Tomomichi Suzuki

Relation of a Common Methylenetetrahydrofolate Reductase Mutation and Plasma Homocysteine With Intimal Hyperplasia After Coronary Stenting

BackgroundHyperhomocysteinemia has been identified as an independent risk factor for coronary artery disease. Recent studies have shown that a common mutation (nucleotide 677 C→T) in the methylenetetrahydrofolate reductase (MTHFR) gene may contribute to mild hyperhomocysteinemia and, therefore, to the incidence of coronary artery disease. No information exists, however, regarding the association between the mutation of the MTHFR gene or plasma homocysteine levels and morphological analysis of coronary atherosclerosis using intravascular ultrasound. Methods and ResultsTo examine the potential influence of MTHFR genotype and homocysteine on coronary arteries morphologically, we screened 62 patients with 65 lesions that were treated with 93 Palmaz-Schatz stents. The plasma homocysteine levels in the patients with the TT genotype were not significantly higher than those in the patients with non-TT (CC+CT) genotypes (13.1±5.5 versus 11.5±3.1 mmol/L, P =0.16). Angiographic analysis showed that the percent diameter stenosis in the patients with the TT genotype was significantly greater than that in those with non-TT genotypes (43.7±17.8% versus 29.0±22.0%, P =0.015). Intravascular ultrasound analysis showed that the TT genotype was significantly associated with greater intimal hyperplasia area (5.70±1.94 versus 3.72±1.38 mm2, P =0.001). In multiple stepwise regression analysis, the number of the T alleles was the only independent predictor of intimal hyperplasia after intervention (r2=0.21, P =0.004). ConclusionsThe homozygous mutant genotype of the MTHFR gene may increase the risk of in-stent restenosis more than does the normal homozygous or heterozygous genotype.

The Glu298Asp polymorphism in endothelial nitric oxide synthase gene is associated with coronary in-stent restenosis

BACKGROUND Reduced or impaired synthesis of nitric oxide promotes the proliferation of vascular smooth muscle cells, and thus may induce the neointimal formation leading to coronary in-stent restenosis. Recent reports have suggested that the Glu298Asp polymorphism in exon 7 of the endothelial nitric oxide synthase gene is associated with coronary spasm and acute myocardial infarction. In this study, we have examined the implication of this polymorphism with regard to coronary restenosis after Palmaz-Schatz stent deployment. METHODS Eighty-nine lesions in 85 consecutive patients were treated with Palmaz-Schatz stents, and were prospectively followed up for 6 months. The lesions were classified into a restenosis group (% diameter stenosis=50%) and a non-restenosis group. Assessment was made using an automated quantitative angiographic system. We performed polymerase chain reaction-restriction fragment length polymorphism analysis to detect the missense Glu298Asp variant in exon 7 of the endothelial nitric oxide synthase gene. RESULTS Coronary risk factors and angiographic findings of stenotic lesions did not differ between the groups. Univariate analyses showed that the missense Glu298Asp variant was the only statistically significant predictor of restenosis (odds ratio, 4.27; P=0.025). In addition, multiple logistic regression analysis revealed the missense Glu298Asp variant as the only independent predictor for in-stent restenosis (odds ratio, 3.90; P=0.036). CONCLUSIONS The missense Glu298Asp variant may be an independent risk factor for in-stent restenosis.

Effect of quinapril on intimal hyperplasia after coronary stenting as assessed by intravascular ultrasound

We studied whether angiotensin-converting enzyme inhibition with quinapril treatment can prevent in-stent restenosis after successful implantation of Palmaz-Schatz stents. Intravascular ultrasound study, but not quantitative coronary angiography analysis, revealed that quinapril treatment significantly prevented the loss of both minimal lumen cross-sectional area and lumen volume in stents, in addition to reducing the increase in intimal hyperplasia volume.