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Genetic factors can influence the risk of coronary artery disease (CAD) and the survival of patients. Our previous research led to the identification of genetic variants predisposing to CAD in the Polish population. Since many of them affect the clinical phenotype of the disease, the aim of this study was searching for genetic factors potentially influencing survival in patients with CAD. The study included 276 patients hospitalized due to coronary artery disease. The database of medical history and genotypic results of 29 polymorphisms were used. The endpoint was defined as death from cardiovascular causes. Survival was defined as the period from angiographic confirmation of CAD to death from cardiovascular causes. Three of all the analyzed genes were associated with survival. In the case of the AGT (rs699) and ABCA1 (rs2230806) genes polymorphisms, the risk of death was higher in GG homozygotes compared to the A allele carriers in the 10-year period. In the case of the CYBA (rs72811418) gene polymorphism, the effect on mortality was shown in both 5- and 10-year periods. The TA heterozygotes were predisposed to a higher risk of death than the TT homozygotes. Concluding, the AGT, ABCA1, and CYBA genes polymorphisms influence the risk of death in patients with CAD.

Genetic factors can influence the risk of coronary artery disease (CAD) and the survival of patients. Our previous research led to the identification of genetic variants predisposing to CAD in the Polish population. Since many of them affect the clinical phenotype of the disease, the aim of this study was searching for genetic factors potentially influencing survival in patients with CAD. The study included 276 patients hospitalized due to coronary artery disease. The database of medical history and genotypic results of 29 polymorphisms were used. The endpoint was defined as death from cardiovascular causes. Survival was defined as the period from angiographic confirmation of CAD to death from cardiovascular causes. Three of all the analyzed genes were associated with survival. In the case of the

Background: The present study aimed to determine whether the polymorphisms of the 11q23.3 locus affect the risk and mortality of coronary artery disease in 5-year and 10-year observations. Methods: The study group consisted of 519 subjects: 276 patients with CAD and 243 blood donors as controls. The genotyping of polymorphisms (rs10750097, rs3741298, and rs1729410) was performed using the TaqMan-PCR method. Survival was defined as the period from the angiographic confirmation of CAD to cardiovascular death, and the endpoint was defined as death from cardiovascular causes. Results: The G allele of the rs1729410 polymorphism increased the risk of CAD (OR = 1.55, p = 0.04) and showed a synergistic correlation with overweight/obesity (additive synergy index (SI) = 11.01, p < 0.001). The carriers of the GG genotype and over-normative LDL levels increased the risk of CAD by over 12-fold higher than expected (multiplicative synergy index (SIM) = 12.34, p < 0.001). In the case of the rs10750097 variant, an effect on mortality was shown in both 5-year and 10-year periods. Conclusion: The results revealed that the rs1729410 polymorphism increases the risk of CAD in synergy with traditional risk factors, and the rs10750097 polymorphism of the 11q23.3 locus affects the risk of death in patients with CAD.

Polymorphic variants of the CYP7A1 gene can increase the risk of atherosclerosis-based coronary artery disease (CAD) and modify serum lipid markers. Method: We studied haplotype-tagging single nucleotide polymorphisms of CYP7A1 in the Caucasian population and if they are associated with CAD, its symptoms, and any of its risk factors. Results: We did not find the genetic variants of CYP7A1 to be associated with an increased risk of CAD. However, we did find that the common rs3808607 variant is associated with modified concentrations of serum total cholesterol and LDL. We also found that the C allele and the CC genotype of the rs11786580 are more frequent in patients with myocardial infarction. This association was especially strong after the group differentiation by sex.

The p22phox is a critical component of vascular NADPH oxidases and is encoded by the CYBA gene. It was shown that functionally relevant polymorphisms of the CYBA gene -930A > G, -852C > G, -675A > T, -536C > T, 214C > T (previously described as 242C > T), *24A > G (previously described as 640A > G), and *49A > G modulate generation of reactive oxygen species (ROS). To analyse whether the CYBA gene polymorphisms -852C > G, -675A > T, and -536C > T were associated with coronary artery disease (CAD), and to designate haplotype blocks. Four hundred and ninety subjects: 245 patients with CAD and 245 age and sex-matched controls. The polymorphisms were genotyped using the PCR-RFLP method and the TagMan® Pre-designed SNP Genotyping Assay. The analysed polymorphisms do not form haplotype blocks. Case-control study revealed that the -930 G/-675T and -930G/*49G diplotypes were a CAD risk factor. The 675T/*49G diplotype can modulate CAD risk in women. The protective effect reducing CAD risk in women was related to the -930A/-675T and -930A/*49A diplotypes. Carrier state of the -852C allele (-852C > G) was associated with multivessel stenosis while the CC genotype of the -536C > T polymorphism was more frequent in patients with peripheral artery disease. Hypercholesterolemic, cigarette smokers had an increased risk of CAD, especially C - 852 allele (-852C > G) carriers (SIM = 3.54; odds ratios (OR) = 10.01, p < 0.000). The CYBA gene polymorphisms modulate the risk of CAD but do not form a haplotype blocks.

The cholesteryl ester transfer protein (CETP) gene encodes a hydrophobic glycoprotein that plays a crucial role in the reverse transport of cholesterol. The aim of the present study was to determine whether CETP polymorphisms (rs1532624, rs247616 and rs708272) are associated with coronary artery disease (CAD) in a Polish population. Serum lipid levels and single nucleotide polymorphisms of CETP genes were determined in 494 subjects: 248 patients with premature CAD and 246 blood donors as controls. Selected polymorphisms were examined using TaqMan PCR analysis. We found that CAD risk was significantly higher for CC homozygotes and C allele carriers of the rs247616 polymorphism than for carriers with the T allele (OR 1.89, 95% CI 1.29–2.76, p = 0.001 and OR 1.51, 95% CI 1.14–1.99, p = 0.003) and likewise for the CC genotype of the rs1532624 polymorphism than for those with the A allele (OR 1.59, 95% CI 1.05–2.40, p = 0.026). Moreover, T allele carriers of the rs708272 polymorphism had significantly higher total cholesterol levels compared to CC homozygotes (p

Polymorphic variants of the

The p22phox is a critical component of vascular NADPH oxidases and is encoded by the

Purpose. Single nucleotide polymorphisms of theCYBAgene may modify the risk of coronary artery disease (CAD). The aim of the present study was to investigate whether the⁎49A>G (rs7195830) polymorphism is associated with CAD.Materials and Methods.CYBAgene⁎49A>G polymorphism was determined in 481 subjects: 242 patients with premature CAD and 239 age and sex matched controls using the fluorescently labeled allele-specific oligonucleotides method.Results. The frequency of the⁎49G allele carrier state was significantly higher in patients than in controls (84.8% versus 76.6%, resp.,P=0.020), as well as the frequency of the⁎49G allele (62.2% versus 54.0%,P=0.009). Both factors were associated with CAD in the analyzed population (OR = 1.70, 95% CI: 1.04–2.76 for GG+AG versus AA and OR = 1.40, 95% CI: 1.08–1.83 for⁎49G versus ⁎49A). Carrier state of the⁎49G allele was a stronger and independent risk factor for CAD among women (OR = 4.35, 95% CI: 1.50–13.20,P=0.002), as well as the⁎49G allele (OR = 2.25, 95% CI: 1.34–3.77,P=0.001). The⁎49G allele carrier state was also associated with left ventricular hypertrophy in patients with coronary artery disease (P=0.015).Conclusion. TheCYBAgene⁎49A>G polymorphism modifies the risk of coronary artery disease.

Completeness of myocardial revascularization is essential in surgical treatment of coronary artery disease. The aim of this study is to determine the effectiveness of coronary endarterectomy as an adjunct to coronary artery bypass grafting (CABG) in the most difficult cases.Among 1559 patients who had CABG in our department, the cases of 17 who underwent an adjunct left anterior descending endarterectomy were analyzed. All procedures were performed with median sternotomy, extracorporeal circulation and in mild hypothermia (34°C), by the same surgeon. No coronary artery endarterectomy was planned before surgery.There was no infarction or cardiac arrest during hospitalization. Only one patient required mechanical circulatory support (intra-aortic balloon counterpulsation). Each patient was contacted and investigation for major adverse cardiac and cerebrovascular events (MACCE) was performed. Eleven patients (65%) already underwent midterm clinical evaluation. There was no death, myocardial infarction or cerebrovascular incident during the entire period (mean follow-up at 15.3 months). One patient required urgent coronarography due to chest pain. No other patient had chest pain or significant deterioration of ventricular function in echocardiography.Outcomes and potential indications for performing left anterior descending coronary endarterectomy as an adjunct to CABG are discussed.Kompletność rewaskularyzacji mięśnia sercowego jest niezbędna w leczeniu chirurgicznym choroby wieńcowej. Celem badania była ocena skuteczności endarterektomii przeprowadzanej jako zabieg dodatkowy przy standardowej procedurze pomostowania aortalno-wieńcowego w najtrudniejszych przypadkach klinicznych.Spośród 1559 pacjentów, którzy przeszli pomostowanie aortalno-wieńcowe na naszym oddziale, wybrano i przeanalizowano przypadki 17 pacjentów, których poddano również wspomagającej endarterektomii w zakresie tętnicy lewej przedniej zstępującej. Wszystkie zabiegi były wykonane przez tego samego chirurga, z zastosowaniem sternotomii pośrodkowej i krążenia pozaustrojowego, w warunkach łagodnej hipotermii (34°C). Żadna z endarterektomii tętnic wieńcowych nie była planowana przedoperacyjnie.W czasie hospitalizacji nie doszło do zawału ani zatrzymania krążenia. Tylko jeden z pacjentów wymagał mechanicznego wspomagania krążenia (kontrapulsacji wewnątrzaortalnej). Nawiązano kontakt ze wszystkimi pacjentami i przeprowadzono badania w kierunku poważnych niepożądanych zdarzeń sercowych i mózgowo-naczyniowych (Artykuł omawia wyniki zabiegów oraz potencjalne wskazania do endarterektomii wieńcowej tętnicy lewej przedniej zstępującej jako leczenia wspomagającego pomostowanie aortalno-wieńcowe.

Single nucleotide polymorphisms (SNPs) of the USF1 gene (upstream stimulatory factor 1) influence plasma lipid levels. This study aims to determine whether USF1 SNPs interact with traditional risk factors of atherosclerosis to increase coronary artery disease (CAD) risk. In the present study serum lipid levels and USF1 gene polymorphisms (rs2516839 and rs3737787) were determined in 470 subjects: 235 patients with premature CAD and 235 controls. A trend of increasing triglycerides (TG) levels in relation to the C allele dose of rs2516839 SNP was observed. The synergistic effect of cigarette smoking and C allele carrier state on CAD risk was also found (SIM = 2.69, p = 0.015). TG levels differentiated significantly particular genotypes in smokers (1.53 mmol/L for TT, 1.80 mmol/L for CT and 2.27 mmol/L for CC subjects). In contrast, these differences were not observed in the non-smokers subgroup (1.57 mmol/L for TT, 1.46 mmol/L for CT and 1.49 mmol/L for CC subjects). In conclusion, the rs2516839 polymorphism may modulate serum triglyceride levels in response to cigarette smoking. Carriers of the C allele seem to be particularly at risk of CAD, when exposed to cigarette smoking.

Paraoxonase-1 (PON1) is the antioxidant marker of high-density lipoproteins protecting against atherosclerosis and coronary artery disease (CAD) phenotype. The purpose of the present study was to determine whether thePON1gene rs854560 polymorphism (163T>A) is associated with CAD in Polish population. rs854560 was genotyped in 494 subjects: 248 patients with premature CAD and 246 blood donors as a control. We found that the risk of CAD was significantly higher in TT homozygotes than in A allele carriers (OR = 1.87,p=0.041). The synergistic effect between the TT genotype and cigarette smoking was observed (SIM = 9.81; SI = 14.70). The relative increase in risk from interaction between factors was over 37 (RERI = 36.13). ThePON1polymorphism did not modulate the risk of CAD in response to exposure to other traditional risk factors. In conclusion, the rs854560 polymorphism may modulate the risk of CAD in response to cigarette smoking in Polish population. Carriers of TT genotype seem to be particularly at risk of CAD, when exposed to cigarette smoking.

Background: The presence of several risk factors (genetic and non-genetic) has greater impact on the risk of premature coronary artery disease (CAD) than single risk factor. Objective: The aim of the study was to establish possible relations between genotypes and alleles of 677C>T polymorphism ofMTHFRgene and some traditional risk factors e.g. elevated levels of lipid parameters and smoking in development of premature CAD. Methods: The groups comprised 152 patients with angiographically documented premature CAD (aged 42.9 ± 5.5) and 121 age-matched blood donors (aged 42.3 ± 6.5) were studied. TheMTHFR677C>T polymorphism was genotyped with Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results: Patients with TT genotype who simultaneously smoked had increased risk of premature CAD compared to non-smoking cases with CC genotype (OR = 24.62). We also found that individuals with TT genotype and elevated LDL-cholesterol (LDL-chol.) level had significantly higher risk of CAD (OR = 9.92) than individuals with normal LDL-chol. level and CC genotype. Conclusions: The present study shows that simultaneous presence ofMTHFRTT genotype and smoking or elevated levels of LDL-chol. influences the risk of premature CAD. This findings give interesting contribution to gene-environment interaction problem that may have clinical implications in the future.

The CYBA gene encodes the p22phox peptide, an essential subunit of vascular NADPH oxidases. The aim of the study was to analyze potential interactions between CYBA gene A640G polymorphism and traditional risk factors of atherosclerosis. We studied 320 subjects: 160 patients with coronary artery disease (CAD) and 160 controls. The results of interactions were interpreted on the basis of synergy index values (SI, SIM). The 640G allele interacted with cigarette smoking (SI = 2.02, SIM = 2.32). Even greater increase of the CAD risk was found whenever the 640G allele interacted with both smoking and hypercholesterolemia (SI = 2.70, SIM = 3.60). The results suggest that the A640G polymorphism may influence individual predispositions to CAD through interactions with smoking and hypercholesterolemia.

Cigarette smoking increases the synthesis of angiotensin-1 converting enzyme (ACE) and induces oxidative modifications of the apolipoprotein E (apo E).Thus we explored the gene-environment interactions between APOE gene epsilon and ACE gene insertion/deletion polymorphisms and cigarette smoking in coronary artery disease (CAD) patients.We analysed 360 subjects: 171 CAD patients and 189 blood donors without a history of cardiovascular diseases. ACE and APOE polymorphisms were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods, respectively. To determine gene-environment interactions, epidemiological methodology was used.The ACE DD genotype was a rather weak risk factor of CAD in the analysed population (OR = 1.87, P = 0.01).The differences in allele and genotype distribution of the APOE polymorphism were not statistically significant.The carriers of the combined genotype ACE(DD) + APOE(epsilon4epsilon4,epsilon3epsilon4,epsilon2epsilon4) were more frequent in patients, however, the differences were on the bound of statistical significance (P = 0.08). Logistic regression analysis showed that the ACE(DD) + apo E(epsilon4epsilon4,epsilon3epsilon4,epsilon2epsilon4) cigarette smokers were much more frequent in the CAD group (OR = 11.68, 95%CI; 1.52-246.43, P = 0.009).We confirmed these results using the 4 x 2 table approach and we found a synergistic effect of the ACE(DD) + APOE(epsilon4epsilon4,epsilon3epsilon4,epsilon2epsilon4) combined genotype and cigarette smoking (SI = 10.52, SIM = 6.09).We demonstrated the existence of the synergistic effect between cigarette smoking and the contemporaneous carrier-state of APOE epsilon4 and ACE D alleles which increased the risk of CAD to a large extent.

Coronary artery disease (CAD) depends on multiple genetic and environmental factors. Adhesion molecules are markers of endothelium dysfunction. Intercellular adhesion molecule-1 (ICAM-1) interacts with leukocyte integrins and promotes atherosclerotic process at the surface of endothelial cells. The aim of the study was to assess the association between ICAM1 rs5498 polymorphism and CAD and to establish whether there are any interactions between this polymorphism and traditional risk factors in determining the risk of CAD. We studied 191 cases with angiographically documented CAD and 203 controls with no signs of cardiovascular diseases. The ICAM1 polymorphism was genotyped using PCR-RFLP method. Data were analyzed with the STATISTICA 7.1 and EpiInfo 6 softwares. We did not observe significant differences in the distribution of genotypes and alleles of rs5498 between cases and controls. We only found a tendency to a higher prevalence of G allele carriers (AG + GG) in patients compared to controls (68 vs. 64%, P = 0.399). A synergistic effect of G allele carrier-state and smoking that had influenced the risk of CAD [synergy index multiplicative (SIM = 2.09)] was observed. Smoking carriers of G allele compared to non-smoking AA were more prevalent in CAD group (39.8%) than among controls (13.3%, P < 0.0001, OR 4.81). Moreover, there was also a synergistic effect between G allele carrier-state and an elevated level of triacylglycerols (TG) (SIM = 1.28) increasing the risk of CAD. There is a synergistic interaction between rs5498 genotype and smoking that increases the risk of CAD.

BACKGROUND: QT/RR relationship was found to be both rate-dependent and rate-independent, what suggests the influence of autonomic drive and other not-autonomic related factors on it. The steeper QT/RR slope in patients after acute myocardial infarction (MI) was described, but the relationship to ventricular arrhythmias is unknown. The purpose of this study was to calculate differences in QT/RR relationship in patients after remote anterior MI with left ventricular dysfunction and different types of ventricular arrhythmias. METHODS: The cohort of 95 patients (age: 63 +/- 11 years, LVEF: 35 +/- 9%) with previous anterior MI (mean 1.1 years) was divided into two well-matched groups-50 patients without episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF) (NoVT/VF: 39 males, 64 +/- 12 years, LVEF 37 +/- 8%) and 45 patients with VT and/or VF (all with ICD implanted) (VT/VF: 35 males, 62 +/- 10 years, LVEF 34 +/- 10%). No true antiarrhythmics were used. QT/RR slope was calculated from 24-hour Holter ECG for the entire recording (E), daytime (D) and nighttime (N) periods. RESULTS: Groups did not differ in basic clinical data (age, LVEF, treatment). QT/RR slopes were steeper in VT/VF than in NoVT/VF group in all analyzed periods: E - 0.195 +/- 0.03 versus 0.15 +/- 0.03 (P < 0.001), N - 0.190 +/- 0.03 versus 0.138 +/- 0.03 (P < 0.001) and D - 0.200 +/- 0.04 versus 0.152 +/- 0.03 (P < 0.001). No significant day-to-night differences were found in both groups. CONCLUSIONS: Steeper QT/RR slope and complete lack of day-to-night differences in VT/VF patients show inappropriate QT adaptation to the heart rate changes. The prognostic significance of this parameter needs prospective studies.

Objective Progression of atherosclerosis, the main reason of cardiovascular diseases, depends on multiple genetic and environmental factors. Polymorphic variants of genes involved in the lipids metabolism may genetically differentiate human populations and determine a susceptibility to the disease. The aim of the present study was to evaluate a possible interaction between R219K polymorphism of ABCA1 gene and G > C polymorphism in intron 7 of PPARA gene in determining the risk of the CAD. Methods We studied 358 subjects: 178 patients with angiographically confirmed CAD and 180 blood donors without history of CAD. Polymorphisms were genotyped using the PCR-RFLP method. Results In spite of a small or no correlation between single polymorphism and CAD we observed that the frequencies of AA + GC,CC genotype pattern (ABCA1 and PPARA gene) were significantly higher in CAD group than in controls. OR values were especially high in multiple logistic regression and were higher for male subgroups. The synergy index value equals 3.98 and indicates a quite strong synergistic effect between the analysed polymorphisms. We also observed that C allele carriers of PPARA gene had a significantly lower total and LDL-cholesterol level. Conclusion The present study shows that R219K polymorphism of ABCA1 gene and G > C polymorphism in intron 7 of PPARA gene act cumulatively and synergistically in determining the risk of premature CAD.

Background. 7-Alpha cholesterol hydroxylase (CYP7A1), the first enzyme of classic conversion pathway leading from cholesterol to bile acids synthesis, is encoded byCYP7A1gene. Its single nucleotide polymorphisms (SNPs) influence serum lipid levels and may be related to impaired lipid profile leading to coronary artery disease (CAD). The aim of the present study was to analyze the possible association between the rs7833904CYP7A1polymorphism and premature CAD.Material and Methods. Serum lipid levels and rs7833904 SNP were determined in 419 subjects: 200 patients with premature CAD and 219 age and sex matched controls.Results. The A allele carrier state was associated with CAD (OR = 1.76, 95% CI; 1.14–2.71,P=0.014). The effect was even stronger in the male subgroups (OR = 2.16, 95% CI; 1.28–3.65,P=0.003). There was no effect in the females. Risk factors of CAD and clinical phenotype of atherosclerosis were not associated with genotype variants of the rs7833904 SNP. Lipid profiles also did not differ significantly between individual genotypes.Conclusion. TheCYP7A1rs7833904 polymorphism may modify the risk of CAD. This effect is especially strong in male subjects. The studied polymorphism does not significantly influence serum lipid levels, in the present study.

Recently, genome-wide association studies have revealed a locus associated with coronary artery disease (CAD) and myocardial infarction, namely, 9p21.3. Its participation in the conditioning of the disease has been proven in many populations of European descent, but not yet in Slavs. Allelic variants of the rs10757278 polymorphism functionally affect the activity of the 9p21.3 locus; therefore, we conducted a study to determine whether the rs10757278 is associated with premature CAD in Polish patients. We studied 320 subjects aged 25–55 years, divided into two groups matched by sex and age: (1) patients with angiographically proven premature CAD (n=160), and (2) blood donors as a control group (n=160). The rs10757278 was genotyped using the method of fluorescently labeled allele-specific oligonucleotides. The frequency of the G allele was significantly higher in patients than in controls (58.2% vs. 42.8%, respectively, p=0.011) and was similar to the frequency of the GG homozygotes (30.6% vs. 17.5%, respectively, p=0.006). Both the GG homozygosity (odds ratio [OR]=2.08, 95% confidence interval [CI]: 1.19–3.66) as well as the G allele (OR=1.49, 95% CI: 1.08–2.07) have been associated with CAD in the analyzed population. These variants may be considered as risk factors, also in the Polish population.

Progression of coronary artery disease (CAD) depends on multiple genetic and environmental factors. Polymorphic variants of genes encoding proteins involved in endothelium dysfunction or proinflammatory state may genetically differentiate the human population and determine a susceptibility to the disease.To find the relationship between single polymorphisms of MTHFR, IL-6 and ICAM1 genes, double or triple combinations among their polymorphic variants and CAD in a patient population from the Upper Silesia region.The study population consisted of 177 patients with angiographically documented CAD and 202 blood donors with no signs of CAD. All examined individuals were white Polish Caucasians aged 18-55 years. The analysis of genetic polymorphisms was performed using the PCR-RFLP method.We observed a weak association between single gene polymorphism and the disease only in the case of the MTHFR T allele. We also found that the frequency of some double or triple combinations among analysed genes, especially for MTHFR+ICAM1 and MTHFR+ICAM1+IL-6 patterns, differentiated the entire patient group from controls (p=0.047 OR=1.75 and p=0.016 OR=1.75, respectively). These two combinations were also significantly more frequent in patients who were age-matched with controls, especially in the female subgroups (for MTHFR+ICAM1 p=0.007, OR=10.32 and for MTHFR+ ICAM1+IL-6, p=0.005, OR=17.95 in females).The present study showed that simultaneous carrier-state of MTHFR, IL-6 and ICAM1 genes increased the risk of CAD.

Coronary artery disease (CAD) is a multifactorial disorder which results from the interactions between a number of genetic and non-genetic factors. Beta-adrenergic receptors are cell-surface receptors which activate adenylyl cyclase by coupling to G proteins. The 46AG and 79CG polymorphisms of the beta2-adrenergic receptor gene (ADRB2) have been associated with altered response to sympathetic stimulation.To assess the relationship between 46AG and 79CG polymorphisms of the ADRB2 gene and CAD as well as the associations between these polymorphic variants and traditional risk factors, e.g. cigarette smoking, hypercholesterolaemia, hypertension and overweight or obesity, in determining the risk of CAD.The study population consisted of 207 individuals (white Polish Caucasians aged 20-55 years): 98 patients with angiographically documented CAD (with more than 50% diameter stenosis of at least one of the major coronary vessels) and 109 blood donors with no signs of CAD. The analysis of genetic polymorphisms was performed by means of PCR-RFLP.The genotype frequencies of both analysed genes in the studied groups were compatible with Hardy-Weinberg equilibrium. We observed higher frequency of the 46A allele in CAD patients than in controls. We also found a tendency to higher prevalence of 46A allele carriers (subjects with genotypes AA+AG) in the CAD group compared to the control group. We did not find any differences in the distribution of genotypes and alleles of 79CG polymorphism between patients and controls. Multivariate analysis showed that smoking and overweight were independent risk factors of CAD in patients. We found a synergistic effect between carrier state of the 46A allele or 79G allele and smoking, which influences the CAD risk. The 46A allele carriers who smoke as well as carriers of the 79G allele who smoke were much more frequent in the CAD group than in controls. The incidence of 46A allele carriers with hypercholesterolaemia is also higher in patients than in the blood donor group.Obtained results indicate a synergistic effect between cigarette smoking and carrier state of 46A allele or 79G allele of ADRB2 in determining the risk of CAD.

Background: QT/RR relationship was found to be both rate‐dependent and rate‐independent, what suggests the influence of autonomic drive and other not‐autonomic related factors on it. The steeper QT/RR slope in patients after acute myocardial infarction (MI) was described, but the relationship to ventricular arrhythmias is unknown. The purpose of this study was to calculate differences in QT/RR relationship in patients after remote anterior MI with left ventricular dysfunction and different types of ventricular arrhythmias. Methods: The cohort of 95 patients (age: 63 ± 11 years, LVEF: 35 ± 9%) with previous anterior MI (mean 1.1 years) was divided into two well‐matched groups—50 patients without episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF) (NoVT/VF: 39 males, 64 ± 12 years, LVEF 37 ± 8%) and 45 patients with VT and/or VF (all with ICD implanted) (VT/VF: 35 males, 62 ± 10 years, LVEF 34 ± 10%). No true antiarrhythmics were used. QT/RR slope was calculated from 24‐hour Holter ECG for the entire recording (E), daytime (D) and nighttime (N) periods. Results: Groups did not differ in basic clinical data (age, LVEF, treatment). QT/RR slopes were steeper in VT/VF than in NoVT/VF group in all analyzed periods: E ‐ 0.195 ± 0.03 versus 0.15 ± 0.03 (P < 0.001), N – 0.190 ± 0.03 versus 0.138 ± 0.03 (P < 0.001) and D ‐ 0.200 ± 0.04 versus 0.152 ± 0.03 (P < 0.001). No significant day‐to‐night differences were found in both groups. Conclusions: Steeper QT/RR slope and complete lack of day‐to‐night differences in VT/VF patients show inappropriate QT adaptation to the heart rate changes. The prognostic significance of this parameter needs prospective studies.

Background: Genetic susceptibility to CAD may be determined by polymorphic variants of genes encoding isoforms involved in the processes important in the pathogenesis of atherosclerosis, including lipids disorders. Participation of single polymorphic variants is relatively small, however its significance may increase in the presence of specific genetic or environmental background.Aim: The aim of the study was an evaluation a possible association between single polymorphic variants ofPON1, APOE, ABCA1andPPARAgenes and CAD and looking for specific multigene genotype patterns which differentiate study groups.Materials and methods: We studied 358 subjects:178 patients with angiographically confirmed CAD and 180 blood donors without history of CAD. Polymorphisms were genotyped using PCR-RFLP method.Results: We observed statistically significant differences in the frequencies of R allele and R allele carriers ofPON1gene between CAD and controls. The distribution of genotypes and alleles of other analyzed genes did not differentiate the study groups, however the presence of specific genotypes (APOE– ɛ3ɛ3, ɛ3ɛ2,ABCA1– AG,PPARA– GG) increased the protective effect of R allele.Conclusion: The present study revealed an independent protective association between carrier-state of PON1 R allele and CAD. This protective effect was especially strong in the presence of specific genotype arrangements of other analyzed genes.

Ischaemic heart disease (IHD), which is a clinical manifestation of atherosclerotic changes in coronary arteries, results from the action of multiple genetic and environmental factors. Genetic susceptibility to IHD may be determined by specific polymorphic variants of genes encoding isoforms involved in processes important in the pathogenesis of atherosclerosis. Due to the multifactorial nature of IHD, participation of a single polymorphism in the determination of the disease risk is relatively small. However, it seems that its significance may increase in the presence of a specific genetic or environmental background.To evaluate a possible association between the epsilon polymorphism of the apolipoprotein E gene (apo E) and premature IHD in the Polish population as well as to determine whether the genotype may modulate the influence of conventional risk factors on IHD.We studied 247 caucasian subjects: 140 patients with angiographically confirmed IHD and 107 blood donors without a history of IHD. Polymorphism epsilon of the apo E gene was genotyped using the PCR-RFLP method.We observed a tendency to a higher prevalence of the epsilon4 allele and carriers of this allele in the IHD group compared to controls. However, these differences were not statistically significant. We also observed a synergistic effect between epsilon4 allele carrier state and smoking, elevated level of total cholesterol and, to a lower degree - LDL cholesterol, on IHD risk.Presented data show the synergistic effects between epsilon4 allele carrier state and some traditional risk factors on determining the risk of premature coronary artery disease.

Coronary artery disease (CAD) is a multifactorial disease that results from the interaction between genetic and traditional risk factors. The endothelium dysfunction plays a key role in the progression of atherosclerotic lesions. E-selectin is a marker of endothelium dysfunction. The aim of the present study was to find a relationship between 561AC and 98GT polymorphisms of E-selectin gene and CAD as well as interactions between these polymorphic variants and traditional risk factors of the disease in determining the susceptibility to CAD. The study population included 191 patients with angiographically documented CAD and 203 blood donors. The analysis of genetic polymorphisms was performed using the polymerase chain reaction-restriction fragment length polymorphism method. We found that the frequencies of 561C and 98T alleles of E-selectin gene and carriers of C and T alleles were similar in the entire groups as well as in the age-and sex-matched subgroups. We observed a strong significant correlation between those two polymorphisms; almost all subjects possessing one "proatherosclerotic" allele of E-selectin gene also had the second allele (r = 0.963, P0.0001). There were also synergistic effects between both polymorphisms and hypercholesterolemia (but not with smoking or overweight) in determining the susceptibility to CAD. The present study points to synergistic interactions between 561AC or 98GT polymorphisms of E-selectin gene and hypercholesterolemia that cause a significant increase in the susceptibility to CAD.

Objectives To assess the relationship between IL-6 and PAI-1 polymorphisms and coronary artery disease (CAD) and to observe the interactions between these polymorphic variants and smoking in the CAD risk. Design and method The study population consisted of 178 patients with angiographically documented CAD and 202 blood donors. The analyses of genetic polymorphisms were performed using the PCR-RFLP method. Results The frequency of PAI-1 5G allele was higher in the entire CAD group than in control group (p = 0.04, OR = 1.35). Also the 5G allele carriers (4G5G + 5G5G) were more frequent in patients than in controls (p = 0.03, OR = 1.93). The number of women carrying 5G allele was again significantly higher among patients (OR = 10.95 p = 0.0075). The IL-6 C allele frequency was higher only in the CAD male subgroup (p = 0.035, OR = 1.44). We found synergistic and cumulative effects between specific genotype patterns and smoking in determining the risk of CAD, especially between PAI-1(4G5G + 5G5G)+IL-6(CC) and smoking (SIM = 4.18 and p = 0.0005, OR = 9.20, respectively). Conclusions There are synergistic and cumulative effects of 5G allele of PAI-1 polymorphism and C allele of IL-6 polymorphism with smoking in determining their associated risk with CAD.

Despite common use of reperfusion therapy, particularly primary PCI during acute myocardial infarction, steadily increasing number of patients with low left ventricular ejection fraction, with heart failure (HF), requiring frequent rehospitalisation justifies the study establishing the best indices of prediction of major adverse cardiac events (MACE) occurrence. The aim of the study was to define the frequency of MACE (death, re MI, sVT, rehospitalisation for HF) in patients with acute anterior wall myocardial infarction in 6 month follow up and the factors determinatig its occurence. The 115 consecutive patients (86 males of age 57.7 +/- 11 yrs) with first anterior MI were studied. After successful PCI (TIMI 3) the angiographic assessment was performed (MBG 0-1 - no perfusion, MBG 2-3 - perfusion preserved). During first 48 hours 12-lead ECG was monitored in order to analyse the time to reduction of ST elevation in the lead with the highest elevation (deltatST 50%). On 2nd day LV function (LVEF and WMSI) and dyssfunctional segment perfusion (RPSI) were assessed. On 5th day Holter monitoring with arrhythmia and time domain parameters (SDNN, rMSSD) of heart rate variability were performed, on 30 day TWA test was done.During 180 follow-up 18 MACE occurred (3 death, 2 MI, 11 rehospitalisations for HF). In univariate analysis cigarette smoking, higher maximum troponin I value, LVEDV, LVESV, ST elevation sum, longer time to reduction of ST elevation, lower LVEF and RPSI, lack of microvessel integrity and positive TWA test had significant relationship with occurrence of MACE. The multivariate analysis of Cox proportional risk regression demonstrated that only lower value of RPSI and LVEF, longer time of ST elevation reduction in the lead with the highest ST elevation and positive TWA test were independent indices of MACE prediction.Cumulative evaluation of LVEF, indices of preserved perfusion and results of TWA test turned out to be the best predictors of MACE occurrence in 6 month follow up in patients after anterior MI treated with PCI.

Background Genetic susceptibility to coronary artery disease (CAD) may be determined by polymorphic variants of genes encoding isoforms involved in the processes important in the pathogenesis of atherosclerosis, including lipoprotein oxidation. Participation of single polymorphic variants is relatively small; however, its significance may increase in the presence of specific environmental background. The aim of the study was an evaluation of a possible association between R192Q polymorphism of PON1 gene and CAD as well as interactions between polymorphic variants and conventional risk factors of CAD in determining the risk of the disease. Methods We studied 358 subjects: 178 patients with angiographically confirmed CAD and 180 blood donors without history of CAD. Polymorphisms were genotyped using PCR-RFLP method. Results We observed statistically significant differences in the frequencies of Q allele and Q allele carriers of PON1 gene between CAD and controls. We also found a strong synergistic effect between Q allele carrier state and smoking, as well as Q allele carrier state and elevated level of total cholesterol. Conclusions The present study revealed an association between carrier state of Q allele of PON1 gene and coronary artery disease as well as synergistic effects between genotype and some conventional risk factors, mainly smoking and elevated level of total cholesterol.

Despite successful reperfusion therapy of acute myocardial infarction and complete restoration of infarct-related artery patency, the improvement of systolic function in long-term outcome depends on preserved microvasculature integrity. Myocardial contrast echocardiography (MCE) is a useful technique for identification of viable myocardium.To assess the value of real-time myocardial contrast echocardiography (rt-MCE) in prediction of left ventricular function improvement in patients with anterior wall acute myocardial infarction as well as selection of the optimal cut-off value for the number of dysfunctional segments with preserved complete perfusion, in order to predict the global left ventricular function improvement during one-month observation.Rt-MCE was performed in 74 patients (50 men, aged 58+/-11 years) with anterior wall myocardial infarction, treated with primary percutaneous coronary intervention (PCI) within 12 hours from the onset of symptoms. After estimation of regional contractility disturbances and global systolic function of the left ventricle, rt-MCE was performed with contrast assessment of dysfunctional segments (normal contrast pattern=2, heterogeneous=1, lack of contrast=0). Regional perfusion score index (RPSI) was calculated by adding the perfusion indices and dividing by the number of dysfunctional segments.Of a total of 1184 visualised segments, 344 (29.1%) were dysfunctional (189 hypokinetic, 155 akinetic). Contractility improvement was observed in 192 segments (preserved viability in 105 hypokinetic and 37 akinetic segments). In a group of 44 patients with systolic function improvement, 34 of them had preserved viability, and in a group of 30 patients without LVEF improvement, in 22 of them myocardium viability was not observed. Sensitivity, specificity and accuracy of rt-MCE in prediction of left ventricular global improvement were 72.7%, 73.3% and 73%, respectively, whereas in prediction of regional function improvement these values were 73.9%, 77% and 75.5%, respectively.Rt-MCE performed in the early phase of myocardial infarction enables the prediction of left ventricular regional and global function improvement in patients treated with primary PCI.

Both the resting electrocardiogram and standard echocardiography have limited value in detecting ischaemic heart disease (IHD) in patients with atypical symptoms or asymptomatic subjects. Tissue tracking (TT) is a novel method based on tissue Doppler echocardiography for the assessment of longitudinal apical myocardial motion.To assess diagnostic utility of TT mode in the diagnosis of IHD.The study was performed in a group of 36 patients (aged 58+/-8 years, 15 males) with good acoustic window, sinus rhythm and normal left ventricular ejection fraction on standard echocardiography who were previously selected for coronary angiography. Systolic displacement of myocardium (TT) was assessed in all patients using apical views (4, 2, and 3-chamber) and 7-colour-coded visualisation expressing various apical displacements of the myocardium during systole. Group IHD(-) consisted of 16 patients with normal coronary angiography or insignificant lesions and group IHD(+) consisted of 20 patients with significant (70%) coronary lesions.Despite similar prevalence of arterial hypertension and diabetes as well as similar pharmacological treatment patients from the IHD(+) group had a lower TT index (ratio of the sum of regional TT values to the number of analysed segments than the IHD(-) (patients 4.5+/-0.8 mm vs 5.9+/-0.9 mm respectively, p0.001).Resting echocardiography with tissue tracking enables fast, non-invasive and semiquantitative evaluation of left ventricular function. This method of assessment of longitudinal layers of the left ventricle may be useful in the diagnosis of ischaemic heart disease.

In patients with atrial fibrillation (AF), significantly symptomatic in particular, restoring and maintaining sinus rhythm is one of treatment strategies. Considering the limited efficacy and side effects of anti-arrhythmic agents, growing hopes are attributed to the developing techniques of percutaneous ablation.To determine the efficacy and safety of circumferential pulmonary vein ablation performed using the CARTO system in patients with paroxysmal or permanent AF.The study involved 94 patients (mean age 54 years, males 65%, structural heart disease 29.4%) with symptomatic, recurrent and AF resistant to antiarrhythmic agents (paroxysmal AF 63.8%), selected for circumferential pulmonary vein ablation with the Pappone method. Follow-up examinations were performed after 1, 3, 6, 9, and 12 months. The symptoms, ECG, 24-hour ECG monitoring and complications were recorded.Mean procedure and fluoroscopy durations were 4.5 hours and 22.4 minutes respectively. The long-term follow-up ranged from 3 to 24 months, with median time of 12 months. At six months, 47.8% of patients remained free from AF, and improvement in terms of infrequent arrhythmia occurrence and low incidence of symptoms in an additional 36.7% was observed. Efficacy was lower in patients with permanent AF (12 months 90% vs 70%). Complications were seen in six (6.4%) patients: cardiac tamponade in two patients; and pericardial effusion, retroperitoneal bleeding, stroke, and pulmonary vein thrombosis each in one patient.Circumferential pulmonary vein ablation leads to resolution of arrhythmia or marked clinical improvement in about 75% of patients with symptomatic, resistant AF. The success rate is lower in patients with permanent rather than paroxysmal AF. As severe complications are not unlikely, the indications for such therapy must be carefully balanced.

Abnormal dispersion of the QT interval (QTd), measured as the interlead variability of QT, reflects an inhomogeneity of ventricular action potentials. In this study we observed both short- and long-term influences of coronary artery bypass grafting (CABG) on rest and exercise QTd in 64 male patients, having a mean age of 54+/-10 years, with coronary heart disease.QTd was measured as the difference between QT maximum and minimum from 12 leads on an averaged ECG (25 mm/s). QTd and QTdc were measured at rest and at peak exercise during symptom-limited treadmill exercise (ET), which was performed before, 6 months after, and 2 years after CABG.There was a significant reduction in rest QTd from before CABG to 6 months and 2 years after (60+/-20 ms vs. 43+/-14 ms and 45+/-13 ms, respectively; p0.001). Similarly, there was a significant reduction in peak QTd from before CABG to 6 months and 2 years after (66+/-22 ms vs. 38+/-11 ms and 36+/-11 ms, respectively; p0.001). Two years after CABG, 17 patients had a recurrence of angina and ET provoked chest pain and/or2 mm ST depression. The resting values did not distinguish patients with ischemia from nonischemic ones. In patients with ischemia, ET provoked an increase in QTdc.Rest and exercise QTd is significantly reduced after CABG. It seems that the measurement of QT dispersion during ET can be helpful in distinguishing patients with a recurrence of ischemia.

Reactive oxygen species (ROS) are involved in the pathogenesis of atherosclerosis and coronary artery disease (CAD). NADPH oxidases are the main source of ROS in the vasculature. p22phox is a critical component of vascular NADPH oxidases and is encoded by the CYBA (cytochrome b245 alpha) gene. The −930A>G CYBA polymorphism (rs9932581:A>G) modulates the activity of the CYBA promoter, and influences CYBA transcriptional activity. The aim of the present study was to analyze a possible association between the −930A>G polymorphism and CAD and to search for gene–traditional risk factors interactions. 480 subjects were studied: 240 patients with premature CAD, 240 age and sex matched blood donors. The −930A>G polymorphism was genotyped using the TaqMan® Pre-designed SNP Genotyping Assay (Applied Biosystems). The −930G allele carrier state was a risk factor for CAD (OR 2.03, 95 % CI 1.21–3.44, P = 0.007). A synergistic effect of the −930G allele with overweight/obesity (BMI ≥ 25) and cigarette smoking was found. The estimated CAD risk for BMI ≥ 25 and the −930G allele interaction was about 160 % greater than that predicted by assuming additivity of the effects, and about 40 % greater for interaction of cigarette smoking and the −930G allele. Overweight/obesity was a risk factor for CAD only in the −930G allele carriers (P G CYBA polymorphism is associated with CAD in the Polish population. The −930G allele carriers are particularly at risk of consequences of obesity and tobacco smoke exposure.