Focal wall overstretching after high-pressure coronary stent implantation does not influence restenosis.

To determine if vessel wall overstretching during coronary stenting is associated with a higher restenosis rate, the intravascular ultrasound morphological evaluation was performed following ultrasound criteria. A total of 468 lesions with successful coronary Palmaz-Schatz stenting guided by intravascular ultrasound were classified into the no overstretching group (n = 295) and the overstretching group (n = 147). There were 26 lesions not classifiable due to the poststent morphology. Balloon-to-vessel ratio was 1.12 +/- 0.17 in the no focal overstretching group and 1. 20 +/- 0.20 in the overstretching group (P < 0.0002). Follow-up angiogram was performed in 77% of no focal overstretching group and in 75% of the focal overstretching group. The restenosis rate of the no focal overstretching group was 19.8% and 20.9% in the focal overstretching group, respectively (P = 0.65). Focal overstretching was more frequent following balloon oversizing. No increase in restenosis rate, found in focal overstretched stented lesions, leads us to the hypothesis of a regulation of smooth-muscle-cell proliferation activated by the normalization of blood flow and of shear stress, when stent implantation succeeds in optimally improving the lumen. Cathet. Cardiovasc. Intervent. 48:24-30, 1999.     

Angiotensin-converting enzyme insertion/deletion gene polymorphism in inflammatory bowel diseases

INTRODUCTION: The renin-angiotensin system is strictly related to the kallikrein-kinin system and both are involved in many physiological and disease conditions and possibly in the pathogenesis of inflammatory bowel disease (IBD). Angiotensin-converting enzyme (ACE) is the pivotal enzyme of the renin-angiotensin system and the main catabolic enzyme of the kallikrein-kinin system. The ACE I/D (insertion/deletion) is a polymorphism of the gene encoding for ACE: participants who are homozygous for the D allele exhibit higher ACE levels, which in turn appear to play a deleterious role in several diseases. AIM: To study the prevalence of ACE I/D polymorphism in IBD patients and its possible association with disease features. METHODS: A total of 232 IBD patients, 124 with ulcerative colitis (UC) and 108 with Crohn's disease and 99 healthy controls were genotyped for the ACE I/D polymorphism. RESULTS: DD, ID and II genotypes distribution did not show significant differences between IBD patients and controls: 42.2 vs. 40.4%, 42.7 vs. 47.5% and 15.1 vs. 12.1%, respectively. No significant difference was observed between Crohn's disease and UC patients. Within UC patients, the presence of DD genotype and the carriage of the D allele were significantly associated with the presence of extraintestinal manifestations: odds ratio (OR) 4.08, 95% confidence interval (CI): 1.62-10.28; P<0.003 and OR=3.07, 95% CI: 1.45-6.48; P<0.003, respectively. No significant association was found with other IBD clinical features. CONCLUSIONS: The ACE I/D polymorphism is not associated with IBDs but the D allele appears to increase the risk of developing extraintestinal manifestations in UC patients.     

Relation between the insertion/deletion polymorphism of the angiotensin I converting enzyme gene and restenosis after coronary stenting

BACKGROUND: Observations with intravascular ultrasound demonstrated that neointimal hyperplasia is the predominant factor responsible for in-stent restenosis. Experimental data suggest that angiotensin I converting enzyme (ACE) plays a role in the thickening of neointima after balloon denudation. Insertion/deletion (I/D) polymorphism of the ACE gene is significantly associated with plasma level of ACE and subjects with D/D genotype have significantly higher plasma levels of ACE than normal. OBJECTIVE: To investigate whether this polymorphism influences the risk of restenosis after coronary stenting. METHODS: We genotyped 158 patients who had undergone single-vessel coronary stenting for the ACE I/D polymorphism. RESULTS: Of the 158 patients, 56 (35%) had the D/D genotype, 71 (45%) had the I/D genotype and 31 (20%) had the I/I genotype. Prevalences of genotypes were compatible with Hardy-Weinberg equilibrium and distributions of ACE genotype among patients and 132 healthy controls from the same geographic area did not differ. At follow-up (after a median duration of 5.4 months), overall rates of angiographic restenosis and of revascularization of target lesion (RTL) were 32.3 and 22.8%, respectively. Of 51 patients with angiographic restenosis, 31 (60.8%) had focal and 20 (39.2%) had diffuse patterns of restenosis. Diffuse in-stent restenosis was significantly more prevalent among patients with D/D genotype (P = 0.016). Multiple stepwise logistic regression analysis identified ACE I/D polymorphism as the independent predictor of angiographic restenosis and RTL. Relative risk of angiographic restenosis was 6.29 [95% confidence interval (CI), 1.80-22.05, P = 0.0004] for D/D genotype and 3.88 (95% CI 1.11-13.12, P = 0.029) for I/D genotype, whereas relative risk of RTL was 7.44 (95% CI 1.60-34.58, P = 0.01) for D/D genotype and 3.88 (95% CI 0.083-18.15, P = 0.085) for I/D genotype. CONCLUSIONS: The ACE I/D polymorphism is significantly associated with risk of angiographic and clinical restenosis after coronary stenting. Angiographic pattern of restenosis is also significantly associated with I/D polymorphism, diffuse type being more prevalent among subjects with D/D genotype.     

Vascular injury in systemic sclerosis: Angiotensin-converting enzyme insertion/deletion polymorphism

The microvascular involvement in systemic sclerosis (SSc) is characterized by endothelial damage and smooth muscle cell migration in the intima. The vascular pathologic modifications in SSc are strikingly similar to those of atherosclerosis. SSc also is characterized by an accelerated macrovascular disease. The gene encoding for angiotensinconverting enzyme (ACE) is a 21-kb, 26-exon gene, localized on chromosome 17 (17q23). Polymorphic sites are an insertion/deletion (I/D) that consists of three genotypes: DD and II homozygotes, and ID heterozygote. ACE gene polymorphisms have been linked to vascular disorders (coronary artery disease, hypertension, cerebrovascular disease, hypertrophic cardiomyopathy, and diabetic or nondiabetic nephropathy). In particular, the possession of ACE D allele was associated with an increased risk of developing malignant vascular injury. ACE D allele frequency of the I/D polymorphism was associated with an increased risk of SSc, suggesting a genetic contribution to the disease. The discrepancy between the high prevalence of D allele and reduced ACE plasma levels in SSc demonstrate the lack of knowledge on the regulation and function of renin-angiotensin system in SSc.     

Angiotensin-converting enzyme insertion/deletion polymorphism and systemic lupus erythematosus: a metaanalysis

OBJECTIVE: To explore whether insertion (I) and deletion (D) polymorphisms within intron 16 of the angiotensin-converting enzyme (ACE) gene confer susceptibility to systemic lupus erythematosus (SLE) and lupus nephritis (LN). METHODS: We surveyed studies of ACE I/D polymorphism and SLE using Medline and manual searches. We conducted a metaanalysis of the DD genotype (recessive effect), DD and DI genotype (dominant effect), and D allele of the ACE overall and in each ethnic population. We performed a metaanalysis of ACE I/D polymorphism in SLE and LN. RESULTS: Thirteen comparison studies were included in our metaanalysis consisting of 1411 patients with SLE and 1551 controls. We found no association of ACE I/D polymorphism with SLE in the total sample and by ethnic groups. There was a trend for association of the DD genotype (OR 1.212, 95% CI 0.966-1.520, p = 0.097) and the D allele with SLE in Caucasian patients (OR 1.157, 95% CI 0.991-1.349, p = 0.064); however, this was not statistically significant. The metaanalysis also showed no association of the ACE I/D polymorphisms with LN. CONCLUSION: This metaanalysis of 2962 subjects showed there is a lack of association of the ACE I/D polymorphism with SLE and LN.     

Metabolic syndrome does not increase angiographic restenosis rates after drug-eluting stent implantation

Metabolic syndrome (MS) is associated with an increased risk of coronary heart disease, stroke, and cardiovascular mortality; but its effect on patients undergoing cardiac revascularization is still unclear. Robust evidence demonstrates that diabetes mellitus and insulin resistance are among the main risk factors for restenosis in patients requiring percutaneous myocardial revascularization. The recent advent of drug-eluting stents (DESs) has significantly reduced the incidence of restenosis compared with bare-metal stents, both in nondiabetic and in diabetic patients. The aim of the study was to evaluate the effect of MS on the risk of binary restenosis in DES implant recipients. One hundred eighty-nine recipients of successful DES implants performed between January and March 2005 for stable coronary artery disease underwent 1-year clinical and angiographic follow-up. Body mass index (BMI), blood pressure, fasting blood glucose, and lipid profile were determined. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria, with the waist criterion being substituted by a BMI>or=28.8 kg/m2. Metabolic and anthropometric information for MS diagnosis was available for 148 of 189 patients; 87 of 148 patients (58%) had MS. Patients with MS had higher BMI (28.4+/-3.8 vs 26+/-2.7 kg/m2, P<.0001), systolic blood pressure (133+/-14 vs 124+/-14 mm Hg, P=.0004), and fasting glucose (113+/-37 vs 92+/-17 mg/dL, P<.0001). They also had higher serum triglycerides (154+/-94 vs 113+/-43, P=.0018) and lower high-density lipoprotein cholesterol levels (39+/-9 vs 46+/-10, P<.0001). Rates of restenosis (10.5% vs 8.1%, P=not significant [NS]), target vessel revascularization (10.5% vs 11.3%, P=NS), and major adverse cardiac events (11.6% vs 14.5%, P=NS) were not significantly different in patients with MS compared with those without MS, nor was any association found between increased end point risk and presence of MS. When patients were subdivided into 6 subgroups by the presence of 0, 1, 2, 3, 4, or 5 of the MS components, restenosis rates were not significantly different among subgroups. In conclusion, MS is not associated with higher rates of restenosis, target vessel revascularization, or major adverse cardiac events; and no additional MS feature was associated with an increased risk.     

The insertion/deletion polymorphism of the angiotensin-converting enzyme gene and the risk for restenosis after PTCA

The therapeutic benefit of percutaneous transluminal coronary angioplasty (PTCA) is limited by restenosis in about 30% of patients. The underlying mechanisms are currently not well understood. Besides clinical and angiographic variables, genetic factors may be involved. We determined the angiotensin I-converting enzyme (ACE) I/D genotype as a possible risk factor for restenosis in 511 consecutive patients who had undergone successful PTCA and follow-up angiography. Clinical and angiographic variables were also considered as possible predictors of restenosis. One hundred sixty patients had restenosis as defined by a greater than 50% progression of residual stenosis of the dilated segment at follow-up angiography. There were significantly more patients with the ACE DD genotype in the restenosis than in the no-restenosis group. This difference did not remain statistically significant in an analysis of covariance that included genetic and clinical variables. Patients who subsequently developed restenosis had a higher degree of stenosis and more severe lesions before PTCA as well as less residual stenosis immediately after PTCA. We conclude that the ACE DD genotype is not an independent risk factor for restenosis after PTCA.Presented in part at the 41st Annual Congress, International College of Angiology, Sapporo, Japan, July 1999.     

Angiotensin-converting enzyme insertion/deletion polymorphism modulates coronary release of tissue plasminogen activator in response to bradykinin.

The aim of this study was to assess the relationship between the angiotensin converting enzyme gene (ACE) genotype and endothelium-dependent coronary vasomotor and fibrinolytic activity. The ACE DD genotype has been reported to be a risk factor for myocardial infarction. However, the mechanism is unknown. The fibrinolytic and renin-angiotensin systems are linked via ACE at the vascular beds. We studied 73 patients (II: n=24; ID: n=37; DD: n=12) who underwent diagnostic cardiac catheterization. Graded doses of bradykinin (BK) (0.2, 0.6, 2.0 microg/min) and acetylcholine (30,100 microg/min) were administered into the left coronary artery. Coronary blood flow (CBF) was evaluated by measuring Doppler flow velocity. Blood samples were taken from the aorta (Ao) and the coronary sinus (CS). Coronary release of tPA antigen was determined as a CS-Ao gradientXCBFX[(100-hematocrit) / 100]. ACE genotypes were determined using polymerase chain reaction. The ACE genotype did not appear to affect coronary macro- and microvascular responses induced by BK or acetylcholine. Coronary tissue plasminogen activator (tPA) release induced by BK was depressed in subjects with the ACE DD genotype. ACE levels in the DD genotype were significantly higher than those in the ID or II genotype. In all of the subjects, there was a significant negative correlation between the serum level of ACE activity and net coronary tPA release in response to BK at 0.6 microg/min. In conclusions, the DD genotype of the ACE gene impairs the coronary release of tPA induced by BK.     

The expression of angiotensin-I converting enzyme in human atherosclerotic plaques is not related to the deletion/insertion polymorphism but to the risk of restenosis after coronary interventions

Plasma and tissue concentrations of the angiotensin-I converting enzyme (ACE) have been shown to be associated with the ACE insertion/deletion (I/D) polymorphism. The purpose of this study was to examine the relation of ACE levels in atherosclerotic plaques to the ACE I/D polymorphism and to restenosis after balloon angioplasty and directional atherectomy (DCA). The study included 104 patients who underwent DCA and received angiographic follow-up at 12 to 18 months. The amount of ACE protein in various morphologically defined plaque components (fibrous, atheromatous, and complicated lesions) of the atherectomy specimens was determined by qualitative and semiquantitative immunohistochemistry. ACE levels were related to the ACE genotype, to plaque morphology and to the risk of restenosis. Sequential staining revealed that pathologic ACE overexpression of the atherosclerotic lesions occurred in intimal smooth muscle cells, fibrocytes/fibroblasts and macrophage/foam cells. The ACE content of the whole plaques and of the single plaque components was not associated with the I/D polymorphism, but with restenosis after coronary interventions. In addition, ACE levels in the atherosclerotic lesions correlated with the severity of vessel wall damage. The ACE phenotype might serve as an indicator for the risk of restenosis after coronary interventions.     

冠心舒通胶囊对冠状动脉支架置入术后支架内再狭窄的影响

目的 研究冠心舒通胶囊对冠脉支架置入术后支架内再狭窄的影响,初步探讨其作用机制.方法 将冠脉支架置入术成功的102例患者随机分为对照组（51例）及冠心舒痛胶囊组（51例）,检测两组患者术前,术后1d、3d、7d、2周时C反应蛋白（CRP）及白细胞介素-6（IL-6）水平.术后6个月,观察两组患者的心血管事件发生率及心电图ST段、心脏彩超左室射血分数变化情况;复查冠脉造影,观察两组患者支架内再狭窄情况.结果 两组患者术后1d、3d、7d时的CRP及IL-6水平均较术前明显升高（P＜0.05）.术后2周冠心舒通胶囊组的CRP及IL-6水平与术前相比差异无统计学意义（P＞0.05）,但对照组较术前仍偏高（P＜0.05）.冠心舒通胶囊组在术后1d、3d、7d、2周时的CRP及IL-6水平与对照组同时间点相比均明显偏低（P＜0.05）.术后6个月时,冠心舒通胶囊组的各种心血管事件发生率均明显低于对照组（P＜0.05）,心电图有效率、左室射血分数显著高于对照组（P＜0.05）;与对照组相比,支架内再狭窄率明显明显降低（P=0.0285）.结论 冠心舒通胶囊能减少冠脉支架置入术后各种心血管事件的发生率,并且能降低冠脉支架置入术后支架内再狭窄.这种作用可能与冠心舒通胶囊降低支架置入术后炎症反应有关.     

Predictors of diffuse-type in-stent restenosis after coronary stent implantation

Diffuse-type in-stent restenosis (ISR) is associated with higher rate of restenosis after balloon angioplasty, requiring new therapeutic modalities; therefore, it is clinically important to identify the determinants of diffuse-type ISR. We evaluate the clinical and angiographic variables to predict diffuse-type ISR after coronary stent placement. Two hundred and ten ISR lesions in 196 patients (diffuse ISR, 114 lesions; focal ISR, 96 lesions) were reviewed in this study. Clinical, procedural and quantitative coronary angiographic parameters were analyzed. Diffuse-type ISR was defined as a ≥50% lumen narrowing and ≥10-mm length. Univariate analysis revealed that initial lesion length, smaller vessel size, diabetes, multivessel disease, multiple stents, and long stent were significantly associated with diffuse-type ISR. However, diabetes was the only independent predictor of diffuse-type ISR by stepwise multiple regression analysis (OR, 3.3; 95% CI, 1.4–7.4, P = 0.001). Diabetes was associated with diffuse-type ISR after coronary stent placement. It may reflect enhanced rate of neointimal hyperplasia within the stent in diabetic patients. Cathet. Cardiovasc. Intervent. 47:406–409, 1999. © 1999 Wiley-Liss, Inc.     

冠脉支架植入术后支架内再狭窄的危险因素研究

目的对冠脉支架植入术后的支架内再狭窄危险因素进行研究。方法在2011年7月-2013年7月期间,我院收治冠脉支架植入术患者120例,对该120例患者术后支架内的再狭窄危险因素进行研究,并采取Logistic多因素分析再狭窄的危险因素。结果通过术后患者危险因素研究可知,与患者的胆固醇、术前狭窄、是否吸烟、有糖尿病及高血压等因素有关,与支架有无药物涂层也有关,表现为负相关,危险度是0.01。结论对糖尿病及高血压患者来说,实施支架植入术之后,出现再狭窄症状的几率增加。同时,冠脉支架患者对危险因素应采取预防措施,如戒烟,避免再狭窄情况出现,提高患者的生存质量。