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The role of genetic, cardiac hemodynamic and metabolic mechanisms in the development of comorbid pathology – essential hypertension and type 2 diabetes

Work number - M 15 AWARDED

Submitted by the Government Institution ‘L.T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine’

Author: Anna S. Shalimova

The aim of the work is the optimization of the diagnosis and the development of  differentiated approaches to the treatment of comorbid pathology (essential hypertension (EH) and type 2 diabetes mellitus (DM2)) based on a study of genetic, cardiohemodynamic and metabolic mechanisms in the development of comorbidity.

On the basis of theoretical studies and experiments, the author assessed the character of structural and functional changes of the heart and vessels, as well as the state of oxidative stress – antioxidant protection in patients with EH and concomitant DM2. The influence of various pathogenetic links of insulin resistance (IR) on the development of the comorbidity has been ascertained; the modulating effect of polymorphism of genetic markers of EH and DM2 on hemodynamics and metabolism has been determined; the main determinants of the development of comorbidity of EH and DM2 have been identified. An algorithm for differentiated treatment was developed taking into account genetic polymorphism.

Scientific foundations have been created to optimize the diagnosis and treatment of EH and concomitant DM2.

The basic conceptual foundations of the medical genetic research have been formed, contributing to the timely prevention and treatment of EH and DM2 in patients with risk factors for these diseases.

New ways to diagnose endothelial dysfunction (ED) and genetically determined IR, methods for the correction of ED and differentiated treatment of patients with EH and concomitant DM2 have been proposed.

A number of diagnostic and treatment activities have been implemented to reduce the risk of cardiovascular complications, preserve health and increase the life expectancy of patients with EH and concomitant DM2.

For the first time in the Ukrainian patient population, it has been established that the complex of genetic polymorphisms AGTR1, PPARγ2, IRS-1 and TCF7L2 is associated with the development of comorbidity of EH and DM2. For the first time, a relationship between the levels of proinflammatory cytokines (TNF-α and IL-6) and the presence of ED in EH and concomitant DM2 was established. For the first time, it has been shown that the effectiveness of the appointment of an angiotensin-converting enzyme inhibitor (ramipril) and an angiotensin II receptor antagonist (telmisartan) on the effect on blood pressure dynamics and leptin levels in EH and concomitant DM2 differs depending on AGTR1 genetic polymorphism.

The implemented algorithm for differential treatment of EH and concomitant DM2 allows the practitioner to prescribe drug therapy to patients with this comorbidity, taking into account genetic polymorphisms, the influence of drugs on cardiac and vascular remodeling, factors of immune inflammation, pro- and antioxidant activity, heart failure.

The economic effect of the introduction is determined by a significant increase in the effectiveness of diagnostic activities that allow timely recognition of diseases and prevent the development of their complications in people of working age. The profitability of the treatment strategy has increased: the cost of treatment has decreased and the effectiveness of treatment has increased.

Number of publications: 90, including 1 monograph, 32 articles (12 in foreign editions). According to the Scopus database, the total number of links to the publications of the author presented in the work is 7, h-index (works) = 3; according to the Google Shcolar database, the total number of links is 32, h-index (works) = 4. Scientific novelty and competitiveness of technical solutions are protected by 5 patents.