The genetic architecture of blood pressure (BP) includes more than 30 genes, the polymorphic variants of which cause phenotypic heterogeneity of BP. Given that a human genetic information is largely stable from birth, it can act as an early predictor of hypertension (HTN). Identification of polymorphic variants of genes associated with a high HTN risk may be one of the promising areas of early diagnosis and prevention of this disease. In addition, the availability of this data will make it possible to clarify the prognosis of patients already with HTN, as well as to personalize the treatment approach. The review analyzes the papers devoted to the molecular genetic basis of hypertension and identifies the possible role of gene polymorphism of the renin-angiotensin-aldosterone system in hypertension development. A large number of studies have revealed an association between HTN and polymorphic variants of the ACE, AGT, AGTR1 genes. In addition, polymorphism of these genes is involved in the development of atherosclerosis and related diseases, kidney and central nervous system disorders, and justifies the effectiveness of angiotensin-converting enzyme inhibitors in the treatment of HTN.

Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 57 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n = 230; 500 mg twice daily) or matching placebo (n = 233) for 14 days. The primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28 and 42 days. Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except nominally for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FIO₂) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FIO₂ levels at or below the median value (≤60%) had better outcomes after opaganib treatment (n = 117) compared to placebo (n = 134). The proportion of patients with ≤60% FIO₂ at baseline that no longer required supplemental oxygen (≥24 h) by day 14 of opaganib treatment increased (76.9% vs. 63.4%; nominal p-value = 0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs. 17.91%; nominal p-value = 0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs. 16.7%; nominal p-value = 0.019) by day 42. No new safety concerns were observed. While the primary analyses were not statistically significant, post-hoc analysis suggests opaganib benefit for patients with severe COVID-19 requiring supplemental oxygen with an FIO₂ of ≤60%. Further studies are warranted to prospectively confirm opaganib benefit in this subpopulation.

Physical activity is a generally accepted means of primary and secondary prevention of cardiovascular diseases, but in some cases, it can be a risk factor for cardiovascular events, including sudden cardiac death (SCD). Most studies analyze the relationship of cardiovascular events with the volume and general directions of exercise. Besides, a significant part of the guidelines and studies are devoted to the effects of aerobic exercise, while the importance of anaerobic exercise remains controversial. The review analyzes works devoted to the influence of strength training, such as weightlifting, bodybuilding, powerlifting, etc., on the cardiovascular system, as well as their relationship with SCD and other cardiovascular events. The design and contingent of the analyzed papers did not allow them to be systematized correctly. Therefore, the review is largely analytical in nature.

The article discusses the results of a comparative phase III clinical trial of the efficacy and safety of the biosimilar Complarate (CPR; JSC Generium, Russia) and the reference drug Actemra (ACT; F. Hoffmann-La Roche Ltd., Switzerland) to assess their equivalence in patients with rheumatoid arthritis, RA (NCT06475508 clinicaltrials.gov).Materials and methods. Male and female patients aged 18–75 years with RA with moderate to high disease activity and insufficient response to methotrexate (MTX) monotherapy and/or poor tolerability of MTX and/or insufficient response or intolerance to other standard DMARDs in combination with or without MTX were enrolled in the study. 464 (89.4%) patients were randomized in a 2:1 ratio into two groups. The study and the reference drug were administered as an intravenous infusion at a dose of 8 mg/kg once every 4 weeks. The primary endpoint was the proportion of patients with an ACR20 after 24 weeks of therapy.Results and discussion. The proportion of responders in CPR group was 91.2%, and in ACT group – 90.7% (p = 0.866). The difference between the groups was 0.5% (95% CI: -5,2%−6,1%), which is fully within the declared boundaries of recognition of therapeutic equivalence. Comparability of the biosimilar CPR and the reference drug ACT is also confirmed by the results of secondary efficacy endpoints: the proportion of patients with ACR50/70, dynamics of the DAS28, SDAI, CDAI, the functional activity of patients (HAQ), laboratory parameters of inflammatory activity (ESR and CRP). Comparability of the study and the reference drugs is also demonstrated by the results of the safety analysis.Conclusion. Based on the results of the clinical study, it has been proven that CPR (JSC Generium, Russia) is a biological analogue of ACT (F. Hoffmann-La Roche Ltd., Switzerland).

Aim.To study the relationship between symptomatic hypotensive episodes (SHEs) and parameters of self-monitoring of blood pressure (SMPB) in patients with hypertension (HTN).Material and methods.A total of 77 patients from 40 to 76 years old with HTN were examined. To identify SHEs, an original questionnaire was used. Patients underwent SMBP in the morning and evening, as well as recorded SHE in the diary. The self-monitoring period lasted 4 weeks. Patients without prior myocardial infarction and/or stroke are conventionally called “uncomplicated” HTN, while with cardiovascular events in history — “complicated” HTN.Results.According to the questionnaire, 48 (62,3%) patients noted SHEs. Uncomplicated HTN was recorded in 19 (51,4%) participants, while complicated one — in 29 (72,5%) (p=0,05). Blood pressure during SHEs was on average higher in patients with complicated HTN than in uncomplicated HTN (103/60 vs 95/60 mm Hg (p=0,05)). With a combination of uncomplicated HTN and SEG, mean systolic blood pressure (SBP) (125,9±10,5 vs 137,9±8,2 mm Hg), evening SBP (125,3±8,1vs 133,3±10,4 mm Hg), maximum SBP (149,8±11,8 vs 161,7±12,1 mm Hg) in the morning, as well as minimum SBP in the evening (101,8±10,8 vs 113,7±9,7 mm Hg) were lower than in patients without SHEs (p<0,05).In complicated HTN, an opposite relationship was observed: patients with SHEs had higher mean SBP (133,49±12,4 vs 118,93±15,3 mm Hg), maximum SBP (162,8±11,6 vs 141,7±12,0 mm Hg), and diastolic blood pressure (DBP) (91,5±5,6 vs 83,5±8,8 mm Hg) in the morning (p<0,05), as well as higher variability of morning (11,8±2,1 vs 8,2±2,7 mm Hg) and evening SBP (11,9±4,2 vs 8,6±3,2 mm Hg) compared with patients without SHEs (p<0,05). There were no significant differences in antihypertensive therapy.Conclusion.More than half of patients with hypertension report SHEs. SHEs in patients without prior myocardial infarction and/or stroke were characterized by lower blood pressure level than in subjects with prior cardiovascular events. Among patients with SHEs without cardiovascular events, the values of morning, evening, and maximum SBP in the morning are lower than in patients without SHEs. In patients with complicated HTN and SHEs, the opposite trend was observed: higher SBP and DBP in the morning, as well as greater variability of morning and evening SBP, in comparison with those without SHEs. These patterns cannot be explained by the antihypertensive drugs taken.

The aim of the study was to evaluate the efficacy and safety of Kolofort® (a complex medicine containing technologically processed forms of antibodies to S-100 protein, tumor necrosis factor-α and histamine) in the management of functional dyspepsia (FD) in outpatient clinical practice.Methods: Outpatients (N = 309) at the age of 18–45 in whom FD was diagnosed according to the Rome IV criteria were enrolled in a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients were randomized in two groups receiving Kolofort^® or placebo 2 tablets tid for 8 weeks. The primary endpoint of the study was a change in the FD symptoms severity score according to the Gastrointestinal symptom score (GIS) at week 8. ITT and [PP] analysis were performed.Results: at week 8 the reduction in GIS sum score was observed in Kolofort® group and placebo group (by 7.2 ± 3.3 [7.2 ± 3.4] and 6.3 ± 4.6 [6.2 ± 4.5], respectively, p = 0.041 [0.039]). The proportion of cases with GIS score reduction by ≥4 was 88,1 % [88.6 %] and 79.1 % [79.6 %] in Kolofort® group and placebo group, respectively (p = 0.046 [p = 0.051]). None of the patients in Kolofort^® group had progression of FD symptoms or required additional therapy. There were 29 adverse events (AEs) recorded in 25 patients including 16 cases in 13 (8.6 %) patients in Kolofort® group and 13 AEs in 12 (7.6 %) patients in placebo group.Conclusion: the clinical trial demonstrates the positive effect of Kolofort^® in FD with a favorable safety profile.