}6.39mg/dL$ vs $113.34{\pm}11.35mg/dL$, P<0.05) were decreased more in the acute febrile period of KD than in the control, but these changes were not correlated with cardiac complications. All lipid profiles were markedly elevated in the subacute stage and normalized in the convalescent stage; there were no changes until 1-year follow up. There were no significant differences in the changes of lipid profiles, including Lp(a) and coronary dilatation, in any time periods. Conclusion : KD is associated with important abnormalities in lipid metabolism, but these changes were transient and appear to be due to the disease itself. These data lead us to infer that KD dose not cause such permanent changes in lipid abnormalities as to be considered a risk factor for atherosclerosis, beyond that caused by the disease itself.

목 적 : 가와사끼병에서의 지질대사의 변화는 특히 이 병이 관상동맥을 직접 침범하는 질환이므로 특히 중요하다고 하겠다. 성인에 있어서 TC의 증가 및 HDL-C의 감소, Lp(a)의 증가는 죽상경화증의 중요한 위험인자의 하나로 알려져 있다. 이에 가와사끼병에서의 혈중 지질성분 및 지단백, Lp(a)의 시기별 변화와 관상동맥 병변과의 상관관계를 알아보고자 하였다. 방 법 : 2002년 1월부터 2003년 12월까지 중앙대학교병원에서 가와사끼병으로 진단되어 고농도 감마글로불린으로 치료한 환아 51명을 대상으로 TL, PL, TG, HDL-C, LDL-C, TC, apo A1, apo B, Lp(a) 등을 급성발열기, 아급성기인 발열 2주, 회복기인 2개월, 1년 후 각각 측정하였고 초음파 검사 소견에 따라 비교 분석 하였다. 또한 대조군으로는 나이와 성별을 고려한 가와사끼병이 아닌 급성발열성 질환으로 입원한 25명을 대상으로 삼았다. 결 과 : 가와사끼병에서 급성 발열기에 대조군에 비하여 HDL-C($33.64{\pm}7.49mg/dL$ vs $50.43{\pm}14.41mg/dL$, P<0.01)과 apo A1($99.75{\pm}6.39mg/dL$ vs $113.34{\pm}11.35mg/dL$, P<0.05)이 통계적으로 의미있게 감소하였다. 그러나 관상동맥 확장이나 심염 등 심합병증 여부에는 큰 차이는 없었다. 아급성기에는 모든 지질성분이 통계적으로 의미있게 증가를 보였으며 발열 2개월째에는 모든 지질성분이 정상화되었고 발병 1년 후에 역시 정상범위였으며 어느 시기에서도 관상동맥 확장이 있었던 군과 정상인 군에서 지질성분의 통계적 차이는 없었다. 결 론 : 가와사끼병의 급성발열기에 HDL-C의 및 apo A1의 감소를 보였으며 발병 2주째에는 모든 지질성분이 일시적으로 통계적으로 의미있게 증가하였다. 그러나 이런 변화는 발열 2달째에는 모두 정상화되었으며 1년 경과 후에도 계속 정상소견을 보였다. 어느 시기에도 관상동맥병변이 있었던 군과 정상관상동맥을 보였던 군에서 지질성분의 의미있는 차이는 없어 이러한 급성기의 일시적인 HDL-C과 apo A1의 감소는 가와사끼병의 관상동맥 병변 여부나 장기적인 예후와는 직접적인 큰 상관은 없고 급성혈관염이라는 염증 반응의 하나의 현상으로 사료된다. 그러나 이들이 후에 성인이 되었을 때 동맥경화발현에 미치는 영향에 대해서는 더 많은 연구가 필요하리라 생각된다.

Keywords

Acknowledgement

Supported by : 중앙대학교

References

  1. Kawasaki T. Acute febrile mucocutaneous lymph node syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children. Jpn J allergy 1967;16:178-222
  2. Senzaki H, Chen CH, Ishido H, Masutani S, Matsunaga T, Taketazu M, et al. Arterial hemodynamics in patients after Kawasaki disease. Circulation 2005;111:2119-25 https://doi.org/10.1161/01.CIR.0000162483.51132.25
  3. Newburger JW. Kawasaki disease : Who is at risk? (Editorial) J Pediatr 2000;137:149-52 https://doi.org/10.1067/mpd.2000.109025
  4. 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;43:120-4 https://doi.org/10.1016/j.jacc.2003.08.030
  5. Noto N, Okada T, Yamasuge M, Taniguchi K, Karasawa K, Ayusawa M, et al. Noninvasive assessment of the early progression of atherosclerosis in adolescents with Kawasaki disease and coronary artery lesions. Pediatrics 2001;107: 1095-9 https://doi.org/10.1542/peds.107.5.1095
  6. Newburger JW, Burns JC, Beiser AS, Loscalzo J. Altered lipid profile after Kawasaki syndrome. Circulation 1991;84: 625-31 https://doi.org/10.1161/01.CIR.84.2.625
  7. Hsieh KS, Weng KP, Lin CC, Hwang DC, Liu WS, Chen FL. The serial change of serum lipid profile in Kawasaki disease. Chest 1997;112:66S
  8. Chiang AN, Hwang B, Shaw GC, Lee BC, Lu JH, Meng CCL, et al. Changes in plasma level of lipids and lipoprotein composition in patients aith Kawasaki disease. Clinic Chimica Acta 1997;260:15-26 https://doi.org/10.1016/S0009-8981(96)06502-3
  9. Choi SM, Choi JH. Levels of serum HDL-cholesterol and total cholesterol in Kawasaki disease and their significance. Korean Circ J 1997;27:1298-302 https://doi.org/10.4070/kcj.1997.27.12.1298
  10. Lee YJ, Lee YS, Hyun MC, Lee SB. Lipid profile changes in Kawasaki disease patients. J Korean Pediatr Soc 2000; 43:216-22
  11. Berg K. Immunochemical studies of the Lp(a) factor. Acta Pathol Microbiol Scand 1964;62:600-12 https://doi.org/10.1111/apm.1964.62.4.600
  12. Marcovina SM, Koschinsky ML, Albers JJ, Skarlatos S. Report of the national heart, lung, and blood institute workshop on Lipoprotein(a) and cardiovascular disease: Recent advances and future directions. Clin Chem 2003;49: 1785-96 https://doi.org/10.1373/clinchem.2003.023689
  13. Stein EA, Myers G. Lipid, apolipoproteins, and lipoproteins In : Burtis CA, Ashwood ER. Trietz fundamentals of clinical chemistry. 4th ed. Philadelphia : WB Saunders, 1996:375-401
  14. Marcovina SM, Koschinsky ML. A critical evaluation of the role of Lp(a) in cardiovascular disease : Can Lp(a) be useful in risk assessment? Semin Vasc Med 2002;2:335-44 https://doi.org/10.1055/s-2002-35404
  15. McLean JW, Tomlinson JE, Kuang WJ, Eaton DL, Chen EY, Fless GM, et al. cDNA sequence of human apolipoprotein( a) is homologous to plasminogen. Nature 1987;330: 132-7 https://doi.org/10.1038/330132a0
  16. Kurotobi S, Nagai T, Kawakami N, Sano T. Coronary diameter in normal infants, children and patients with Kawasaki disease. Pediatr int 2002;44:1-4 https://doi.org/10.1046/j.1442-200X.2002.01508.x
  17. Cabana VG, Gidding SS, Getz GS, Chapman J, Shulman ST. Serum amyloid A and high density lipoprotein participate in the acute phase response of Kawasaki disease. Pediatr Res 1997;42:651-5 https://doi.org/10.1203/00006450-199711000-00017
  18. Salo E, Pesonen E, Viikari J. Serum cholesterol levels during and after kawasak disease. J Pediatr 1991;119:557-61 https://doi.org/10.1016/S0022-3476(05)82404-7
  19. Okada T, Harada K, Okuni M. Serum HDL-cholesterol and lipoprotein fraction in Kawasaki disease(acute mucocutaneous lymphnode syndrome). Jpn Circ J 1982;46:1039-42 https://doi.org/10.1253/jcj.46.1039
  20. Silva AA, Maeno Y, Hasbmi A, Smallborn JF, Silverman ED, McCrindle BW. Cardiovascular risk factors after Kawasaki disease a case-control study. J Pediatr 2001;138: 400-5 https://doi.org/10.1067/mpd.2001.111430
  21. Chenaud C, Merlani PG, Roux-Lombard P, Burger D, Harbarth S, Luyasu S, et al. Low apolipoprotein A-I level at intensive care unit admission and systemic inflammatory response syndrome exacerbation Crit Care Med 2004;32: 632-7 https://doi.org/10.1097/01.CCM.0000114820.47460.0A
  22. Hyka N, Dayer JM, Modoux C, Kohno T, Edwards CK, Roux-Lombard P, et al. Apolipoprotein A-I inhibits the production of interleukin-1 and tumor necrosis factor alpha by blocking contact-mediated activation of monocytes by T lymphocytes. Blood 2001;97:2381-9 https://doi.org/10.1182/blood.V97.8.2381
  23. Van Leeuwen HJ, Heezius EC, Dallinga GM, van Strijp JA, Verhoef J, van Kessel KP. Lipoprotein metabolism in patients with severe sepsis. Crit Care Med 2003;31:1359-66 https://doi.org/10.1097/01.CCM.0000059724.08290.51
  24. Fahie-Wilson M, Mills R, Wilson K. HDL cholesterol and the acute phase reaction following myocardial infarction and acute pancreatitis. Clin Chim Acta 1987;167:197-209 https://doi.org/10.1016/0009-8981(87)90372-X
  25. Fraunberger P, Nagel D, Walli AK, Seidel D, Walli K, Seidel D. Serum cholesterol and mortality in patients with multiple organ failure. Crit Care Med 2000;28:3574-5 https://doi.org/10.1097/00003246-200010000-00047
  26. Gordon BR, Parker TS, Levine DM, Saal SD, Wang JC, Sloan BJ, et al. Low lipid concentrations in critical illness : Implications for preventing and treating endotoxemia. Crit Care Med 1996;24:584-9 https://doi.org/10.1097/00003246-199604000-00006
  27. Pajkrt D, Manten A, van der Poll T, Tiel-van Buul MM, Jansen J, Wouter ten Cate J, et al. Modulation of cytokine release and neutrophil function by granulocyte colony-stimulating factor during endotoxemia in humans. Blood 1997; 90:1415-24
  28. Suzuki A, Miyagawa-Tomita S, Komatsu K, Nishikawa T, Sakomura Y, Horie T, et al. Active Remodeling of the coronary arterial lesions in the late phase of Kawasaki disease immunohistochemical study. Circulation 2000;101:2935-41 https://doi.org/10.1161/01.CIR.101.25.2935
  29. Dhillon R, Clarkson P, Donald AE, Powe AJ,Nash M, Novelli V, Dillon MJ, Deanfield JE. Endothelial dysfunction late after Kawasaki disease. Circulation 1996;94:2103-6 https://doi.org/10.1161/01.CIR.94.9.2103