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Background: Plasminogen activator inhibitor-1 (PAI-1) has been proposed as a candidate risk factor for restenosis after coronary artery stenting. Transcription, level, and activity of PAI-1 are influenced by the 4G/5G polymorphism in the promoter region of PAI-1 gene. The polymorphism may therefore affect wound-healing processes in injured blood vessels and influence restenosis., Methods: In 1850 consecutive patients, angiographic measures of restenosis and the clinical outcome at 30 days and 1 year after stent implantation were evaluated. Angiographic restenosis was defined as > or =50% diameter stenosis determined at follow-up angiography, performed 6 months after stenting. The 4G/5G genotypes were determined with TaqMan technique., Results: Among the patients, the frequency of the 4G allele was 0.55. Follow-up angiography was done in 84% of the patients. We observed restenosis in 32.5% of 4G/4G carriers, 32.2% of 4G/5G carriers, and 35.7% of 5G/5G carriers (P =.52). The occurrence of a major adverse event (death, myocardial infarction, or target vessel revascularization due to restenosis-induced ischemia) was 5.6% in 4G/4G carriers, 5.3% in 4G/5G carriers, and 4.6% in 5G/5G carriers at 30 days (P =.80), and 24.7% in 4G/4G carriers, 23.0% in 4G/5G carriers, and 26.2% in 5G/5G carriers at 1 year (P =.45)., Conclusion: The 4G/5G polymorphism of the PAI-1 gene is not associated with an increased risk of thrombotic and restenotic events after coronary artery stenting.

Objectives: We tested the hypothesis that patients with the DD genotype of the angiotensin I-converting enzyme (ACE) gene who are treated with ACE inhibitors are at a higher risk of restenosis after coronary stent placement than patients who do not receive ACE inhibitors., Background: Two recent studies with a limited series of patients carrying the DD genotype suggested an unfavorable impact of the use of ACE inhibitors on the restenotic process after implantation of stents in coronary arteries. Because these findings may question the use of ACE inhibitors after coronary stenting, we examined this important issue in a large series of patients., Methods: We determined the ACE gene I/D genotype of 2,222 consecutive patients with symptomatic coronary artery disease who underwent stent implantation. The patients with the DD genotype (n = 612) constituted the study population. The primary end point was in-stent restenosis, which was assessed as angiographic restenosis (> or =50% diameter stenosis at six-month follow-up) and clinical restenosis (need for target vessel revascularization due to symptoms or signs of ischemia in the presence of angiographic restenosis over one year after the intervention)., Results: Of the 612 patients with the DD genotype, 403 (65.8%) were treated with ACE inhibitors and 209 (34.2%) did not receive ACE inhibitors. The angiographic and clinical restenosis rates were not significantly different between the group treated with ACE inhibitors and the group not receiving ACE inhibitors (p = 0.55). Continuous measures of restenosis, minimal lumen diameter, diameter stenosis, late lumen loss, and loss index were also similar in both groups (p > or = 0.55). In addition, one-year survival free of myocardial infarction was not significantly different between the two groups (p = 0.27)., Conclusions: In contrast to previous reports, our study provides evidence that patients carrying the DD genotype are not exposed to an increased risk of restenosis after stent placement when treated with ACE inhibitors.

Platelets are thought to contribute to development of restenosis following percutaneous coronary interventions. The glycoprotein Ia/IIa complex is a major platelet collagen receptor, its surface expression being influenced by two, linked single nucleotide polymorphisms (C807T and G873A) in the glycoprotein Ia gene. T807 is associated with increased expression of this integrin receptor. We assessed whether T807 is associated with an increased risk of restenosis in 1769 consecutive patients treated with coronary stenting. 6-month follow-up angiograms were available in 82.4% of the patients. C807T genotype distribution was CC in 35.8%, CT in 47.6% and TT in 16.6% of the patients. Restenosis (diameter stenosis > or =50% at follow-up angiography) occurred in 32.9% of CC, 31.5% of CT and 32.1% of TT patients (P=0.87). The rate of major adverse cardiac events (death, myocardial infarction or need of reintervention) within 1 yr was 21.6% for CC, 21.7% for CT and 21.2% for TT patients (P=0.98). Thus, carriage of the GP Ia T807 allele is not associated with an increased risk of restenosis or unfavorable late outcome following coronary artery stenting.

Objectives: To test the hypothesis that interleukin-1 receptor antagonist (IL-1ra) gene polymorphism contributes to the risk of restenosis after coronary stenting., Background: Cytokines of the interleukin-1 (IL-1) family play a central role in regulating inflammatory responses. There is strong evidence to support IL-1 involvement in smooth muscle cell mitogenesis and extracellular matrix metabolism. The IL-1ra counters the proinflammatory effects of IL-1. The interleukin-1 receptor antagonist gene (IL-1RN) contains several well-characterized polymorphic sites that correlate with altered IL-lra levels., Methods: In 1,850 consecutive patients, clinical and angiographic measures ofrestenosis were evaluated over one year after coronary stent placement. Repeat angiography at six months was achieved in 84% of the patients; angiographic restenosis was defined < or =50% diameter stenosis at follow-up. Genotyping for an exon 2 polymorphism (+2,018) of IL-1RN (alleles 1 and 2) was based on a polymerase chain reaction technique., Results: Allele 2 frequency was 0.28. Carriers of allele 2 had a significantly lower risk for angiographic restenosis, odds ratio (OR) of 0.78 (95% confidence interval, 0.63 to 0.97) and target vessel revascularization, OR of 0.73 (0.58 to 0.92) compared with noncarriers. Risk reduction was especially significant in patients <60 years (n = 696), with OR of 0.63 (0.43 to 0.91) for angiographic restenosis and 0.55 (0.39 to 0.78) for target vessel revascularization., Conclusions: Allele 2 of the IL-1ra gene was associated with a lower incidence of restenosis after coronary stenting, particularly in younger patients. This finding supports a role of inflammation in the development of restenosis after stent placement.

Background: The renin-angiotensin system is thought to play a role in coronary thrombosis and restenosis. Plasma angiotensin I-converting enzyme (ACE) activity is associated with an insertion/deletion polymorphism in the gene coding for ACE. The objective of this study was to test the hypothesis that the D allele of the ACE gene is associated with a higher risk for restenosis after coronary stent placement., Methods and Results: This prospective study included 1850 consecutive patients with coronary artery disease who underwent intracoronary stent implantation. The adverse clinical events recorded were death, myocardial infarction, and target vessel revascularization. The primary end point of the study was restenosis (>/=50% diameter stenosis at follow-up angiography performed in 84% of the patients). The secondary end point was clinical outcome 1 year after the procedure. The restenosis rate at the 6-month angiographic follow-up was 32.8% in patients with the II genotype, 34.0% for patients with the ID genotype, and 31.2% for patients with the DD genotype (P=0.62). One-year event-free survival was 77.7% in patients with genotype II, 75.2% in patients with genotype ID, and 75.5% in patients with genotype DD (P=0.54). The lack of association was also present in the subgroup of patients with a low risk for restenosis: the restenosis rate was 21.7% in II carriers, 23.4% in ID carriers, and 19.7% in DD carriers (P=0.83)., Conclusions: The ACE DD genotype or D allele does not influence the 1-year clinical and angiographic outcome of patients undergoing coronary stent placement. These data suggest that routine determination of the ACE genotype may not help identify patients who are at a higher risk of thrombotic and restenotic events after coronary stent placement.

Objective: We designed this prospective study to test the hypothesis that platelet antigen (PlA) polymorphism of glycoprotein (GP) IIIa is associated with an increased risk for adverse events after coronary stent placement., Background: Platelets play a central role in arterial thrombosis. The PlA polymorphism of GP IIIa, a constituent of the fibrinogen receptor, may influence the platelet function and, thereby, the early outcome of patients after coronary stent placement., Methods: The study included 1,759 consecutive patients with stable or unstable angina and successful coronary stent placement. Platelet antigen genotypes were determined by allele-specific restriction enzyme analysis. The end point of the study was a composite of death, myocardial infarction and urgent revascularization during the first 30 days after stent placement., Results: The PlA1 genotype of the patients included was: 70.2% were homozygous for platelet antigen 1 (PlA1), 2.6% homozygous for platelet antigen 2 (PlA1), and 27.2% were heterozygous (PlA1/A2). The incidence of the composite end point was 5.5% among PlA2 carriers and 5.4% in homozygous PlA1 subjects (p = 0.94). It was 5.4% in PlA1/A1 patients, 4.8% in PlA1/A2 patients and 13.0% in PlA2A2 patients (p = 0.06). The combined incidence of death or myocardial infarction was 4.3% in PlA1/A1 patients, 4.2% in PlA1/A2 patients and 13.0% in PlA2/A2 patients (p = 0.02)., Conclusions: The isolated presence of the PlA2 allele in heterozygous patients is not associated with any detectable increase in the risk for an adverse 30-day outcome after coronary stenting. This study suggests also that an increased risk is likely to be present in homozygous carriers of the PlA2 allele, but this should be confirmed in a much larger series of patients.

The glycoprotein complex Ia/IIa (GP Ia/IIa) is a major collagen receptor on platelets and other cell types. Recently, linked polymorphisms within the coding region of the GP Ia gene (C807T and G873A) were identified that are related to GP Ia/IIa surface expression. The T807/A873 allele is associated with high expression, whereas the C807/G873 allele is associated with low surface expression of GP Ia/IIa. Subsequently, the T807 allele was found to be associated with coronary and cerebral infarction in younger patients. Platelet adhesion to the vessel wall plays a pivotal role in thrombosis after coronary artery stent placement. The goal of this study was to test whether C807T polymorphism is associated with a higher incidence of thrombotic events following coronary stenting. Consecutive patients treated with coronary stent placement (n = 1797) were genotyped for C807T polymorphism with polymerase chain reaction and allele-specific fluorogenic probes. The composite end point was defined as death, myocardial infarction, or urgent target vessel revascularization within 30 days of stent implantation. The genotype distribution of the study population was CC in 36.5%, CT in 46.7%, and TT in 16.8% of the patients. The incidence of the composite end point was 6.5% in T allele carriers and 5.3% in noncarriers (odds ratio for T allele carriage 1.23 [95% confidence interval, 0.81-1.86], P =.33). After adjusting for other baseline characteristics, the odds ratio for the composite end point was 1.15 (0.76-1.75). Therefore, C807T genotype has no significant influence on the major adverse events occurring after coronary artery stenting.

Both glycoprotein (GP) IIb and IIIa of platelet fibrinogen receptor are polymorphic proteins. Unlike GPIIIa, there is little information about the clinical significance of the GPIIb polymorphism. We designed this prospective study to assess whether patients with the human platelet antigen (HPA)-3 polymorphism of GPIIb are more susceptible to developing thrombosis and restenosis after coronary stent placement. We included 2,178 consecutive patients with coronary artery disease who underwent intracoronary stent implantation, 789 (36.2%) with HPA-3a/a, 1,023 (47.0%) with HPA-3a/b, and 366 (16.8%) with HPA-3b/b genotype. The incidence of stent thrombosis was 1.7% in HPA-3a/a, 1.7% in HPA-3a/b, and 1.6% in HPA-3b/b patients (p = 0.999). The incidence of stent restenosis was 37.3% in HPA-3a/a, 36.2% in HPA-3a/b, and 34.6% in HPA-3b/b patients (p = 0.724). Event-free survival 1 year after stent placement was 76.1% for HPA-3a/a, 76.5% for HPA-3a/b, and 76.4% for HPA-3b/b patients (p = 0.968). We conclude that the HPA-3 polymorphism of platelet GPIIb is not associated with an increase in the risk of thrombosis and restenosis over 1 year after coronary stent placement. These data indicate that unlike the HPA-1 polymorphism of GPIIIa, the HPA-3 polymorphism of GPIIb may not serve as a useful genetic marker for the risk assessment of patients treated with intracoronary stenting.

Background: Platelets play a central role in the process of restenosis after percutaneous coronary interventions. A polymorphism of platelet glycoprotein IIIa (PlA) has been associated with a higher risk of coronary thrombosis. We designed this prospective study to test the hypothesis that PlA polymorphism of glycoprotein IIIa is associated with an increased risk for restenosis after coronary stent placement., Methods and Results: The study included 1150 consecutive patients with successful coronary stent placement and 6-month follow-up with coronary angiography. The end point of the study was the incidence of angiographic restenosis (>/=50% diameter stenosis) at follow-up. Of the 1150 patients, 72.5% were homozygous for PlA1, 24.7% were heterozygous (PlA1/A2), and 2.8% were homozygous for PlA2. Patients with the PlA2 allele demonstrated a significantly higher restenosis rate than did those without (47% versus 38%; OR, 1.42; 95% CI, 1.09 to 1.84). The risk was highest in homozygous carriers of PlA2 (53.1% restenosis rate). After adjustment for several clinical and angiographic characteristics, the presence of the PlA2 allele remained a significantly independent risk factor for restenosis (adjusted OR, 1.35; 95% CI, 1.07 to 1.70). The influence of the PlA2 allele on restenosis was stronger in women. Women with PlA2 had a restenosis rate of 52% compared with the 33% incidence among women homozygous for PlA1 (OR, 2.21; 95% CI, 1.27 to 3.85)., Conclusions: This study showed a significant association between the PlA polymorphism of glycoprotein IIIa and the risk of restenosis after coronary stent placement. The risk was more pronounced in patients homozygous for PlA2 allele and in female patients.