Objective. The cytochrome 11B2 aldosterone synthase gene (CYP11B2) that links to aldosterone synthase enzyme synthesis changes and blood pressure regulation is of particular interest among the renin-angiotensin-aldosterone system encoding genes.Methods. One-hundred hypertensive patients with target-organ damaging (2nd stage), moderate, high or very high cardiovascular risk were involved in the case-control study. Mean age was 59.87±8.02 years. Diabetes Mellitus type 2 (DM2) was in 28 persons. Chronic kidney disease (CKD) was diagnosed in 29 persons according to the National Kidney Foundation recommendations (2012) after glomerular filtration rate (GFR) decline <60 ml/min/1.73m2 for ≥3 months (measured by CKD-EPI equations). Aldosterone, cystatin-C, and creatinine levels were measured in serum. Control group included 48 practically healthy persons of relevant age. Gene’s nucleotide polymorphism CYP11B2 (-344C/T) was examined by polymerase chain reaction.Results. CKD evolution in hypertensive patients followed by higher systolic and diastolic blood pressure (SBP, DBP) values increased creatinine, cystatin-C, and aldosterone serum concentrations by 28.76%, 28.41% and 29.43% (р<0.05), respectively. Polymorphic site of CYP11B2 (rs1799998) gene is associated with SBP and DBP increase (p<0.05), reduced GFR preferably calculated by CKDEPI-cystatin C (F=10.79–14.45; p<0.001) and elevated aldosterone content (F=55.84; p<0.001), creatinine and cystatin-С as well (F=4.16–5.08; p<0.05) mainly in the ТТ-genotype female carriers (p<0.001). Hypertensive women with DM2 demonstrated stronger relations of CYP11B2 gene polymorphic site with the increased aldosterone content (F=47.52; p<0.001), than women without DM2 (p<0.001) and male patients (p=0.014).Conclusions. Genetic variations involving CYP11B2 might influence the kidney function, hypertension course, and severity via aldosterone secretion upregulation.

Objective. The aim of the present study was to clarify the endothelial function biomarkers and carotid “intima media” thickness (IMT) changes in relation to GNB3 (rs5443) and NOS3 (rs2070744) genes polymorphism in the essential arterial hypertension (EAH). Methods. One-hundred EAH patients (48 – control) participated in the case-control study. Soluble vascular cell adhesion molecule (sVCAM-1), total NO metabolites (NO2 –+NO3 –), transcriptional activity of NOS3 gene, endothelium-dependent flow-mediated dilation of the brachial artery (FMD BA), and carotid IMT were studied. GNB3 (rs5443) and NOS3 (rs2070744) genotyping was performed by TaqMan probes (CFX96™Real-Time PCR). Results. The connection of NOS3 (rs2070744) with decreased total NO metabolites (F=71.11; p<0.001), reduced NOS3 genes transcription activity (F=8.71; p<0.001) and increased sVCAM-1 (F=6.96; p=0.002), especially in the C-allele carriers (particularly in CC-genotype patients with lower NO – 16.46% and 40.88%; p<0.001), lowered the transcription activity of NOS3 gene – 46.03% 7 times (p<0.001), and become higher sVCAM-1 – 35.48% and 89.48% (p<0.001), respectively. ANOVA did not confirm the association of GNB3 (rs5443) gene with endothelial function and carotid IMT. Severe EAH was associated with increased carotid IMT – 50.0% (p<0.001) and 57.14% (p=0.007), wider carotid arteries – 17.36% (p=0.012) and 21.79% (p=0.004), and decreased NOS3 genes transcription activity – 34.54% (p=0.003). Atherosclerotic plaques were unilateral – 24.77% (χ2=5.35; p=0.021) or bilateral – 27.62% (χ2=5.79; p=0.016). IMT---gt---0.9 mm was followed by a higher BP (p<0.001), FMD BA 11.80% decrease with compensatory increase in carotid arteries diameters – 17.38% and 21.99% (p<0.001) and sVCAM-1 by 20.49% (p=0.005). Conclusion. NOS3 (rs2070744), but not GNB3 (rs5443), gene associated with the essential arterial hypertension severity relying upon the endothelial function impairment and NOS3 genes reduced transcription activity.

The study aim was to analyse the frequency of polymorphic variants of angiotensinogen gene polymorphism (AGT 704T>C, rs699) in essential arterial hypertension (EAH) patients. METHODS: Seventy-two individuals with EAH and hypertension-mediated organ damage (stage 2), moderate, high or very high cardiovascular risks were involved in the case-control study. Among them, 70.84 % (51) were females and 29.16 % (21) were males; mean age was 59.87±7.98 y. The control group consisted of fi fty practically healthy individuals at relevant age (49.13±6.28 y) and with relevant sex distribution (62 % were females, 38 % were males). AGT (704T>C) gene polymorphism was examined by RT-PCR. RESULTS: The distribution of genotypes in the study group was as follows: TT -14 %, TC -60 %, CC -26 %, which corresponded to the distribution in the control group -16 %, 54 % and 30 %, respectively, and did not deviate from the Hardy-Weinberg equilibrium. Smoking, type 2 diabetes mellitus (DM2) and obesity increased the relative risk of EAH in the examined population 2.5 times [OR=2.81; p=0.049], 3.75 times [OR=4.68; p=0.005] and almost twofold [OR=2.90; p=0.004], respectively. The probability of EAH increases fourfold with the angiotensin II elevation in the serum. Genotypes and alleles of the AGT (704T>C) gene were not signifi cant risk factors for EAH and DM2 in the studied population. However, the TC-genotype (lesser T-allele) increases the risk of obesity in EAH patients more than 1.5 times [OR=2.93; p=0.03]. In addition, the T-allele increases the risk for blood pressure (BP) to elevate up to grade 2-3 [OR=3.64; p < 0.001]. CONCLUSIONS: One-way ANOVA analysis confi rmed the AGT (704T>C) gene polymorphism to be associated with systolic and diastolic BP elevation (F=7.80; p < 0.001 and F=4.90; p=0.01, respectively), especially in TT-genotype carriers (p < 0.05), and with body mass index increase, albeit only in women (F=13.94; p < 0.001) (Tab. 4, Fig. 3, Ref. 26).

BACKGROUND: Cardiovascular (CV) diseases are the most spread cause of mortality in the world. Essential arterial hypertension (EAH), as a major risk factor for the development of CV diseases, is a multifactorial disease involving environmental and genetic factors together with risk-conferring behaviors. AIM: The purpose of this study was to analyze lipid metabolism changes in patients with EAH depending on the Vitamin D receptor (VDR rs2228570 (aka rs10735810)) and angiotensinogen (AGT rs699) genes polymorphism. MATERIALS AND METHODS: The single-stage study involved 100 patients suffering from Stage 2 EAH, 1–3 degrees of blood pressure increase, high and very high CV risks, 21% (21) men, and 79% (79) women. The average age of patients was 59.86 ± 6.22 years old. The control group included 60 practically healthy individuals of an appropriate age and sex distribution. To examine the VDR gene (rs10735810, rs2228570) and AGT gene (rs699) polymorphism, a qualitative real-time polymerase chain reaction was made. The lipid metabolism was studied by determining the blood plasma content of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TGs). RESULTS: Т allele of AGT gene is associated with reduced HDL-C level in men and increased TGs level in women. The EAH risk increases 4.5 times as much among the ТС-genotype carriers and lowered HDL-C level (odds ratio [OR] = 6.43; p = 0.01). The EAH risk increases as far as the HDL-C level reduction, irrespective of the VDR gene alleles condition 1.83 times (OR = 2.37; OR 95% confidence interval [CI]: 1.02–5.51; p = 0.04) and 1.9 times (OR=2.43; OR 95% CI: 0.99–5.97; p = 0.04). HDL-C reduction and LDL-C elevation in women increase the EAH risk 2.4 times (OR = 3.27; p = 0.01) and 1.24 times (OR = 3.67; p = 0.01), respectively. CONCLUSIONS: The EAH risk increases with a reduced HDL-C level in the TC genotype carriers of the AGT gene and irrespective of VDR gene polymorphic variants.

Background The incidence of the highly morbid and potentially lethal gangrenous cholecystitis was reportedly increased during the COVID-19 pandemic. The aim of the ChoCO-W study was to compare the clinical findings and outcomes of acute cholecystitis in patients who had COVID-19 disease with those who did not. Methods Data were prospectively collected over 6 months (October 1, 2020, to April 30, 2021) with 1-month follow-up. In October 2020, Delta variant of SARS CoV-2 was isolated for the first time. Demographic and clinical data were analyzed and reported according to the STROBE guidelines. Baseline characteristics and clinical outcomes of patients who had COVID-19 were compared with those who did not. Results A total of 2893 patients, from 42 countries, 218 centers, involved, with a median age of 61.3 (SD: 17.39) years were prospectively enrolled in this study; 1481 (51%) patients were males. One hundred and eighty (6.9%) patients were COVID-19 positive, while 2412 (93.1%) were negative. Concomitant preexisting diseases including cardiovascular diseases (p < 0.0001), diabetes (p < 0.0001), and severe chronic obstructive airway disease (p = 0.005) were significantly more frequent in the COVID-19 group. Markers of sepsis severity including ARDS (p < 0.0001), PIPAS score (p < 0.0001), WSES sepsis score (p < 0.0001), qSOFA (p < 0.0001), and Tokyo classification of severity of acute cholecystitis (p < 0.0001) were significantly higher in the COVID-19 group. The COVID-19 group had significantly higher postoperative complications (32.2% compared with 11.7%, p < 0.0001), longer mean hospital stay (13.21 compared with 6.51 days, p < 0.0001), and mortality rate (13.4% compared with 1.7%, p < 0.0001). The incidence of gangrenous cholecystitis was doubled in the COVID-19 group (40.7% compared with 22.3%). The mean wall thickness of the gallbladder was significantly higher in the COVID-19 group [6.32 (SD: 2.44) mm compared with 5.4 (SD: 3.45) mm; p < 0.0001]. Conclusions The incidence of gangrenous cholecystitis is higher in COVID patients compared with non-COVID patients admitted to the emergency department with acute cholecystitis. Gangrenous cholecystitis in COVID patients is associated with high-grade Clavien-Dindo postoperative complications, longer hospital stay and higher mortality rate. The open cholecystectomy rate is higher in COVID compared with non -COVID patients. It is recommended to delay the surgical treatment in COVID patients, when it is possible, to decrease morbidity and mortality rates. COVID-19 infection and gangrenous cholecystistis are not absolute contraindications to perform laparoscopic cholecystectomy, in a case by case evaluation, in expert hands. Graphical abstract