The dissertation deals with optimization of diagnostics, prediction of chronic heart failure in coronary artery disease and obesity patients as determined by polymorphisms of genes associated with neurohumoral activation, endothelial dysfunction, immune inflammation and disorder of adipocytokine and lipid metabolisms; customization of therapeutic tactics. The scientific novelty lies in concept development for optimization of diagnostics, course predication and customization of the therapeutic tactics in patients with chronic heart failure on the background of coronary artery disease and obesity based on the study of genetic determinants of comorbid pathology development; and extent of their effect on variation in anthropometric, hemodynamic, echocardiographic and metabolic signs was evaluated. Based on the comprehensive evaluation of molecular and genetic mechanisms of heart failure development, genetic variants of polymorphic loci of genes associated with chronic heart failure development risk, severity and course in coronary artery disease and obesity patients were identified for the first time, and their contribution to various pathogenic links of the above comorbidity. Candidate allelic variants of chronic heart failure development and favorable course were identified. Augmentation of chronic heart failure severity was established to be due to more frequent identification of pathologic alleles and genotypes of the studied genes in patients with comorbid course of coronary artery disease and obesity. As reported by Cox proportional hazards regression model, the following genotypes were shown to be independent predictors of chronic heart failure patients' survival: TT of М235Т polymorphic locus in angiotensinogen gene, AA of G-308A polymorphic locus in tumour necrosis factor alpha gene, GG of C-174G polymorphic locus in interleukin-6 gene, GG of Glu298Asp polymorphic locus in endothelial NO synthase gene, CC of AC polymorphic locus in oxidized low-density lipoprotein receptor-1gene, GG of Gln27Glu polymorphic locus in ?2-adrenoreceptors gene, GG of Arg223Gln polymorphic locus in leptin gene. Insulin level in excess of 19.76 µU/ml, body mass index over 27.6 kg/sq. m., end-systolic volume over 186 ml, ejection fraction lower than 33 %, and presence of TT genotype of М235Т polymorphic locus in angiotensinogen gene, and AA genotype of G-308A polymorphic locus in tumour necrosis factor alpha were proved to be markers of complicated chronic heart failure course in coronary artery disease and obesity patients. Carriage of T allele of М235Т polymorphism in angiotensinogen gene, G allele and GG genotype of Glu298Asp polymorphic locus in endothelial NO synthase gene, AA genotype of G-308A polymorphism in tumour necrosis factor alpha gene in men, and carriage of C allele of polymorphism in oxidized low-density lipoprotein receptor-1(A/C) gene in women were identified to be associated with chronic heart failure development risk and unfavorable course; while variability rate for M allele of М235Т polymorphism in angiotensinogen gene proved to be a protective factor. Quality of life was evaluated in chronic heart failure patients, and presence of links and associations with gene polymorphisms was established. Scientific rationale was given to prescription of comprehensive therapy for chronic heart failure and efficiency of using various treatment regimens in coronary artery disease and obesity patients depending on an unfavorable combination of genotypes was evaluated. A method for differentiated therapeutic correction of dyslipidemia in coronary artery disease and obesity patients with regard for genotypes of the studied genes was developed. Efficiency of rosuvastatin administration was proved in carriers of the following genotypes: TT of М235Т polymorphic locus in angiotensinogen gene, GG of Gln27Glu polymorphic locus in ?2-adrenoreceptors gene, AA of G-308A polymorphic locus in tumour necrosis factor alpha gene, GG of leptin gene polymorphism (Arg223Gln); and that of atorvastatin in carriers of the genotypes: MM of М235Т polymorphic locus in angiotensinogen gene, GG of G-308A polymorphic locus in tumour necrosis factor alpha gene, and AA of leptin gene polymorphism (Arg223Gln).
