Homocysteine and stroke prevention: Have the trials settled the issue?

International Journal of Stroke

Volumn 1, Issue 4, 2006, Pages 242-244

  Spence, J David ^a  

^a Stroke Prevention and Atherosclerosis Research Centre   (Canada)

Author keywords

B12; Cardiovascular; Homocysteine; Prevention; Stroke; Vitamin

Indexed keywords

BETAINE; CYANOCOBALAMIN; FOLIC ACID; HOMOCYSTEINE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PLACEBO; PYRIDOXINE; THIOL DERIVATIVE; VITAMIN;

ARTICLE; ATHEROSCLEROTIC PLAQUE; BLOOD CLOTTING; CARDIOVASCULAR DISEASE; CEREBROVASCULAR ACCIDENT; CLINICAL TRIAL; CYANOCOBALAMIN DEFICIENCY; DRUG EFFICACY; EVIDENCE BASED MEDICINE; HUMAN; LIPID OXIDATION; OXIDATIVE STRESS; PERIPHERAL VASCULAR DISEASE; PRIORITY JOURNAL; RISK FACTOR; TRANSLUMINAL CORONARY ANGIOPLASTY; VASCULAR ENDOTHELIUM; VITAMIN SUPPLEMENTATION;

CLINICAL TRIALS AS TOPIC; HOMOCYSTEINE; HUMANS; HYPERHOMOCYSTEINEMIA; STROKE; VITAMINS;

EID: 33749644500     PISSN: 17474930     EISSN: 17474949     Source Type: Journal    
DOI: 10.1111/j.1747-4949.2006.00057.x     Document Type: Article

References (37)

1. Carson NAJ, Neill DW: Metabolic abnormalities detected in a survey of mentally backward individuals in Northern Ireland. Arch Dis Child 1962; 37: 505-13.
2. Gerritsen T, Vaughn JG, Waisman HA: The identification of homocystine in the urine. Biochem Biophys Res Commun 1962; 9: 493-6.
3. McCully KS: Vascular pathology ofIhomocysteinemia: implications for the pathogenesis of atherosclerosis. Am J Pathol 1969; 56: 111-28.
4. Boers GHJ, Smala AG, Trijbels FJM et al. Heterozygosity for homocystinuria in premature peripheral and cerebral occlusive arterial disease. N Engl J Med 1985; 313: 709-15.
5. Graham IM, Daly L, Refsum H et al. Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. JAMA 1997; 277: 1775-81.
6. Nygård O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE: Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 1997; 337: 230-6.
7. Hankey GJ, Eikelboom JW: Homocysteine and vascular disease. Lancet 1999; 354: 407-13.
8. Spence JD, Howard VJ, Chambless LE et al. Vitamin Intervention for Stroke Prevention (VISP) trial: Rationale and design. Neuroepidemiology 2001; 20: 16-25.
9. Ubbink JB, Vermaak WJ, van der Merwe A, Becker PJ, Delport R, Potgieter HC: Vitamin requirements for the treatment of hyperhomocysteinemia in humans. J Nutr 1994; 124: 1927-33.
10. Chambers JC, McGregor A, Jean-Marie J, Kooner JS: Acute hyperhomocysteinaemia and endothelial dysfunction. Lancet 1998; 351: 36-7.
11. Macko R, Kittner SJ, Refsum H et al. Effect of vitamin therapy on plasma homocysteine, endogenous fibrinolysis, and markers of endothelial injury in stroke patients: A placebo-controlled trial. Stroke 1998; 29: 286.
12. Van den Berg M, Boers GH, Franken DG et al. Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive disease. Eur J Clin Invest 1995; 25: 176-81.
13. Wheeler DC: Cardiovascular disease in patients with chronic renal failure. Lancet 1996; 348: 1673-4.
14. Naruszewicz M, Klinke M, Dziewanowski K, Staniewicz A, Bukowska H: Homocysteine, fibrinogen, and lipoprotein(a) levels are simultaneously reduced in patients with chronic renal failure treated with folic acid, pyridoxine, and cyanocobalamin. Metabolism 2001; 50: 131-4.
15. Peterson JC, Spence JD: Vitamins and progression of atherosclerosis in patients with hyper-homocyst(e)inemia. Lancet 1998; 351: 263.
16. Hackam DG, Peterson JC, Spence JD: What level of plasma homocyst(e)ine should be treated? Effects of vitamin therapy on progression of carotid atherosclerosis in patients with homocyst(e)ine levels above and below 14mol/L. Am J Hypertens 2000; 13: 105-10.
17. Vermeulen EG, Stehouwer CD, Twisk JW et al. Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: A randomised, placebo-controlled trial. Lancet 2000; 355: 517-22.
18. Schnyder G, Roffi M, Pin R et al. Decreased rate of coronary restenosis after lowering of plasma homocysteine levels. N Engl J Med 2001; 345: 1593-600.
19. Schnyder G, Roffi M, Flammer Y, Pin R, Hess OM: Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: The Swiss Heart study: A randomized controlled trial. JAMA 2002; 288: 973-9.
20. Lange H, Suryapranata H, De LG et al. Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med 2004; 350: 2673-81.
21. Toole JF, Malinow MR, Chambless LE et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: The Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 2004; 291: 565-75.
22. Bonaa KH, Njolstad I, Ueland PM et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006; 354: 1578-88.
23. Lonn E, Yusuf S, Arnold MJ et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006; 354: 1567-77.
24. Thomas PK, Hoffbrand AV: HereditaryAtranscobalamin II deficiency: a 22 year follow up. J Neurol Neurosurg Psychiatry 1997; 62: 197.
25. Teplitsky V, Huminer D, Zoldan J, Pitlik S, Shohat M, Mittelman M: Hereditary partial transcobalamin II deficiency with neurologic, mental and hematologic abnormalities in children and adults. Isr Med Assoc J 2003; 5: 868-72.
26. Miller JW, Garrod MG, Rockwood AL et al. Measurement of total vitamin B12 and holotranscobalamin, singly and in combination, in screening for metabolic vitamin B12 deficiency. Clin Chem 2006; 52: 278-85.
27. Andres E, Loukili NH, Noel E et al. Vitamin B12 (cobalamin) deficiency in elderly patients. Can Med Assoc J 2004; 171: 251-9.
28. Quinlivan EP, McPartlin J, McNulty H et al. Importance of both folic acid and vitamin B12 in reduction of risk of vascular disease. Lancet 2002; 359: 227-8.
29. Robertson J, Iemolo F, Stabler SP, Allen RH, Spence JD: Vitamin B12, homocysteine and carotid plaque in the era of folic acid fortification of enriched cereal grain products. Can Med Assoc J 2005; 172: 1569-73.
30. Rajan S, Wallace JI, Brodkin KI, Beresford SA, Allen RH, Stabler SP: Response of elevated methylmalonic acid to three dose levels of oral cobalamin in older adults. J Am Geriatr Soc 2002; 50: 1789-95.
31. van Oort FV, Melse-Boonstra A, Brouwer IA et al. Folic acid and reduction of plasma homocysteine concentrations in older adults: A dose-response study. Am J Clin Nutr 2003; 77: 1318-23.
32. Spence JD, Cordy P, Kortas C, Freeman D: Effect of usual doses of folate supplementation on elevated plasma homocyst(e)ine in hemodialysis patients: No difference between 1 and 5 mg daily. Am J Nephrol 1998; 19: 405-10.
33. Loscalzo J: Homocysteine trials - clear outcomes for complex reasons. N Engl J Med 2006; 354: 1629-32.
34. House AA, Eliasziw M, Urquhart BL, Freeman DJ, Spence JD: Dimercaptosuccinic acid for the treatment of hyperhomocysteinemia in hemodialysis patients: A placebo-controlled, double-blind, randomized trial. Am J Kidney Dis 2004; 44: 689-94.
35. Urquhart BL, House AA, Cutler MJ, Spence JD, Freeman DJ: Thiol exchange: an in vitro assay that predicts the efficacy of novel homocysteine lowering therapies. J Pharm Sci 2006 In press.
36. Olthof MR, van VT, Boelsma E, Verhoef P: Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women. J Nutr 2003; 133: 4135-8.
37. TRe VITATOPS (Vitamins to Prevent Stroke): Trial: rationale and design of an international, large, simple, randomised trial of homocysteine-lowering multivitamin therapy in patients with recent transient ischaemic attack or stroke. Cerebrovasc Dis 2002; 13: 120-6.