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Thromb Haemost 1998; 80(06): 874-877
DOI: 10.1055/s-0037-1615380
Letters to the Editor
Schattauer GmbH

Hyperhomocysteinemia and Venous Thrombosis: A Meta-analysis

Martin den Heijer
1   Department of Hematology, Leyenburg Hospital, The Hague
,
Frits R. Rosendaal
2   Department of Clinical Epidemiology and Department of Hematology, University Hospital Leiden
,
Henk J. Blom
3   Laboratory of Paediatrics and Neurology, University Hospital Nijmegen, The Netherlands
,
Wim B. J. Gerrits
1   Department of Hematology, Leyenburg Hospital, The Hague
,
Gerard M. J. Bos
1   Department of Hematology, Leyenburg Hospital, The Hague
› Author AffiliationsPresent addresses: Dr. Gerard M. J. Bos is presently a fellow of the Dutch Cancer Foundation.
Further Information

Publication History

Received 19 March 1998

Accepted after resubmission 20 August 1998

Publication Date:
07 December 2017 (online)

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Summary

Hyperhomocysteinemia is an established risk factor for atherosclerosis and vascular disease. Until the early nineties the relationship with venous thrombosis was controversial. At this moment ten case-control studies on venous thrombosis are published. We performed a meta-analysis of these reports.

We performed a MEDLINE-search from 1984 through June 1997 on the keywords “homocysteine” or “hyperhomocysteinemia” and “venous thrombosis”, which yielded ten eligible case-control studies.

We found a pooled estimate of the odds ratio of 2.5 (95% CI 1.8-3.5) for a fasting plasma homocysteine concentration above the 95th percentile or mean plus two standard deviations calculated from the distribution of the respective control groups. For the post-methionine increase in homocysteine concentration we found a pooled estimate of 2.6 (95% CI 1.6-4.4).

These data from case-control studies support hyperhomocysteinemia as a risk factor for venous thrombosis. Further research should focus on the pathophysiology of this relationship and on the clinical effects of reducing homocysteine levels by vitamin supplementation.

 

  • References

  • 1 du Vigneaud V, Ressler C, Rachele JR. The biological synthesis of “labile methyl groups”.. Science 1950; 112: 267-71.
    CrossrefPubMedGoogle Scholar
  • 2 Carson NAJ, Neill DW. Metabolic abnormalities detected in a survey of mentally backward individuals in Northern Ireland.. Arch Dis Child 1962; 37: 505-13.
    CrossrefPubMedGoogle Scholar
  • 3 Gerritsen T, Vaughn JG, Weisman HA. The identification of homocysteine in the urine.. Biochem Biophys Res Commun 1962; 9: 493.
    CrossrefPubMedGoogle Scholar
  • 4 Gerritsen T, Waisman HA. Homocystinuria, an error of metabolism of methionine.. Pediatrics 1964; 33: 413-20.
    PubMedGoogle Scholar
  • 5 Mudd SH, Finkelstein JD, Irreverre F, Laster L. Homocystinuria: an enzymatic defect.. Science 1964; 143: 1443-5.
    CrossrefPubMedGoogle Scholar
  • 6 Boushy CJ, Beresford SAA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease – probable benefits of increasing folic acid intakes.. JAMA 1995; 274: 1049-57.
    CrossrefPubMedGoogle Scholar
  • 7 Mudd SH, Skovby F, Levy HL. et al. The natural history of homocystinuria due to cystathionine beta synthase deficiency.. Am J Hum Genet 1985; 37: 131.
    PubMedGoogle Scholar
  • 8 Bienvenu T, Ankri A, Chadefaux B, Kamoun P. Plasma homocysteine assay in the exploration of thrombosis in young subjects.. Presse Med 1991; 20: 9858.
    PubMedGoogle Scholar
  • 9 Brattström L, Tengborn L, Israelsson B, Hultberg B. Plasma homocysteine in venous thromboembolism.. Haemostasis 1991; 21: 517.
    PubMedGoogle Scholar
  • 10 Bienvenu T, Ankri A, Chadefaux Montalescot G, Kamoun P. Elevated total plasma homocysteine, a risk factor for thrombosis, relation to coagulation and fibrinolytic parameters.. Thromb Res 1993; 70: 123-9.
    CrossrefPubMedGoogle Scholar
  • 11 Beaumont V, Malinow MR, Sexton G, Wilson D, Lemort N, Upson B, Beaumont JL. Hyperhomocyst(e)inemia, anti-estrogen antibodies and other risk factors for thrombosis in women on oral contraceptives.. Atherosclerosis 1992; 94: 147-52.
    CrossrefPubMedGoogle Scholar
  • 12 Falcon CR, Cattaneo M, Panzeri D, Martinelli I, Munnucci PM. High prevalence of hyperhomocyst(e)inemia in patients with juvenile venous thrombosis.. Arterioscler Thromb 1994; 14: 1080-3.
    CrossrefPubMedGoogle Scholar
  • 13 Heijer M den, Blom HJ, Gerrits WBJ, Rosendaal FR, Haak HL, Wijermans PW, Bos GMJ. Is hyperhomocysteinaemia a risk factor for recurrent venous thrombosis?. Lancet 1995; 345: 882-5.
    CrossrefPubMedGoogle Scholar
  • 14 Amundsen T, Ueland PM, Waage A. Plasma homocysteine levels in patients with deep venous thrombosis.. Arterioscler Thromb Vasc Biol 1995; 15: 1321-3.
    CrossrefPubMedGoogle Scholar
  • 15 Fermo I, D’Angelo SV, Paroni R, Mazzola G, Calori G, D’Angelo A. Prevalence of moderate hyperhomocysteinemia in patients with early-onset venous and arterial occlusive disease.. Ann Intern Med 1995; 123: 747-53.
    CrossrefPubMedGoogle Scholar
  • 16 den Heijer M, Koster T, Blom HJ, Bos GMJ, Briët E, Reitsma P, Vandenbroucke JP, Rosendaal FR. Hyperhomocysteinemia as a risk factor for deep-vein thrombosis.. N Engl J Med 1996; 334: 759-62.
    CrossrefPubMedGoogle Scholar
  • 17 Cattaneo M, Martinelli I, Mannucci PM. Hyperhomocysteinemia as a risk factor for deep-vein thrombosis [letter].. N Engl J Med 1996; 335: 974-5.
    CrossrefPubMedGoogle Scholar
  • 18 Simioni P, Prandoni P, Burlina A, Tormene D, Sardella C, Ferrari V, Benedetti L, Girolami A. Hyperhomocysteinemia and deep-vein thrombosis. A case-control study.. Thromb Haemost 1996; 76: 883-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Ridker PM, Hennekens CH, Selhub J, Miletich JP, Malinow MR, Stampfer MJ. Interrelation of hyperhomocyst(e)inemia, factor V Leiden, and the risk of future venous thrombosembolism.. Circulation 1997; 95: 1777-82.
    CrossrefPubMedGoogle Scholar
  • 20 Kyrle PA, Stumpflen A, Hirschl M, Bialonczyk C, Herkner K, Speiser W. et al. Levels of prothrombin fragment F1+2 in patients with hyperhomocysteinemia and a history of venous thromboembolism.. Thromb Haemost 1997; 78: 1327-31.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Rothman KJ. Modern epidemiology.. Boston/Toronto: 1986
    PubMedGoogle Scholar
  • 22 Greenland S. Quantitative methods in the review of epidemiologic literature.. Epidemiol Rev 1987; 9: 1-30.
    CrossrefPubMedGoogle Scholar
  • 23 Rees MM, Rodgers GM. Homocysteinemia: association of a metabolic disorder with vascular disease and thrombosis.. Thromb Res 1993; 71: 337-59.
    CrossrefPubMedGoogle Scholar
  • 24 Ueland PM, Refsum H, Brattstrom L. Plasma Homocysteine and Cardiovascular Disease.. In: Atherosclerotic Cardiovascular Disease, Hemostasis, and Endothelial Function.. Francis Jr. RB. ed. New York; Basel, Hong Kong: Marcel Dekker, Inc.,: 1993. pp 183-236.
    Google Scholar
  • 25 Stamler JS, Slivka A. Biochemical chemistry of thiols in the vasculature and in vascular-related disease.. Nut rev 1996; 54: 1-30.
    PubMedGoogle Scholar
  • 26 Homocysteine Lowering Trialists’ Collaboration.. Lowering blood homo-cysteine with folic acid based supplements: meta-analysis of randomised trials.. BMJ 1998; 316: 894-8.
    CrossrefPubMedGoogle Scholar
  • 27 den Heijer M, Brouwer IA, Bos GMJ, Blom HJ, van der Put NMJ, Spaans AP, Rosendaal FR, Thomas CMG, Haak HL, Wijermans PW, Gerrits WBJ. Vitamin supplementation reduces blood homocysteine levels. A controlled trial in patients with venous thrombosis and healthy volunteers.. Arterioscler Thromb Vasc Biol 1998; 18: 356-61.
    CrossrefPubMedGoogle Scholar
  • 28 den Heijer M, Bos GMJ, Gerrits WBJ, Blom HJ. Will a decrease of blood homocysteine by vitamin supplementation reduce the risk for vascular disease?. Fibrinolysis 1994; 8 (02) 91-2.
    PubMedGoogle Scholar