“To determine neurohumoral and metabolic features of arterial hypertension in children”
(research supervisor – Doctor of Medical Sciences, professor M.M. Korenev, 2009−2011 yrs)
Some peculiarities in neurohumoral relations concerning formation of metabolic disorders have been determined in adolescents with AH considering BMI.
Research object : indices of blood lipid spectrum, carbohydrate metabolism, and neurohumoral regulation systems, markers of endothelial dysfunction, and the status of the target organs in adolescents with different variants of arterial hypertension (AH).
Objective: to establish some mechanisms of metabolic disorders formation in adolescents with different AH variants on the basis of determining markers of endothelial dysfunction, inflammatory factors, blood lipid spectrum and carbohydrate metabolism disorders.
Methods: clinical, instrumental (electrocardiography, echo-cardiography, and daily blood pressure monitoring), biochemical (blood lipid spectrum, carbohydrate metabolism indices, adrenalin, noradrenalin, and melatonin in a daily urine), immunofermental (microalbuminuria, interleukin-6, and C-reactive protein), radioisotope (renin, angiotensin-II, aldosterone, and endothelin-I).
Theoretical and practical results: disorders in blood lipid and lipoproteid spectra were found in adolescents with AH under investigation, but their frequency prevailed in adolescents with AH and overweight (OW). In the latter group a correlation between beta- and prebeta-lipoprotein sum and alpha-lipoprotein level significantly exceeded the value of the indices in boys with primary arterial hypertension (PAH). At the same time, in adolescents with AH and OW there was found a significant activation of lipid peroxidation processes without adequate response of antioxidant protection system which can be one of the factors of lipoproteide complexes pathological interaction with vascular endothelium. In adolescents with AH and OW average values of HOMA-IR index were also significantly higher than its level in adolescents with PAH. Selective contribution of catecholamine to carbohydrate metabolism characters in adolescents with AH, regardless of body mass index (BMI), as well as statistically significant impact of melatonin elevated level in adolescents with PAH in the daytime and in adolescents with AH and OW at night were established in the study. Plasma renin activity (PRA) together with A-II effects determined total cholesterol and triglyceride levels, as well as the atherogenity coefficient, in adolescents with PAH, and in persons with AH and OW a statistically significant impact exercised angiotensin-II - aldosterone link. In adolescents with AH and OW development of endothelial dysfunction in the form of inadequate vascular reaction was revealed both in endothelium-dependent and endothelium-stimulated samples, accompanied by a significant increase in endothelial factors level (endothelin-1, microalbuminuria) and factors of nonspecific systemic inflammation (C-reactive protein). It was revealed that in adolescents with AH and OW biventricular heart remodeling took place with predominantly eccentric myocardium hypertrophy of the left ventricle, with the same frequency of developing both concentric and eccentric hypertrophy.
Novelty: a novel model of metabolic disorders formation in adolescents with AH, taking into account BMI, has been worked out in the study. According to it SAS and RAAS activation in the absence of an adequate increase in melatonin was one of the elements in the pathogenesis of carbohydrate metabolism disturbances. A significant effect on the blood lipid spectrum parameters in adolescents with PAH performed ARP and angiotensin-II, and in adolescents with AH and OW it rendered angiotensin-II in combination with aldosterone, confirming the interaction and synergism of prohypertesive and proatherogenic mechanisms in the formation of both metabolic disorders and cardiovascular complications in adolescents with AH, especially with concomitant OW.
Effectiveness: the developed method for predicting atherosclerotic complications in adolescents with AH in comparison with previous elaborations is more efficient (by 30–40%).
Application fields: pediatric cardiorheumatology and pediatrics.