Ultrasound Atherosclerosis Burden Score as a tool for predicting adverse cardiovascular events in patients with various cardiovascular risks aged 40-64 years

Aim. To investigate the prognostic significance of the Atherosclerosis Burden Score (ABS) in relation to the development of major adverse cardiovascular events in patients of different cardiovascular risks (CVR) aged 40 to 64 years.Material and methods. Men and women aged 40 to 64 years were included in the study. All the patients underwent duplex scanning of the carotid arteries and lower limb arteries. The total ABS was calculated by assessing the presence of plaque in the carotid and femoral bifurcations on both sides. The combined endpoint was cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or peripheral artery revascularization.Results. The study included 232 patients who met the inclusion criteria, with a median age of 55,0 years. Very high CVR was established in 94 (40,5%) patients, while high CVR — in 48 (20,7%) patients, and low and intermediate CVR — in 90 (38,8%) patients. The follow-up period lasted 23,6 (15,5; 51,2) months, providing 632,6 patient-years of follow-up. Events within composite endpoint occurred in 28 (12,1%) patients. Increased cumulative risk of adverse cardiovascular events was observed for ABS ≥2, with a significant increase in relative risk (RR) for ABS ≥3. According to Cox regression analysis, ABS 3 was associated with a 3,71-fold (95% CI 1,18-11,6; p=0,025) increase in the RR of adverse cardiovascular events after adjustment for sex, age, baseline CVR, obesity, smoking, diabetes, CAD, a history of myocardial revascularization, type 2 diabetes, drug therapy, and levels of non-high density lipoprotein cholesterol, highly sensitive C-reactive protein, and glomerular filtration rate.Conclusion. In patients of various CVR aged 40-64 years, an ABS ≥3 was associated with a 3,71-fold (95% CI, 1,18-11,6; p=0,025) increase in relative risk of adverse cardiovascular events after adjusting for potential confounders, including sex, age, baseline CVR, CAD, and type 2 diabetes

CARDIAC ARRHYTHMIAS IN CERTAIN INTERNAL DISEASES (review)

Heart rhythm disorders are considered as changes in the normal frequency, regularity, and source of depolarization of the heart, as well as impulse conduction disorders. Cardiac arrhythmias can be caused by numerous reasons, as well as their combination. The review presents current data on the frequency, risk stratification and prognostic value of cardiac arrhythmias in patients with various internal diseases. The data on the increased risk of atrial fibrillation in gastroesophageal reflux disease, gastric diseases and inflammatory bowel diseases are presented. The spectrum of the most common arrhythmias in patients with chronic obstructive pulmonary disease and asthma, as well as thyroid diseases, diabetes mellitus and acromegaly is considered. The options for cardiac arrhythmias associated with the use of chemotherapeutic drugs in the treatment of hemoblastosis are considered separately. Modern ideas about the mechanisms of development of arrhythmias in various internal diseases are discussed. In most cases, cardiac arrhythmias are associated with both the direct effect of the underlying disease on the cardiovascular system and the systemic reactions that occur. However, to date, the question remains to what extent the myocardial state that precedes the underlying disease plays a role in the occurrence of cardiac arrhythmias. The significance of various congenital and genetic factors has not been clarified. These questions are essential for everyday clinical practice and require detailed scientific study

Antioxidants of Belgorod State University Botanical Garden Plants: Ribes Aureum Fruits Anthocyanins

According to the results of the study, it was found that currant berries of this species contain four main anthocyanins: delfinidin-3-glucoside, delfinidin-3-rutinroside, cyanidin-3-glucoside and cyanidin-3-rutinosid

Relationships between serum HMGB1 concentration and subpopulation composition of circulating monocytes in patients with subclinical atherosclerosis

Chronic non-infectious inflammation of low intensity is the most important mechanism of development and progression in atherosclerosis. Under the conditions of persistent non-resolving inflammation observed in the vascular wall and atherosclerotic plaque (ASB), permanent tissue damage occurs, thus leading to increased formation of endogenous danger-associated molecular patterns (DAMPs). The non-histone chromosomal protein HMGB1 may be regarded as a prototypical DAMPs. HMGB1 acts as a DAMP if entering the extracellular space, causing inflammation by its binding to pattern-recognizing receptors (TLR2, TLR4, RAGE, CD36, etc.). A number of clinical studies have revealed higher HMGB1 levels in the blood of patients with coronary heart disease and atherosclerotic disease of the lower limb arteries, as well as its interrelations with the burden of coronary artery atherosclerosis. Currently, the mechanisms of HMGB1-mediated atherosclerosis progression are studied only fragmentary. The aim of our study was to investigate relationships between the serum HMGB1 level and subsets of circulating monocyte subpopulations in patients with subclinical atherosclerosis.The study enrolled patients aged 40-64 years with subclinical atherosclerosis of peripheral arteries. Serum HMGB1 concentration was determined using enzyme immunoassay kits (Human HMGB1/HMG-1 ELISA Kit, NBP2-62766, Novus Biologicals, USA). The serum HMGB1 threshold was 18.75 pg/ml, whereas the measurement range was 31.25 to 2000 pg/ml. Phenotyping of the blood monocyte subpopulations was performed by flow cytometry using Navios 6/2 device (Beckman Coulter, USA).An increase in serum HMGB1 concentration was associated with decreased number of classical M2 monocytes, and an increase in intermediate and M1 monocytes. Moreover, an increase in HMGB1 concentration was associated with higher numbers of classical, intermediate, and non-classical monocytes expressing CD36 and TLR2. Increased HMGB1 concentration (from Q1 to Q4) correlated with higher numbers of classical (p = 0.001) and intermediate monocytes (p = 0.006) but not with non-classical phenotypes (p = 0.147). Upon increase of HMGB1 concentration (Q1 to Q4), we have found an increase in the number of classical (p < 0.0001), intermediate (p < 0.0001), and non-classical (p < 0.0001), CD36-expressing monocytes. An increased number of intermediate (p = 0.022; p1, 4 = 0.034) and non-classical, TLR2-expressing monocytes was also revealed (p = 0.002; p1, 4 = 0.035). By mean of correlation analysis, IL-1β concentrations showed direct correlation with the number of M1 monocytes (r = 0.268; p = 0.035) and inverse relation with the number of M2 monocytes (r = -0.376; p = 0.003).Increased serum HMGB1 concentration in patients with subclinical atherosclerosis was associated with decreased numbers of classical and M2 monocytes, as well as higher numbers of intermediate and M1 monocytes, like as with increased contents of intermediate and non-classical monocytes expressing CD36 and TLR2. IL-1β levels directly correlated with HMGB1 concentration and the number of Mi-monocytes

Interactions between immunosuppressor neutrophiles, innate and adaptive immunity indexes in the patients with subclinical atherosclerosis

The last fifteen years have been marked by rapid progress in the study of neutrophils. The discovery of transcriptional plasticity of neutrophils, their phenotypic and functional heterogeneity contributed to launching active interdisciplinary studies on the role of neutrophils in various chronic inflammatory diseases. Increased systemic circulation of immunosuppressive neutrophils can be observed not only in sepsis, but also in chronic systemic inflammation, which, along with disorders of lipid metabolism, is the major mechanism of atherosclerosis development and progression. Monocytes, dendritic cells, Tlymphocytes and neutrophils are key participants and modulators of inflammation in atherosclerosis. Potential significance of immunosuppressive neutrophils in atherogenesis and regulation of inflammatory response in atherosclerosis has not been currently established. However, taking into account their possible effects upon T lymphocytes and innate immunity cells, the study of immunosuppressive neutrophils seems promising in the context of atherosclerosis and atherosclerotic cardiovascular diseases. The purpose of this study was to evaluate relationship between the numbers of circulating immunosuppressive neutrophils and subpopulations of T cells and monocytes in the patients with subclinical atherosclerosis. The study enrolled patients aged 40-64 years with subclinical atherosclerosis of peripheral arteries. Subpopulations of neutrophils, lymphocytes and monocytes were phenotyped by flow cytometry using “Navios 6/2” (Beckman Coulter). 133 patients, 65 (48.8%) males and 68 (51.2%) females were included into the study. Correlation analysis showed that increased number of circulating CD16hiCD11bloCD62Lbr neutrophils was associated with increased number of regulatory T lymphocytes. The patients with subclinical atherosclerosis and absolute numbers of circulating immunosuppressive neutrophils within the first quartile (<136 cells/μL) had a statistically significantly lower number of regulatory T lymphocytes compared with patients in the 2-4 quartiles. An increase in immunosuppressive neutrophils was associated with decreased number of classical monocytes expressing TLR4 (r = -0.335; p = 0.004), and a decrease in TLR2 surface expression intensity (r = -0.268; p = 0.023) on the non-classical monocytes. In patients with subclinical atherosclerosis of 40-64 years old, an increase in immunosuppressive CD16hiCD11bloCD62Lbr neutrophils was associated with increase in regulatory T lymphocytes and nonclassical monocytes, as well as decrease in classic monocytes expressing TLR4, and lower intensity of TLR2 expression on the non-classical monocytes

Practical efficacy and safety of Konsilar D24 in patients with hypertension: data from the KONSONANS program

Aim. In practice, to evaluate the efficacy, safety and long-term adherence to therapy with a fixed-dose combination of ramipril/indapamide (Konsilar-D24) in patients with grade 1-2 hypertension (HTN) who have not achieved blood pressure (BP) control with prior therapy or have not taken antihypertensive therapy.Material and methods. This multicenter open-label observational program included 524 patients with grade 1-2 HTN who did not take antihypertensive therapy or did not reach the target BP level with mono or dual antihypertensive therapy, as well as patients shifted to Konsilar-D24 therapy no later than two weeks before the start of the program. All patients signed a written informed consent to participate in the program. The safety analysis set includes all patients who have taken at least one dose of a fixed-dose combination of ramipril/indapamide and have visited physician at least once during the program. The effectiveness analysis set included all patients in the safety population who completed the study in accordance with protocol (n=511). Clinical systolic blood pressure (SBP), diastolic BP (DBP) and heart rate were assessed at baseline, as well as at 0,5, 1, 3 and 6 months of treatment. A post hoc subgroup analysis of changes in BP and heart rate was performed depending on age, sex and baseline body mass index.Results. The fixed-dose combination of ramipril with indapamide significantly reduced SBP and DBP after 2-week treatment (-20,9±10,1 mm Hg; pConclusion. Despite the limitations inherent in observational studies, the KONSONANS program has demonstrated high efficacy and safety of fixed-dose combination of ramipril/indapamide taken once a day in hypertensive patients. Ramipril/indapamide fixed-dose combination therapy significantly improved BP control and achieved even lower individual target BP levels in the majority of hypertensive patients

The Role of Red Yeast Rice Based Preparations for Non-Pharmacological Correction of Dyslipidemia in Patients with Low and Moderate Cardiovascular Risk (Expert Opinion)

The Russian Federation is among countries with high cardiovascular risk. Hypercholesterolemia is a leading risk factor for the development of atherosclerotic cardiovascular diseases. To achieve low-density lipoprotein cholesterol (LDL-C) targets, such approaches as lifestyle changes and pharmacological correction, based on the use of statins, are applied. At the same time, a significant proportion of the population has moderate hypercholesterolemia and is characterized by low or moderate cardiovascular risk. Although first-line recommendations should be followed, a healthy lifestyle alone is not enough to achieve target levels of LDL-C, which means that even people with low to moderate risk may end up with the prospect of lifelong therapy with lipid-lowering drugs. These individuals do not have an indication for lipid-lowering therapy, and they are usually recommended a change in diet and supplementation. Innovative nutritional strategies have been developed to manage dyslipidemia. They were based either on changing some "risky" food components or on encouraging the consumption of "healthy" functional foods and/or nutraceuticals. Nutraceuticals (registered as food supplements in Russia) is an innovative way to help control LDL-C at low and moderate risk individuals without lipid-lowering drugs and as nutritive support for the cholesterol-lowering diet. Red yeast rice (RYR) based preparations have been already developed and available at the moment. RYR based preparations can be considered in patients with low and moderate cardiovascular risk, who have not reached the target level of LDL-C and have no indications for statin therapy or have statin intolerance. RYR based preparations contains a statin-like substance monacolin K in a dose of 3 mg. In randomized clinical trials, it was proved that the use of high-quality RYR nutraceutical leads to a decrease in LDL-C by an average of 20% without increasing the risk of side effects like for statins. Evaluation of dietary supplements and functional foods should necessarily include not only evidence of beneficial effects with respect to effects on the lipid profile and atherosclerosis, but also proven good tolerability. The manufacturing standard for these products is also important, guaranteeing component standardization and quality. RYR analogues should guarantee the absence of mycotoxin in their composition. In Russia, programs are needed for the primary prevention of atherosclerotic cardiovascular diseases with effects on hypercholesterolemia at the population level

Research of hemodynamic in visceral branches of the abdominal aorta in patients with nonalcoholic fatty liver disease

Aim. Rate particular regional hemodynamics in unpaired visceral branches of the abdominal aorta in patients with nonalcoholic fatty liver disease (NAFLD), depending on the severity of liver fibrosis, established by circumstantial laboratory markers. Materials and Methods. The study included 53 patients of both sexes, older than 50 years. The first group consisted of 17 people with NAFLD and liver fibrosis, established by Forns - index and the value of more than 6.9. The second group included 36 people with the value Forns - index less than 6.9. The examination included the study of clinical and anamnestic parameters, evaluation of laboratory parameters, instrumental examination of the gastrointestinal tract. Biochemical parameters of the study completed hyperlipidemia. All patients underwent transabdominal duplex scanning unpaired visceral branches of the abdominal aorta, will allow to estimate blood flow velocity parameters and calculate the shear rate. Results. Patients in both groups were matched for age and sex. When analyzing the structure of comorbid diseases of the digestive tract in patients with hepatic fibrosis in NAFLD, the most frequently detected Chronic Biliary pancreatitis. The study of lipid metabolism, showed significantly lower cholesterol levels in patients with NAFLD and Forns index of more than 6.9, with a peak performance speed of blood flow and shear rate in the splenic artery were significantly lower in this group of patients. Conclusion. Patients with nonalcoholic fatty liver disease and hepatic fibrosis, established by indirect laboratory markers (Forns-index) did not differ in age and gender composition and comorbid diseases from patients without liver fibrosis. The low shear rate in the splenic artery in patients with hepatic fibrosis steatosis suggests developing a violation of local splanchnic hemodynamics in the pool against the backdrop of liver fibrosis and can then be used as one of the proxy indicators that reflect morphological changes in the liver.Цель. Оценить особенности региональной гемодинамики в непарных висцеральных ветвях брюшной аорты у пациентов с неалкогольной жировой болезнью печени (НАЖБП) в зависимости от выраженности фиброза печени. Материалы и методы. В исследование включены 53 пациента обоего пола старше 50 лет. Первую группу составляли 17 человек с НАЖБП и фиброзом печени, установленным по Forns - индексу и значением более 6,9. Во вторую группу вошли 36 человек со значением Forns - индекс менее 6,9. Обследование включало изучение клинико-анамнестических параметров, оценку лабораторных показателей, инструментальное исследование желудочно-кишечного тракта. Биохимическое исследование дополнено изучением параметров липидемии. Всем пациентам выполнено трансабдоминальное дуплексное сканирование непарных висцеральных ветвей брюшной аорты, позволившее оценить скоростные параметры кровотока и рассчитать скорости сдвига. Результаты. Больные обеих групп были сопоставимы по полу и возрасту. При анализе структуры коморбидной патологии пищеварительного тракта у пациентов, страдающих фиброзом печени на фоне НАЖБП, наиболее часто выявлялся хронический билиарнозависимый панкреатит. Исследование липидного обмена, выявило достоверно более низкий уровень холестерина у пациентов с НАЖБП и индексом Forns более 6,9. При этом показатели пиковой скорости кровотока и скорость сдвига в селезеночной артерии были достоверно ниже у данной группы пациентов. Выводы. Пациенты с неалкогольной жировой болезнью печени и фиброзом печени, установленным по косвенному лабораторному маркеру (Forns-индекс), не отличались по возрастно-гендерному составу и коморбидным заболеваниям от пациентов без фиброза печени. Низкая скорость сдвига в селезеночной артерии у пациентов с фиброзом печени на фоне жирового гепатоза свидетельствует о развивающемся нарушении локальной гемодинамики в спланхническом бассейне на фоне фиброза печени и может в дальнейшем использоваться как один из косвенных показателей, отражающих морфологические изменения в печени

Эхогенность каротидных атеросклеротических бляшек как предиктор неблагоприятных сердечно-сосудистых событий у пациентов 40–64 лет: проспективное исследование

INTRODUCTION: Noninvasive assessment of carotid atherosclerotic plaque (CAP) morphology represents a promising direction, allowing to optimize not only cardiovascular event risk assessment, but also the selection of patients for carotid revascularization. Determination of CAP echogenicity by means of GSM-analysis can be used as part of multiparametric assessment of CAP instability and prediction of adverse cardiovascular events.OBJECTIVE: To assess the predictive value of echogenicity of carotid atherosclerotic plaques in relation to the development of adverse cardiovascular events in patients 40–64 years old.MATERIALS AND METHODS: The study included 191 patients with carotid atherosclerosis aged 40–64 years. All patients underwent duplex scanning of the arteries of the carotid basin with determination of the echogenicity of carotid ASBs. The combined end point (CEP) consisted of the following possible events: nonfatal myocardial infarction or unstable angina, nonfatal stroke, coronary revascularization or peripheral artery revascularization, and death from cardiovascular causes. Data on the onset of CVD were collected during follow-up visits and using medical information systems. Statistics: Data were analyzed using MedCalc software (version 20.216). Frequencies and percentages were used to describe nominal data, and medians and quartiles were used for quantitative data. The Kaplan-Meier survival analysis method was used to estimate the probability of events constituting the combined endpoint. Cox regression analysis was used to estimate the risk of the event and the influence of independent variables on the risk.RESULTS: By correlation analysis, carotid AP echogenicity (GSM) was inversely correlated with BMI (r=-0,355; p<0,0001), waist circumference (r=-0.37; p<0.0001), triglyceride levels (r=-0.163; p=0.027), uric acid (r=-0.188; p=0.028). The duration of the follow-up period was 15.1 (12.2; 22.9) months. Events constituting CEP occurred in 15 (7.85%) patients: nonfatal myocardial infarction in 2 (1.05%) patients, nonfatal stroke in 2 (1.05%) patients, myocardial revascularization in 6 (3.14%) patients, unstable angina in 5 (2.61%) patients. The presence of carotid AP with echogenicity ≤39 conventional units allowed predicting the development of events constituting CEP with sensitivity of 53.3% and specificity of 80.7%. Kaplan-Meier survivalanalysis revealed that cumulative survival of patients with carotid AP with echogenicity ≤39 conventional units was statistically significantly lower compared to patients with carotid ASB with echogenicity >39 conventional units.DISCUSSION: It should be noted that in the presented study, decreased echogenicity of carotid AP was associated with the risk of adverse cardiovascular events only in the simple and sex- and age-adjusted models, but not in the full-adjusted model. It is likely that this may be due to the fact that the echogenicity of CAP is closely related to the cumulative burden of cardiovascular risk factors, which has been shown in earlier studies including. Probably, combined assessment of carotid atherosclerosis burden and morphological features of CAP may be the most promising approach to obtain additional prognostic information in patients with carotid atherosclerosis.CONCLUSION: Among patients with carotid atherosclerosis 40–64 years old, the presence of ACS with echogenicity ≤39 conventional units was associated with a 3.44 (95% CI 1.19–9.91) fold increase in the relative risk of events constituting the combined endpoint after adjusting for sex and age.ВВЕДЕНИЕ: Неинвазивная оценка морфологии каротидных атеросклеротических бляшек (АСБ) представляет собой перспективное направление, позволяющее оптимизировать не только оценку риска сердечно-сосудистых событий, но и отбор пациентов для реваскуляризации сонных артерий. Определение эхогенности АСБ посредством GSM-анализа может быть использовано в рамках мультипараметрической оценки нестабильности АСБ и прогнозирования неблагоприятных сердечно-сосудистых событий.ЦЕЛЬ: Оценить предиктивную ценность эхогенности каротидных атеросклеротических бляшек в  отношении развития неблагоприятных сердечно-сосудистых событий у пациентов 40–64 лет.МАТЕРИАЛЫ И  МЕТОДЫ: В  исследование был включен 191 пациент с  каротидным атеросклерозом в  возрасте 40–64 лет. Всем пациентам проводили дуплексное сканирование артерий каротидного бассейна с определением эхогенности каротидных АСБ. Комбинированная конечная точка (ККТ) состояла из  следующих возможных событий: нефатальный инфаркт миокарда или нестабильная стенокардия, нефатальный инсульт, коронарную реваскуляризацию или реваскуляризацию периферических артерий, смерть от сердечно-сосудистых причин. Сбор данных о наступлении ККТ, проводили во время повторных визитов и с помощью медицинских информационных систем.Статистика: Анализ данных проводили с помощью программного обеспечения MedCalc (версия 20.216). Для описания номинальных данных использовали частоты и проценты, для количественных данных медиану и квартили. Для оценки вероятности развития событий, составляющих комбинированную конечную точку, применяли метод анализа выживаемости Каплана–Майера. С целью оценки риска наступления события и влияния независимых переменных на указанный риск применяли регрессионный анализ Кокса.РЕЗУЛЬТАТЫ: По результатам корреляционного анализа эхогенность каротидных АСБ (GSM) обратно коррелировала с ИМТ (r=–0,355; p<0,0001), окружностью талии (r=–0,337; p<0,0001), уровнем триглицеридов (r=–0,163; p=0,027), мочевой кислотой (r=–0,188; p=0,028). Длительность периода наблюдения составляла 15,1 (12,2; 22,9) мес. События, составляющие ККТ, произошли у 15 (7,85%) пациентов: нефатальный инфаркт миокарда — у 2 (1,05%) пациентов, нефатальный инсульт — у 2 (1,05%), реваскуляризация миокарда — у 6 (3,14%), нестабильная стенокардия — у 5 (2,61%) пациентов. Наличие каротидных АСБ с эхогенностью ≤39 усл.ед. позволяло прогнозировать развитие событий, составляющих ККТ, с чувствительностью 53,3% и специфичностью 80,7%. По результатам анализа выживаемости Каплана–Мейера было установлено, что кумулятивная выживаемость пациентов, имеющих каротидные АСБ с  эхогенностью ≤39 усл.ед., была статистически значимо ниже, в сравнении с пациентами, имеющими каротидные АСБ с эхогенностью >39 усл.ед.ОБСУЖДЕНИЕ: Необходимо отметить, что в представленном исследовании снижение эхогенности каротидных АСБ было связано с  риском неблагоприятных сердечно-сосудистых событий только в  простой модели и  модели с  поправкой на  пол и возраст, но не в модели с полной поправкой. Вероятно, это может быть связано с тем, что эхогенность АСБ тесно связана с кумулятивным бременем кардиоваскулярных факторов риска, что было показано в том числе в более ранних исследованиях. Вероятно, комбинированная оценка бремени каротидного атеросклероза и морфологических особенностей АСБ может быть наиболее перспективным подходом к получению дополнительной прогностической информации у пациентов с каротидным атеросклерозом.ЗАКЛЮЧЕНИЕ: Среди пациентов с каротидным атеросклерозом 40–64 лет наличие АСБ с эхогенностью ≤39 усл. ед. ассоциировалось с  увеличением относительного риска развития событий, составляющих комбинированную конечную точку в 3,44 (95% ДИ 1,19–9,91) раза после поправки на пол и возраст