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Inclisiran is a novel hypolipidemic drug that inhibits synthesis of the PCSK9 protein through the process called RNA interference. Inclisiran is a double-stranded, modified RNA bound to the N-acetylgalactosamine (GalNAc) carbohydrate molecule, a ligand of the acialoglycoprotein receptor, that is expressed by hepatocytes. After entering hepatocytes, inclisiran cleaves matrix RNA and, thereby, reduces the PCSK9 protein synthesis. This, in turn, enhances the uptake of circulating low-density lipoproteins (LDL) by specific receptors on hepatocytes, thereby lowering LDL levels in circulation. Efficacy and safety of inclisiran for lowering LDL cholesterol (C) in blood and its effect on the risk of clinical complications of atherosclerosis have been studied in the ORION program that includes multiple clinical trials. According to results of this program, inclisiran effectively reduces both LDL-C levels and the incidence of cardiovascular complications in the absence of clinically significant adverse reactions. An important advantage of inclisiran compared with other lipid-lowering drugs is the administration schedule (twice a year), which allows a considerable improvement of patients' compliance with the treatment and also of the effectiveness of the hypolipidemic treatment.Objective Early diagnosis of hypertension (HT) is a critical issue for physicians. This study was conducted to determine if morning surge blood pressure (MSBP) could be used to predict future HT. The study also examined which demographic data in a regression model might help to detect future HT without any invasive procedure.Material and methods A young population between 18 and 40 yrs of age was included in the study. MSBP and demographic data were used to determine an optimal model for predicting future HT by using Bayesian information criteria and binary logistic regression.Results 1321 patients with 24 hr ambulatory blood pressure monitoring were included in this study. The odds ratio of 10 units of increase in diastolic MSBP was 1.173511 in the model, which indicates that a 10 mmHg increase in diastolic MSBP increases the odds of future HT in the patient by 17.4 %. The odds ratio of age was 1.096365, meaning that at each age above 18 yrs, the patients' odds of future HT rise by 9.6 %. The odds ratios for gender (male) and previous HT were 1.656986 and 3.336759, respectively. The odds of future HT in males were 65 % higher than for females, and a history of HT implies that the odds of future HT were higher by 230 %.Conclusion Diastolic MSBP can be used to predict HT in young individuals. In addition, age, male gender, and previous HT add more predictive power to diastolic MSBP. This statistically significant, predictive model could be useful in lessening or preventing future HT.Aim Cardiac autonomic dysfunction is encountered in approximately 25 % of patients with metabolic syndrome (MetS). 24 hr Holter-ECG based heart rate variability (HRV) and heart rate turbulence (HRT) parameters are used to evaluate cardiac autonomic function. We aimed to investigate the relationship between a novel insulin resistance marker, triglyceride glucose (TyG) index and cardiac autonomic dysfunction in patients with MetS.Material and methods We examined a total of 400 non-diabetic subjects, 136 with MetS and 264 without MetS. All underwent TyG index calculations, and 24 hr Holter-ECG recordings for the measurement of HRV and HRT parameters.Results HRV and HRT parameters were lower or higher in patients with MetS than in subjects without MetS, indicating cardiac autonomic dysfunction. We observed significant correlations between TyG index and measures of cardiac autonomic function. Multiple linear regression analysis showed that the TyG index was an independent predictor of almost all HRV and HRT parameters.Conclusion This study demonstrates the independent relationship between cardiac autonomic dysfunction and the TyG index, a novel marker of insulin resistance in non-diabetic patients with MetS.Aim To evaluate the outpatient physical exercise (PE) compliance and the affecting factors in patients after coronary bypass (CB).Material and methods The study included 67 men with ischemic heart disease younger than 75 years who had had CB. All patients were randomized to 2 groups group 1 exercised on a bicycle ergometer at the rehabilitation center, under the monitoring of medical staff; patients of group 2 performed home-based exercise (HBE) by dosed walking. In the preoperative period, at one month after CB, and after 3 months of exercise, the following was evaluated clinical condition of patients in different groups, plasma concentrations of lipids, body weight index, waist circumference, echocardiography and bicycle ergometry data, and questionnaire data (SF-36, Bek's Depression Inventory). At 3 months of follow-up, the outpatient exercise compliance and the affecting factors were also evaluated.Results The study demonstrated the effectiveness of the proposed alternative 3-month program of home-based Pr risk factors, increased ET, optimization of the psychological status and quality of life, and improved compliance with drug therapy. However, despite the proposed alternative, home-based 3-month physical rehabilitation programs aimed at increasing the treatment compliance, the level of ET remained low. This requires further improvement of methods for monitoring and motivation of patients to physical rehabilitation and psychological support that would start already at the preoperative stage.Aim To determine the applicability of speckle-tracking EchoCG (STE) and the Valsalva maneuver for diagnosis of heart failure with preserved left ventricular ejection fraction (CHFpEF).Material and methods Transthoracic STE with simultaneous electrocardiogram (ECG) recording was performed for patients with CHFpEF and healthy sex- and age-matched subjects (control group) at rest and during the Valsalva maneuver. The study was conducted in compliance with standards of Good Clinical Practice and principles of the Helsinki Declaration. The study protocol was approved by the Ethical Committee of the St. Petersburg State University.Results During the Valsalva maneuver, deviations of both global and segmental myocardial strain were more pronounced than at rest. In patients of the study group performing the Valsalva maneuver, LV end-diastolic volume and LV end-systolic volume (99 %) were increased. Heart rate was considerably reduced (significance of difference >99%) in patients with CHFpEF during the Valsalva maneuver compared to the control group. The increased predictive value of these parameters during the Valsalva maneuver can justify the inclusion of this method in early detection and prognostic assessment of CHFpEF.Conclusion Speckle-tracking EchoCG with the Valsalva maneuver is a noninvasive, generally available, and easily reproducible outpatient method for diagnosis of CHFpEF.Aim To identify risk factors for recurrence of atrial fibrillation (AF) following cryoballoon ablation (CBA).Material and methods This prospective study included patients with paroxysmal AF who had undergone CBA (141 patients, median age 60 years, 3% men). The evaluation prior to CBA included clinical instrumental parameters (electrocardiography (ECG), 24-h ECG monitoring, echocardiography, contrast-enhanced cardiac multispiral computed tomography). Also, possible intraoperative indexes that could affect the CBA effectivity, were evaluated. The postoperative follow-up duration was 12 months. Effectivity was assessed during in-person visits at 3, 6, and 12 months, when questioning of patients and 24-h ECG monitoring were performed. CBA was considered ineffective if the patient had recurrences of any atrial tachyarrhythmia longer than 30 sec after the end of the 3-month "blind" period.Results During the 12-month follow-up, recurrences of atrial tachyarrhythmia were observed in 46 (32.6 %) patients. Patients with ineffective CBA more frequently had AF during the first 3 months (71.7 % vs. 11.6 %; р<0.001). Fulvestrant concentration Such patients had a history of multiple ineffective treatments with antiarrhythmic drugs (AAD), common pulmonary venous (PV) collector (41.3 % vs. 20.0 %; р=0.008), and stroke/recurrent ischemic attacks (15.2 % vs. 5.2 %; р=0.047). Multifactorial regression analysis showed that the factors of AF recurrence included common PV collector (relative risk (RR) 2.35; 95 % confidence interval (CI) 1.29-4.25; р=0.005), multiple ineffective AADs (RR 1.42; 95 % CI 1.08-1.86; р=0.011), and early AF recurrence (RR 7.57; 95 % CI 3.84-14.90; р<0.001).Conclusion Common PV collector and multiple ineffective AADs are risk factors of ineffective CBA. Early recurrences during the first 3 postoperative months are a significant risk factor of long-term AF recurrences.Aim To study the association between vascular wall stiffness and known markers for accumulation of senescent cells in blood, cells, and tissues of old patients.Material and methods This study included male and female patients aged 65 years and older who were referred to an elective surgical intervention, that included a surgical incision in the area of the anterior abdominal wall or large joints and met the inclusion and exclusion criteria. For all patients, traditional cardiovascular (CV) risk factors and arterial wall stiffness (pulse wave velocity, PWV) were evaluated. Also, biomaterials (peripheral blood, skin, subcutaneous adipose tissue) were collected during the surgery and were used for isolation of several cell types and subsequent histological analysis to determine various markers of senescent cells.Results The study included 80 patients aged 65 to 90 years. The correlation analysis identified the most significant indexes that reflected the accumulation of senescent cells at the systemic, tissue, an PWV significantly correlates with a number of plasma, tissue, and cellular markers for accumulation of senescent cells. This fact suggests PWV as a candidate for inclusion in the panel of parameters for evaluation and monitoring of the biological age during the senolytic therapy.Aim The aim of the study was evaluation of the effect of the coenzyme Q10 (Q10) treatment on all-cause and cardiovascular mortality of patients with chronic heart failure (CHF). Q-10 increases the electron transfer in the mitochondrial respiratory chain and exerts anti-inflammatory and antioxidant effects. These effects improve the endothelial function and reduce afterload, which facilitates the heart pumping function. Patients with reduced left ventricular (LV) ejection fraction (EF) (CHFrEF) have low Q10.Material and methods Criteria of inclusion in the meta-analysis 1) placebo-controlled studies; 2) enrollment of at least 100 patients; 3) publications after 2010, which implies an optimal basic therapy for CHF; 4) duration of at least 6 months; 5) reported cardiovascular and/or all-cause mortality; 6) using sufficient doses of Q10 (>100 mg/day). The search was performed in CENTRAL, MEDLINE, Embase, Web of Science, E-library, and ClinicalTrials.gov databases. All-cause mortality was the primary efficacy ef two RCTs (863 patients). The decrease in the risk associated with the Q10 treatment was significant, 55% (OR=0.45, 95 % CI 0.32-0.64, р=0.00001). In this case, the data heterogeneity was also low (Chi2=0.41; p=0.52; I2=0 %).Conclusion The meta-analysis confirmed the beneficial effect of coenzyme Q10 on the prognosis of patients with CHFrEF receiving the recommended basic therapy.

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