Insertion/deletion polymorphism of the Angiotensin I-Converting Enzyme gene and risk of restenosis after directional coronary atherectomy followed by stent implantation

Background: The renin-angiotensin system is involved in neointimal hyperplasia in response to arterial injury. The insertion/deletion (I/D) polymorfism of the Angiotensin Converting Enzyme (ACE)gene largely controls plasma levels. It has been reported that D allele is associated with increased risk of restenosis after coronary stenting. However, plaque remodelling may also be an important determinant of restenosis after stent implantation. Debulking the lesion before stent implantation by means of directional coronary atherectomy (DCA) reduce the influence of plaque remodelling leaving neointimal hyperplasia as the major mechanism of restenosis. Therefore, DCA followed by stent implantation represents an ideal model to investigate the relationship between ACE I/D polymorphism and restenosis. Methods: We prospectively evaluated 113 consecutive patients (102 male, 90%; mean age 57±9 yrs) who underwent seccessful (residual stenosis <20%) DCA followed by stent implantation for de novo coronary lesion. Angiographic criteria for enrolment include significant, >75% and <100% of coronary stenosis with a lesion length <15 mm. Genomic DNA was prepared from peripheral blood leukocytes and analysed by means of PCR amplification. Baseline, post-DCA, post-stent and follow-up angiograms, performed after 6-12 months, were quantitatively analysed. Subjects were divided into three groups, according to the genotype (DD, ID, II). Results: The observed genotype distribution was in agreement with the expected Hardy-Weinberg proportion. No significant differences were observed among the three groups in terms of acute gain (DD=2.27±0.49 mm;ID=2.16±0.57 mm; 11=2.24±0.38 mm; p=ns), late loss (DD=0.73±0.73 mm; ID=0.9±0.72 mm; 11=0.63±0.65 mm; p=ns), net gain (DD=1.54±0.72 mm; ID=1.25±0.78 mm; 11=1.62±0.78 mm; p=ns) or percent of patients developing angiographic restenosis (DD=8.8%; ID=7.2%; 11=9.8%). Conclusion: Our data indicate that ACE I/D gene polymorphism is not associated with the risk of developing restenosis in a model of plaque debulking plus stent implantation.