Homocysteine, Lipoprotein(a), and Restenosis
Homocysteine, Lipoprotein(a), and Restenosis
Background: Restenosis complicates 30% to 40% of angioplasty procedures and may be unrelated to traditional coronary risk factors. Homocysteine, lipoprotein(a), and methylenetetrahydrofolate reductase (MTHFR 677T) (a genetic determinant of plasma homocysteine concentrations) are novel risk factors for coronary artery disease. Their roles in restenosis are unclear, and the potential synergism between homocysteine and lipoprotein(a) has not previously been studied. The objective of this study was to determine the relations among homocysteine, lipoprotein (a), MTHFR 677T, and restenosis after percutaneous transluminal coronary angioplasty.
Methods: This prospective study enrolled patients with successful elective percutaneous transluminal coronary angioplasty or stenting of a single, de novo, native coronary lesion. Fasting blood was drawn the morning of the procedure for homocysteine, lipoprotein(a), and MTHFR 677T. Follow-up angiography was performed 6 months after the procedure or earlier if clinically indicated. All cineangiograms were analyzed quantitatively.
Results: A total of 144 (92%) of 156 eligible patients underwent follow-up coronary angiography. The overall angiographic restenosis rate (residual stenosis >50%) was 31%. Mean homocysteine concentration was 10.1 ± 3.7 µmol/L. Plasma homocysteine concentrations were not significantly different in patients with or without angiographic restenosis (9.6 ± 3.3 vs 10.3 ± 3.8 µmol/L; P = .31). Mean lipoprotein(a) concentration was 21.2 ± 20.1 mg/dL. Plasma lipoprotein(a) concentrations were not significantly different in patients with or without restenosis (21.9 ± 21.8 vs 20.9 ± 19.5 mg/dL). Homozygosity for MTHFR 677T was present in 6.5% and was not associated with increased restenosis. No interaction between homocysteine and lipoprotein(a) was detected.
Conclusions: Homocysteine, lipoprotein(a), and MTHFR 677T are not associated with restenosis after percutaneous transluminal coronary angioplasty.
Percutaneous transluminal coronary angioplasty (PTCA) is an established treatment for coronary artery disease (CAD). However, the use of this technique is limited by vascular remodeling and late neointimal proliferation, which results in restenosis of the coronary artery segment undergoing angioplasty. Restenosis complicates 30% to 40% of angioplasty procedures, almost exclusively within the first 6 months. Risk factors for the development of restenosis are multifactoral, but with the notable exception of diabetes mellitus the traditional atherosclerotic risk factors have not been associated with restenosis. This suggests that restenosis has a distinct mechanistic basis.
Elevated plasma concentrations of homocysteine and lipoprotein(a) have been implicated as novel risk factors for CAD and have been shown to interact synergistically both in vitro and in vivo. In addition, an elevated plasma concentration of lipoprotein(a) has been suggested in some, but not all, studies to be a risk factor for restenosis after PTCA. Homocysteine has not been studied in this context. However, a common variation in the gene encoding methylenetetrahydrofolate reductase (MTHFR 677T), a minor genetic determinant of the plasma concentration of homocysteine when present in the homozygous genotype, has been studied with no apparent association.
Of particular interest is the possible interaction between homocysteine and lipoprotein(a). Lipoprotein(a) contains apolipoprotein(a) linked by a disulfide bond to apolipo-protein B-100. Apolipoprotein(a) is homologous to plasminogen, which allows it to bind to fibrin, thus potentially linking this plasma lipoprotein with thrombosis. The presence of the disulfide bond allows this interaction to be modified by the presence of other sulfhydryls. Physiologic concentrations of homocysteine enhance the binding of lipoprotein(a) to fibrin, establishing a possible relation between these proatherogenic agents.
The purpose of this prospective study was to determine whether plasma concentrations of homocysteine and lipoprotein(a) or homozygosity for MTHFR 677T are associated with the development of restenosis in a sample of patients undergoing PTCA. In addition, the possible interaction between lipoprotein(a) and homocysteine was investigated.
Background: Restenosis complicates 30% to 40% of angioplasty procedures and may be unrelated to traditional coronary risk factors. Homocysteine, lipoprotein(a), and methylenetetrahydrofolate reductase (MTHFR 677T) (a genetic determinant of plasma homocysteine concentrations) are novel risk factors for coronary artery disease. Their roles in restenosis are unclear, and the potential synergism between homocysteine and lipoprotein(a) has not previously been studied. The objective of this study was to determine the relations among homocysteine, lipoprotein (a), MTHFR 677T, and restenosis after percutaneous transluminal coronary angioplasty.
Methods: This prospective study enrolled patients with successful elective percutaneous transluminal coronary angioplasty or stenting of a single, de novo, native coronary lesion. Fasting blood was drawn the morning of the procedure for homocysteine, lipoprotein(a), and MTHFR 677T. Follow-up angiography was performed 6 months after the procedure or earlier if clinically indicated. All cineangiograms were analyzed quantitatively.
Results: A total of 144 (92%) of 156 eligible patients underwent follow-up coronary angiography. The overall angiographic restenosis rate (residual stenosis >50%) was 31%. Mean homocysteine concentration was 10.1 ± 3.7 µmol/L. Plasma homocysteine concentrations were not significantly different in patients with or without angiographic restenosis (9.6 ± 3.3 vs 10.3 ± 3.8 µmol/L; P = .31). Mean lipoprotein(a) concentration was 21.2 ± 20.1 mg/dL. Plasma lipoprotein(a) concentrations were not significantly different in patients with or without restenosis (21.9 ± 21.8 vs 20.9 ± 19.5 mg/dL). Homozygosity for MTHFR 677T was present in 6.5% and was not associated with increased restenosis. No interaction between homocysteine and lipoprotein(a) was detected.
Conclusions: Homocysteine, lipoprotein(a), and MTHFR 677T are not associated with restenosis after percutaneous transluminal coronary angioplasty.
Percutaneous transluminal coronary angioplasty (PTCA) is an established treatment for coronary artery disease (CAD). However, the use of this technique is limited by vascular remodeling and late neointimal proliferation, which results in restenosis of the coronary artery segment undergoing angioplasty. Restenosis complicates 30% to 40% of angioplasty procedures, almost exclusively within the first 6 months. Risk factors for the development of restenosis are multifactoral, but with the notable exception of diabetes mellitus the traditional atherosclerotic risk factors have not been associated with restenosis. This suggests that restenosis has a distinct mechanistic basis.
Elevated plasma concentrations of homocysteine and lipoprotein(a) have been implicated as novel risk factors for CAD and have been shown to interact synergistically both in vitro and in vivo. In addition, an elevated plasma concentration of lipoprotein(a) has been suggested in some, but not all, studies to be a risk factor for restenosis after PTCA. Homocysteine has not been studied in this context. However, a common variation in the gene encoding methylenetetrahydrofolate reductase (MTHFR 677T), a minor genetic determinant of the plasma concentration of homocysteine when present in the homozygous genotype, has been studied with no apparent association.
Of particular interest is the possible interaction between homocysteine and lipoprotein(a). Lipoprotein(a) contains apolipoprotein(a) linked by a disulfide bond to apolipo-protein B-100. Apolipoprotein(a) is homologous to plasminogen, which allows it to bind to fibrin, thus potentially linking this plasma lipoprotein with thrombosis. The presence of the disulfide bond allows this interaction to be modified by the presence of other sulfhydryls. Physiologic concentrations of homocysteine enhance the binding of lipoprotein(a) to fibrin, establishing a possible relation between these proatherogenic agents.
The purpose of this prospective study was to determine whether plasma concentrations of homocysteine and lipoprotein(a) or homozygosity for MTHFR 677T are associated with the development of restenosis in a sample of patients undergoing PTCA. In addition, the possible interaction between lipoprotein(a) and homocysteine was investigated.
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