miR-196a2 (rs11614913) polymorphism is associated with coronary artery disease, but not with in-stent coronary restenosis.

OBJECTIVE: The aim of the study was to evaluate the association of miRNA-146a G/C (rs2910164), and miRNA-196a2 C/T (rs11614913) polymorphisms with the presence of coronary artery disease (CAD) and/or restenosis in patients with coronary stent. MATERIALS AND METHODS: The polymorphisms were determined in 218 patients with CAD who underwent coronary artery stenting (66 with restenosis and 152 without restenosis) and 611 healthy controls using 5' exonuclease TaqMan assays. RESULTS: The distribution of both polymorphisms was similar in patients with and without restenosis. However, when the whole group of patients (with and without restenosis) was compared to healthy controls, under co-dominant, dominant and additive genetic models, the T allele of the miRNA-196a2 C/T (rs11614913) polymorphism was associated with increased risk of CAD (OR = 2.18, Pco-dom = 0.006, OR = 1.86, Pdom = 0.002, and OR = 1.52, Padd = 0.002, respectively). All models were adjusted for age, type 2 diabetes mellitus, dyslipidemia, hypertension and smoking habit. The "GT" haplotype was associated with increased risk of developing CAD (OR = 1.36, P = 0.046). CONCLUSIONS: Our data suggests that the T allele of the miRNA-196a2 C/T (rs11614913) polymorphism is associated with the risk of developing CAD, but no association with restenosis was observed.

The T29C (rs1800470) polymorphism of the transforming growth factor-ß1 (TGF-ß1) gene is associated with restenosis after coronary stenting in Mexican patients.

The aim of the present study was to establish the role of IL-6 and TGF-ß1 gene polymorphisms in the risk of developing in-stent restenosis. Two IL-6 [rs1800796 (-572 G>C), rs2069827 (-1426 T>G)] and two TGF-ß1 [rs1800469 (-509 T>C), rs1800470 (T29C)] gene polymorphisms were analyzed by 5' exonuclease TaqMan genotyping assays in a group of 244 patients, who underwent coronary artery stenting. Basal and procedure coronary angiography were analyzed, looking for angiographic predictors of restenosis and follow-up angiography was performed to screen for binary restenosis. Under the dominant and additive models adjusted for hypertension, stable angina, stent used, and diameter of stent, the TGF-ß1 T29C (rs1800470) polymorphism was significantly associated with an increase risk of restenosis when compared to patients without restenosis (OR=2.06, 95% CI: 1.03-4.11, P(Dom)=0.034 and OR=1.64, 95% CI: 1.09-2.45, PAdd=0.016). TGF-ß1 polymorphisms were in linkage disequilibrium and one haplotype (TT) was significantly increased in patients with restenosis when compared to patients without restenosis (OR=2.03, P=0.041). In summary, our results suggest that the TGF-ß1 T29C gene polymorphism could be involved in the risk of developing restenosis after coronary stent placement.

The C4280A (rs5705) gene polymorphism of the renin (REN) gene is associated with risk of developing coronary artery disease, but not with restenosis after coronary stenting.

The aim of the present study was to evaluate the role of AGT and REN gene polymorphisms as susceptibility markers for coronary artery disease (CAD) and/or restenosis after coronary stent placement in a group of Mexican patients. Five polymorphisms of the AGT (rs699, rs4762, rs5051, rs5049, rs5046) and two of the REN (rs5707, rs5705) genes were analyzed by 5' exonuclease TaqMan genotyping assays in 240 patients with CAD who underwent coronary artery stenting (76 with restenosis and 164 without restenosis). A group of 610 individuals without clinical and familial antecedents of cardiovascular diseases were included as controls. The results showed that the distribution of AGT and REN polymorphisms were similar in patients with and without restenosis. However, when the whole group of patients (with and without restenosis) was compared to healthy controls, under co-dominant, dominant, heterozygous and additive models, the REN A4280C (rs5705) polymorphism was associated with increased risk of CAD (OR=1.76, PCo-dom=0.006, OR=1.81, PDom=0.001, OR=1.75, PHet=0.003 and OR=1.59, PAdd=0.003, respectively). All models were adjusted for age, gender, diabetes, dyslipidemia, hypertension and smoking habit. The TC haplotype of the REN gene was associated with increased risk of CAD (OR=1.53, P=0.014). The data suggest that the REN C4280A (rs5705) polymorphism plays an important role in the risk of developing CAD with the highest risk for C allele, but do not support its role as a risk factor for developing restenosis after coronary stenting.

Haplotypes of the angiotensin-converting enzyme (ACE) gene are associated with coronary artery disease but not with restenosis after coronary stenting.

The aim of the present study was to establish the role of ACE gene polymorphisms in the risk of developing in-stent 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.

The DEFB1 gene rs11362 A/G genetic variant is associated with risk of developing CAD: a case-control study.

BACKGROUND: In the present study, we evaluated whether DEFB1 gene polymorphisms are associated with the presence of coronary artery disease (CAD). METHODS: Two rs11362 A/G, and rs1800972 C/G gene polymorphisms of DEFB1 gene were genotyped by 5'exonuclease TaqMan assays in 219 patients with CAD and 522 control individuals. RESULTS: The distribution of rs1800972 C/G polymorphisms was similar in patients with CAD and healthy controls. Nonetheless, under the co-dominant, dominant, recessive, and additive models, the AA genotype of the rs11362 A/G polymorphism was associated with the risk of developing CAD (OR = 1.89 pCCo-Dom = 0.041, OR = 1.46, pCDom = 0.034, OR = 1.69, pCRes = 0.039, and OR = 1.37, pCAdd = 0.012, respectively). In addition, the linkage disequilibrium showed that the 'AG' haplotype was associated with an increased risk of developing CAD (OR = 1.23, p = 0.042). According, with the Genotype-Tissue Expression (GTEx) consortium data, the rs11362 AA genotype is associated with a low mRNA expression of the ß-defensin-1 in tissues, such as artery aorta, artery coronary, heart left ventricle, and heart atrial appendage (p < 0.001). CONCLUSION: This study demonstrates that rs11362 A/G polymorphism of the DEFB1 gene is involved in the risk of developing CAD, and with a low RNA expression of the ß-defensin-1 in heart tissue.

Risk Factors Control After an Acute Coronary Syndrome and Association with Major Adverse Cardiovascular Events: A Single Center Experience in Latin-America.

INTRODUCTION: An important challenge in the secondary prevention of cardiovascular diseases is the optimization of risk factors (RFs) after hospital discharge. These have been shown to be insufficiently controlled in clinical practice. AIM: To evaluate whether secondary prevention goals were met at our institution at 12 months after an acute coronary syndrome (ACS) index event, as well as analyzing if achieving these goals was associated with a lower incidence of major adverse cardiovascular events (MACE). METHODS: Retrospective cohort of patients with a former diagnosis of ACS over a period of 4 years. To evaluate the proportion of patients who met RF control goals at 12 months after the index event, we used two sets of preestablished goals: stringent and lenient. During follow-up we evaluated the occurrence of MACE, defined by the following: ACS, coronary revascularization, stroke, hospitalization because of acute heart failure and cardiovascular death. RESULTS: We included 468 patients during the study period. The mean age of the patients was 60 ± 10.76 years, 20.5% were women, and mean follow-up was 41.8 ± 22.0 months. The proportion of patients that met all secondary prevention stringent and lenient goals accounted for 5.5% and 17.2%, respectively, and 8% did not achieve any target. Overall, 9.6% presented the composite of MACE during follow-up. The number of RFs in control at 12 months was associated with a lower rate of MACE, both with stringent and lenient goals. CONCLUSION: Achieving established goals for modifiable RFs can lower the incidence of MACE during long-term follow-up.

CASP1 Gene Polymorphisms and BAT1-NFKBIL-LTA-CASP1 Gene-Gene Interactions Are Associated with Restenosis after Coronary Stenting.

In the present study, we evaluated the association of the BAT1, NFKBIL, LTA, and CASP1 single nucleotide polymorphisms and the gene−gene interactions with risk of developing restenosis after coronary stenting. The allele and genotype determination of the polymorphisms (BAT1 rs2239527 C/G, NFKBIL1 rs2071592 T/A, LTA rs1800683 G/A, CASP1 rs501192 A/G, and CASP1 rs580253 A/G) were performed by 5'exonuclease TaqMan assays in 219 patients: 66 patients with restenosis and 153 without restenosis. The distribution of rs2239527 C/G, rs2071592 T/A, and rs1800683 G/A polymorphisms was similar in patients with and without restenosis. Nonetheless, under recessive (OR = 2.73, pCRes = 0.031) and additive models (OR = 1.65, pCAdd = 0.039), the AA genotype of the rs501192 A/G polymorphism increased the restenosis risk. Under co-dominant, dominant, recessive, and additive models, the AA genotype of the rs580253 A/G was associated with a high restenosis risk (OR = 5.38, pCCo-Dom = 0.003; OR = 2.12, pCDom = 0.031; OR = 4.32, pCRes = 0.001; and OR = 2.16, 95%CI: 1.33−3.52, pCAdd = 0.001, respectively). In addition, we identified an interaction associated with restenosis susceptibility: BAT1-NFKBIL1-LTA-CASP1 (OR = 9.92, p < 0.001). In summary, our findings demonstrate that the rs501192 A/G and rs580253 A/G polymorphisms, as well as the gene−gene interactions between BAT1-NFKBIL1-LTA-CASP1, are associated with an increased restenosis risk after coronary stenting.

The rs4783961 and rs708272 genetic variants of the CETP gene are associated with coronary artery disease, but not with restenosis after coronary stenting.

OBJECTIVE: We evaluated whether cholesteryl ester transfer protein (CETP) gene polymorphisms are associated with the presence of coronary artery disease (CAD) and/or restenosis in patients with coronary stent. METHODS: Two polymorphisms of the CETP gene [-971 A/G (rs4783961), and Taq1B A/G (rs708272)] were genotyped by 5'exonuclease TaqMan assays in 219 patients with CAD (66 patients with restenosis and 153 without restenosis) and 607 control individuals. RESULTS: The distribution of polymorphisms was similar in patients with and without restenosis. However, when the whole group of patients (with and without restenosis) was compared to healthy controls, under dominant model, the G allele of the Taq1B A/G polymorphism was associated with increased risk of CAD (odds ratio [OR] = 1.48, pCDom = 0.032). In the same way, under codominant, dominant, and additive models, the A allele of the -971 A/G polymorphisms was associated with an increased risk of developing CAD (OR = 2.03, pCCo-dom = 0.022, OR = 1.83, pCDom = 0.008, and OR = 1.39, pCAdd = 0.011, respectively). In addition, the linkage disequilibrium showed that the "AG" haplotype was associated with increased risk of developing CAD (OR = 1.28, p = 0.03). CONCLUSION: This study demonstrates that CETP Taq1B A/G and CETP -971 A/G polymorphisms are associated with an increased risk of developing CAD, but no association with restenosis was observed.

OBJETIVO: Evaluamos si los polimorfismos del gen CETP están asociados con la presencia de enfermedad arterial coronaria (EAC) y/o restenosis en pacientes con stent coronario. MÉTODOS: En este estudio se genotiparon dos polimorfismos del gen CETP [−971 A/G (rs4783961) y Taq1B A/G (rs708272)] mediante ensayos de 5'exonucleasa TaqMan en 219 pacientes con EAC (66 pacientes con restenosis y 153 sin restenosis), y 607 individuos de control. RESULTADOS: La distribución de polimorfismos fue similar en pacientes con y sin restenosis. Sin embargo, cuando se comparó todo el grupo de pacientes (con y sin restenosis) con controles sanos, bajo el modelo dominante el alelo G del polimorfismo Taq1B A/G se asocia con un mayor riesgo de EAC (OR = 1.48, pCDom = 0.032). De la misma manera, bajo los modelos co-dominante, dominante y aditivo, el alelo A de los polimorfismos −971 A/G se asocia con un mayor riesgo de desarrollar EAC (OR = 2.03, pCCo-dom = 0.022, OR = 1.83, pCDom = 0,008 y OR = 1.39, pCAdd = 0.011, respectivamente). Adicionalmente, el desequilibrio de ligamiento mostró que el haplotipo "AG" se asocia con un mayor riesgo de desarrollar EAC (OR = 1.28, p = 0.03). CONCLUSIÓN: En resumen, este estudio demuestra que los polimorfismos CETP Taq1B A/G y CETP −971 A/G están asociados con un mayor riesgo de desarrollar CAD, pero no se observó asociación con restenosis.

Tumor necrosis factor alpha and interleukin 10 promoter polymorphisms in Mexican patients with restenosis after coronary stenting.

To test for an association with risk for restenosis after coronary stent placement, the TNF-alpha and IL-10 polymorphisms were analyzed by 5' exonuclease TaqMan assays in 162 patients who initially underwent coronary stenting. Analysis of basal and procedure coronary angiographies revealed a higher proportion of restenosis in lesions treated with bare metal stents compared with those treated with drug-eluting stents (P < 0.001). Distribution of TNF-alpha genotypes was similar in patients with and without restenosis. The IL-10 polymorphisms showed a moderate protective trend of the -819 TT genotype against restenosis when the lesions were analyzed (P = 0.071, OR = 0.471). Multivariate analysis confirmed a protective role for drug-eluting stents (P < 0.001, OR = 0.199) and the -819 TT genotype (P = 0.037, OR = 0.391). These results suggest the IL-10 -819 TT genotype has a protective role against in-stent restenosis.

The interleukin 1B-511 polymorphism is associated with the risk of developing restenosis after coronary stenting in Mexican patients.

Inflammation is the primary response to vessel wall injury caused by stent placement in coronary arteries. Cytokines of the interleukin-1 family are central regulators in immunoinflammatory mechanisms. The objective of this study was to test for association between IL-1 family gene polymorphisms and risk for restenosis after coronary stent placement. The IL-1B-511, IL-1F10.3, RN.4T>C, RN.6/1C>T, RN.6/2C>G, and IL-1RN VNTR polymorphisms were analyzed by 5' exonuclease TaqMan genotyping assays and polymerase chain reaction in a group of 165 patients who underwent coronary artery stenting. Basal and procedure coronary angiography were analyzed in search of angiographic predictors of restenosis and follow-up angiography was analyzed in search of binary restenosis. Patients with IL-1B-511 TT genotype had a 1.89-fold increased risk of developing restenosis. The analysis considering the lesions treated demonstrated that the lesions of patients with IL-1B-511 TT genotype had a 3.44-fold increased risk of developing restenosis. When the analysis considered the type of stent, the risk of developing restenosis was increased in lesions of patients with TT genotype (odds ratio = 4.50) who underwent coronary bare-metal stent implantation. Multiple logistic analysis identified IL-1B-511 TT genotype as an independent predictor for restenosis. The results suggest that IL-1B-511 polymorphism could be involved in the risk of developing restenosis after coronary stent placement.

No association found between the insertion/deletion of a 287-bp alu repeat sequence within intron 16 of the angiotensin-I-converting enzyme (ACE) gene in Mexican patients and binary restenosis after coronary stenting.

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.

Predictors of mortality and adverse outcome in elderly high-risk patients undergoing percutaneous coronary intervention.

OBJECTIVES: We sought to identify predictors of in-hospital and long-term (> 1 year) mortality and major adverse cardiac events (MACE) in elderly patients referred for percutaneous coronary intervention (PCI). METHODS: Seventy-three patients (> or = 80 years) were included. Clinical and interventional characteristics were collected retrospectively. Primary end points were in-hospital and long-term mortality, and a composite of non-fatal myocardial infarction, target vessel revascularization, urgent coronary artery bypass graft surgery, and death (MACE). RESULTS: Eighty-three percent of the patients had acute coronary syndromes, 43% three-vessel disease, and 42% heart failure. In-hospital mortality and MACE were 16.4% and 19%, respectively. Long-term mortality and MACE were 11.3% and 16.4%, respectively. Univariate characteristics associated with in-hospital mortality and MACE were: Killip Class III-IV, heart failure, cardiogenic shock, TIMI 0-2 flow prior and after intervention, diabetes mellitus, contrast nephropathy, and presence of A-V block or atrial fibrillation (AF). Long term predictors for mortality were the presence of heart failure, cardiogenic shock, diabetes mellitus, TIMI flow 0-2 before and after intervention, and A-V block or AF. CONCLUSION: The identification of the factors previously mentioned may help to predict complications in elderly patients.

The rs4783961 and rs708272 genetic variants of the CETP gene are associated with coronary artery disease, but not with restenosis after coronary stenting / Los polimorfismos rs4783961 y rs708272 del gen CETP son asociados con la enfermedad arterial coronaria y no con la restenosis tras el implante de un stent coronario

Abstract Objective: We evaluated whether cholesteryl ester transfer protein (CETP) gene polymorphisms are associated with the presence of coronary artery disease (CAD) and/or restenosis in patients with coronary stent. Methods: Two polymorphisms of the CETP gene [−971 A/G (rs4783961), and Taq1B A/G (rs708272)] were genotyped by 5'exonuclease TaqMan assays in 219 patients with CAD (66 patients with restenosis and 153 without restenosis) and 607 control individuals. Results: The distribution of polymorphisms was similar in patients with and without restenosis. However, when the whole group of patients (with and without restenosis) was compared to healthy controls, under dominant model, the G allele of the Taq1B A/G polymorphism was associated with increased risk of CAD (odds ratio [OR] = 1.48, pCDom = 0.032). In the same way, under codominant, dominant, and additive models, the A allele of the −971 A/G polymorphisms was associated with an increased risk of developing CAD (OR = 2.03, pCCo-dom = 0.022, OR = 1.83, pCDom = 0.008, and OR = 1.39, pCAdd = 0.011, respectively). In addition, the linkage disequilibrium showed that the "AG" haplotype was associated with increased risk of developing CAD (OR = 1.28, p = 0.03). Conclusion: This study demonstrates that CETP Taq1B A/G and CETP −971 A/G polymorphisms are associated with an increased risk of developing CAD, but no association with restenosis was observed.

Resumen Objetivo: Evaluamos si los polimorfismos del gen CETP están asociados con la presencia de enfermedad arterial coronaria (EAC) y/o restenosis en pacientes con stent coronario. Métodos: En este estudio se genotiparon dos polimorfismos del gen CETP [−971 A/G (rs4783961) y Taq1B A/G (rs708272)] mediante ensayos de 5'exonucleasa TaqMan en 219 pacientes con EAC (66 pacientes con restenosis y 153 sin restenosis), y 607 individuos de control. Resultados: La distribución de polimorfismos fue similar en pacientes con y sin restenosis. Sin embargo, cuando se comparó todo el grupo de pacientes (con y sin restenosis) con controles sanos, bajo el modelo dominante el alelo G del polimorfismo Taq1B A/G se asocia con un mayor riesgo de EAC (OR = 1.48, pCDom = 0.032). De la misma manera, bajo los modelos co-dominante, dominante y aditivo, el alelo A de los polimorfismos −971 A/G se asocia con un mayor riesgo de desarrollar EAC (OR = 2.03, pCCo-dom = 0.022, OR = 1.83, pCDom = 0,008 y OR = 1.39, pCAdd = 0.011, respectivamente). Adicionalmente, el desequilibrio de ligamiento mostró que el haplotipo "AG" se asocia con un mayor riesgo de desarrollar EAC (OR = 1.28, p = 0.03). Conclusión: En resumen, este estudio demuestra que los polimorfismos CETP Taq1B A/G y CETP −971 A/G están asociados con un mayor riesgo de desarrollar CAD, pero no se observó asociación con restenosis.

Predictors of mortality and adverse outcome in elderly high-risk patients undergoing percutaneous coronary intervention / Predictores de mortalidad y mal pronóstico en pacientes ancianos y de alto riesgo que van a ser sometidos a intervención coronaria percutánea

OBJECTIVES: We sought to identify predictors of in-hospital and long-term (> 1 year) mortality and major adverse cardiac events (MACE) in elderly patients referred for percutaneous coronary intervention (PCI). METHODS: Seventy-three patients (> or = 80 years) were included. Clinical and interventional characteristics were collected retrospectively. Primary end points were in-hospital and long-term mortality, and a composite of non-fatal myocardial infarction, target vessel revascularization, urgent coronary artery bypass graft surgery, and death (MACE). RESULTS: Eighty-three percent of the patients had acute coronary syndromes, 43% three-vessel disease, and 42% heart failure. In-hospital mortality and MACE were 16.4% and 19%, respectively. Long-term mortality and MACE were 11.3% and 16.4%, respectively. Univariate characteristics associated with in-hospital mortality and MACE were: Killip Class III-IV, heart failure, cardiogenic shock, TIMI 0-2 flow prior and after intervention, diabetes mellitus, contrast nephropathy, and presence of A-V block or atrial fibrillation (AF). Long term predictors for mortality were the presence of heart failure, cardiogenic shock, diabetes mellitus, TIMI flow 0-2 before and after intervention, and A-V block or AF. CONCLUSION: The identification of the factors previously mentioned may help to predict complications in elderly patients.