Association Between Metabolic Syndrome and Plasma Homocysteine Level in Patients with Ischemic Stroke

허혈성 뇌졸중 환자에서 대사증후군과 호모시스테인의 관계

Park, Jong-Ho;Shin, Dong-Jin;Park, Hyeon-Mi;Lee, Yeong-Bae;Shin, Won-Chul
박종호;신동진;박현미;이영배;신원철

  • Published : 2005.02.01

Abstract

Background: Metabolic syndrome (MS) and homocysteine (Hcy) are known to contribute to developing atherosclerothrombosis in ischemic stroke. However, there have been controversies regarding the relationship between insulin resistance and plasma Hcy levels in healthy subjects. Our aim was to determine the possibility of a relationship between MS and elevated Hcy in ischemic stroke patients. Methods: We investigated demographic features and risk factors in 221 patients from Gachon Stroke Registry between March 2003 and February 2004. The stroke subtypes were categorized as large artery atherosclerosis (LAA), small artery occlusion (SAO) and cardioembolism (CE). MS was defined as the followings; impaired fasting glucose, impaired glucose tolerance or IDDM with two or more among 1) hypertension (antihypertensive treatment and/or BP 160/90 mmHg), 2) dyslipidemia (TG $\geq$150 mg/dL and/or HDL-C (<35 in men, <39 mg/dL in women)), 3) obesity (BMI $\geq$25 kg/m2 or waist circumference 90 in men, 80 cm in women). Results: Hcy, total cholesterol, and fibrinogen levels were higher in MS(+) than in MS(-) (p=0.026, 0.021 and 0.025). The Hcy level was higher in LAA patients than in SAO and CE patients (14.1${\pm}$6.8, 12.0${\pm}$6.2, 11.0${\pm}$4.3 mol/L, p=0.009). It was significantly higher in MS(+) than is MS(-) in SAO patients (15.4${\pm}$9.5 vs 10.5${\pm}$2.9 mol/L, p=0.016), while not observed in LAA or CE patients. Among the MS(+), LAA was more prevalent (48.6%) than SAO (36.1%) and CE (15.3%). Conclusions: Elevated Hcy level may be associated with ischemic stroke with MS. Further studies remain to be investigated to clarify whether lowering the elevated Hcy can be an another important asset in reducing the risk not only for stroke, but also for MS.

Keywords

References

  1. Kernan WN, Inzucchi SE, Viscoli CM, Brass LM, Bravara DM, Horwitz RI. Insulin resistance and risk for stroke. Neurology 2002; 59:809-815 https://doi.org/10.1212/WNL.59.6.809
  2. Reilly MP, Rader DJ. The metabolic syndrome: more than the sum of its parts? Circulation 2003;108:1546-1551 https://doi.org/10.1161/01.CIR.0000088846.10655.E0
  3. Lee KU. Oxidative stress markers in Korean subjects in insulin resistance syndrome. Diabetes Res Clin Pract 2001;54(Suppl 2): 29-33 https://doi.org/10.1016/S0168-8227(01)00282-0
  4. Giltay EJ, Hoogeveen EK, Elbers JM, Gooren LJ, Asscheman H, Stehouwer CD. Insulin resistance is associated with elevated plasma total homoysteine levels in healthy non-obese subjects. Atherosclerosis 1998; 139: 197 -198 https://doi.org/10.1016/S0021-9150(98)00067-7
  5. Nagai Y, Takamura T, Nohara E, Yamashita H, Kobayashi K. Acute hyperinsulinemia reduces plasma concentrations of homocysteine in healthy men. Diabetes Care 1999;22:1004
  6. Jermendy G, Hrdvegi T, Hetyesi K. Plasma homocysteine levels in hyperinsulinemic subjects. Diabetes Care 2000;23: 1852-1853 https://doi.org/10.2337/diacare.23.12.1852
  7. Bar-On H, Kidron M, Friedlander Y, Ben-Yehuda A, Selhub J, Rosenberg IH, et aI. Plasma total homocysteine levels in subjects with hyperinsulinemia. J Intern Med 2000;247:287-294 https://doi.org/10.1046/j.1365-2796.2000.00592.x
  8. Godsland IF, Rosankiewicz JR, Proudler AJ, John DG. Plasma total homocysteine concentrations are unrelated to insulin sensitivity and components of the metabolic syndrome in healthy men. J Clin Endocrinol Metab 2001;86:719-723 https://doi.org/10.1210/jc.86.1.9
  9. Hankey GJ, Eikclboom JW. Homocysteine and vascular disease. Lancet 1999;354:407-413 https://doi.org/10.1016/S0140-6736(98)09374-X
  10. Meiklejohn DJ, Vickers MA, Dijkhuisen R, Greaves M. Plasma homocysteine concentrations in the acute and convalescent periods of atherothrornbotic stroke. Stroke 2001;32:57-62 https://doi.org/10.1161/01.STR.32.1.57
  11. Report of the Expert Committee on the Diagnosis of Diabetes Mellitus. Diabetes Care 1997;20:1183-1197 https://doi.org/10.2337/diacare.20.7.1183
  12. Alberti KG, Zimmer PZ. Definirion, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus: provisional report of a WHO consultation. Diabet Med 1998;15:539-553 https://doi.org/10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S
  13. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18: 499-502
  14. Wesrern Pacific Regional Office of the World Health Organization, The International Obesity Task Force: The Asia-Pacific perspective: redefining obesity and its treatment. Sydney: Health Communications Australia, 2000 http://www.obesityasiapacific.com
  15. Chung HW, Kim DJ, Kim HD, Choi SH, Ahn CW, Cha BS, et al. Prevalence of metabolic syndrome according to the new criteria for obesity. J Kor Diabetes Asso 2002;26:431-442
  16. Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in multicenter clinical trial. TOAST. Stroke 1993;24:35-41 https://doi.org/10.1161/01.STR.24.1.35
  17. Reaven GM. Role of insulin resistance in human disease. Diabetes 1988;37: 1595-1607 https://doi.org/10.2337/diabetes.37.12.1595
  18. Reaven GM. Role of insulin resistance in human disease (syndrome X): an expanded definition. Annu Rev Med 1993;44:121-131 https://doi.org/10.1146/annurev.me.44.020193.001005
  19. Chambers JC, McGregor A, Jean-Marie J, Kooner JS. Acute hyperhomocysteinemia and endothelial dysfunction. Lancet 1998; 351:36-37
  20. Tawakol A, Omland T, Gerhard M, Wu JT, Creager MA. Hyperhomocyst(e)inaemia is associated with impaired endotheliumdependent vasodilatation in humans. Circulation 1997;85: 1119-1121
  21. Bellamy MF, McDowell IF, Ramsay MW, Brownlee M, Bones C, Newcombe RG, et al. Hyperhomocyst(e)inaemia afrer an oral methionine load acutely impairs endothelial function in healthy adults. Circulation 1998;98:1848-1852 https://doi.org/10.1161/01.CIR.98.18.1848
  22. Evers S, Koch HG, Grotemeyer KH, Lange B, Deufcl T, Ringelsrein EB. Features, symptoms, and neurophysiological findings in stroke associated with hyperhomocysteinemia. Arch Neurol 1997;54: 1276-1282 https://doi.org/10.1001/archneur.1997.00550220074017
  23. Fassbender K, Mieke 0, Bertsch T, Nafe B, Froschen S, Hennerici M. Homocysteine in cerebral macroangiopathy and microan-giopathy. Lancet 1999;353:1586-1587 https://doi.org/10.1016/S0140-6736(98)11181-9
  24. Eikelboom JW, Hankey GJ, Anand SS, Lofthouse E, Staples N, Baker RI. Association between high homocysteine and ischemic stroke due to large- and small-artery disease but not other etiologic subtypes of ischaemic stroke. Stroke 2000;31: 1069-1075 https://doi.org/10.1161/01.STR.31.5.1069
  25. Jeong DS, Song lW, Cho SG, Sung KB, Park HK, Chang SG, et al. A pilot study on total plasma homocysteine level of patients with cerebral infarction. J Korean Neurol Assoe 1999;17:26-31
  26. Shinozaki K, Naritorni H, Shimizu T, Suzuki M, lkebuchi M, Sawada T, et al. Role of insulin resistance associated with compensatory hyperinsulinemia in ischemic stroke. Stroke 1996;27: 37-43 https://doi.org/10.1161/01.STR.27.1.37
  27. Fonseca VA, Mudaliar S, Schmidt B, Fink LM, Kern PA, Henry RR. Plasma homocysteine concenttations arc regulated by acute hyperinsulinemia in nondiabetic but not type 2 diabetic subjects. Metabolism 1998;47:686-689 https://doi.org/10.1016/S0026-0495(98)90031-2
  28. Emoto M, Kanda H, Shoji T, Kawagishi T, Komatsu M, Mori K, et al. Impact of insulin resistance and nephropathy on homocysteine in type 2 diabetes. Diabetes Care 2001;24:533-538 https://doi.org/10.2337/diacare.24.3.533
  29. Aliza D-B, Vivian AF, Louis MF, Philip AK. The effect of glucose and insulin on the activity of enzymes in homocysteine metabolism (Abstract). Diabetes 1999;48(Suppl I): 135
  30. Welch GN, Loscalzo J. Homocysteine and atherothrombosis. N Engl J Med 1998;338: 1042-1050 https://doi.org/10.1056/NEJM199804093381507
  31. Meigs JB, Jacques PF, Selhub J, Singer DE, Nathan DM, Rifai N, et al. Fasting plasma homocysteine levels in the insulin resistance syndrome. The Framingham Offspring Study. Diabetes Care 2001; 24:1403-1410 https://doi.org/10.2337/diacare.24.8.1403
  32. Passaro A, Calzoni F, Volpato S, Nora E. Dalla, Pareschi PL, Zamboni PF, et al. Effect of metabolic control on homocysteine levels in type 2 diabetic patients: a 3-year follow-up. J Intern Med 2003;254:264-271 https://doi.org/10.1046/j.1365-2796.2003.01184.x
  33. Haffner SM, Miettinen H, Stern MP. The homeostasis model in the San Antonio Heart Study. Diabetes Care 1997;20:1087-1092 https://doi.org/10.2337/diacare.20.7.1087