Aim — the analysis of the effect of Cytoflavin on molecular mechanisms of myocardial and vascular wall remodeling in patients with idiopathic systolic arterial hypertension (ISAH). Material and methods. Prospective, selective, randomized controlled trial was performed in two centers. 306 persons were included, individuals without ISAH (group I, n=60) and patients with ISAH grade 1 and 2 (group II, n=246) according to inclusion/non-inclusion criteria in 2 subgroups: IIa (n=125; 65—74 years], IIb (n=121; 75 years and older], all patients took valsartan 80 mg/day and amlodipine 5 mg/day (n=40) for 2 years. Optimization of therapy included 10-day dose of Cytoflavin i.v. in a volume of 10 ml in dilution for 200 ml of 0.9% sodium chloride solution once a day with subsequent intake of 2 tablets twice a day for 80 days. Evaluation of the efficacy and safety of therapy was performed after 2 years and 3 months of the 3rd year after inclusion in the study. Methods of investigation: the assessment of complaints, 24-hour ECG-monitoring, echocardiography, volumetric sphygmography, lipidogram and coagulogram, molecular phenotyping of blood plasma (MALDI-TOF-TOF-MS), concentration of TGFβ-1, HIFIa, apoD by ELISA, ADR. Results. Cytoflavin with standard therapy of ISAH led to significant restoration of hemodynamic, structural and geometric parameters of cardiovascular system, lipidogram and coagulogram, compared to patients with standard therapy. Molecular mechanisms of cardio- and angioprotective activity of Cytoflavin included regulation of cellular signaling pathways through intermolecular interactions of TGFβ-1, HIFIa and apoD. Optimized ISAH therapy was recommended.