Homocysteine and Its Effects on In-Stent Restenosis

Abstract

Despite the significant reduction in restenosis observed with the use of bare metal stents,1,2 results are still unsatisfactory for high-risk subsets of patients, such as those with diabetes, long lesions, small vessels, bifurcations, and restenotic lesions,3,4 with a restenosis rate up to 30% to 50%. Mounting interest emerged about hyperhomocystinemia as an independent risk factor for atherothrombotic disease,5–9 and several experimental studies have shown that it may affect in-stent restenosis.10–12 Homocysteine is an intermediary amino acid formed by the conversion of methionine to cysteine (Figure 1). Normal homocysteine plasma levels range between 5 and 15 μmol/L, and hyperhomocystinemia levels have been classified as moderate (15 to 30 μmol/L), intermediate (30 to 100 μmol/L), or severe (>100 μmol/L).13 However, normal basal homocysteine does not exclude an abnormality of this metabolic pathway. Such subtle abnormalities can potentially be uncovered by the use of methionine-load test.14 Figure 1. Graph shows vitamin coenzymes and substrates involved in homocysteine metabolism. THF indicates tetrahydrofolate; VIT B2, riboflavin; VIT B6, vitamin B6; VIT B12, methyl cobalamin; DMG, dimethylglycine; MS, methionine synthase; MTHFR, methylene tetrahydrofolate reductase; CS, cystathionine-beta synthase; CL, cystathionine-gamma-lyase; and BHMT, betaine homocysteine methyl transferase. Severe hyperhomocystinemia is a rare genetic disorder characterized by marked elevations in plasma and urine homocysteine concentrations that are associated with osteoporosis, ocular abnormalities, developmental delay, thromboembolic disease, and severe premature atherosclerosis. Less marked elevations in plasma homocysteine (15 to 30 μmol/L) are much more common, occurring in 5% to 7% of the population.14 An example of a patient with mild hyperhomocystinemia is a 50-year-old man who was hospitalized for non–ST-segment elevation myocardial infarction. There were no major …