Skip to main content
SpringerLink
Log in

Homocysteine and Cerebral and Peripheral Vascular Disease

  • Chapter
Homocysteine Metabolism: From Basic Science to Clinical Medicine

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 196))

  • 133 Accesses

Abstract

Severe hyperhomocysteinemia due to inherited deficiency of cystathionine β-synthase, 5,10-methylenetetrahydrofolate reductase (MTHFR), or certain enzymes in cobalamin metabolism results in life-threatening arteriosclerosis and venous and arterial thromboembolism in the very young [1–2]. In untreated hyperhomocysteinemia due to cystathione β-synthase deficiency, more than 50% of the cases will develop at least one thromboembolic event before the age of 30 [3]. Of interest is that only about 5% of the vascular events in cystathionine β-synthase deficiency affect the coronary arteries. In contrast, about 30% of the events are cerebrovascular, about 10% affect peripheral arteries, and more than 50% of the events are venous [4].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Mudd SH, Levy HL, Skovby. Disorders of transulfuration. In: Scriver CR, Beaudet AL, Sly WS (eds) Metabolic Basis of Inherited Disease. New York: McGraw-Hill, 1989, pp 693–734.

    Google Scholar 

  2. Ueland PM, Refsum H, Brattström L. Plasma homocysteine and cardiovascular disease. In: Francis RB Jr (ed) Atherosclerotic Cardiovascular Disease, Hemostasis, and Endothelial Function. New York: Marcel Dekker, Inc., 1992, pp 183–235.

    Google Scholar 

  3. Mudd SH, Skovby F, Levy HL et al. The natural history of homocystinuria due to cystathionine β-synthase deficiency. Am J Hum Genet 37:1–31, 1985.

    PubMed  CAS  Google Scholar 

  4. Wilcken DEL, Dudman NPB. Homocystinuria and atherosclerosis. In: Lusis AJ, Rotter JI, Sparkes RS (eds) Molecular Genetics of Coronary Artery Disease: Candidate Genes and Processes in Atherosclerosis. Basel, Switzerland: Karger, 1992, pp 311–324.

    Google Scholar 

  5. Brattström L. Homocysteine in vascular disease: A clinical study of homocysteine metabolism in health and in vascular disease. Thesis, University of Lund, Sweden, 1989.

    Google Scholar 

  6. McCully KS, Wilson RB. Homocysteine theory of arteriosclerosis. Atherosclerosis 22:215–217, 1975.

    Article  PubMed  CAS  Google Scholar 

  7. Brattström LE, Hardebo JE, Hultberg BL. Moderate homocysteinemia: A possible risk factor for arteriosclerotic cerebrovascular disease. Stroke 15:1012–1016, 1984.

    Article  PubMed  Google Scholar 

  8. Boers GHJ, Smals AGH, Trijbels FJM et al. Heterozygosity for homocystinuria in premature peripheral and cerebral occlusive arterial disease. N Engl J Med 313:709–715, 1985.

    Article  PubMed  CAS  Google Scholar 

  9. Araki A, Sako Y, Fukushima Y et al. Plasma sulfhydryl-containing amino acids in patients with cerebral infarction and in hypertensive subjects. Atherosclerosis 79:139–146, 1989.

    Article  PubMed  CAS  Google Scholar 

  10. Malinow MR, Kang SS, Taylor LM et al. Prevalence of hyperhomocyst(e)inemia in patients with peripheral arterial occlusive disease. Circulation 79:1180–1188, 1989.

    Article  PubMed  CAS  Google Scholar 

  11. Coull BM, Malinow MR, Beamer N et al. Elevated plasma homocyst(e)ine concentration as a possible independent risk factor for stroke. Stroke 21:572–576, 1990.

    Article  PubMed  CAS  Google Scholar 

  12. Brattström L, Israelsson B, Norrving B et al. Impaired homocysteine metabolism in early-onset cerebral and peripheral occlusive arterial disease: Effects of pyridox-ine and folic acid treatment. Atherosclerosis 81:51–60, 1990.

    Article  PubMed  Google Scholar 

  13. Brattström L, Tengborn L, Lagerstedt C, Israelsson B, Hultberg B. Plasma homocysteine in venous thromboembolsim. Haemostasis 21:51–57, 1991.

    PubMed  Google Scholar 

  14. Mereau-Richard C, Muller JP, Faivre E, Ardouin P, Rousseaux J. Total plasma homoycsteine determination in subjects with premature cerebral vascular disease. Clin Chem 37:126, 1991.

    PubMed  CAS  Google Scholar 

  15. Taylor FM, DeFrang RD, Harris EJ, Porter JM. The association of elevated plasma homocyst(e)ine with progression of symptomatic peripheral arterial disease. J Vasc Surg 13:128–136, 1991.

    Article  PubMed  Google Scholar 

  16. Clarke R, Daly L, Robinson K et al. Hyper-homocyst(e)inemia: an independent risk factor for vascular disease. N Engl J Med 324:1149–1155, 1991.

    Article  PubMed  CAS  Google Scholar 

  17. Brattström L, Lindgren A, Israelsson B et al. Hyper-homocysteinaemia in stroke: Prevalence, cause, and relationships to type of stroke and stroke risk factors. Eur J Clin Invest 22:214–221, 1991.

    Article  Google Scholar 

  18. Mölgaard J, Malinow MR, Lassvik C et al. Hyper-homocyst(e)inemia: An independent risk factor for intermittent claudication. J Intern Med 231:273–279, 1992.

    Article  PubMed  Google Scholar 

  19. Bergmark C, Mansoor Ma, Swedenborg J et al. Hyper-homocysteinemia in patients operated for lower extremity ischemia below the age of 50: Effect of smoking and extent of disease. Eur J Vasc Surg 7:391–396, 1993.

    Article  PubMed  CAS  Google Scholar 

  20. Dudman NPB, Wilcken DEL, Wang J et al. Disordered methionine/homocysteine metabolism metabolism in premature vascular disease. Arterioscler Thromb 13:1253–1260, 1993.

    Article  PubMed  CAS  Google Scholar 

  21. Bienvenu T, Ankri A, Chadefaux B, Montalescot G, Kamoun P. Elevated total plasma homocysteine, a risk factor for thrombosis: Relation to coagulation and fibrinolytic parameters. Thromb Res 70:123–129, 1993.

    Article  PubMed  CAS  Google Scholar 

  22. Malinow MR, Nieto FJ, Szklo M, Chambless LE, Bond G. Carotid artery intimal-medial wall thickening and plasma homocyst(e)ine in asymptomatic adults. Circulation 87:1107–1113, 1993.

    Article  PubMed  CAS  Google Scholar 

  23. Franken DG, Boers GHJ, Blom HJ, Trijbels FJM, Kloppenborg PWC. Treatment of mild hyper-homocysteinemia in vascular disease patients. Arterioscler Thromb 14:465–470, 1994.

    Article  PubMed  CAS  Google Scholar 

  24. Falcon Cr, Cattaneo M, Panzeri D, Martinelli I, Mannucci PM. High prevalence of hyper-homocyst(e)inemia in patients with juvenile venous thrombosis. Arterioscler Thromb 14:1080–1083, 1994.

    Article  PubMed  CAS  Google Scholar 

  25. Aronson DC, Onkenhout W, Raben AMTJ et al. Impaired homocysteine metabolism: A risk factor in young adults with atherosclerotic arterial occlusive disease of the leg. Br J Surg 81:1114–1118, 1994.

    Article  PubMed  CAS  Google Scholar 

  26. Verhoef P, Hennekens CH, Malinow MR et al. A prospective study of plasma homocyst(e)ine and risk of ischemic stroke. Stroke 25:1924–1930, 1994.

    Article  PubMed  CAS  Google Scholar 

  27. Alfthan G, Pekkanen J, Jauhianinen M et al. Relation of serum homocysteine and lipoprotein (a) concentrations of atherosclerotic disease in a prospective Finnish population based study. Atherosclerosis 106:9–19, 1994.

    Article  PubMed  CAS  Google Scholar 

  28. van den Berg M, Franken DG, Boers GHJ et al. Combined vitamin B6 plus folic acid therapy in young patients with arteriosclerosis and hyperhomocysteine-mia. J Vasc Surg 20:933–940, 1994.

    Article  PubMed  Google Scholar 

  29. Selhub J, Jacques PF, Bostom AG et al. Plasma homocysteine and extracranial carotid stenosis in the Framingham Heart Study. N Engl J Med 332:289–291, 1995.

    Article  Google Scholar 

  30. den Heijer M, Blom HJ, Gerrits WBJ et al. Is hyperhomocysteinaemia a risk factor for recurrent venous thrombosis? Lancet 345:882–885, 1995

    Article  Google Scholar 

  31. Lindgren A, Brattström L, Norrving B et al. Plasma homocysteine in the acute and convalescent phases after stroke. Stroke 26:795–800, 1995.

    Article  PubMed  CAS  Google Scholar 

  32. Graham I. Interactions between hyperhomocysteinaemia and conventional risk factors in vascular disease. Eur Heart J 15:530, 1994.

    Article  Google Scholar 

  33. Arnadottir M, Brattström L, Simonsen O et al. The effect of high-dose pyridoxine and folic acid supplementation on serum lipids and plasma homocysteine concentrations in dialysis patients. Clin Nephr 40:236–240, 1993.

    CAS  Google Scholar 

  34. Kang SS, Wong PWK, Susmano A et al. Thermolabile methylenetetrahydrofolate reductase: An inherited risk factor for coronary artery disease. Am J Hum Genet 48:536–545, 1991.

    PubMed  CAS  Google Scholar 

  35. Engbersen AMT, Franken DG, Boers GHJ et al. Thermolabile 5,10-methylenetetrahydrofolate reductase as a cause of mild hyperhomocysteinemia. Am J Hum Genet 56:142–150, 1995.

    PubMed  CAS  Google Scholar 

  36. Brattström L, Israelsson B, Lindgärde F, Hultberg B. Higher total plasma homocysteine in vitamin B12 deficiency than in heterozygosity for homocysteinuria due to cystathionine beta-synthase deficiency. Metabolism 37:175–178, 1988.

    Article  PubMed  Google Scholar 

  37. Kang S, Wong PWK, Norusis M. Homocysteinemia due to folate deficiency. Metabolism 36:458–462, 1987.

    Article  PubMed  CAS  Google Scholar 

  38. Whitehead AS, Ward P, Tan S et al. The molecular genetics of homocystinuria, hyperhomocysteinaemia, and premature vascular disease in Ireland. In: Mato JM, Caballero A (eds) Methionine Metabolism: Molecular Mechanisms and Clinical Implications. Madrid, Spain: Consejo Superior de Investigaciones Cientificas, 1994, pp 80–83.

    Google Scholar 

  39. Wilcken DEL, Wilcken B. The pathogenesis of coronary artery disease: A possible role for methionine metabolism. J Clin Invest 57:1079–1082, 1976.

    Article  PubMed  CAS  Google Scholar 

  40. Andersson A, Brattström L, Israelsson B et al. Plasma homocysteine before and after methionine loading with regard to age, gender, and menopausal status. Eur J Clin Invest 22:79–87, 1992.

    Article  PubMed  CAS  Google Scholar 

  41. Mudd SH, Havli R, Levy HL, McKusick VA, Feinleib M. A study of cardiovascular risk in heterozygouss for homocystinuria. Am J Hum Genet 33:883–893, 1981.

    PubMed  CAS  Google Scholar 

  42. Miller JW, Nadeau MR, Smith D, Selhub J. Vitamin B6 deficiency vs folate deficiency: Comparison of responses to methionine loading in rats. Amer J Clin Nutr 59:1033–1039, 1994.

    PubMed  CAS  Google Scholar 

  43. Guttormsen AB, Schneede J, Fiskestrand T, Ueland PM, Refsum HM. Plasma concentrations of homocysteine and other aminothiol compounds are related to food intake in healthy human subjects. J Nutr 124:1934–1941, 1994.

    PubMed  CAS  Google Scholar 

  44. Stampfer MJ, Malinow MR, Willett WC et al. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA 268:877–881, 1992.

    Article  PubMed  CAS  Google Scholar 

  45. Israelsson B, Brattström L, Refsum H. Homocysteine in frozen samples: A short cut to establish hyperhomocysteinemia as a risk factor for arteriosclerosis? Scand J Clin Lab Invest 53:465–469, 1993.

    Article  PubMed  CAS  Google Scholar 

  46. Brattström L, Lindgren A, Israelsson B, Andersson A, Hultberg B. Homocysteine and cysteine: Determinants of plasma levels in middle-aged elderly subjects. J Intern Med 236:633–641, 1994.

    Article  PubMed  Google Scholar 

  47. Selhub J, Jacques PF, Wilson PWF, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of homocysteinemia in the elderly. JAMA 270:2693–2698, 1994.

    Article  Google Scholar 

  48. Pancharuniti N, Lewis CA, Sauberlich HE et al. Plasma homocyst(e)ine, folate, and vitamin B12 concentrations and risk for early coronary artery disease. Am J Clin Nutr 59:940–948, 1994.

    PubMed  CAS  Google Scholar 

  49. Brattström L. Vitamins as homocysteine-lowering agents. J Nutr 126:1276S–1280S, 1996.

    Google Scholar 

  50. Brattström LE, Hultberg BL, Hardebo JE. Folic acid responsive postmenopausal homocysteinemia. Metabolism 34:1073–1077, 1985.

    Article  PubMed  Google Scholar 

  51. Brattström L, Israelsson B, Heppsson JO, Hultberg B. Folic acid: An innocuous means of reducing plasma homocysteine. ScandJ Clin Invest 48:215–221, 1988.

    Article  Google Scholar 

  52. Landgren F, Israelsson B, Lindgren A, et al. Plasma homocysteine in acute myocardial infarction: Homocysteine-lowering effect of folic acid. J Intern Med 237:381–388, 1995.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Lars Brattström
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. The Adelaide Hospital, Trinity College, Dublin, Ireland

    Ian Graham MD

  2. Department of Clinical Biology, University of Bergen, Bergen, Norway

    Helga Refsum MD  & Per Magne Ueland MD  & 

  3. Jean Mayer Usda Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA

    Irwin H. Rosenberg MD

  4. Tufts University School of Nutrition Science and Policy, Medford, MA, USA

    Jill M. Shuman MS, RD, ELS

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer Science+Business Media New York

About this chapter

Cite this chapter

Brattström, L. (1997). Homocysteine and Cerebral and Peripheral Vascular Disease. In: Graham, I., Refsum, H., Rosenberg, I.H., Ueland, P.M., Shuman, J.M. (eds) Homocysteine Metabolism: From Basic Science to Clinical Medicine. Developments in Cardiovascular Medicine, vol 196. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5771-5_28

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-5771-5_28

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7645-3

  • Online ISBN: 978-1-4615-5771-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation