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Article

Homocysteine and stroke

  • K Zaw (a1), M T Hasan (a2), B Bhowmick (a1), P B Khanna (a3) and E A Freeman (a4)...
Extract

Interest in homocysteine's role in vascular disease was stimulated by the paper of McCully (1969) in which, based on autopsy evidence of extensive arterial thrombosis in two children with elevated plasma homocysteine concentrations and homocystinuria, he proposed that elevated plasma homocysteine (hyperhomocysteinaemia) can cause atherosclerotic vascular disease. A meta-analysis of subsequent prospective observational studies concluded that elevated homocysteine is indeed a modest independent predictor of ischaemic heart disease and stroke risk in healthy populations with a 25% reduction in serum homocysteine concentration, a reduction of approximately 3 micromol per litre (μmol/l) being associated with a 19% lower risk of stroke (odds ratio, 0.81; 95% confidence interval (CI), 0.69 – 0.95). In the nationally representative sample of US adults, elevated homocysteine concentration was independently associated with an increased likelihood of non-fatal stroke in both black and white adults. In this article, the current concepts relating homocysteine to ischaemic stroke are reviewed.

Copyright
COPYRIGHT: © Cambridge University Press 2007
Corresponding author
Address for correspondence: Khin Zaw, Torfaen Intermediate Care, County Hospital Coed-Y-Gric, Griffithstown, Pontypool, NP4 5YA, Wales, UK.
References
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1McCully, KS. Vascular pathology of homocysteinaemia: implication for the pathogenesis of arteriosclerosis. Am J Pathol 1969; 56: 111–28.
2Homocysteine Studies Collaboration. Homocysteine and risk of ischaemic heart disease and stroke: a meta-analysis. JAMA 2002; 288: 2015–22.
3Giles, WH, Croft, JB, Greenland, KJ, Ford, ES, Kittner, SJ. Total homocysteine concentration and the likelihood of nonfatal stroke. Results from the third National Health and Nutrition Examination Survey, 1988–1994. Stroke 1998; 29: 2473–77.
4Mayer, EL, Jacobsen, DW, Robison, K. Homocysteine and coronary atherosclerosis. J Am Coll Cardiol 1996; 27; 517–27.
5Verhof, P, Stampfer, MJ, Buring, JE et al. Homocysteine metabolism and risk of myocardial infarction: relation with vitamin B6, B12 and folate. Am J Epidemiol 1996; 143: 845–59.
6Rees, MM, Rodgers, GM. Homocysteinaemia : association of a metabolic disorder with vascular disease and thrombosis. Thromb Res 1993; 71: 337–59.
7Ubbink, JB. Assay methods for the measurement of total homocysteine in plasma. Semin Thromb Hemost 2006; 26: 233–41.
8Ueland, PM, Refsum, H, Stabler, SP, Malinow, MR, Andersson, A, Allen, RH. Total homocysteine in plasma or serum : methods and clinical applications. Clin Chem 1993; 39: 1764–79.
9Kang, SS, Wong, PW, Malinow, MR. Hyperhomocysteinaemia and risk factors for occlusive vascular disease. Ann Rev Nutr 1992; 12: 279–98.
10Malinow, MR. Homocysteine, vitamins and genetic interaction in vascular disease. Can J Cardiol 1999; 15 (suppl B): 31B–34B.
11Robinson, K, Mayer, E, Jacobson, DW. Homocysteine and coronary artery disease. Cleve Clin J Med 1994; 61: 438–50.
12Brattstrom, L, Wilcken, DE, Onrik, J, Brudin, L. Common methylene tetrahydrofolate reductase gene metabolism leads to hyperhomocysteinaemia, but not to vascular disease: result of a meta-analysis. Circulation 1998; 98: 2520–26.
13Wilken, B, Bamforth, F et al. Geographical and ethnic variation of the 677 C → T allele of 5, 10 methyltetrahydrofolate reductase MTHFR: finding over 7000 newborns from 16 areas worldwide. J Med Genet 2003; 40: 619–25.
14Frost, P, Bloom, HJ, Milos, R et al. A candidate genetic risk factor for vascular disease : a common mutation in methylene tetrahydrofolate reductase. Nat Genet 1995; 10: 111–13.
15Bruschi, F, Daguati, R, Parazzini, F et al. Age, menopausal status and homocysteine levels in women around menopause. Eur J Obstet Gynaecol Reprod Biol 2005; 120: 195–97.
16Lindgren, A, Brattstrom, L, Norving, B, Hultberg, B, Anderson, A, Johansen, BB. Plasma homocysteine in the acute and convalescent phase after stroke. Stroke 1995; 26: 795–800.
17Meiklejohn, DJ, Vickers, MA, Dijkhuisen, R, Greaves, M. Plasma homocysteine concentration in the acute and convalescent periods of atherothrombotic stroke. Stroke 2001; 32: 57–62.
18Howard, VJ, Sides, EG, Newman, GC et al. Stability of Plasma Homocysteine in Acute Stroke Patients (SHASP) Study Investigators. Changes in plasma homocysteine in the acute phase after stroke. Stroke 2002; 33: 473–78.
19Alfthan, G, Pekkanen, J, Jauhiainen, M et al. Relationship of serum homocysteine and lipoprotein concentrations to atherosclerotic disease in a prospective Finnish population-based study. Atherosclerosis 1994; 106: 9–19.
20Verhoef, P, Hennekens, CH, Malinow, MR et al. A prospective study of plasma homocysteine and risk of ischaemic stroke. Stroke 1994; 25: 1924–30.
21Nygard, O, Vollset, SE, Refsum, H, Stensvold, I et al. Total plasma homocysteine and cardiovascular risk profile : the Hordaland Homocysteine study. JAMA 1995; 274: 1526–33.
22Perry, IJ, Refsum, H, Morris, RW, Ebrahim, SB, Cleland, PM, Sharper, AG. Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. Lancet 1995; 346: 1395–98.
23Toole, JF, Malinow, MR, Chamblers, LE et al. Lowering homocysteine in patients with ischaemic stroke to prevent recurrent stroke, myocardial infarction and death: the Vitamin Intervention for Stroke Prevention VISP randomised controlled trial. JAMA 2004; 291: 565–75.
24Bots, ML, Launer, LJ, Lindemans, et al. Homocysteine and short-term risk of myocardial infarction and stroke in the elderly : the Rotterdam Study. Arch Intern Med 1999; 159: 38–44.
25Homocysteine Studies Collaboration. Homocysteine and risk of ischaemic heart disease and stroke. JAMA 2002; 288: 2015–23.
26Bostom, AG, Rosenberg, IH, Silbershatz, H, Jacques, PF et al. Non-fasting plasma total homocysteine levels and stroke incidence in the elderly person: The Framingham Study. Ann Int Med 1999; 131: 352–55.
27Eikelboom, JW, Hankey, GJ, Anand, SS, Lofthouse, E, Staples, N, Baker, RI. 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: 1069–75.
28Tan, NC-K, Vanketasubramanian, N, Saw, SM, Tjia, HTL. Hyperhomocysteinaemia and risk of ischaemic stroke among young Asian adults. Stroke 2002; 33: 1956–62.
29Van Der Meer, IM, de Maat, MPM, Hak, AE et al. C reactive protein predicts progression of atherosclerosis measured at various sites in the arterial tree. The Rotterdam study. Stroke 2002; 33: 2750–55.
30Harker, LA, Stichter, SJ, Scott, CR, Ross, R. Homocysteinaemia: vascular injury and arterial thrombosis. N Eng J Med 1974; 291: 537–43.
31Harker, LA, Ross, R, Stichter, SJ, Scott, CR. Homocysteine-induced arteriosclerosis: the role of endothelial cell injury and platelet response in its genesis. J Clin Invest 1976; 58: 731–41.
32Ratnoff, OD. Activation of Hageman factor by L-homocysteine. Science 1968; 162: 1007–9.
33Rodgers, GM, Kane, WH. Activation of endogenous factor V by a homocysteine-induced vascular endothelial cell activator. J Clin Invest 1986; 77: 1909–16.
34Rodgers, GM, Conn, MT. Homocysteine, an atherogenic stimulus, reduces protein C activation by arterial and venous endothelial cells. Blood 1990; 75: 895–901.
35Lentz, SR, Sadler, JE. Inhibition of thrombomodulin surface expression and protein C activation by the thrombogenic agent homocysteine. J Clin Invest 1991; 88: 1906–14.
36Fryer, RH, Wilson, BD, Eubler, DB, Fitzgerald, LA, Rodgers, GM. Homocysteine, a risk factor for premature vascular disease and thrombosis, induces tissue factor activity in endothelial cells. Arterioscler Thromb 1993; 13: 1327–33.
37Nishinaga, M, Ozawa, T, Shimade, K. Homocysteine, a thrombogenic agent, suppresses anticoagulant heparin sulfate expression in cultured porcine aortic endothelial cells. J Clin Invest 1993; 92: 1381–6.
38Tsai, JC, Wang, H, Perrella, MA et al. Induction of cyclin A gene expression by homocysteine in vascular smooth muscle cells. J Clin Invest 1996; 97: 146–53.
39Hermann, W, Hermann, M, Obeid, R. Hyperhomocysteinaemia: a critical review of old and new aspects. Curr Drug Metab 2007; 8: 17–31.
40The Heart Outcome Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Eng J Med 2006; 354: 1567–77.
41Bonaa, KH, Njostad, I, Cleland, PM et al. Homocysteine-lowering and cardiovascular events after acute myocardial infarction. N Eng J Med 2006; 354: 1578–88.
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Reviews in Clinical Gerontology
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  • EISSN: 1469-9036
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