관상동맥협착 환자의 혈장 총 Homocysteine, 엽산 및 비타민 $B_{12}$ 농도

Plasma Total Homocysteine, Folate and Vitamin $B_{12}$ Concentrations in Patients with Coronary Stenosis

  • 임현숙 (전남대학교 생활과학대학 식품영양학과) ;
  • 허영란 (전남대학교 생활과학대학 식품영양학과)
  • Lim Hyeon Sook (Department of Food and Nutrition Chonnam National University) ;
  • Heo Young-Ran (Department of Food and Nutrition Chonnam National University)
  • 발행 : 2005.12.01

초록

Recently elevated plasma homocysteine concentration is considered an independent risk factor for atherosclerosis and thrombosis with coronary artery disease. Folate and vitamin $B_{12}$ are cofactors and closely related with metabolism of homocysteine. The purpose of this study is to evaluate the correlation between homocysteine and folate and vitamin $B_{12}$ in patients with ischemic heart disease. Twenty-six patients, in whom coronary angiographic finding revealed more than $50\%$ of stenosis at least in one coronary vessel were enrolled as the patient group, and thirty subjects, in whom angiographic finding revealed in not significant stenosis, but complained of chest pain, were selected as the control group. Fasting venous blood was obtained and measured the concentration of plasma total homocysteine, folate and vitamin $B_{12}$ by high performance liquid chromatography and fluorescence detection method. We examined the correlation between homocysteine and folate and/or vitamin $B_{12}$ in the control group and the patient group, respectively. Compared with the control group, the patient group had relatively higher plasma total homocysteine concentration ($10.7\pm4.2\;vs\;9.6\pm3.5$ umol/L), but showed no significant difference. Folate and vitamin $B_{12}$ concentration are low in the patient group, but showed no significant difference between patient and control group. Plasma total homocysteine concentration showed negative correlation with folate and vitamin $B_{12}$ in both the control group and the patient group, and showed significantly negative correlation in patient group {r = -0.550 (p < 0.01) vs r = -0.609 (p < 0.01)}. We knew that the plasma total homocysteine concentration were relatively elevated in patient group compared with the control group. Because plasma total homocysteine concentrations are closely negative correlated with folate and vitamin $B_{12}$ in the patient group, folate and vitamin $B_{12}$ supplement can lower the mortality and morbidity of ischemic heart disease. (Korean J Community Nutrition 10(6) : $963\∼970$, 2005)

키워드

참고문헌

  1. Araki A, Sako Y (1987): Determination of free and total homocysteine in human plasma by high performance liquid chromatography with fluorescence detection. J Chromatogr 422 (27) : 43-52 https://doi.org/10.1016/0378-4347(87)80438-3
  2. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG (1995): A quantitative assessment of plasma homocysteine as a risk factor for . vascular disease. J Am Med Assoc 274(13): 1049-1057 https://doi.org/10.1001/jama.274.13.1049
  3. Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, Fowler B, Graham I (1991): Hyperhomocysteinernia: An independent risk factors for vascular disease. N Engl J Med 324 (17): 1149-1155 https://doi.org/10.1056/NEJM199104253241701
  4. Genest JJ, Mcnamara JR, Salem DN. Wilson PWF. Shaefer EJ, Malinow MR (1990): Plasma homocysteine levels in men with premature coronary artery disease. J Am Coli Cardiol 16(5): 1114-1119 https://doi.org/10.1016/0735-1097(90)90542-W
  5. Heinecke JW, Rosen H, Suzuki LA, Chait A (1987): The role of sulfurcontaining amino acids in superoxide production and modification of low density lipoprotein by arterial smooth muscle cells. J Biol Chem 262(21): 10098-10103
  6. Israelsson B, Bratistrom LE. Hulberg BL (1998): Homocysteine and myocardial infarction. Theroscler 74: 227-233
  7. Lentz SR. Sadler JE (1991): Inhibition of thrombomodulin surface expression and protein C activation by the thrombogenic agent homocysteine. J Clin Invest 88(6): 1906-1914 https://doi.org/10.1172/JCI115514
  8. Lim HS, Heo YR (2002): Plasma total homocysteine, Folate and Vitamin $B_{12}$ Statues in Korean Adults. J Nutr Sci Vitaminol 48 (4): 290-297 https://doi.org/10.3177/jnsv.48.290
  9. Malinow MR (1996): Plasma homocyst (e) ine: a risk factor for arterial occlusive diseases. J Nutr 126 (4): 1238S-1243S
  10. Mayer EL, Jacobsen DW. Robinson K (1996): Homocysteine and coronary atherosclerosis. JACC 27 (3): 517-527 https://doi.org/10.1016/0735-1097(95)00508-0
  11. McDonald L, Bray C, Field C, Love F, Davis B (1964): Homocystinuria, thrombosis and the blood-platelets. Lancet 15 (4) : 745-746
  12. Naurath HJ, Joosten E. Riezler R. Stabler SP, Allen RH. Lindenbaum J (1995): Effect of vitamin $B_{12}$ folate, and vitamin $B_6$ supplements in elderly people with normal serum vitamin concentration. Lancet 346 (8967) : 85-88 https://doi.org/10.1016/S0140-6736(95)92113-3
  13. Nygard GN, Nordrehang E, Refsum H, Ueland PM, Farstad M. Vollset SE (1997): Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 337 (4) : 230-236 https://doi.org/10.1056/NEJM199707243370403
  14. Nygard O. Refsum H, Ueland PM, Vollset SE (1998): Major lifestyle determinants of plasma total homocysteine distribution: The Hordaland homocysteine study. Am J Clin Nutri 67 (2) : 263-270 https://doi.org/10.1093/ajcn/67.2.263
  15. Pancharuniti N, Lewis CA, Sauberlich HE, Perkins LL, Go RC, Alvarez JO. Macaluso M. Acton RT, Copeland RB. Cousins AL (1994): Plasma homocysteine. folate and vitamin $B_{12}$ concentrations and risk for early-onset coronary artery disease. Am J Clin Nutr 59 (4) : 940-948 https://doi.org/10.1093/ajcn/59.4.940
  16. Perterson JC, Spence JD (1998): Vitamins and progression of atherosclerosis in hyperhomocysteinemia. Lancet 351 (9098): 263
  17. Pfeiffer CM (1998): Rapid and accurate HPLC assay for total plasma homocysteine and cysteine in a clinical Lab setting. FASEB J 12 (4): A550
  18. Robinson K, Arheart K, Refsum H, Brattstrom L, Boers G, Ueland P, Rubba P, Palma-Reis R, Meleady R, Daly L, Witteman J, Graham I (1998): Low circulating folate and vitamin $B_6$ concentrations: Risk factors for stroke, peripheral vascular disease, and coronary artery disease. COMAC group. Circulation 97 (5) : 437-443 https://doi.org/10.1161/01.CIR.97.5.437
  19. Rodgers GM, Kane WH (1986): Activation of endogenous factor v by a homocysteine-induced vascular endothelial cell activator. J Clin Invest 77 (6) : 1909-1916 https://doi.org/10.1172/JCI112519
  20. Savage DG, Lindenbaum J, Stabler SP, Allen RH (1994): Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamine and folate deficiencies. Am J Med 96 (3) : 239-246 https://doi.org/10.1016/0002-9343(94)90149-X
  21. Selhub J, Miller JW (1992): The pathogenesis of homocystemia: interruption of the coordinat regulation by S-adenosylmethionine of the remethylation and transsulfuration. Am J Clin Nutr 55 (1): 131-138 https://doi.org/10.1093/ajcn/55.1.131
  22. Stabler SP, Marcell PD, Podell ER, Allen RH, Savage DG, Lindenbaum J (1988): Elevation of total homocysteine in the serum of patients with cobalamine or folate deficiency detected by capillary gas chromatography-mass spectrometry. J Clin Invest 81 (2): 466-474 https://doi.org/10.1172/JCI113343
  23. Stampfer MJ, Malinow MR, Willett WC, Newcomer LM, Upson B, Ullmann D, Tishler PV, Hennekens CH (1992): A prospective study of plasma homocysteine and risk of myocardial infarction in US physition. JAMA 268(7): 877-881 https://doi.org/10.1001/jama.268.7.877
  24. The Homocystein Lowering Trials' Collaboration (1998): Lowering blood homocysteine with folic acid based supplements: meta-analysis randomised trials. BMJ 316 (21): 894-898 https://doi.org/10.1136/bmj.316.7135.894
  25. Tsai JC, Perrella MA, Yoshizumi M, Hsieh CM, Haber E, Schlegel R, Lee ME (1994): Promotion of vascular smooth muscle cell growth by homocysteine: A link to atherosclerosis. Proc Natl Acad Sci USA 91 (14): 6369-6373
  26. Ueland PM, Mansoor MA, Guttormsen AB, Muller F, Aukrust P, Refsum H, Svardal AM (1996): Reduced, oxidized and protein-bound forms of homocysteine and other aminothiols in plasma comprise the redox thiol status-A possible element of the extracellular antioxidant defense system. J Nutr 126 (4): 1281S-1284S
  27. Verhoef P, Stampfer MJ, Buring JE, Gaziano JM, Allen RH, Stabler SP, Reynolds RD, Kok FJ, Hennekens CH, Willett WC (1996): Homocysteine metabolism and risk of myocardial infarction: Relation with vitamin $B_6$, $B_{12}$, and folate. Am J Epidemiol 143 (9): 845-859
  28. Vester B, Rasmussen K (1991): High performance liquid chromatography method for rapid and accurate determination of homocysteine in plasma and serum. Clin Biochem 29 (9) : 549-554 https://doi.org/10.1016/S0009-9120(96)00102-6
  29. Willems FF, Aengevaeren WR, Boers GH, Blom HJ, Verheugt FW (2002): Coronary endothelial function in hyperhomocysteinemia: improvement after treatment with folic acid and cobalamin in patients with coronary artery disease. J Am Coil Cardiol 40(4): 766-772 https://doi.org/10.1016/S0735-1097(02)02016-8
  30. Woodside JV, Yarnell JW, McMaster D, Young IS, Harmon DL, McCrum EE, Patterson CC, Gey KF, Whitehead AS, Evans A (1998): Effect of group vitamins and antioxidant vitamins on hyperhomocysteinemia: A double-blind, randomized, factorial-design, controlled trial. Am J Clin Nutr 67 (5) : 858-866 https://doi.org/10.1093/ajcn/67.5.858