Podluzhniy S. The influence of neurohumoral factors on the course of paroxysmic atrial fibrillation among patients with ischemic heart disease in combination with hypertension

The thesis is devoted to the development of a model for stratification of paroxysmal atrial fibrillation recurrence among the patients with coronary heart disease combined with hypertension by determining the clinical and functional characteristics of patients, analysis of renin-angiotensin-aldosterone and sympatho-adrenal systems mediators, endothelial function and intracardiac hemodynamics. For the first time, the role of RAAS mediators (angiotensin II, aldosterone) in comparison with polymorphisms of genes that regulate it (AGTR1, AGT) among patients with paroxysmal atrial fibrillation, coronary heart disease and hypertension and their significance on predicting arrhythmia recurrence was determined. According to the results of a multivariate model of logistic regression of arrhythmia recurrence as an independent predictor among the patients with paroxysmal atrial fibrillation, coronary heart disease and hypertension, angiotensin II was reliably detected with sensitivity of 58,33 % and specificity of 76,47 %, with that level more than 827,78 pg/ml increases the relative risk of arrhythmia recurrence 2,53 times, and when combined with the allelic gene C of the A1166C polymorphism, the relative risk increases by 2,95 times. It was found that the endothelial dysfunction, by the amount of metabolites of nitric oxide, occurs gradually with increasing class of EHRA. The significantly lowest value of NO2+NO3 was in the subgroup of III class EHRA and amounted to 16.28 [14.06; 17.81] μmol/L. Significant correlation was determined between the following indicators: the level of NO2 and angiotensin II (R = -0.21, p <0.05), the level of NO3 and angiotensin II (R = -0.23, p <0.05) , the level of NO2+NO3 and angiotensin II (R = -0.30, p <0.05). It was determined that a more pronounced significant reduction, during the observation period of 6 months, the risk of arrhythmia occurred among the patients with the C allele of polymorphism A1166C, who used combination therapy with losartan. Received further development of the study of changes in intracardiac hemodynamics under the influence of treatment for a follow-up period of 6 months.