Drugs affecting homocysteine metabolism: Impact on cardiovascular risk

Cyrus Desouza, Mary Keebler, Dennis B. McNamara, Vivian Fonseca

Research output: Contribution to journalReview article

101 Citations (Scopus)

Abstract

Elevated total plasma homocysteine has been established as an independent risk factor for thrombosis and cardiovascular disease. A strong relationship between plasma homocysteine levels and mortality has been reported in patients with angiographically confirmed coronary artery disease. Homocysteine is a thiol containing amino acid. It can be metabolised by different pathways, requiring various enzymes such as cystathionine β-synthase and methylenetetrahydrofolate reductase. These reactions also require several co-factors such as vitamin B6 and folate. Medications may interfere with these pathways leading to an alteration of plasma homocysteine levels. Several drugs have been shown to effect homocysteine levels. Some drugs frequently used in patients at risk of cardiovascular disease, such as the fibric acid derivatives used in certain dyslipidaemias and metformin in type 2 (non-insulin-dependent) diabetes mellitus, also raise plasma homocysteine levels. This elevation poses a theoretical risk of negating some of the benefits of these drugs. The mechanisms by which drugs alter plasma homocysteine levels vary. Drugs such as cholestyramine and metformin interfere with vitamin absorption from the gut. Interference with folate and homocysteine metabolism by methotrexate, nicotinic acid (niacin) and fibric acid derivatives, may lead to increased plasma homocysteine levels. Treatment with folate or vitamins B6 and B 12 lowers plasma homocysteine levels effectively and is relatively inexpensive. Although it still remains to be demonstrated that lowering plasma homocysteine levels reduces cardiovascular morbidity, surrogate markers for cardiovascular disease have been shown to improve with treatment of hyperhomocystenaemia. Would drugs like metformin, fibric acid derivatives and nicotinic acid be more effective in lowering cardiovascular morbidity and mortality, if the accompanying hyperhomocysteinaemia is treated? The purpose of this review is to highlight the importance of homocysteine as a risk factor, and examine the role and implications of drug induced modulation of homocysteine metabolism.

Original languageEnglish (US)
Pages (from-to)605-616
Number of pages12
JournalDrugs
Volume62
Issue number4
DOIs
StatePublished - Jan 1 2002

Fingerprint

Homocysteine
Metabolism
Pharmaceutical Preparations
Plasmas
Fibric Acids
Niacin
Metformin
Folic Acid
Vitamin B 6
Cardiovascular Diseases
Cystathionine
Cholestyramine Resin
Morbidity
Methylenetetrahydrofolate Reductase (NADPH2)
Hyperhomocysteinemia
Mortality
Vitamin B 12
Medical problems
Dyslipidemias
Sulfhydryl Compounds

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Drugs affecting homocysteine metabolism : Impact on cardiovascular risk. / Desouza, Cyrus; Keebler, Mary; McNamara, Dennis B.; Fonseca, Vivian.

In: Drugs, Vol. 62, No. 4, 01.01.2002, p. 605-616.

Research output: Contribution to journalReview article

Desouza, Cyrus ; Keebler, Mary ; McNamara, Dennis B. ; Fonseca, Vivian. / Drugs affecting homocysteine metabolism : Impact on cardiovascular risk. In: Drugs. 2002 ; Vol. 62, No. 4. pp. 605-616.
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