The relationship between angiotensin converting enzyme gene polymorphism, coronary artery disease, and stent restenosis: the role of angiotensin converting enzyme inhibitors in stent restenosis in patients with diabetes mellitus

Patients with diabetes mellitus (DM) have advanced atherosclerosis compared with nondiabetics. Restenosis after intracoronary stent implantation occurs frequently in diabetic patients. Angiotensin II is an important growth factor for the development of neointimal hyperplasia after vascular injury. The aim of our study was to evaluate the relationships between angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and coronary artery disease (CAD) and stent restonosis in diabetic patients. One hundred and thirty consecutive patients with CAD and 47 consecutive patients (14 males, mean age, 58.0 +/- 10.0) without CAD were enrolled in the study. All patients had type 2 (noninsulin dependent) DM. The patients with CAD underwent percutaneous transluminal coronary angioplasty (PTCA) and stenting. Ninety-four (59 males, mean age, 60.3 +/- 9.8) underwent control coronary angiography at the end of the follow-up period (mean duration, 9.1 +/- 2.9 months). ACE gene I/D genotyping was identified in all patients. No significant difference was found among patients with and without CAD with respect to ACE gene I/D polymorphism (P = 0.460). In the control coronary angiography, stent restenosis and new lesion development were comparable in each genotyping subgroup. However, a significant relationship was observed between restenosis and the use of ACE inhibitors (ACEI) in patients with D allele (ACEI ratio, 43.5% in the restenosis group and 56.5% in non-restenotic group, P < 0.05). We did not find any relationship between ACE gene I/D polymorphism and CAD and stent restenosis and new lesion development in diabetic patients. On the other hand, ACEI treatment may reduce stent restenosis in type 2 diabetic patients with D allele (DD or ID).     

Angiotensin I-converting enzyme (ACE) inhibitors and restenosis after coronary artery stenting in patients with the DD genotype of the ACE gene

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.     

Predictors of coronary in-stent restenosis: importance of angiotensin-converting enzyme gene polymorphism and treatment with angiotensin-converting enzyme inhibitors

OBJECTIVES: This study aimed to clarify the role of the angiotensin-converting enzyme (ACE) gene polymorphism in the development of in-stent restenosis. BACKGROUND: In-stent restenosis occurs after treatment of coronary artery stenosis in 12% to 32% of coronary interventions with stents. Experimental and clinical studies have suggested that the deletion/insertion (D/I) polymorphism of the ACE gene plays a role in this. METHODS: Quantitative coronary angiography before, immediately after and six months after stent implantation were compared in 369 patients, in whom D/I typing of the ACE gene was performed. RESULTS: At follow-up we found no differences between the three genotypes in minimal lumen diameter (homozygotes with two deletion alleles in the ACE gene [DD], 2.20 mm; heterozygotes with one deletion and one insertion allele in the ACE gene [DI], 2.19 mm; and homozygotes with two insertion alleles in the ACE gene [II], 2.25 mm). The corresponding diameter stenoses were: DD: 25%, DI: 27%, II: 27% (p = NS), and the frequency of restenosis (>50% diameter stenosis) was: DD: 15.7%, DI: 11.0% and II: 16.4% (p = NS). Logistic regression analysis identified diabetes (odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.0 to 8.7), lesion length (OR: 1.1, 95% CI: 1.01 to 1.30) and minimal lumen diameter immediately after the intervention (OR: 0.3, 95% CI: 0.14 to 0.85) as predictors of in-stent restenosis. In a post hoc analysis of patients treated versus those not treated with an ACE-inhibitor antagonist or an angiotensin receptor antagonist, we found an increased frequency of in-stent restenosis in the DD genotypes (40% vs. 12%, p = 0.006). CONCLUSIONS: The D/I polymorphism is not an independent predictor of coronary in-stent restenosis in general, but it may be of clinical importance in patients treated with ACE inhibitors or angiotensin receptor antagonists.     

Intracoronary β-irradiation prevents excessive in-stent neointimal proliferation in de novo lesions of patients with high plasma ACE levels. The BetAce randomized trial

BACKGROUND: This study evaluated vascular brachytherapy (VBT) as a potent antiproliferative treatment to prevent in-stent restenosis (ISR) after coronary angioplasty of de novo lesions in patients carrying the D allele of the I/D polymorphism of the ACE gene and high ACE plasma levels (>34 U/l). METHODS AND MATERIALS: A prospective randomized trial was designed to detect a 30% improvement in the minimal lumen diameter (MLD) of the stenotic artery, as measured by quantitative coronary analysis (QCA), 6 months following VBT at the time of stented angioplasty. All patients were carriers of the D allele of the ACE gene, with plasma ACE levels >34 U/l. RESULTS: Thirty-one patients (33 stenoses) were allocated to stent implantation (control group) and 30 patients (31 stenoses) to VBT and stented angioplasty. After angioplasty, in-stent MLD was similar in the two groups. At 6 months in the control group, in-stent MLD had decreased to 1.74+/-0.8 versus 2.25+/-1.05 mm in the VBT group (P=.04). The mean in-stent diameter was 2.3+/-0.8 mm in the control group versus 2.9+/-1.05 mm after VBT (P=.02), and the restenosis rate was 37.5% versus 17.9%, respectively (P=.08). At 6 months, a higher need for target vessel revascularization (TVR) was observed in the control group: 35.5% versus 13.3% (P=.04). CONCLUSIONS: This randomized study confirms that patients with high plasma ACE concentrations are exposed to an increased risk for ISR after coronary stenting. The preventive use of VBT in these patients reduced neointimal formation by 65% such that the MLD at follow-up was increased by 29% compared with the control group.     

Angiotensin-converting enzyme insertion/deletion polymorphism does not influence the restenosis rate after coronary stent implantation

BACKGROUND: Experimental studies have shown an activation of the angiotensin-converting enzyme (ACE) system as a response to endothelial injury. Recent publications have elucidated the hypothesis that the ACE gene polymorphism may influence the level of late luminal loss after coronary stent implantation. It is still unclear whether the polymorphism of the angiotensin gene is a major predictor of the extent of neointimal hyperplasia. In this multicenter study, we therefore tested the relationship between the ACE gene polymorphism and the restenosis rate after coronary stent implantation. METHODS: As a substudy of the optimization with intracoronary ultrasound (ICUS) to reduce stent restenosis (OPTICUS) study, we analyzed ACE serum levels and the ACE gene polymorphism in 154 patients at 9 different centers. All patients underwent elective coronary stent implantation in a stenosis of a major coronary vessel. Balloon inflations were repeated until a satisfactory result was achieved in on-line quantitative coronary angiography or ICUS fulfilling the OPTICUS study criteria. After follow-up of 6 months, all patients underwent reangiography under identical projections as the baseline procedure. A blinded quantitative analysis of the initial procedure as well as the follow-up examinations were performed by an independent core laboratory. ACE gene polymorphism and ACE serum activity were measured at the 6-month follow-up in a double-blinded setting. RESULTS: With respect to the ACE gene polymorphism, there were three subgroups: DD genotype (48 patients), ID (83 patients) and II (23 patients). The subgroups did not differ in regard to age, gender, extent of coronary artery disease, stenosis length, initial degree of stenosis or degree of stenosis after stent implantation. In all, 39 patients (25.3%) had significant restenosis: 12 DD patients (25.0%), 18 ID patients (21.7%) and 9 II patients (39.1%) (odds ratio 2.164, 95% confidence interval 0.853-5.493). We obtained the following results for ACE serum levels: 0.53 micromol/l/s in the DD subgroup, 0.29 micromol/l/s in the ID subgroup and 0.09 micromol/l/s in the II subgroup (p < 0.001). Multivariate logistic regression analysis of the influence of ACE gene polymorphism on the restenosis rate after coronary stent implantation adjusted for lesion length (>12 mm), ACE inhibitor or hydroxymethylglutaryl coenzyme A reductase (CSE) inhibitor treatment, age, male gender, diabetes mellitus, hypertension, high cholesterol, family history, smoking and three-vessel disease did not uncover any statistic significance. CONCLUSIONS: In contrast to other study groups, we were unable to disclose that the DD polymorphism of the ACE gene was associated with a higher rate of restenosis after coronary stent implantation in this multicenter study. In addition, patients with higher ACE serum levels did not show a higher restenosis rate in this trial. We conclude that the pathogenesis of restenosis is a multifactorial process involving various genetic and nongenetic factors.     

D/D genotype of the gene for angiotensin converting enzyme as a risk factor for post-stent coronary restenosis]

INTRODUCTION: Although intracoronary stenting has decreased restenosis rate compared to percutaneous balloon angioplasty, still a high number of patients develop in-stent restenosis, which is an entity primarily due to tissue proliferation. Experimental studies have indicated that the renin-angiotensin system is involved in neointimal hyperplasia. Plasma and cellular levels of ACE are associated with an I/D polymorphism in the ACE gene. Indeed, DD subjects have the higher ACE levels. The purpose of this study was to explore the possibility that the I/D polymorphism might be related with in-stent restenosis. METHODS: We studied the ACE polymorphism in 48 consecutive patients who underwent successful implantation of an elective coronary stent in native coronary vessels and had a 6 month angiographic follow up. Restenosis (50% of the reference vessel) was observed in 23/48 patients. Patients with or without restenosis did not differ in demographic or clinical variables like diabetes, plasma cholesterol levels or in quantitative angiographic parameters such as vessel reference size or minimal lumen diameter after stent implantation. RESULTS: I/D polymorphism was distributed as follows: 22.9% of the patients were D/D; 14.5% were I/I and 62.5% of the patients were heterozygous I/D. The presence of restenosis was strongly related with the I/D polymorphism: 81.8% of the patients with D/D genotype had restenosis, compared with 40.0% of I/D patients and only 14.2% of the I/I patients (chi 2 p < 0.01). CONCLUSIONS: In this limited cohort, homocygous D/D of the ACE gene was significantly associated with in-stent restenosis, whereas restenosis was infrequent in patients with the I/I genotype.     

ACE gene polymorphism and coronary restenosis.

In humans, circulating levels of angiotensin-converting enzyme (ACE) are linked with an insertion (I)/deletion (D) polymorphism in the ACE gene: DD genotype bearers have higher levels of ACE than either ID or II genotype bearers. Recent studies have suggested that the ACE DD genotype might be associated with a higher risk of coronary artery disease. The aim of this paper is to review studies on the influence of the I/D polymorphism on coronary restenosis. The renin-angiotensin system has been implicated in the pathogenesis of neointimal hyperplasia in experimental models. In humans, the I/D polymorphism is not associated with restenosis after balloon angioplasty, but is strongly associated with restenosis after coronary stent implantation. This may be explained by the fact that the contribution of neointimal hyperplasia to restenosis is much more important after coronary stent implantation than after balloon angioplasty.     

ACE基因I/D多态性与冠状动脉支架内再狭窄相关性研究

目的研究冠状动脉内行药物洗脱支架置入术患者,术后支架内再狭窄发生情况与ACE基因I/D多态性的关系。方法所有患者行冠状动脉造影检查,PCR方法测定ACE基因型。根据血管造影结果分为再狭窄组（病变狭窄≥50%）和无再狭窄组（病变狭窄〈50%）。采用SPSS18.0软件比较再狭窄组与无再狭窄组的临床基本特征、冠脉造影资料,以及与ACE基因型的关系。结果此次研究共纳入396名行药物洗脱支架置入术的冠心病患者,支架内再狭窄发生40例,再狭窄率为10.1%。再狭窄组与无再狭窄组的临床基本资料、冠脉造影资料均无显著性差异（P〉0.05）。再狭窄组的ACEDD基因型35.56%、ACEDI基因型16.39%、ACEII基因型3.85%。再狭窄组与ACE基因I/D多态性具有相关性（P〈0.001）。结论冠状动脉内行药物洗脱支架置入术患者术后支架再狭窄发生与ACEDD基因型具有显著相关性。     

Pharmacogenetic analysis of the effect of angiotensin-converting enzyme inhibitor on restenosis after percutaneous transluminal coronary angioplasty.

Angiotensin-converting enzyme (ACE) inhibitors are reported to prevent neointimal formation after balloon injury in animal models, but in most prospective studies in humans, ACE inhibitors failed to prevent restenosis after percutaneous transluminal coronary angioplasty (PTCA). The ACE genotype assigned by an insertion/deletion (I/D) polymorphism is known to affect the potency of ACE inhibitors in several renal diseases. The authors attempted to clarify whether the effect of ACE inhibitors on restenosis might be modified by the ACE genotype. A total of 126 patients was randomly and prospectively assigned to the control group and the imidapril group. In the imidapril group, patients received 5 mg imidapril daily, starting 1 day before PTCA and continuing for 3 to 6 months. Forty-six control (65 vessels) and 32 imidapril patients (43 vessels) completed the study. The minimal lumen diameter before and after the procedure did not differ significantly among the groups with the three genotypes (II, ID, and DD) in both the control and imidapril groups. Late luminal loss during the follow-up period was not related to the ACE genotype in the control group but was significantly related in the imidapril group (II, 0.63+/- 0.19 mm; ID + DD, 1.12+/-0.14 mm, p<0.05). Furthermore, in the II genotype, imidapril significantly reduced late loss and restenosis rate as defined by most of the frequently used definitions. In conclusion the ACE I/D polymorphism may influence the effect of ACE inhibitors in preventing restenosis after PTCA.     

Influence of angiotensinogen M253T gene polymorphism and an angiotensin converting enzyme inhibitor on restenosis after percutaneous coronary intervention

We studied the relation between renin-angiotensin system (RAS) related gene polymorphisms, such as angiotensin converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen (AGT) M253T and angiotensin II type 1 receptor (AT1R) A1166C, and the effect of quinapril, an ACE inhibitor with high tissue-binding affinity, on preventing restenosis after percutaneous coronary intervention (PCI). A total of 253 patients successfully treated for coronary artery disease were randomly assigned to quinapril or control. Of the 215 patients who completed the follow-up, we determined gene polymorphisms in 204 patients with 241 lesions who provided blood samples for genotype determination. In the control, the ACE D homozygotes showed a smaller minimal lumen diameter (MLD) at follow-up (P=0.063). The other two genotypes of AGT and AT1R did not affect restenosis after PCI. According to quinapril treatment, the AGT T homozygotes significantly showed a beneficial effect of quinapril on MLD (P=0.013) and late lumen loss (P=0.013). The ACE I homozygotes also exhibited beneficial effects of quinapril on larger MLD (P=0.065). The AT1R genotype did not influence the quinapril effect. In conclusion, the AGT T homozygotes might benefit from effects of quinapril on preventing restenosis after PCI.     

Effect of angiotensin-converting enzyme inhibition on restenosis after coronary stenting

The Plasma level of angiotensin-converting enzyme (ACE) has been identified as a major risk factor for restenosis after coronary stent implantation in selected patients; ACE inhibition may therefore contribute to prevent its occurrence. The effect of oral ACE inhibition at conventional doses was analyzed retrospectively in a series of 897 patients with ischemia who received >or=1 coronary stent on 998 lesions and underwent angiographic follow-up; no exclusion criteria were introduced in this analysis. The restenosis rate in 282 patients (31.4%) taking ACE inhibitors was 36.6% compared with 22.9% in 615 non-ACE-inhibited patients (p = 0.00001, odds ratio [OR] 1.94, 95% confidence interval [CI] 1.45 to 2.59), and the late loss in minimum lumen diameter was 1.25 +/- 0.8 versus 0.96 +/- 0.8 mm, respectively (p = 0.0001). During univariate analysis, a negative effect of the drug on restenosis was observed in all subgroups of patients (i.e., hypertensives, diabetics, women, and patients with previous myocardial infarction). Similar effects were observed independently of the ACE gene insertion/deletion polymorphism. During multivariate analysis, ACE inhibition was confirmed as an independent risk factor for restenosis (OR 1.84, 95% CI 1.35 to 2.51, p = 0.0001). Other predictors were the implantation of multiple stents (OR 2.41, 95% CI 1.60 to 3.64, p <0.0001), diabetes (OR 2.34, 95% CI 1.61 to 3.41, p <0.0001), and vessel reference diameter before angioplasty (OR 0.51, 95% CI 0.38 to 0.69, p <0.0001). Although unexplained and apparently contradictory, our data suggest that the use of conventional oral doses of ACE inhibitors in a "real-world" population who underwent coronary stent implantation increases the incidence of in-stent restenosis. Such a finding does not negate the known clinical benefits of ACE inhibitors, but it may deserve attention when a patient treated with ACE inhibitors becomes a candidate for stent implantation.     

Intracoronary Stenting for Restenosis: Long-Term Follow-up: A Single Center Experience

One-hundred thirteen stents (78 Wallstents, 29 Palmaz-Schatz and 6 Wiktor) were implanted in 106 patients aged 63 +/- 5 years to treat a restenosis following previous angioplasty in a native coronary artery (86 cases) and in a venous graft (20 cases). Implantation was technically possible in all cases. The native vessels had a mean reference diameter of 3.3 +/- 0.3 mm and their mean minimal lumen diameter increased from 1.2 +/- 0.3 mm before angioplasty to 2.8 +/- 0.8 after stent implantation. The venous grafts mean reference diameter was 4.4 +/- 0.7 mm and their mean minimal lumen diameter increased from 1.3 +/- 0.4 mm before angioplasty to 4.0 +/- 0.7 mm after implantation. Percentage stenosis in the native arteries and in the venous grafts were respectively 78 +/- 13% and 69 +/- 14% before angioplasty and 24 +/- 8% and 22 +/- 8% after stent implantation. Complications at 6 months, presented as a ranking scale with 100% follow-up rate were, overall, of 20% clinical events (4% deaths, 6% myocardial infractions, 2% coronary artery bypass grafting and 8% re-angioplasty). Angiographic complications were of 8% subacute thrombosis and 19% restenosis and chronic occlusions. Long-term, at 65 +/- 9 months, clinical (86% follow-up) and angiographic (74% follow-up) showed that only a further 9% clinical events and 14% restenosis (12% of them between 6 and 12 months) occurred after 6 months. At an estimated follow-up time of 104 months, 70% patients remain event-free and the survival rate is 95%. In conclusion, stent implantation in the treatment of restenosis following conventional balloon angioplasty is a valid strategy with good long-term results.     

Comparison of selective AT1-receptor blockade versus ACE inhibition for restenosis prophylaxis in patients with peripheral occlusive arterial disease after stent angioplasty: a randomized, controlled, proof-of-concept study

Different components of the renin-angiotensin system (RAS) have been demonstrated in atherosclerotic plaques. However, the involvement of the RAS in the complex process of in-stent restenosis is not yet clear. In this prospective, randomized, double-blind, controlled proof-of-concept study, we compared the 2 different pharmacological approaches, selective AT(1)-receptor-blockade with candesartan vs ACE inhibition with quinapril to reduce in-stent restenosis after stent angioplasty of the superficial femoral artery. Twenty-two hypertensive patients with stage IIb peripheral occlusive arterial disease and severe claudication who had been successfully treated with percutaneous transluminal angioplasty (PTA) and stent implantation were randomly assigned to receive daily doses of either candesartan (32 mg) or quinapril (20 mg). Primary end point was restenosis 6 months after intervention, assessed by angiography. Secondary end points were pain-free walking distance, determined by treadmill ergometry; determination of crurobrachial indices; and intima-media thickness (IMT). At 6 months, the rate of restenosis on angiography was 34% in the candesartan group and 71% in the quinapril group (P = .043). Relevant restenosis was found in 3 patients (27%) in the candesartan group and in 7 patients (64%) in the quinapril group. Patients in the candesartan group were able to walk farther on a treadmill (increase: 135 m +/- 20 m) compared with patients in the quinapril group (increase: 83 m +/- 21 m). The IMT at the stent edge was not significantly different in the 2 groups (candesartan: 1.9 mm +/- 0.5 mm; quinapril: 2.0 mm +/- 0.3 mm). This study revealed significant benefit of a pharmacological restenosis regimen using the AT(1)-receptor antagonist candesartan in patients with severe atherosclerosis after superficial femoral artery stenting compared with treatment with the ACE inhibitor quinapril. Further prospective studies in patients are required to confirm these results.     

Ace D/I polymorphism and incidence of post-PTCA restenosis: a prospective, angiography-based evaluation

Early restenosis is the major complication of percutaneous transluminal coronary angioplasty (PTCA), occurring in approximately 30% of all initially successful procedures. The D/I polymorphism of the ACE gene, which has variably been reported to represent a risk factor for manifestations of ischemic heart disease, has recently been implicated in the pathophysiology of restenosis after PTCA by some investigators but not by others. All studies conducted thus far involved relatively small sample sizes. We investigated the possible association of ACE D/I genotype and post-PTCA restenosis in a large, prospective sample of patients followed by quantitative coronary angiography. The ACE D/I gene polymorphism was characterized in a cohort of 779 patients, of whom 342 (cases) had developed restenosis (as defined by >50% loss of lumen compared with immediate postprocedure results) at repeat quantitative coronary angiography at 6 months after PTCA. Allele frequencies for the ACE D and I: alleles were 0.58 and 0.42 in cases and 0.58 and 0.42 in control subjects. All observed genotype frequencies were in Hardy-Weinberg equilibrium. There was no evidence for an association between genotype and restenosis or degree of lumen loss. The data from this largest study of its kind conducted so far provide no evidence for an association of the ACE D/I allelic polymorphism with incidence of restenosis after PTCA. On the basis of the power of this study, we conclude that in a general population, the ACE D/I polymorphism is not a useful marker to assess risk of post-PTCA restenosis.     

Does quinapril improve coronary vasoconstriction in vasospastic angina?

OBJECTIVES: Endothelial dysfunction is one of the important mechanisms of coronary spasm. Recently, the angiotensin converting enzyme (ACE) inhibitor quinapril, which has a high affinity for vascular ACE, has improved endothelial dysfunction in coronary artery disease. This study investigated whether quinapril improves coronary vasoconstriction induced by acetylcholine in vasospastic angina. METHODS: Twenty-four patients with vasospastic angina without significant organic stenosis diagnosed by the acetylcholine provocation test (vessel with spasm defined as > or = 90% stenosis provoked with chest pain and/or ischemic ST change) were enrolled in this study. Patients were randomly assigned to 2 groups: the quinapril group (receiving quinapril 20 mg/day, n = 12), and the non-quinapril group (not receiving quinapril, n = 12). All patients received calcium antagonist. Six months later, coronary angiography was repeated and changes in coronary spasm were compared between the groups. Seven patients were withdrawn from this study, so 17 patients were evaluated (the quinapril group: 8 patients, the non-quinapril group: 9). RESULTS: Angina symptoms were completely or almost suppressed in all patients during the study period. Angiographically, the number of patients with improvement of spasm, patients with deterioration of spasm and patients with stability of spasm were 1, 0, 7 in the quinapril group versus 0, 1, 8 in the non-quinapril group, respectively. There was no significant change between the 2 groups. Quantitative angiographic analysis showed that the coronary spasm rate (percentage of minimal lumen diameter at the site of spasm after administration of acetylcholine to minimal lumen diameter after administration of isosorbide dinitrate) at the first and second angiography were 71 +/- 10% and 62 +/- 21% in the quinapril group versus 73 +/- 14% and 67 +/- 15% in the non-quinapril group, respectively. There were no significant interval changes between the 2 groups (p = 0.60). CONCLUSIONS: Our results did not indicate that quinapril had improved coronary vasoconstriction induced by acetylcholine in patients with vasospastic angina.     

血管紧张素转换酶基因多态性与冠脉病变严重程度的相关性研究

目的探讨血管紧张素转换酶(ACE)基因I/D多态性与冠心病及冠脉病变严重程度的关系.方法对122例冠心病患者进行冠状动脉造影,判定冠脉病变支数(狭窄程度≥75%)和危险记分.用聚合酶链式反应(PCR)技术检测病例组和80例健康人群ACE基因多态性.结果ACE基因型分布和等位基因频率在病例组和对照组间差异有显著性,病例组DD基因型(38.5%)和D等位基因频率(55%)显著高于对照组(13.7%,41%;P＜0.05).冠脉病变支数和危险记分在ACE基因型间差异无显著性(P＞0.05).结论ACE基因多态性中DD型和D等位基因是冠心病发病的独立危险因素,但与冠脉病变严重程度不相关.     

The 4G/5G promotor polymorphism of the plasminogen activator inhibitor-1 gene and late lumen loss after coronary stent placement in smoking and nonsmoking patients

BACKGROUND: Instent restenosis remains a significant clinical problem. Identification of patients at risk for instent restenosis may allow selection of individualized appropriate therapeutic approaches. Genetic polymorphisms have been suggested to be associated with the risk of instent restenosis. Smoking is known to influence hemostatic parameters. HYPOTHESIS: This study investigated the influence of the 4G/5G promotor polymorphism of the plasminogen activator inhibitor type I (PAI-1) gene on instent restenosis in smoking and nonsmoking patients. METHODS: In all, 300 consecutive patients (133 nonsmoking; 167 smoking) with elective coronary stent placement and 6-month angiographic follow-up were studied. Quantitative coronary angiography and genotyping with polymerase chain reaction analysis were performed in all patients. RESULTS: Nonsmoking PAI-1 4G/4G carriers showed a significantly greater late lumen loss (n = 38; 0.54 +/- 0.53 mm) compared with nonsmoking PAI-1 4G/5G (n = 68; 0.38 +/- 0.45 mm) or 5G/5G (n = 27; 0.19 +/- 0.23 mm) carriers, analysis of variance (ANOVA) p < 0.001. Smoking patients with the genotypes 4G/4G (n = 46; 0.53 +/- 0.54 mm) and 4G/5G (n = 79; 0.37 +/- 0.41 mm) had a late loss similar to that of nonsmoking patients. Smoking 5G/5G carriers had the highest late loss of all smoking patients (n = 42; 0.63 +/- 0.50); ANOVA p < 0.05; nonsmoking 5G/5G vs. smoking 5G/5G p < 0.001. CONCLUSION: The promotor polymorphism of the PAI-1 gene has a significant influence on instent restenosis after coronary stent implantation. The 5G/5G genotype predisposes nonsmoking gene carriers to less late lumen loss, whereas in smoking gene carriers this genotype is associated with the greatest late lumen loss. This might be explained by an altered expression pattern of hemostatic parameters.     

Thiazolidinedione treatment attenuates diffuse neointimal hyperplasia in restenotic lesions after coronary stent implantation in type 2 diabetic patients: an intravascular ultrasound study

OBJECTIVES: Thiazolidinedione treatment reduces neointimal tissue proliferation after coronary stent implantation in diabetic patients. However, in-stent restenosis still persists in patients treated with thiazolidinedione. The effect of thiazolidinedione treatment on the pattern of in-stent restenosis remains unclear. This study investigated whether thiazolidinedione treatment attenuates diffuse neointimal hyperplasia in restenotic lesions after coronary stent implantation in diabetic patients. METHODS: Volumetric intravascular ultrasound was performed at 6 months after coronary stent implantation in 76 patients with restenotic lesions who received either conventional anti-diabetic treatment (control group, n = 56) or thiazolidinedione treatment (thiazolidinedione group, n = 20). RESULTS: There were no significant differences between the two groups in stent volume (99 +/- 32 vs 90 +/- 20 mm3, respectively, p = 0.26) or in minimal lumen area in the stent (1.4 +/- 0.6 vs 1.6 +/- 0.5 mm2, respectively, p = 0.11). However, there were significant reductions in neointimal volume (56 +/- 25 vs 36 +/- 11 mm3, respectively, p < 0.01)and neointimal index (56 +/- 11% vs 41 +/- 8%, respectively, p < 0.01) in the thiazolidinedione group. Coefficient of variation of neointimal tissue accumulation was greater in the thiazolidinedione group (45.5%) than in the control group (25.2%). CONCLUSIONS: Intravascular ultrasound study demonstrated that together with reduction of overall neointimal tissue proliferation, thiazolidinedione treatment caused greater point-to-point heterogeneity in the neointimal tissue accumulation in restenotic lesions after coronary stent implantation. This finding strongly suggests that thiazolidinedione treatment attenuates diffuse in-stent restenosis in diabetic patients.     

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.     

G protein beta3 subunit polymorphism and risk of thrombosis and restenosis following coronary stent placement

C825T polymorphism in the G protein beta3 subunit gene (GNB3) has been associated with arterial hypertension, coronary artery disease and myocardial infarction. On the cellular level, C825T polymorphism is associated with altered transmembrane signaling via adenylyl cyclase inhibiting (G(i)) G proteins. This study was designed to test whether C825T polymorphism has an impact on the processes leading to restenosis and thrombosis following coronary stenting. The primary endpoint of the study was angiographic restenosis (> or =50% diameter stenosis) at 6-month follow-up. Secondary endpoint was angiographically proven stent thrombosis within 30 days of implantation. In the 562 consecutive patients C825T genotype was CC, 46.1%, CT, 45.2% and TT, 8.7%. The incidence of angiographic restenosis was 32.7% in homozygous carriers of the C allele, 28.2% in CT patients and 33.3% in homozygous carriers of the T allele (P = 0.563). C825T genotype distribution in 34 consecutive patients with subacute stent thrombosis (44.0% CC, 50.0% CT, and 6.0% TT) was not different from that of 451 patients with angiographically patent stented vessel (45.4% CC, 44.6% CT, 10.0% TT; P = 0.644). In conclusion, C825T polymorphism has no appreciable impact on the mechanisms leading to thrombosis and restenosis following coronary stent placement.