Plasma activity and insertion/deletion polymorphism of angiotensin I–converting enzyme: a major risk factor and a marker of risk for coronary stent restenosis (original) (raw)
Related papers
Clinical Science, 2004
The ID (insertion/deletion) polymorphism of the ACE (angiotensin-converting enzyme) gene controls plasma ACE levels. Both have been correlated with ISR (in-stent restenosis) in preliminary analyses, but not confirmed in larger studies. In the present study, baseline and 6-month quantitative coronary analysis were performed in 897 patients who had stent implantation and the ID polymorphism genotyped. Plasma ACE levels were measured in 848 patients (95 %). Restenosis rates among genotypes were 31.2 % DD, 25.5 % ID and 28.8 % II (not significant). Plasma ACE levels were significantly higher in restenotic patients compared with patients without restenosis (30.7 + − 18.6 units/l compared with 22.8 + − 12.8 units/l; P = 0.0001) and a strong independent predictor of ISR [OR (odds ratio) = 3.70; 95 % CI (confidence interval), 2.40-5.71; P < 0.0001], except in diabetics. In the subgroup of diabetics and patients with AMI (acute myocardial infarction), the DD genotypes actually had a lower risk of ISR than the II genotypes (diabetics, OR = 0.16; 95 % CI, 0.04-0.69; P = 0.014; and patients with AMI, OR = 0.21; 95 % CI, 0.061-0.749; P = 0.016). After exclusion of diabetics and patients with AMI, ISR rates for genotypes in 632 patients were 31.7 % DD, 24.3 % ID and 17.6 % II (P = 0.02; DD compared with non-DD OR = 1.57; 95 % CI, 1.09-2.25). The association between the D allele and ISR observed in selected populations does not hold with a larger sample size. Other than sample size, clinical variables can modulate the association between ID polymorphism and ISR. Plasma ACE level is a risk factor for ISR, independently of the ID genotype.
Experimental and Molecular Pathology, 2014
The aim of the present study was to establish the role of ACE gene polymorphisms in the risk of developing instent restenosis and/or coronary artery disease (CAD). Eight ACE gene polymorphisms were genotyped by 5′ exonuclease TaqMan genotyping assays in 236 patients with CAD who underwent coronary artery stenting. Basal and procedure coronary angiographies were analyzed searching for angiographic predictors of restenosis and follow-up angiography was analyzed looking for binary restenosis. A group of 455 individuals without clinical and familial antecedents of cardiovascular diseases were included as controls. Haplotypes were constructed after linkage disequilibrium analysis. Distribution of ACE polymorphisms was similar in patients with and without restenosis. Similar results were observed when the analysis was made comparing the whole group of patients (with and without restenosis) and healthy controls. Six out of eight polymorphisms were in high linkage disequilibrium and were included in five haplotypes (AAAGCA, GGGATG, GAGATG, AGAGCA and AAGACA). The distribution of these haplotypes was similar in patients with and without restenosis. However, CAD patients showed an increased frequency of the AAAGCA haplotype (OR = 1.31, 95% CI: 1.04-1.66, P = 0.018) and decreased frequencies of GAGATG (OR = 0.47, 95% CI: 0.25-0.88, P = 0.011) and AGAGCA (OR = 0.15, 95% CI: 0.02-0.65, P = 0.002) haplotypes when compared to healthy controls. Haplotypes of the ACE gene could be a genetic factor related to coronary artery disease in the Mexican individuals, but do not support its role as a risk factor for developing restenosis after coronary stenting.
GENES and In-Stent Restenosis: Review
International Journal of Research in Pharmaceutical Sciences
The initiation of coronary stents is a vast landmark in the practice of interventional cardiology. The vascular injury sustained during the percutaneous coronary intervention (PCI) leads to a complicated inflammatory and repairing process. Therefore, stent restenosis arises. Diabetes mellitus is the highest-risk clinical predictor of ISR. Genetics has an important role in the development of ISR. There is a suggested association between the appearance of stent restenosis and certain genetic polymorphisms. Examples of these single nucleotide polymorphisms are endothelial nitric oxide synthase gene (eNOS), the angiotensin converting enzyme gene (ACE), the angiotensin II type 1 receptor gene (AT1R), TGF-β, and VEGF. CYP2C19 variants can help change the medical strategy to a more individualized therapeutic regimen either by altering the therapeutic dose depending on the genotype or using an alternative drug that does not worsen the patient’s case. However, eNOS polymorphism produces gene...
Atherosclerosis, 2014
The aim of the present study was to establish the role of ACE gene polymorphisms in the risk of developing instent restenosis and/or coronary artery disease (CAD). Eight ACE gene polymorphisms were genotyped by 5′ exonuclease TaqMan genotyping assays in 236 patients with CAD who underwent coronary artery stenting. Basal and procedure coronary angiographies were analyzed searching for angiographic predictors of restenosis and follow-up angiography was analyzed looking for binary restenosis. A group of 455 individuals without clinical and familial antecedents of cardiovascular diseases were included as controls. Haplotypes were constructed after linkage disequilibrium analysis. Distribution of ACE polymorphisms was similar in patients with and without restenosis. Similar results were observed when the analysis was made comparing the whole group of patients (with and without restenosis) and healthy controls. Six out of eight polymorphisms were in high linkage disequilibrium and were included in five haplotypes (AAAGCA, GGGATG, GAGATG, AGAGCA and AAGACA). The distribution of these haplotypes was similar in patients with and without restenosis. However, CAD patients showed an increased frequency of the AAAGCA haplotype (OR = 1.31, 95% CI: 1.04-1.66, P = 0.018) and decreased frequencies of GAGATG (OR = 0.47, 95% CI: 0.25-0.88, P = 0.011) and AGAGCA (OR = 0.15, 95% CI: 0.02-0.65, P = 0.002) haplotypes when compared to healthy controls. Haplotypes of the ACE gene could be a genetic factor related to coronary artery disease in the Mexican individuals, but do not support its role as a risk factor for developing restenosis after coronary stenting.
Pre-procedural ACE-activity does not predict symptomatic in-stent restenosis
International Journal of Cardiology, 2005
Background: Several studies indicate that ACE-activity is related to atherosclerosis. We investigated the correlation between ACE-activity, in plasma as well as in the atherosclerotic plaque, and in-stent restenosis. Methods and results: ACE-activity was measured in blood samples from 178 patients who underwent a percutaneous coronary intervention with stent placement. During 8 months follow-up, 51 of these patients had an adverse clinical event. ACE-activity did not differ between patients with or without adverse events (21.5 vs. 23.1 nM/ml/min; P=0.36). Tissue samples were obtained with an atherectomy catheter before elective stent placement in another group of 13 patients with de novo stenosis. In this tissue, we determined the ACE-content immunohistologically. These patients were scheduled for follow-up quantitative coronary angiography after 12 months. In this group, the quantity of ACE was not correlated to the late luminal loss (0.31 vs. 0.38 mm; P=0.76). Conclusion: In this study, pre-procedural ACE-activity, in plasma as well as in the atherosclerotic plaque, does not predict the occurrence of in-stent restenosis.
2008
"BACKGROUND: It has been suggested that the incidence of coronary restenosis after a percutaneous coronary intervention is much higher in patients with a 287-bp alu repeat sequence within intron 16 of the angiotensin-I-converting enzyme (ACE) gene (deletion allele) than in others, but published studies are conflicting. METHODS: The presence (insertion) or absence (deletion) of a 287-bp alu repeat sequence within intron 16 of the ACE gene (I/D polymorphism) was analyzed by polymerase chain reaction in a group of 168 patients with coronary artery disease who underwent coronary artery stenting. Basal and procedure coronary angiographies were analyzed searching for angiographic predictors of restenosis and follow-up angiography was analyzed looking for binary restenosis. RESULTS: Distribution of angiotensin converting enzyme I/D polymorphisms was similar in patients with and without restenosis. Similar results were observed when the analysis was made considering the type of stent implanted. On the other hand, the whole group of coronary artery disease patients showed increased frequencies of the D allele (p=0.00001, OR=2.17, 95% CI=1.49-3.16) and ID genotype (p=0.0002, OR=2.58, 95%CI=1.49-4.47) when compared to healthy controls. CONCLUSIONS: Genetic variations of the ACE gene could be a genetic factor related to coronary artery disease in the Mexican mixed racial ancestry individuals, but do not support its role as a risk factor for developing restenosis after coronary stenting."
International heart journal, 2005
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 ...
Plasma Activity and Insertion/Deletion Polymorphism of Angiotensin I–Converting Enzyme
Circulation, 1998
Background —Tissue proliferation is almost invariably observed in recurrent lesions within stents, and ACE, a factor of smooth muscle cell proliferation, may play an important role. Plasma ACE level is largely controlled by the insertion/deletion ( I/D ) polymorphism of the enzyme gene. The association among restenosis within coronary stents, plasma ACE level, and the I/D polymorphism is analyzed in the present prospective study. Methods and Results —One hundred seventy-six consecutive patients with successful, high-pressure, elective stenting of de novo lesions in the native coronary vessels were considered. At follow-up angiography, recurrence was observed in 35 patients (19.9%). Baseline clinical and demographic variables, plasma glucose and serum fibrinogen levels, lipid profile, descriptive and quantitative angiographic data, and procedural variables were not significantly different in patients with and without restenosis; mean plasma ACE levels (±SEM) were 40.8±3.5 and 20.7±1....