Aetiology and treatment of hyperhomocysteinaemia causing ischaemic stroke

International Journal of Clinical Practice

Volumn 55, Issue 4, 2001, Pages 262-268

  Sarkar, P K ^a   Lambert, L A ^a  

^a UNIVERSITY HOSPITALS BIRMINGHAM NHS FOUNDATION TRUST   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); BETAINE; CHOLESTEROL; CYANOCOBALAMIN; CYSTATHIONINE BETA SYNTHASE; FOLIC ACID; FOLIC ACID ANTAGONIST; HOMOCYSTEINE; LIPOPROTEIN; METHIONINE SYNTHASE; METHOTREXATE; PHENYTOIN;

AGE; ATHEROSCLEROSIS; CARCINOMATOSIS; CARDIOVASCULAR RISK; CEREBROVASCULAR ACCIDENT; CEREBROVASCULAR DISEASE; CHRONIC KIDNEY FAILURE; CORONARY ARTERY DISEASE; GENDER; GENE MUTATION; GENETIC POLYMORPHISM; HEREDITY; HIGH RISK PATIENT; HUMAN; HYPERHOMOCYSTEINEMIA; HYPERTENSION; HYPOTHYROIDISM; MENOPAUSE; NUTRITIONAL DEFICIENCY; PERNICIOUS ANEMIA; PRIORITY JOURNAL; REVIEW; RISK ASSESSMENT; RISK FACTOR; RISK MANAGEMENT; THROMBOEMBOLISM; VEIN THROMBOSIS; VITAMIN SUPPLEMENTATION;

ANEMIA, PERNICIOUS; BRAIN ISCHEMIA; FEMALE; HOMOCYSTEINE; HUMANS; HYPERHOMOCYSTEINEMIA; HYPOTHYROIDISM; KIDNEY FAILURE, CHRONIC; MALE; NEOPLASMS; RISK ASSESSMENT; RISK FACTORS; THROMBOSIS;

EID: 0034981429     PISSN: 13685031     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (85)

1. McCully KS. Vascular pathology of homocysteinaemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969; 56: 111-128.
2. Ueland PM, Refum H. Plasma homocysteine, a risk factor for vascular disease: plasma levels in health, disease and drug therapy. J Lab Clin Med 1989; 114:473-501.
3. McCully KS. Homocysteine and vascular disease. Nat Med 1996; 2: 386-389.
4. Brattstrom LE. Vitamins as homocysteine lowering agents. J Niitr 1996: 126: I276S-1280S.
5. Boers GHJ. Smals AGH, Trijbels FJM et al. Heterozygosity for homocysteinuria in premature peripheral and cerebral occlusive arterial disease. N Engt J Med 1985; 313: 709-715.
6. Selhub J, Jacques PF, Bostom AC et al. Association between plasma homocysteine concentrations and extracranial carotid artery stenosis. N Engl J Med 1995: 332: 286-291.
7. Clarke R, Daly L, Robinson K et al. Hyperhomocysteinaemia: an independent risk factor for vascular disease. N Engl J Med 1991: 324: 1149-1155.
8. Pancharuniti N, Lewis CA, Sauberlich HE et al. Plasma homocysteine, folate and vitamin B12 concentrations and risk for early onset coronary artery disease. Am J Clin Nulr 1994; 59: 940-948.
9. Perry IJ. Refsum H. Morris RW et al. Prospective study of serum total homocysteine concentrations and risk of stroke in middle-aged British men. Lancet 1995:346: 1395-1398.
10. Boushey CJ, Beresford SA, Omenn OS, Motulsky AC. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA 1995; 274: 1049-1057.
11. Ridker PM. Hennekens CH, Selhub J et al. Interrelation of hyperhomocysteinaemia, factor V Leiden, and risk of future venous thromboembolism. Circulation 1997; 95: 1777-1782.
12. Brattstrom L, Israelsson B, Norrving B et al. Impaired metabolism in early-onset cerebral and peripheral occlusive arterial disease. Atherosclerosis 1990; 81: 51-60.
13. Dudman NPB. An alternative view of homocysteine. Lancet 1999; 354: 2072-2074.
14. Mudd SH, Levy HL, Skovby F. Disorders of transsulphuration. In: Scriver CR, Beaudet al, Sly WS, Valle D, Eds. The metabolic and molecular bases of inherited disease, vol 1, 7th edn. New York: McGraw-Hill 1995; 1279-1327.
15. Mudd SH, Skovby F, Levy HL et al. The natural history of homocystineuria due to cystathionine beta-synthase deficiency. Am J Hum Genet 1985; 37: 1-31.
16. Hankey GJ, Elkelboom JW. Homocysteine and vascular disease. Lancet 1999:354:407-413.
17. Kraus JP. Biochemistry and molecular genetics of cystathionine betasynthase deficiency. Eur J Paediatr 1998; 157(suppl 2): S50-S53.
18. Mudd SH, Uhlendorf BW, Freeman JM et al. Homocysteinuria associated with decreased methylenetetrahydrofolate reductase activity. Biochem Biaphys Res Commun 1972; 46: 905-912.
19. Nygard O, Vollset SE, Refsum H et al. Total homocysteine and cardiovascular disease. J Intern Med 1999; 246: 425-454.
20. Frosst P, Blom HJ. Milos R et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995; 10: 111-113.
21. Kang S-S, Zhou J, Wong PWK et al. Intermediate homocysteinaemia: a thermolabile variant of methylenetetrahydrofolate reductase. Am J Hum Genet 1988; 43: 414-421.
22. Kang S-S. Critical points for determining moderate hyperhomocysteinaemia. Eur J Clin Invest 1995; 25: 806-808.
23. Guttormsen AB, Ueland PM, Nesthus I et al. Determinants and vitamin responsiveness of intermediate hyperhomocysteinaemia (40 umol). The Hordaland Homocysteine Study. J Clin Invest 1996; 98: 2174-2183.
24. Franco RF, Araujo AG, Guerreiro JF et al. Analysis of the 677 C-T mutation of the methylenetetrahydrofolate reductase gene in different ethnic groups. Thromb Haemost 1998; 79: 119-121.
25. Stevenson RE, Schwartz CE, Du YZ, Adams MJJ. Differences in methylenetetrahydrofolate reductase genotype frequencies between whites and blacks. Am J Hum Genet 1997; 60: 229-230.
26. Hegele RA, Tully C, Young TK, Connelly PW. V677 mutation of methylenetetrahydrofolate reductase and cardiovascular disease in Canadian Inuil. Lancet 1997; 349: 1221-1222.
27. Sacchi E, Tagliabue L, Duca F, Mannucci PM. High frequency of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in Northern Italy. Thromb Haemost 1997; 78: 963-964.
28. Arruda VR, von Zuben PM, Chiaparini LC et al. The mutation Ala677Val in the methylenetetrahydrofolate reductase gene: a risk factor for arterial disease and venous thrombosis. Thromb Haemost 1997: 77: 818-821.
29. Morita H. Kurihara H et al. Methylenetetrahydrofolate reductase gene polymorphism and ischaemie stroke in Japanese. Arlerioscler Thomh Vase Biol 1998:18: 1465-1469.
30. Sarkar P K, Lambert LA. Can lowering homocystine levels reduce the incidence of stroke? J Clin Pharm Therapeut 1999; 24: 331-338.
31. Brattstrom L. Israelsson B, Lindgarde F. Hultberg B. Higher total plasma homocysteine in vitamin BI2 deficiency than in heterozygosity for homocysteinuria due to cystathionine beta-synthase deficiency. Metabolism 1988:37: 175-178.
32. Kang SS. Wong PWK. Norusis M. Homocysteinaemia due to folate deficiency. Metabolism 1987: 36: 458-462.
33. Stabler SP, Marcell PD, Podell ER et al. Elevation of total homocysteine in the serum of patients with cobalamin or folate deficiency detected by capillary gas chromatography-mass spectrometry. J Clin Invest 1988; 81: 466-474.
34. Wilcken DE, Gupta VJ. Sulphur containing amino acid in chronic renal failure with particular reference to homocysteine and cysteine-homocysteine mixed desulphide. F.ur J Clin Invest 1979; 9: 301-307.
35. Chauveau P. Chadefaux B, Coude M et al. Hyperhomocysteinaemia, a risk factor for atherosclerosis in chronic uretnic patients. Kidney Int Sttppl 1993:41: S72-S77.
36. Bostom AG. Lathrop L. Homocysteinaemia in end-stage renal disease: prevalence, etiology, and potential relationship to arteriosclerotic outcomes. Kidney Int 1997:52: 10-20.
37. van Guldener C. Donker AJM. Jakobs C et al. No net renal extraction of homocysteine in fasting humans. Kidney Int 1998; 54: 166-169.
38. Brattstrom L, Lindgren A, Israelsson B et al. Homocysteine and cysteine: determinants of plasma levels in middle-aged and elderly subjects. J Intern Mcd 1994; 236: 631-641.
39. Norlund L. Grubb A. Fex G et al. The increase of plasma homocysteine concentrations with age is partly due to the deterioration of renal function as determined by plasma cystatin C. Clin Chem Lab Met! 1998; 36: 175178.
40. Lien EA, Nedreb BG, Varhaug JE et al. Plasma total homocysteine levels during short-term iatrogenic hypothyroidism. J Clin Endocrinol Metab 2000:85(3): 1049-1053.
41. Savage DG, Lindenbaum J, Stabler SP, Allen RH. Sensitivity of serum methylmalonic acid and total homocysteine determinants for diagnosing cobalamin and folate deficiencies. Am J Med 1994; 96: 239-246.
42. Mayer EL, Jacobsen DW, Robinson K. Homocysteine and coronary atherosclerosis. J Am Coll Cardiol 1996: 27: 517-527.
43. Uelemd PM. Refsum H, Brattstrom L. Plasma homocysteine and cardiovascular disease. In Francis RB Ed. Atherosclerosis cardiovascular disease, haemostasia and endothelial function. New York: Marcel Dekker 1992: 183-236.
44. Girelli D, Friso S. Trabetti E et al. Methylenetetrahydrofolate reductase C677T mutation, plasma homocysteine, and folate in subjects from Northern Italy with or without angiographically documented severe coronary atherosclerotic disease: evidence for an important genetic-environmental interaction. Blond 1998; 91: 4158-4163.
45. James TN. The spectrum of diseases of small coronary arteries and their physiologic consequences. J Am Coll Cordial 1990; 15: 763-774.
46. Tsai JC.Perrella MA. Yoshi/umi M et al. Promotion of Vascular smooth muscle cell growth by homocysteine: a link to atherosclerosis. Proe NatI AcadSei USA 1994: 91: 6369-6373.
47. Wall RT, Harlan JM. Harker LA, Striker GE. Homocysteine-induced endothelial cell injury in vitro: a model for the study of vascular injury. Thromb Res 1980; 18: 113-121.
48. de Groot PG. Willcms C. Boers GH et al. Endothelial cell dysfunction in homocysteinuria. Ear J Clin Invest 1983; 13: 405-410.
49. Starkcbaum G. Harlan JM. Endothelial cell injury due to copper-catalysed hydrogen peroxide generation from homocysteine../C7/n Invest 1986; 77: 1370-1376.
50. Misra HP. Generation of Superoxide free radical during the auto-oxidation of thiols. J Biol Chem 1974; 249: 2151-2155.
51. Rowley DA. Halliwell B. Superoxide-dependent formation of hydroxyl radicals in the presence of thiol compounds. FEES Lett 1982: 138: 33-36.
52. Harker LA, Slichter SJ. Scott CR, Ross R. Homocysteinaemia: vas-cuhir injury and arterial thrombosis. N Engl .1 Med 1974; 291: 537-543.
53. Hcinecke JW. Superoxide-mediated oxidation of low density lipoprotein by thiols. In: Ccrruti PA. Fridovich I, McCord JM, Eds. Oxyradicals in molecular biology and pathologv. New York: Alan R Liss 1988; 443-457.
54. Loscalzo J. The oxidant stress of hyperhomocysteinaemia. J Clin Invest 19%; 98: 5-7.
55. Welch GN, Upchurch GR Jr, Farivar RS el at. Homocysteine-induced nitric oxide production in vascular smooth muscle cells by NF-kB dependent transcriptional activation of NOs 2. Proc Am Assoc Phyx 1998; 110: 22-31.
56. Bellas RE, Lee JS, Sonenshein GE. Expression of a constitutive NFkappa B-like activity is essential for proliferation of cultured bovine vascular smooth muscle cells. J Clin Invest 1995; 96: 2521-2527.
57. Bellas RE. Lee JS, Sonenshein GE. Chemical pathology of homocysteine. II. Carcinogenesis and homocysteine thiolactonc metabolism. Ann Clin Lab Sei 1994; 24: 27-59.
58. Bellas RE, Lee JS, Sonenshein GE. Homocysteine metabolism in scurvy, growth and arteriosclerosis. Nature 1971; 231: 391-392.
59. Morel DW, Hessler Chisolm GM. Low density lipoprotein cytotox-icity induced by free radical peroxidation of lipid. ./ Ijpid Rex 1983; 24: 1070-1076.
60. Hughes H, Mathews B, Lenz ML Guyton Cytotoxicity of oxidized LDLto porcine aortic smooth muscle cells is associated with the oxysterols 7-ketocholesterol and 7-hydroxycholesterol. ArteriosclerThromb 1994: 14: 1175-1185.
61. Berliner JA, Heinceke JW. The role of oxidiJ.ed lipoproteins in atherogenesis. Free Radie Biol Med 1996: 20: 707-727.
62. Harpel PC, Chang VT, Borth W. Homocysteine and other sulfhydryl compounds enhance the binding of lipoproteins(a) to fibrin: a potential biochemical link between thrombosis, atherogenesis. and sulfhydryl compound melabohm. Proc Nail Acad Sei 1992:89: 10193-10197.
63. Heinecke JW. Kawamura M, Suzuki L, Chait A. Oxidation of low density lipoprotein by thiol: superoxide-dependent and independent mechanisms. J Lipid Res 1993 ; 34: 2051 -2061.
64. Parthasarathy S. Oxidation of low-density lipoprotein by thiol compounds leads to its recognition by the acetyl LDL receptor. Riochem BiophyxActa 1987; 917: .337-340.
65. Graham IM, Daly LE. Refsum HM et al. Plasma homocysteine as a risk factor of vascular disease; the Europena Concerted Action Project. JAMA 1997:277: 1775-1781.
66. Wald NJ. Watt HC, Law MR et al. Homocysteine and ischaemic heart disease: results of a prospective study with implications regarding prevention. Arch Intern Med 1998; 158: 862-867.
67. Ridker PM, Manson JE. Buring JE et al. Homocysteine and risk of cardiovascular disease among postmenopausal women. JAMA 1999; 281: 1817-1821.
68. Giles WH. Croft JB, Greenlund KJ et al. Total homocysteine concentration and the likelihood of nonfatal stroke: Results from the third national health and nutrition examination survey. 1988-1994. Stroke 1998: 29: 2473-2477.
69. Kittner SJ, Giles WH, Macko RF et al. Homocysteine and risk of cerebral infarction in a biracial population: the stroke prevention in young women study. Stroke 1999:30: 1554-1560.
70. Yoo J-H. Chung C'-S, Kang S-S. Relation of plasma homocysteine to cerebral infarction and cerebral atherosclerosis. Stroke 1998: 29: 24782483.
71. Izumi M, Iwai N. Ohmichi N et til. Molecular variant of 5.10-mcthylenetetrahydrofolate reductase is a risk factor of ischaemic heart disease in the Japanese population. Atherosclerosis 1996; 121: 293-294.
72. Morita H, Taguchi J, Kurihara H et al. Gene polymorphism of 5,10mcthylenetetrahydrofolate reductase (MTHFR) as a risk factor for coronary artery disease. Circulation 1997; 95: 2032-20.36.
73. Ou T, Yamakawa-Kobayashi K, Arinami T et al. Mcthylenetctrahydrofolate reductase and apolipoprotein E polymorphisms are independent risk factors for coronary heart disease in Japanese: a case control study. Atherosclerosis 1998; 137: 23-28.
74. Nakata Y, Katsuya T, Takami S et al. Methylenetetrahydrofolate reductase gene polymorphism: relation to blood pressure and cerebrovascular disease./1m J Hypertens 1998; 11: 1019-1023.
75. Stehouwer CD, Weijenberg MP, van den Berg M et al. Serum homocysteine and risk of coronary heart disease and cerebrovascular disease in elderly men: a 10 year follow up. Anerioscler Thromb Vase Biol 1998; 12: 1895-1901.
76. Kristensen B, Malm J, Nilsson TK et al. Hyperhomocysteinaemia and hypofibrinolysis in young adults with ischaemic stroke. Stroke 1999; 30(5): 974-980.
77. Willinek WA, Ludwig M, Lennarz M et al. High-normal serum homocysteine concentrations are associated with an increased risk of early atherosclerotic carotid artery wall lesions in healthy subjects. J Hypertens 2000; 18(4): 425-430.
78. Eikelboom JW, Hankey GJ, Anand SS et al. Association between high homocysteine and ischaemic stroke due to large- and small-artery disease but not other aetiologic subtypes of ischaemic stroke. Stroke 2000; 31(5): 1069-1075.
79. Brattstrom LE, Israelsson B, Jeppsson JO, Hultberg BL. Folic acid: an innocuous means to reduce plasma homocysteine. Scand J Clin Lab Invest 1988; 48: 215-221.
80. Saltzman E, Mason JB, Jacques PF étal. B vitamin supplementation low-ers homocysteine levels in heart disease. Clin Res 1994; 42: 172A. Abstract. 81. Landgren F. Israelsson B, Lindgren A et al. Plasma homocysteine in acute myocardial infarction: homocysteine-lowering effect of folic acid. J Intern Med 1995; 237: 381-388.
81. Solberg LA, Strong JP. Risk factors and atherosclerotic lesions: a review of autopsy studies. Atherosclerosis 1983; 3: 187-198.
82. Ubbink JB. van der Merwe A, Vermaak WJH, Delport R. Homocysteinaemia and the response to vitamin supplements. Clin Invest 1993; 71: 993-998.
83. Peterson JC, Spence JD. Vitamins and progression of atherosclerosis in hyperhomocyst(e)inaemia. Lancet 1998; 351: 263.
84. Gerhard GT, Duell PB. Homocysteine and atherosclerosis. Curr Opin Lipidol 1999; 10(5): 417-428.
85. Larkin M. Is high homocysteine clinically relevant? Lancet 1999; 353: 1770.