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.     

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.     

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.     

Hypertensive left ventricular remodeling and ACE-gene polymorphism.

OBJECTIVE: To evaluate the relationship between ACE-gene polymorphism and left ventricular geometry in never treated hypertensives. METHODS: We enrolled 200 hypertensive outpatients that underwent clinical and ambulatory blood pressure measurements, echocardiographic evaluation and analysis for insertion (I)/deletion (D) polymorphism by PCR. Patients with normal or increased (> 125 g/m2 in males and > 110 g/m2 in females) left ventricular mass were considered to have concentric remodeling or concentric left ventricular hypertrophy if their relative wall thickness was > or = 0.45. RESULTS: The left ventricular mass index values (g/m2) were 136 +/- 30 in DD genotype, 124 +/- 26 in ID genotype, and 116 +/- 20 in II genotype (DD vs. ID P < 0.005; DD vs. II P < 0.05), and were unrelated to blood pressure. Ninety-six patients presented left ventricular hypertrophy (48.0%): 51 with concentric and 45 with eccentric hypertrophy. The eccentric left ventricular hypertrophy was detected in 32 (36.8%) DD patients, in ten (10.5%) ID patients (P < 0.05), and in three (16.6%) II patients. The relative septal thickness was 0.43 +/- 0.09 in DD genotype, 0.45 +/- 0.08 in ID genotype, and 0.43 +/- 0.10 in II genotype. In DD and ID genotypes, the relative posterior wall thickness (0.37 +/- 0.07 vs. 0.41 +/- 0.07; P < 0.0001) and the end-diastolic left ventricular internal dimension (52.8 +/- 3.3 mm vs. 48.3 +/- 2.8 mm; P < 0.0001) were statistically different. CONCLUSIONS: The DD genotype of the ACE-gene is associated with an increased left ventricular mass and with a significantly higher prevalence of eccentric left ventricular hypertrophy, when compared to ID genotype.     

Angiotensin converting enzyme gene deletion allele is independently and strongly associated with coronary atherosclerosis and myocardial infarction.

OBJECTIVE--To investigate the association of the three angiotensin converting enzyme (ACE) genotypes, DD, ID, and II, with the occurrence or absence of coronary atherosclerosis and with myocardial infarction and hypertension. DESIGN--Cohort analysis study. SETTING--North-Italy reference centre. SUBJECTS--388 white Italian patients (281 males; mean age 60.7 (SD 12.5) years) with proven coronary atherosclerosis (n = 255) or with angiographically normal coronary arteries (n = 133). A further group of 290 healthy blood donors was tested for allele frequency comparison. INTERVENTIONS--ACE/ID polymorphism was analysed with polymerase chain reaction on DNA from white blood cells. MAIN OUTCOME MEASURES--Coronary atherosclerosis, myocardial infarction, hypertension. RESULTS--The D and I allele frequencies were respectively 0.63 and 0.37 in the overall healthy blood donor group and 0.66 and 0.34 in the overall study group. In the latter, univariate analysis showed (1) that coronary atherosclerosis (255 patients) was associated with the deletion allele, with an odds ratio (OR) of 5.78 for DD/II, P < 0.001, and 2.39 for ID/II, P = 0.006; and (2) that myocardial infarction (154 patients) was associated with the DD genotype (OR DD/II = 2.56, P = 0.007), but not with the ID genotype (OR DD/II = 1.96, P = 0.056). Finally, hypertension proved to be unrelated with the ACE genotype. The distribution between the three genotypes of known risk factors for coronary artery disease was similar. Logistic regression modelling, performed to test the association of the selected risk factors simultaneously with coronary atherosclerosis and myocardial infarction, showed that the deletion allele (whether DD or ID) was the strongest risk factor for atherosclerosis, and that the D allele was significantly associated with the risk of infarction (although to a lesser extent than with coronary atherosclerosis). CONCLUSION--ACE deletion polymorphism is strongly and independently associated with coronary atherosclerosis and, to a lesser extent, with myocardial infarction. As such, the results are analogous to what has already been reported in French white, Japanese, and Welsh coronary patients.     

Long-term follow-up after coronary stenting and intravascular red laser therapy

A high restenosis rate remains a limiting factor for coronary angioplasty and stenting. Recently, use of intravascular red light therapy (IRLT) has been shown to be effective in different animal models and in humans in reducing the restenosis rate. Sixty-eight patients were treated with IRLT in conjunction with coronary stenting procedures. Mean age was 64 +/- 9 years. Treated lesions were type A (11), type B (42), and type C (18) with a mean lesion length of 16.5 +/- 2.4 mm. Reference vessel diameter and minimal lumen diameter (MLD) before therapy were 2.90 +/- 0.15 and 1.12 +/- 0.36 mm, respectively. After stenting and laser irradiation, MLD was 2.76 +/- 0.39 mm. No procedural complications or in-hospital adverse events occurred. All patients were followed up as depicted in the protocol. Sixty-one patients underwent angiographic restudy, which revealed restenosis in 9 patients (14.7%). Observed restenosis rate by artery size was > 3 mm (n = 21, 0%), 2.5 to 3.0 mm (n = 28, 14.2%), and <2.5 mm (n = 12, 41.6%). We conclude that IRLT is safe and feasible and reduces the expected restenosis rate in patients after coronary stenting in arteries of >2.5 mm.     

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.     

Angiotensin-converting enzyme gene polymorphism in coronary artery disease in north India

BACKGROUND: The aim of this study was to investigate the role of angiotensin-converting enzyme gene polymorphism in patients with coronary artery disease in north India. METHODS AND RESULTS: One hundred forty-six patients with angiographically proven atherosclerotic coronary artery disease, and 146 age- and sex-matched control subjects (treadmill-negative) were included in the study. Genomic DNA was extracted and analyzed for angiotensin-converting enzyme insertion/deletion polymorphism. Two independent investigators scored the genotypes. CONCLUSIONS: When we compared the genotypes of patients with coronary artery disease with those of normal controls, it was seen that all three genotypes, i.e. DD, ID and II, were not statistically different among patients and controls. Further, we categorized the patient and control groups into 2 subgroups, i.e. below and above 50 years of age. Interestingly, it was observed that the DD genotype was significantly higher in patients in the higher age group (i.e. above 50 years of age). However, this needs further validation by studying patients with coronary artery disease from other parts of India.     

Effect of cilostazol on restenosis after coronary angioplasty and stenting in comparison to conventional coronary artery stenting with ticlopidine

BACKGROUND: The role of antiplatelet therapy with ticlopidine plus aspirin in the prevention of subacute thrombosis after coronary artery stenting has been established. However, restenosis remains a major limitation in coronary artery stenting. METHODS: To compare the effect of cilostazol on restenosis after coronary angioplasty and stenting with that of ticlopidine after coronary artery stenting, 213 patients with 230 lesions who underwent successful coronary interventions were evaluated. Optimal results (residual stenosis less than 30%) were obtained by balloon angioplasty in 112 lesions, 64 lesions were treated with aspirin 81 mg/day (balloon-aspirin group) and 48 lesions with cilostazol 200 mg/day and aspirin 81 mg/day (balloon-cilostazol group). Stent implantation was performed in the remaining 118 lesions; 55 lesions were treated with ticlopidine 200 mg/day and aspirin 243 mg/day (stent-ticlopidine group) and 63 lesions with cilostazol 200 mg/day and aspirin 81 mg/day (stent-cilostazol group). Concomitant medications were continued for 4 to 6 months of follow-up. RESULTS: No adverse events including acute occlusion and subacute thrombosis occurred in any groups. Although immediate gain and minimal lumen diameter immediately after angioplasty were significantly larger in stent groups than those in balloon groups, net gain at follow-up was significantly larger in cilostazol groups (1.54+/-0.83 mm in balloon-cilostazol group and 1.65+/-0.78 mm in stent-cilostazol group) than other groups (1.02+/-0.81 mm in balloon-aspirin group and 1.21+/-0.70 in stent-ticlopidine group) as a result of significantly lower late loss and loss index in cilostazol groups. The restenosis rate was significantly lower in cilostazol groups (12.5% in balloon-cilostazol group and 14.3% in stent-cilostazol group) than other groups (43.8% in balloon-aspirin group and 32.7% in stent-ticlopidine group). The rate of recurrent angina was significantly lower in cilostazol groups (4.3% in balloon-cilostazol group and 1.9% in stent-cilostazol group) than in other groups (17.5% in balloon-aspirin group and 14.0% in stent-ticlopidine groups). CONCLUSIONS: Both optimal balloon angioplasty with cilostazol and coronary artery stenting with cilostazol have a potential to reduce restenosis compared with optimal balloon angioplasty with aspirin or conventional coronary artery stenting with ticlopidine plus aspirin.     

Quinapril prevents restenosis after coronary stenting in patients with angiotensin-converting enzyme D allele.

Restenosis after coronary artery stent implantation is attributed chiefly to intimal hyperplasia, which is prevented experimentally by angiotensin-converting enzyme (ACE) inhibitors. Therefore, the present study investigated whether the effect of quinapril, a tissue-specific ACE inhibitor, on the prevention of coronary restenosis differs according to ACE polymorphism. One hundred consecutive patients with successful stent implantation were randomly assigned to quinapril and control groups. Both follow-up angiography and ACE polymorphism analysis were obtained from 92 patients (control, 46; quinapril treatment, 46). The prevalence of risk factors did not differ statistically according to quinapril treatment or ACE genotypes. There was no statistically significant difference in the occurrence of restenosis 6 months after stenting between the groups. Quantitative coronary angiography revealed that quinapril treatment resulted in significantly higher minimal lumen diameter and significantly lower percent diameter stenosis (22.9 +/- 22.6 vs 37.1 +/- 19.7% in the control group, p < 0.05) in patients with the D allele although there was no difference in those with the II genotype. In addition, intravascular ultrasound revealed that quinapril treatment significantly prevented the loss of minimal lumen cross-sectional area and the increase in percent area stenosis (34.5 +/- 14.0 vs 53.3 +/- 16.4% in the control group, p < 0.05) in patients with the D allele compared to those with the II genotype. These results suggest that the administration of ACE inhibitors for the attenuation of lumen loss after coronary stent implantation is best for subjects with the D allele of the ACE genotype.     

Relation of a common methylenetetrahydrofolate reductase mutation and plasma homocysteine with intimal hyperplasia after coronary stenting

BACKGROUND: Hyperhomocysteinemia 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 RESULTS: To examine the potential influence of MTHFR genotype and homocysteine on coronaryarteries 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). CONCLUSIONS: The homozygous mutant genotype of the MTHFR gene may increase the risk of in-stent restenosis more than does the normal homozygous or heterozygous genotype.     

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.     

Angiotensin I-converting enzyme insertion/deletion polymorphism and cardiac mortality and morbidity after coronary artery bypass graft surgery

STUDY OBJECTIVES: This study was designed to evaluate whether the insertion (I)/deletion (D) polymorphism of the angiotensin I-converting enzyme (ACE) gene is associated with mortality and cardiac morbidity after coronary artery bypass graft surgery (CABG). METHODS AND RESULTS: The ACE I/D genotype was determined in 249 consecutive patients who underwent CABG. Follow-up information (after 2 years) was obtained in 247 patients (99.2%). The primary end point was total mortality; the secondary end point was mortality from cardiac reasons, or the need for myocardial revascularization (coronary angioplasty or recurrent CABG) during follow-up. At follow-up, total mortality was 9.7% (all patients). None of the 51 patients with the ACE II genotype, 14 of 125 patients with the ACE ID genotype (11.2%), and 10 of 71 with the ACE DD genotype (14.1%) died during follow-up (p < 0.05). The ACE DD genotype, older age, diabetes mellitus, decreased left ventricular ejection fraction, and lack of internal mammary artery graft were independently related to an increased mortality after CABG. The incidence of the secondary end point was 14.5% (all patients): ACE II, 5.8%; ACE ID, 9.4%; ACE DD, 30.3% (p < 0.05). The ACE DD genotype and the presence of a left main coronary artery stenosis >or= 50% were independent predictors for the secondary end point. CONCLUSION: The ACE DD genotype is associated with increased midterm mortality and cardiac morbidity after CABG.     

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).     

Long-term clinical outcome after implantation of medium Palmaz (biliary) stents in very large native coronary arteries.

Intracoronary stenting has been shown to improve acute and long-term clinical results compared with coronary angioplasty. However, clinical outcome after medium Palmaz biliary (PB) stent implantation in very large native coronary arteries (> 4 mm in diameter) is unknown. This study evaluated restenosis and long-term clinical outcome after PB stenting in large native coronary arteries. Between June 1993 and December 1998, 55 patients with 56 lesions were treated with PB stents. Intracoronary stent deployment was successful in all 56 vessels attempted (100%). The mean stenosis was reduced from 65% +/- 10% to 4% +/- 14%. In 48 of the 56 vessels (86%), vessel size was greater than 4.0 mm in diameter and the mean reference vessel diameter was 4.73 +/- 0.7 mm after stenting. Angiographic success was achieved in 100%. Five patients had postprocedural cardiac enzyme elevation. There was no periprocedural death, emergency coronary artery bypass surgery, repeat target lesion revascularization, or acute stent thrombosis. Long-term clinical follow-up at mean of 28 +/- 15 months was obtained in 96% of the patients. Clinical restenosis rate occurred in 18% of ostial (6/34) and 0% of nonostial (0/22) lesions (P < 0.0001) with an overall clinical restenosis rate of 11%. Repeat angioplasty were performed in these six patients. There were three cardiac and three noncardiac deaths. The overall event-free survival at 1 and 3 years was 92% +/- 4% and 80% +/- 6%, respectively. PB stent implantation in very large native coronary arteries can be performed with a high degree of procedural success and low in-hospital complications. The long-term clinical outcome of patients undergoing PB stenting is associated with excellent event-free survival. However, stenting of ostial lesions remains as an important factor for restenosis even in very large coronary artery stenting.     

Atherosclerosis of carotid arteries and the ace insertion/deletion polymorphism in subjects with diabetes mellitus type 2.

BACKGROUND: The aim of the present study was to investigate the association of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism with the ultrasonographically evaluated severity and characteristics of carotid artery atherosclerosis in subjects with diabetes mellitus type 2. METHODS: We assessed 184 subjects with diabetes mellitus type 2, 75 males and 109 females, mean age 61.4+/-7.7 years. All subjects were receiving oral antidiabetic drugs for glycemic control and were free of cardiovascular events. The ACE genotype was analyzed by the polymerase chain reaction (PCR) technique. The ultrasonographic examination of the carotid arteries was performed in both B-mode imaging and Doppler ultrasound. The common carotid artery intima-media thickness was assessed 15-20 mm proximal to the dilatation of the carotid bulb. The atheromatous lesions were classified according to their echogenic characteristics as predominantly echolucent, mixed and predominantly echogenic with under 30, 30-70 and over 70% of the total plaque area echogenicity, respectively. RESULTS: From the total cohort 29 (15.8%) subjects had the II, 86 (46.7%) the ID and 69 (37.5%) the DD ACE genotypes. The mean carotid artery diameter stenosis was 37+/-17%, 43+/-19% and 40+/-20% (p=NS) and the intima media thickness was 0.94+/-0.24 mm, 0.97+/-0.20 mm and 0.98+/-0.20 mm (p=NS) in the II, ID and DD subgroups, respectively. When the echogenicity was analyzed according to the ACE I/D polymorphism, 12 subjects (41.4%), 13 (44.8%) and 4 (13.8%) with II genotype had predominantly echogenic, mixed and predominantly echolucent lesions, respectively. The ID genotype diabetics were found to have predominantly echogenic plaques in 41 cases (47.7%), mixed in 30 (34.9%) and predominantly echolucent in 15 cases (17.4%). From the 69 DD subjects 19 (27.5%) had predominantly echogenic plaques, 26 (37.7%) had mixed and 24 (34.8%) had predominantly echolucent lesions. Predominantly echolucent plaques were more frequently encountered among diabetics with the DD genotype (p<0.05), even after correction for demographic characteristics, the main risk factors of atherosclerosis and blood glucose control. CONCLUSIONS: The ACE genotype seems to be associated with the echogenicity of carotid artery atheromatosis but not with the common carotid artery intima media thickness or the degree of internal carotid artery stenosis in subjects with type 2 diabetes mellitus. The DD genotype may be implicated in the increased cardiovascular risk that characterizes echolucent plaques.     

Accelerated plasminogen activator inhibitor may prevent late restenosis after coronary stenting in acute myocardial infarction

BACKGROUND: Although acceleration of plasma plasminogen activator inhibitor-1 (PA-1) level after emergent coronary angioplasty in acute myocardial infarction (AMI) has been documented, its pathophysiologic role is still unknown. HYPOTHESIS: This study was designed to elucidate the role of PAI-1 in the development of restenosis after primary coronary stenting in AMI. METHODS: We selected for this study 66 patients with AMI, who underwent primary coronary stenting for infarct-related coronary artery lesions in an emergent situation. In all patients, plasma PAI-1 level was measured at admission, and at 3 h, 24 h, 48 h, and 1 month after coronary stenting. RESULTS: At admission, the PAI-1 level was equivalent in 24 patients who experienced restenosis and in 42 patients without restenosis (28 +/- 4 vs. 29 +/- 4 ng/ml). In patients with restenosis, the levels did not change during the course after coronary stenting. In patients without restenosis, however, the level significantly increased at 3 h (48 +/- 9 ng/ml, p < 0.001), 24 h (42 +/- 9, p < 0.01), and 48 h (38 +/- 7, p < 0.05) after coronary stenting, and was restored to the level equivalent to that at admission (27 +/- 2 ng/ml) I month aftercoronary stenting. The PA-1 level at 3 h after coronary stenting in patients without restenosis was significantly higher (p < 0.05) than the level (33 +/- 6 ng/ml) in patients with restenosis. Multiple logistic regression analysis indicated that the PAI-1 level 3 h after coronary stenting was an independent predictor of restenosis (Wald chi2 = 3.826, p = 0.019, odds ratio 0.921, 95% confidence interval 0.866-0.961). CONCLUSION: Accelerated PAI-1 after coronary stenting in patients with AMI may protect against the development of late restenosis.     

Early experience with coronary stenting.

From April 1988 to December 1991, we implanted 75 coronary stents (29 self-expanding and 46 balloon expandable) in 62 patients. All had New York Heart Association class II to IV angina, and 11 (18%) had prior coronary artery bypass grafting (CABG). Thirty nine patients (63%) had 1 vessel disease, and 23 (37%) had multivessel disease. The mean left ventricular ejection fraction was 63 +/- 11%. The indications for coronary stenting were acute post percutaneous transluminal coronary angioplasty (PTCA) occlusion in 45 (73%) (bail out stenting) and restenosis in 17 (24%) (elective stenting). There were 52 single stent (84%), 7 double stent (11%), and 3 triple stent procedures (5%). The mean stent diameter was 3.8 +/- 0.5 mm, and the mean stent length 21 +/- 7 mm. The attempted vessels were the left main coronary artery in 2(3%), left anterior descending coronary artery in 27 (44%), left circumflex coronary artery in 8 (13%), right coronary artery in 17 (27%), and a saphenous vein graft in 8 (13%). Technical success was achieved in 74 stent implantations (98%). Technical failure occurred in 1 case with a self expanding stent because of inability to reach the lesion. In hospital complications (mean hospital stay 10 +/- 10, range 2-60 days) included temporary stent occlusion in 2 patients (3%) treated by balloon dilatation and thrombolysis with intravenous urokinase, permanent stent occlusion in 5 patients (8%), Q-wave infarction in 5 patients (8%), CABG in 4 patients (11%), and death in 3 patients (5%). At least 1 major complication (Q wave infarction, CABG, or death) occurred in 8 patients (13%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Lack of association between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and vasospastic angina

Background and hypothesis: It has been suggested that the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is an independent risk factor for coronary atherosclerosis and myocardial infarction, but its relation to vasospastic angina has not been fully proven. In the present study, we investigated the possible relationship between the ACE I/D genotype and vasospastic angina. Methods: We explored the distribution of the ACE genotype in 20 patients with vasospastic angina without fixed coronary artery stenosis, 55 angina patients with fixed coronary artery stenosis, and 30 control subjects without coronary artery disease. Results: The frequency of the DD genotype in patients with vasospastic angina (DD: 30.0%, ID: 20.0%, II: 50.0%) did not differ from that in the control subjects (DD: 23.3%, ID: 26.7%, II: 50.0%), while the frequency in patients with coronary artery stenosis (DD: 43.7%, ID: 21.8%, II: 34.5%) was significantly higher than that in the control subjects. The frequency of the D allele also did not differ between patients with vasospastic angina (0.40) and control subjects (0.37), while the frequency was significantly higher in patients with coronary artery stenosis (0.55). Conclusions: These findings suggest that the ACE DD genotype is a potent genetic risk factor for organic coronary artery disease, while it confers no appreciable increase in risk of vasospastic angina. These results also suggest the diversity of the pathogenesis of vascular lesions in these two types of coronary artery disease.