I. Homocysteine Metabolism
II. Homocysteine and Vascular Disease
III. Clinical Studies
IV. Conditions Causing Hyperhomocystinemia
V. Screening
VI. Management of Hyperhomocystinemia
VII. Benefits of Decreasing Homocysteine Levels
VIII. Clinical Studies

methionine is demethylated to yield adenosine and homo-cysteine. In a reaction requiring the vitamin B6-dependent enzyme cystathionine, beta-synthase homocysteine becomes irreversibly transsulfurated to cysteine. In addition, homo-cysteine can be remethylated back to methionine in a pathway that utilizes vitamin B12-dependent methionine synthase.

GLOSSARY
atheroma same as atherosclerosis, raised plaques filled with
cholesterol, calcium, and other substances on the inner wall
of arteries that obstruct the lumen and the flow of blood;
the plaque of atheroma hardens the artery, hence the term
atherosclerosis (sclerosis ¼ hardening). endothelial pertaining to the innermost part of the intima that
comes in contact with circulating blood. myocardial infarction death of an area of heart muscle due to
blockage of a coronary artery by blood clot and atheroma;
medical term for heart attack or coronary thrombosis.
HYPERHOMOCYSTINEMIA HAS BEEN IDENTIFIED AS a possible risk factor in the development of cardiac, cerebral, and peripheral vascular disease as well as acute thrombotic events. Unfortunately this assumption is based mainly on the results of case control studies and prospective studies have not been as compelling. In addition, there is growing belief that atheromatous disease of arteries itself may elevate homocysteine levels, and that this controversial risk factor is only a silent bystander and should be considered a marker rather than a true risk factor.

• I. HOMOCYSTEINE METABOLISM
  Homocysteine, a sulfa-containing amino acid, is an inter¬mediate formed during the metabolism of the essential amino acid methionine. In this metabolic pathway,
• II. HOMOCYSTEINE AND VASCULAR DISEASE
  Epidemiologic studies suggest that hyperhomocystinemia may be an independent risk factor for developing athero-thrombotic vascular disease. Although the mechanism for accelerated atherosclerosis is unclear, proposed mecha¬nisms for increased risk of coronary artery disease include endothelial dysfunction and toxicity, induction of vascular smooth muscle cell proliferation, impairment of nitric oxide, increased LDL oxidation, and enhanced thrombosis. Hyperhomocystinemia has not been shown in animals or in humans to cause atheroma formation, which leads to obstructive lesions in coronary arteries, cerebral arteries, the aorta, or vessels leading to the legs. Pathologic lesions in arteries of experimental animals indicate disease diffusely involves the outer layer, the adventitia and the media with little involvement of the intima and without the formation of segmental atheromatous obstructive lesions. The lesion has a more arteriosclerotic nature rather than athero¬sclerotic (see the chapters Arteriosclerosis and Athero-sclerosis/Atherothrombosis).
• III. CLINICAL STUDIES
  A. Willems et al.
• IV. CONDITIONS CAUSING HYPERHOMOCYSTINEMIA
  A. Medical Conditions
• V. SCREENING
  Screening recommendations for hyperhomocystinemia remain controversial and diverse. The lack of evidence substantiating clinical benefit of treatment of hyperhomo-cystinemia as well as unnecessary laboratory costs are potent arguments against recommending widespread screening. A. American Heart Association Recommendation
• VI. MANAGEMENT OF HYPERHOMOCYSTINEMIA
  A. Folic Acid Intake
• VII. BENEFITS OF DECREASING HOMOCYSTEINE LEVELS
  Unfortunately no benefit to cardiovascular mortality or morbidity has been observed in randomized clinical trials, except in patients who had successful coronary angioplasty. A modest decreased rate of coronary restenosis following coronary angioplasty has been noted after lowering of plasma homocysteine levels, but this requires confirmation that is unlikely to be forthcoming.
• VIII. CLINICAL STUDIES
  In a meta-analysis of predominantly case control studies, 14 of 17 papers supported the link between elevated homocysteine and an increase risk for vascular disease. Although these data appear impressive, there are several limitations to case control studies and the data from prospective studies are not convincing.
• BIBLIOGRAPHY
  ¨ Brattstro¨m, L., Wilcken, D. E. L., Ohrvik, J. et al. Common