RESUMEN
Aim of investigation - to study effect of angiotensin-converting enzyme (ACE) gene polymorphism as a dominant risk factor of development of chronic heart failure (CHF) and target for effective therapy with ACE inhibitor enalapril in patients with ischemic heart disease. We followed 226 patients with CHF on stable permanent basic therapy comprising -adrenoblocker, diuretic, aldosterone antagonist, digoxin, and ACE inhibitor. Seventy eight patients received enalapril (starting dose 2.5 mg twice daily with subsequent titration up to 10-20 mg twice daily). Control group comprised 136 patients without cardiovascular abnormalities. Allele D of polymorphic locus I/D of ACE gene in homozygous state was associated with high risk of development and severity of clinical manifestations of CHF. In patients with D/D genotype of ACE gene at the background of therapy with enelapril we noted more pronounced lowering of CHF functional class and augmentation of left ventricular ejection fraction compared with patients having I/I and I/D genotypes. We revealed associative interrelationships of ACE gene polymorphism (polymorphic locus I/D) with development and severity of CHF as well as effectiveness of therapy with an ACE inhibitor enalapril.
Asunto(s)
Enalapril/administración & dosificación , Insuficiencia Cardíaca , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Función Ventricular Izquierda/efectos de los fármacos , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Predisposición Genética a la Enfermedad , Técnicas de Genotipaje , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Farmacogenética/métodos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
AIM: To study the impact of angiotensinogen (AGT) and angiotensin II receptor type 1 (AGTR1) gene polymorphisms on the development and course of chronic heart failure (CHF) in patients with coronary heart disease (CHD). SUBJECTS AND METHODS: Two hundred and twenty-six patients (149 men and 77 women; mean age 55.9 +/- 5.8 years) with CHF were examined. Genotypes were identified by the restriction fragment length polymorphism analysis of polymerase chain reaction products. A control group comprised 136 subjects (63 men and 73 women; mean age 53.6 +/- 4.8 years) without signs of cardiovascular diseases, as evidenced by the examination. RESULTS: The T allele of the M235T polymorphism in the AGT gene was found to be associated with the development and unfavorable course of CHF in patients with CHD. At the same time, carriage of the M allele of the M235T polymorphism in the AGT gene reflected the favorable course of this disease. That of the C allele and A/C genotype of the A1166C polymorphism in the AGTR1 gene was associated with the development of CHF and the A allele and A/A genotype manifested themselves as protective factors. According to the severity of CHF and the nature of its course, the distribution of frequencies of the genotypes and alleles of the A1166C polymorphism in the AGTR1 gene showed no significant differences between the patient groups. CONCLUSION: There were associations of the polymorphisms of the AGT gene (the M235T polymorphic marker) and the AGTR1 gene (the A1166C polymorphic marker) with the development of CHF in patients with CHD.
Asunto(s)
Angiotensinógeno/genética , ADN/genética , Predisposición Genética a la Enfermedad , Insuficiencia Cardíaca/genética , Polimorfismo Genético , Receptor de Angiotensina Tipo 1/genética , Sistema Renina-Angiotensina/genética , Anciano , Alelos , Angiotensinógeno/metabolismo , Progresión de la Enfermedad , Femenino , Frecuencia de los Genes , Genotipo , Insuficiencia Cardíaca/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Receptor de Angiotensina Tipo 1/metabolismoRESUMEN
UNLABELLED: URGENCY: Despite substantial progress in the treatment of coronary heart disease (CHD) and chronic heart failure (CHF) prognosis in these conditions remains extremely serious. This warrants their timely prevention and early detection. Aim. To study influence of inducible NO synthase (iNOS) (CCTTT)n, Glu298Asp and diallel polymorphism in the fourth intron (4a/4b polymorphism) of endothelial NO synthase gene (eNOS gene) on the state of endothelial function and risk of development of CHF in patients with CHD. MATERIALS AND METHODS: 165 patients with CHD were studied (121 male and 44 female, mean age 56.7 + or - 5.3 years). Vasomotor endothelial function was evaluated using ultrasound method in the reactive hyperemia and trinitroglycerol tests. Genotypes were identified using RFLP analysis of PCR products. Control group consisted of 114 persons (54 male and 60 female, mean age 53.2 + or - 4.9 years). RESULTS: It was determined that the number of repeats of polymorphic locus (CCTTT)n of the iNOS gene and Glu allele of the polymorphic locus Glu298Asp of eNOS gene in the homozygous state were associated with the risk of development of CHD and class of severity of CHF clinical manifestation. In addition Glu allele of the polymorphic locus Glu298Asp of eNOS gene in the homozygous state was associated with the severity and unfavorable development of CHF. The endothelial-dependent dysfunction was more severe in homozygotes of Glu allele of the polymorphic locus Glu298Asp of eNOS gene than in carrier of allele 298Asp. Associations between polymorphic variant of VNTR intron 4 gene eNOS and CHF with the risk of development and endothelial dysfunction were not found. CONCLUSION: An association between polymorphism of iNOS gene (CCTTT)n, eNOS gene (Glu298Asp) with development of CHD and severity of CHF was shown. The polymorphism of eNOS gene (Glu298Asp) was associated with endothelial dysfunction.
Asunto(s)
ADN/genética , Insuficiencia Cardíaca/genética , Isquemia Miocárdica/complicaciones , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo II/genética , Polimorfismo Genético , Anciano , Alelos , Endotelio Vascular/fisiopatología , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Insuficiencia Cardíaca/enzimología , Insuficiencia Cardíaca/etiología , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/enzimología , Isquemia Miocárdica/genética , Óxido Nítrico Sintasa de Tipo II/sangre , Óxido Nítrico Sintasa de Tipo III/sangre , Vasodilatación/fisiologíaRESUMEN
AIM: To study beta1-adrenoceptor gene (ADRB1) polymorphism on the development and course of chronic heart failure (CHF) and on the efficiency of its treatment with the beta-adrenoblocker carvedilol in patients with coronary heart failure. SUBJECTS AND METHODS: Two hundred and twenty-six patients (149 males and 77 females; mean age 55.9 +/- 5.8 years) with CHF, who received continuous basic therapy: angiotensin-converting enzyme inhibitors, a diuretic, an aldosterone antagonist, digoxin, and a beta-adrenoblocker, were examined; 68 patients were given for 24 weeks carvedilol (its starting dose was 3.125 mg twice daily with its further adjustment until an individually tolerable dose was achieved). Genotypes were identified by the restriction fragment length polymorphism analysis of polymerase chain reaction products. A control group comprised 136 subjects (63 males and 73 females; mean age 55.9 +/- 5.8 years) without signs of cardiovascular disorders, as evidenced by the examination. RESULTS: In patients with CHF, the Gly allele of the Gly389Arg polymorphic locus of the ADRB1 gene in homozygous state was associated with the high individual risk for CHF, the severity of its clinical manifestations and the nature of its course while carriage of the Arg allele of the Gly39Arg polymorphic locus manifested itself as a protective factor. During long-term carvedilol therapy, CHF patients with the Arg/Arg genotype of the ADRB1 gene were observed to have a more pronounced decrease in the functional class of heart failure, a significant increase in left ventricular ejection, and a decrease in left ventricular end-systolic and end-diastolic sizes as compared with patients with the Gly/Arg genotype. CONCLUSION: There were associations of the polymorphism of ADRB1 gene (the Gly39Arg polymorphic locus) with the development and severity of CHF and with the efficacy of therapy with beta-adrenoblocker carvedilol.
Asunto(s)
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapéutico , Carbazoles/uso terapéutico , ADN/genética , Insuficiencia Cardíaca/genética , Polimorfismo Genético , Propanolaminas/uso terapéutico , Receptores Adrenérgicos beta 1/genética , Antagonistas de Receptores Adrenérgicos alfa 1/administración & dosificación , Anciano , Alelos , Carbazoles/administración & dosificación , Carvedilol , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Genotipo , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/etiología , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Propanolaminas/administración & dosificación , Estudios Prospectivos , Receptores Adrenérgicos beta 1/efectos de los fármacos , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIM: To study long-term results of 3-42-month (mean 18.1 +/- 1.2 month) of a prospective clinically and angiologically controlled follow-up after coronary endovascular revascularisation with sirolimus-eluting stents (SES) in patients with coronary heart disease (CHD) comorbid with type 2 diabetes mellitus (DM). MATERIAL AND METHODS: A total of 108 CHD patients with angina pectoris resistant to antianginal therapy were divided into 2 groups: 51 CHD patients with mild and moderate type-2 DM (group 1); 57 CHD patients free of diabetes (group 2). All the patients have undergone successful coronary endovascular revascularisation with SES. Anti-ischemic efficacy and safety of stenting were studied in the course of 18-month prospective follow-up. RESULTS: An anti-ischemic effect of stenting in hospital setting was achieved in all the patients. 18 months after stenting frequency and severity of anginal attacks reduced in group 1 by 70.6%, daily need in nitroglycerine--by 71.9%, in group 2--by 87.1 and 93.1%, respectively. As a result, exercise tolerance improved in group 1 by 38.3%, in group 2--by 40.8%. Quality of life improved by 22.7 and 25.1%, respectively. Most of the patients showed no deterioration of carbohydrate and lipid metabolism compensation. Recurrent angina and symptoms of painless myocardial ischemia occurred in 39.3 and 14% patients of group 1 and 2, respectively. More frequent causes of the recurrence were progression of coronary artery atherosclerosis de novo and Cypher stent restenosis (11.8 and 3.5% in group 1 and 2, respectively). CONCLUSION: SES implantation provided good anti-ischemic efficacy in 60.7 and 86% CHD patients with and without DM, respectively. It significantly improved exercise tolerance and quality of life.
Asunto(s)
Reestenosis Coronaria/prevención & control , Diabetes Mellitus Tipo 2/complicaciones , Stents Liberadores de Fármacos , Isquemia Miocárdica/terapia , Revascularización Miocárdica/métodos , Sirolimus/uso terapéutico , Angiografía Coronaria , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/complicaciones , Estudios Prospectivos , Calidad de Vida , Sirolimus/administración & dosificación , Factores de Tiempo , Resultado del TratamientoRESUMEN
The aim of this work was to evaluate anti-ischemic and angiographic efficiency of endovascular revascularization of ischemic myocardium by implantation of Sirolimus-eluting stents from the results of a 18 moth-long prospective study of patients with coronary heart disease and/or type 2 diabetes mellitus (DM). The study included 108 patients with angina of effort randomized into two groups: CHD with DM (n = 51) and CHD without DM (n = 57). All of them received anti-ischemic and antihypertensive therapy and two desaggregants; DM patients also used oral hypoglycemic preparations. The patients underwent implantation of Sirolimus-eluting stents. The frequency of restenosis of the target arteries, development of serious cardio-vascular events (death, MI, cerebral stroke, and the need in repeat revascularization) were compared within 18 months after primary endovascular revascularization. Although Sirolimus-eluting stents markedly improved long-term prognosis in DM patients, results of their implantation were worse than in patients with CHD without DM.