Skip to main content
Log in

Hyperhomocysteinaemia: a risk factor for extracranial carotid artery atherosclerosis

  • Published:
Irish Journal of Medical Science Aims and scope Submit manuscript

Abstract

Hyperhomocysteinemia arising from impaired methionine metabolism, and usually due to a deficiency of cystathionine ß-synthase is a significant and independent risk factor for symptomatic vascular disease. It is not known if hyperhomocysteinemia in apparently healthy asymptomatic subjects is associated with atherosclerosis and whether such a relationship is independent of conventional risk factors. The prevalence of asymptomatic extracranial carotid artery atherosclerosis was determined by duplex ultrasound examination in 25 obligate heterozygotes with respect for cystathionine ß-synthase deficiency (whose children were known to be homozygous for this genetic defect) and in 21 controls. Hyperhomocysteinemia was determined by a standard methionine-loading test and conventional risk factors were also recorded. Twelve of 25 obligate heterozygotes and 8 of 21 normal controls had evidence of extracranial carotid artery atherosclerosis. Hyperhomocysteinemia as a genetic trait was not a significant risk marker, but the actual homocysteine level was associated with an increased risk of carotid disease. After adjustment for the effects of other significant risk factors, the odds ratio of hyperhomocysteinemia for carotid disease was 1.038 per unit increase in homocysteine level (P=0.03). Hyperhomocysteinemia is a weak risk factor for asymptomatic extracranial carotid atherosclerosis and the relative risk associated with this genetic trait is less than that observed in a study of patients presenting with clinical manifestations of vascular disease.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Arteriosclerosis: Report of the Working Group on Arteriosclerosis of the National Heart Lung and Blood Institute: Vol. 2, Washington DC 1981, US Department of Health and Human Services (Publication no. 82-2035).

  2. Salonen, J. T., Salonen, R. Association of serum low density lipoprotein cholesterol, smoking and hypertension with different manifestations of atherosclerosis. Int. J. Epidemiology 1990: 19, 1–7.

    Article  Google Scholar 

  3. Crouse, J. R., Toole, J. F., McKinney, W. M.et al. Risk factors for extracranial carotid artery atherosclerosis. Stroke 1987: 18, 990–996.

    PubMed  CAS  Google Scholar 

  4. Mudd, S. H., Levy, H. L., Skovby, F. Disorders of transulfuration. In: Scriver, Beaudet, A. L., Sly, W. S., Valle, D., eds. The metabolic basis of inherited disease. 6th Edit. New York: McGraw-Hill 1989: 893- 734.

    Google Scholar 

  5. Clarke, R., Daly, L., Robinson, R.et al. Hyperhomocysteinemia: an independent risk factor for vascular disease. N. Engl. J. Med. 1991:324, 1149–55.

    PubMed  CAS  Google Scholar 

  6. Boers, G. H., Smais, A. G., Trijbels, F. J.et al. Heterozygosity for homocystinuria in premature peripheral and cerebral occlusive arterial disease. N. Engl. J. Med. 1985: 313, 709–15.

    PubMed  CAS  Google Scholar 

  7. Brattstrom, L. E., Hardebo, J. E., Hultberg, B. L. Moderate homocys-teinemia - a possible risk factor for arteriosclerotic cerebrovascular disease. Stroke 1984: 15, 1012–6.

    PubMed  CAS  Google Scholar 

  8. Araki, A., Sako, Y., Fukushima, Y., Matsumoto, M., Asada, T., Kita, T. Plasma sulfhydril-containing amino acids in patients with cerebral infarction and in hypertensive subjects. Atherosclerosis 1989: 79, 139–46.

    Article  PubMed  CAS  Google Scholar 

  9. Malinow, M. R., Kang, S. S., Taylor, L. M.et al. Prevalence of hyperhomocyst(e)inemia in patients with peripheral arterial occlusive disease. Circulation 1989: 79, 1180–8.

    PubMed  CAS  Google Scholar 

  10. Wilcken, D. E., Wilcken, B. The pathogenesis of coronary artery disease, a possible role formethionine metabolism. J. Clin. Invest. 1976: 57, 1079–82.

    Article  PubMed  CAS  Google Scholar 

  11. Wilcken,D. E., Reddy.G. S., Gupta,V. J. Homocysteinemia, ischaemic heart disease, and the carrier state for homocystinuria. Metabolism 1983: 32, 363–70.

    Article  PubMed  CAS  Google Scholar 

  12. Murphy-Chutorian, D. R., Wexman, M. P., Grieco, A. J.et al. Methionine intolerance: a possible risk factor for coronary artery disease. J. Am. Coll. Cardiol. 1985: 6, 725–30.

    Article  PubMed  CAS  Google Scholar 

  13. Israelsson,B., Brattstrom, L. E., Hultberg, B. L. Homocysteine and myocardial infarction. Atherosclerosis 1988: 71, 227–33.

    Article  PubMed  CAS  Google Scholar 

  14. Kang, S. S., Wong, P. W., Cook, H. Y., Norusis, M., Messer, J. V. Protein-bound homocyst(e)ine: a possible risk factor for coronary artery disease. J. Clin. Invest. 1986: 77, 1482–6.

    Article  PubMed  CAS  Google Scholar 

  15. Olszewski, A. J., Szostak, W. B. Homocysteine content of plasma proteins in ischemic heart disease. Atherosclerosis 1988: 69, 109–13.

    Article  PubMed  CAS  Google Scholar 

  16. Mudd, S.H., Havlik,R., Levy, H. L., McKusick, V. A., Feinleib, M. A study of cardiovascular risk in heterozygotes for homocystinuria. Am. J. Human Genet. 1981: 33, 883–93.

    CAS  Google Scholar 

  17. Swift, M., Morrei, D. Cardiovascular risk in homocystinuria family members. Am. J. Hum. Genet. 1982: 34, 1016–18.

    PubMed  CAS  Google Scholar 

  18. Rubba, P., Faccenda, P., Carbone, L.et al. Early signs of vascular disease in homocystinuria: a noninvasive study by ultrasound methods in eight families with cystathionine ß-synthase deficiency. Metabolism 1990: 39, 1191–5.

    Article  PubMed  CAS  Google Scholar 

  19. Pignoli, P., Tremoli, E., Poli, A., Oreste, P., Paoletti, R. Intimai plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. Circulation 1986: 74, 1399–1406.

    PubMed  CAS  Google Scholar 

  20. The ARIC Investigators. The Atherosclerosis Risk in Communities (ARIC) study; design and objectives. Am. J. Epidemiol. 1989: 129, 687–702.

    Google Scholar 

  21. Frimpter, G. W. The disulfide of L-cysteine and L-homocysteine in urine of patients with cystinuria. J. Biol. Chem. 1961: 236, 51–3.

    Google Scholar 

  22. SAS Institute Inc. A SASR language guide for personal computers. 6th Edition. Cary, N. SAS Institute Inc., 1985.

  23. Harker, L. A., Ross, R., Slichter, S. J., Scott, R. Homocystine-induced arteriosclerosis: The role of endothelial cell injury and the platelet response in its genesis. J. Clin. Invest. 1976: 58, 731–41.

    Article  PubMed  CAS  Google Scholar 

  24. Wall, R. T., Harlan, J. M., Harker, L. A., Striker, G. E. Homocysteine-induced endothelial cell injury in vitro: A model for the study of vascular injury. Thromb. Res. 1980: 18, 113–21.

    Article  PubMed  CAS  Google Scholar 

  25. Parthasarathy, S. Oxidation of low density lipoprotein by thiol compounds leads to its recognition by the acetyl-LDL receptor. Biochim. Biophys. Acta 1987: 917, 337–40.

    PubMed  CAS  Google Scholar 

  26. Heinecke, J. W., Rosen, H., Suzuki, L. A. The role of sulfur-containing amino acids in Superoxide production and modification of low density lipoprotein by arterial smooth muscle cells. J. Biol. Chem. 1987: 262, 10098–103.

    PubMed  CAS  Google Scholar 

  27. Graeber, J. E., Slott, J. H., Ulane, R. E., Schulman, J. D., Stuart, M. J. The effect of homocysteine and homocystine on platelet and vascular arachidonic acid metabolism. Pediatr. Res. 1982: 16, 490–3.

    Article  PubMed  CAS  Google Scholar 

  28. McCully, K. S., Carvalho, A. C. Homocysteine thiolactone, N-homocysteine thiolactonyl retinamide and platelet aggregation. Res. Commun. Chem. Pathol. Pharmol. 1987: 56, 349–60.

    CAS  Google Scholar 

  29. Rodgers, G. M., Kane, W. H. Activation of endogenous factor V by homocysteine-induced vascular endothelial cell activator. J. Clin. Invest. 1986: 77, 1909–16.

    Article  PubMed  CAS  Google Scholar 

  30. Rogers, G. M., Conn, M. T. Homocysteine, an atherogenic stimulus, reduces protein activation by arterial and venous endothelial cells. Blood 1990: 75, 875–901.

    Google Scholar 

  31. Panganamala, R. V., Karpen, W., Merola, A. J. Peroxide mediated effects of homocysteine on arterial prostacyclin synthesis. Prostaglandins Leukotrienes Med. 1986: 22, 349–56.

    Article  CAS  Google Scholar 

  32. Robinson, K. (ed.). Homocysteinemia and vascular disease, Proceedings of the European Community COMAC-Epidemiology Expert Group Workshop. Luxembourg: Office of official publications of the European communities, 1990 (publication no. CD-NA-12834).

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported in part by a grant from the Health Research Board of Ireland.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Clarke, R., Fitzgerald, D., O’Brien, C. et al. Hyperhomocysteinaemia: a risk factor for extracranial carotid artery atherosclerosis. I.J.M.S. 161, 61–65 (1992). https://doi.org/10.1007/BF02983714

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02983714

Keywords

Navigation