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Review ArticleReview

Homocysteine Determinants and the Evidence to What Extent Homocysteine Determines the Risk of Coronary Heart Disease

Angelika De Bree, W. M. Monique Verschuren, Daan Kromhout, Leo A. J. Kluijtmans and Henk J. Blom
Pharmacological Reviews December 2002, 54 (4) 599-618; DOI: https://doi.org/10.1124/pr.54.4.599
Angelika De Bree
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W. M. Monique Verschuren
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Daan Kromhout
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Leo A. J. Kluijtmans
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Henk J. Blom
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Abstract

Cardiovascular diseases (CVD), especially coronary heart disease (CHD), are the most important causes of death in industrialized countries. Increased concentrations of total plasma homocysteine (tHcy) have been associated with an increased risk of CHD. Assuming that this relation is causal, a lower tHcy concentration will reduce the occurrence and recurrence of CHD. Therefore, it is important to know which factors determine the tHcy concentration. In the general population, the most important modifiable determinants of tHcy are folate intake and coffee consumption. Smoking and alcohol consumption are also associated with the tHcy concentration, but more research is necessary to elucidate whether these relations are not originating from residual confounding due to other lifestyle factors. The most important nonmodifiable determinant is the 677 C>T polymorphism in the gene that encodes methylenetetrahydrofolate reductase (MTHFR), a regulating enzyme in homocysteine metabolism. Especially subjects with the homozygous form of this polymorphism (i.e., 677TT genotype) and a low folate status have elevated tHcy concentrations. Specific clinical conditions like the use of antiepileptic drugs or methotrexate, renal failure, cancer, rheumatoid arthritis, and hypothyroidism may lead to elevated tHcy concentrations. The available epidemiological evidence indicates that an increased tHcy concentration is not an important risk factor for CHD in healthy subjects. However, prospective studies, which included subjects at high risk of CHD, and secondary prevention trials with intermediary endpoints consistently show that elevations in the tHcy concentration may be an important risk factor in these subjects for a (recurrent) CHD event. The induction of vascular endothelial dysfunction by homocysteine may underlie this increased risk. Ongoing intervention trials will indicate whether homocysteine-lowering through vitamin supplementation, prevents CHD in the treatment groups.

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Pharmacological Reviews: 54 (4)
Pharmacological Reviews
Vol. 54, Issue 4
1 Dec 2002
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Review ArticleReview

Homocysteine Determinants and the Evidence to What Extent Homocysteine Determines the Risk of Coronary Heart Disease

Angelika De Bree, W. M. Monique Verschuren, Daan Kromhout, Leo A. J. Kluijtmans and Henk J. Blom
Pharmacological Reviews December 1, 2002, 54 (4) 599-618; DOI: https://doi.org/10.1124/pr.54.4.599

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Review ArticleReview

Homocysteine Determinants and the Evidence to What Extent Homocysteine Determines the Risk of Coronary Heart Disease

Angelika De Bree, W. M. Monique Verschuren, Daan Kromhout, Leo A. J. Kluijtmans and Henk J. Blom
Pharmacological Reviews December 1, 2002, 54 (4) 599-618; DOI: https://doi.org/10.1124/pr.54.4.599
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  • Article
    • Abstract
    • I. Introduction
    • II. History of Homocysteine As a Risk Factor for Vascular Diseases
    • III. Homocysteine Metabolism
    • IV. Determinants of Homocysteine Concentration in the General Population
    • V. Drugs and Diseases As Determinants of Homocysteine Concentrations
    • VI. Homocysteine and the Risk of Coronary Heart Disease
    • VII. Directions for Future Research
    • VIII. Implications for Prevention and Treatment
    • Acknowledgments
    • Footnotes
    • Abbreviations
    • References
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