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Despite a variety of lipid-lowering drugs, mostly pelleted, aimed at reducing low-density lipoprotein cholesterol and triglycerides, only a small number of patients achieve their target levels. The reasons are insufficient adherence to treatment, rare use of combined lipid-lowering therapy regimens by attending physicians, low availability and high cost of injected lipid-lowering agents. With the advent of technologies for targeted therapy for hyperlipidemia, a new era in cardiology opens. These innovations will lead to higher goal achievement rates through a personalized and precision approach to hyperlipidemia treatment. Novel lipid-lowering drugs are directed at the molecular targets of hypercholesterolemia, hyperlipoproteinemia(a) and hypertriglyceridemia. The review purpose is to systematize following information about innovative lipid-lowering drugs: mechanism of action, stage of development, effectiveness and safety.

The federal program of preferential drug provision in cardiology shows its effectiveness. However, hypercholesterolemia (HCH) remains a significant problem in patients in whom high-dose statin therapy does not provide the target level of low-density lipoprotein cholesterol (LDL cholesterol). The solution to the problem lies in the plane of prescribing lipid-lowering drugs of a different mechanism of action, for example, inhibitors of the PCSK9 enzyme. To recommend the inclusion of such kind drugs in the program, it is necessary not only to have evidence of their life-saving effect, but also the economic feasibility of their use. Aim: to evaluate the economic efficacy of alirocumab (INN) including in the federal program for patients who have suffered an acute coronary event, are receiving statins and have an LDL CH level of 5.0 mmol/l and higher.Materials and methods. Modeling was applied in a target group of 3029 patients of working age who had undergone ACS during the previous 12 months with severe, including familial, HCH, with LDL cholesterol 5.0 mmol/l and higher, receiving statins taking into account previously determined outcomes when using alirocumab + statins for 5 years. Direct medical and non-medical costs, as well as indirect costs, are identified. The cost-effectiveness analysis was applied from the point of view of the effectiveness of treatment (effects on mortality, temporary disability, disability) and direct health care costs (additional drug provision and outpatient follow-up, specialized, including high-tech, medical care in a 24‑hour hospital). Two healthcare technologies were compared: statin therapy and use of alirocumab + statins. The calculations used according to domestic methods used the cost of medical treatment, temporary disability, hospitalizations, loss of GDP and other parameters.Results. Modeling has shown a decrease in mortality, morbidity and disability when using alirocumab in even the first year of use. The economic effect of alirocumab from a decrease in temporary disability in the 1st year is 304.5 mln rub., in the 2nd — 301.5 mln rub., in the 3rd — 321.1 mln rub., in the 4th — 333.1 mln rub. The estimated amount of prevented GDP losses from mortality in the target group for 4 years in the case of alirocumab use amounted to 1,260.2 mln rub. The annual amount of avoidable GDP losses from mortality in the target group in the case of alirocumab is 27–30 %. The annual average savings per patient in the case of alirocumab use are from 7 to 17 %. The greatest impact on reducing losses from disability and mortality of the target group is noted in the group of people aged 40–59 years. Only for this group, if alirocumab is used, it is possible to reduce losses from disability and mortality by 159.2 million rubles per year (83 % of the total economic effect). Starting from the 4th year of alirocumab use, it is possible to obtain a positive economic effect in terms of hospitalization costs.Conclusion. When alirocumab is included in the program of additional drug provision in cardiology, the share of costs for the purchase of alirocumab for the target group may be only 0.01 %. At the same time, the economic effect of inclusion in the first year alone will amount to at least 393.4 million rubles of budget funds. The total amount of avoidable losses due to the alirocumab usage may amount to 1,638 million rubles over 4 years.

The novelty of the 2023 National Guidelines for Lipid Metabolism Disorders is presented regarding the categorization of cardiovascular risk, target and optimal levels of blood lipids, diagnosis and therapeutic approaches to the treatment of dyslipidemia.

Aim. To study the frequency of prescriptions of various types of lipid-lowering therapy and their effectiveness in outpatient clinical practice based on the results of a questionnaire of primary care physicians.Material and methods. The study was performed in 2022 in 75 constituent entities of the Russian Federation with the participation of 1117 doctors working in outpatient clinics. Most of the doctors had work experience of 10-20 years or more. Doctors of polyclinics (therapists and cardiologists, etc.) before the start of the study received instructions, questionnaires for filling out, developed by the National Atherosclerosis Society. The frequency of prescriptions by primary care physicians of various types of lipid-lowering therapy and their effectiveness in terms of the frequency of achieving target levels of low-density lipoprotein cholesterol (LDL-C) was studied based on the results of a questionnaire.Results. Monotherapy with statins was prescribed in 55.2% of cases, free combination of rosuvastatin with ezetimibe – in 17.2%, single pill combination of rosuvastatin with ezetimibe – in 23.2%, combination therapy with PCSK9 inhibitors – in 4.1% of cases. Target levels of LDL-C ˂ 1.8 mmol/l and ˂ 1.4 mmol/l were achieved with statin monotherapy in 42.6% and 28.2% of cases, respectively, free combination of rosuvastatin with ezetimibe – in 61.7% and 39 .5%, a fixed combination of rosuvastatin with ezetimibe – in 67.8% and 48.5%, combination therapy with PCSK9 inhibitors – in 96.8% and 92.8% of cases.Conclusion. The single pill combination of rosuvastatin with ezetimibe is more effective in achieving target levels of LDL-C compared with statin monotherapy and therapy with free combination of statin with ezetimibe. Despite the fact that the target values of LDL-C when prescribing a combination with PCSK9 inhibitors were achieved in 96.8% and 92.8% of cases, they were used quite rarely at the outpatient stage of treatment in the Russian Federation.

The Russian Society of Cardiology (RKO)With the participation of: The National Society for the Study of Atherosclerosis (NOA), the Russian Association of Endocrinologists (RAE), the Russian Society of Cardiosomatic Rehabilitation and Secondary Prevention (RosOKR), the Russian Scientific Medical Society of Therapists (RNMOT), the Eurasian Association of Cardiologists, the Eurasian Association of Therapists (EAT), the Russian Association of Gerontologists and Geriatricians

On July 6, 2022, an interdisciplinary meeting of the Expert Council was held on the topic "Control of dyslipidemia in the prevention of acute and recurrent ischemic cerebrovascular accidents". The conclusion of the Expert Council was that after verification of a lipid metabolism abnormality, in patients with ischemic stroke (IS) and transient ischemic attack (TIA) it is recommended to start or continue statin therapy as early as possible. For secondary prevention of IS, it is necessary to achieve the target level of low-density lipoprotein cholesterol (LDL-C) set for each category of cardiovascular risk, with consistent administration of the maximum tolerated dose of statins with biochemical monitoring of the effectiveness and safety of therapy in the interval of 4–12 weeks. The insufficient effectiveness of statins requires the inclusion of ezetimibe therapy and the decision to increase the dose of statins; in case of intolerance to statins and / or contraindications to their administration, early administration of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors: evolocumab, alirocumab – or an PCSK9 synthesis inhibitor, inclisiran, should be considered. At a LDL-C level of >5.0 mmol/l in patients of the extreme or very high risk group who have had atherothrombotic IS / TIA, necessary administration of a combination including a statin, ezetimibe and an PCSK9 inhibitor (evolocumab, alirocumab) or a PCSK9 synthesis inhibitor (inclisiran) should be considered as early as possible.

The COVID-19 (COronaVIrus Disease 2019) pandemic caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2) continues to be a global threat to people and health systems. As of March 21, 2022, there are more than 460 million cases and more than 6 million deaths worldwide, and more than 17 million and 360,000 respectively in the Russian Federation. Due to the rapid spread of the new coronavirus infection, since the beginning of the pandemic, tremendous efforts have been made to create new pharmacological agents to reduce morbidity and mortality, and tactics have been used to repurpose existing medications in treatment regimens for patients with COVID-19, particularly statins. Statins represent one of the most widely used and prescribed classes of drugs in the world. The hypolipidemic properties of statins are actively used to treat hyperlipidemia and primary and secondary prevention of cardiovascular diseases and their complications. Statins have a known safety profile, are inexpensive and accessible. In addition to their hypolipidemic effects, statins have a wide range of pleiotropic anti-inflammatory, antiviral, and antithrombotic effects potentially useful in the treatment of COVID-19. Presumably, the use of statins can reduce SARS-CoV-2-induced organ and tissue damage and improve lung function. The use of statins, particularly atorvastatin, as one of the most effective, widely prescribed and studied drugs in this class, as a safe, affordable and relatively inexpensive therapy may be a promising therapeutic approach in the fight against a new coronavirus infection.

The existing system of medical care for patients with acute cerebrovascular accident of atherothrombotic genesis, namely lipid metabolism disorders, the modern evidence base for lipid-lowering therapy in this category of patients and the feasibility of interdisciplinary interaction of cardiologists and neurologists were discussed at a meeting of the expert council of cardiologists and neurologists in Moscow on 2021 July 7.

According to the latest international and Russian guidelines for the treatment of dyslipidemias, statins are defined as the main group of drugs that significantly reduce the level of low-density lipoprotein cholesterol (LDL-C) effectively prevent atherosclerotic cardiovascular diseases (CVD) and complications and can slow down the progression of atherosclerosis. The principle “the lower LDL-C, the better” is especially relevant in categories of patients with very high and extreme cardiovascular risk, and therefore, in order to achieve target LDL-C values (≤1.4 is optimal ≤1.0) in this category of patients, high-intensity lipid-lowering therapy should be used. Rosuvastatin remains the most effective statin. Its use makes possible to achieve target lipid values at the starting dose of treatment, enhances adherence to treatment, and also reduces the frequency of side effects associated with the use of high doses of other statins. In addition, the proven ability of rosuvastatin to reduce the volume of atherosclerotic plaque, by reducing the level of pro-inflammatory cytokines and C-reactive protein, normalizing endothelial function, antiplatelet action, that is, rosuvastatin, in addition to its powerful lipid-lowering effect, has anti-inflammatory and anti-ischemic effects. Also, rosuvastatin can be successfully used in the presence of comorbidities, including chronic kidney disease and chronic heart failure. Taking into consideration the urgency of the fight against the COVID-19 pandemic (coronavirus Disease 2019), which covered 220 countries, due to the lack of effective etiotropic drugs, the possibility of using statins, including rosuvastatin, for the treatment of comorbid patients with COVID-19, was evaluated.

Стандартные протоколы ультразвукового исследования включают исследования всех сосудов анализируемой области, во всех режимах сканирования, с полным набором измерений, и требуют высокой квалификации специалистов и больших временных затрат. Однако для ряда клинических задач достаточно выполнения фокусированного протокола ультразвукового исследования, т.е. ориентированного на решение конкретной проблемы и, следовательно, сокращенного по времени, тем самым позволяющего увеличить число обследуемых. Оценка сердечно-сосудистого риска с помощью выявления атеросклеротических бляшек в сонных и бедренных артериях, скрининг на наличие аневризмы аорты, выявление проксимального тромбоза глубоких вен нижних конечностей – это те направления в медицине, где фокусированные протоколы ультразвукового исследования могут повысить долю обследуемых и способствовать своевременной диагностике и профилактике заболеваний. Доступность фокусированного ультразвукового исследования и развитие образовательных структур позволят расширить круг специалистов, способных выполнять подобные исследования (кардиологи, терапевты, врачи общей практики, сосудистые хирурги). Сегодня существует много вопросов по организации проведения фокусированных протоколов в клинической практике. Данный консенсусный документ направлен на повышение информированности широкого круга специалистов о задачах, принципах проведения и применении фокусированного УЗИ.

Aim. To evaluate the prevalence of familial hypercholesterolemia (FH) and hyperlipoproteinemia(a) (HLP(a)) in patients with premature acute coronary syndrome (ACS).Material and methods. The study included 120 patients with ACS up to 60 years (mean age, 53±7 years, 104 (87%) men) and 44 people from the comparison group without atherosclerotic cardiovascular diseases and dyslipidemia (mean age, 48±11 years, 19 (43%) men). All patients with ACS underwent coronary angiography. The lipid profile and lipoprotein(a) (Lp(a)) were determined in all patients.Results. The prevalence of HLP(a) in patients with premature manifestation of ACS was 41% (n=49), possible FH — 25% (n=30), combination of FH and HLP(a) — 13% (n=15). In the comparison group, an increased concentration of Lp(a) was detected in 14% (n=6). Based on the analysis of operating characteristic curves, Lp(a) ≥30 mg/dL had the maximum significance for ACS with a sensitivity of 40% and a specificity of 86% (area under the curve, 0,6; 95% confidence interval (CI), 0,5-0,7, p15 mg/dl was associated with two or more coronary artery lesions with a sensitivity of 67% and a specificity of 65% (area under the curve, 0,7; 95% CI, 0,6-0,7, p

Aim. To assess the relationship between premature coronary artery disease (CAD) and various lipid parameters.Material and methods. This retrospective longitudinal study included 166 men aged 57±9 years with coronary CAD with onset before age of 55. The control group consisted of 62 men (60±8 years old) who did not have CAD and peripheral arterial disease. In all patients, data on following lipid profile parameters were collected: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) and lipoprotein(a) (Lp(a)) at the time of CAD onset, while in control group patients — at the first visit to the A.L. Myasnikov Institute of Clinical Cardiology. These indicators were measured in blood plasma at the time of enrollment in all patients. In addition, the concentration of LDL-C corrected for Lp(a)-cholesterol (LDL-Ccorr) was calculated. Hypercholesterolemia was diagnosed with an initial level of TC >5 mmol/l, or LDL-C ≥3,0 mmol/l, or non-HDL-C ≥3,8 mmol/l, while hyperlipoproteinemia(a) (HLP(a)) — at the level of Lp(a) ≥30 mg/dl.Results. Lipid metabolism disorders were significantly more common in patients with premature CAD compared to the control group. Lp(a) concentration ≥30 mg/dl, along with elevated levels of non-HDL-C or LDL-Ccorr, were associated with premature CAD, regardless of heredity and smoking, in the general cohort of examined men. Kaplan-Meier survival analysis showed that any type of lipid metabolism disorder was associated with an increased risk of premature CAD. In addition, patients with isolated elevated Lp(a) concentrations lived to the CAD onset 8 years earlier — 47 vs 55 years, p

Aim. To analyze the relationship of blood lipid profile parameters, including the level of lipoprotein(a) (Lp(a)), and the content of circulating CD4+ T-lymphocytes with premature coronary artery disease (CAD).Material and methods. This retrospective cross-sectional study included 76 men aged 40 to 79 years. Patients were divided into following groups: main group — patients with CAD (58 [54;64] years, n=56) onset before the age of 55; control group — patients (62 [57;66] years, n=20) without CAD and obstructive CAD and peripheral arterial disease. Statins were taken by 51 (91%) and 9 (45%) patients in the main and control groups, respectively. In serum and plasma samples, lipid spectrum parameters and Lp(a) concentration were determined. Cellular phenotyping was performed by direct immunofluorescence in a culture of mononuclear leukocytes isolated from blood. To determine cytokines, cells were in vitro activated with inhibitor of intracellular transport of secretory proteins. Cell fluorescence was determined using flow cytometry.Results. Patients of both groups were comparable in age, body mass index, prevalence of hypertension and diabetes. Blood Lp(a) concentrations were higher in the CAD group than in the control group (49 [10;102] mg/dL vs 12 [4,3;32] mg/ dL, p14% of Th17) independently of each other, atherogenic lipoprotein cholesterol levels, classical risk factors, and statin use were associated with premature CAD in the general group of patients with odds ratio (OR) of 4,6 (95% confidence interval (CI), 1,1-20,2) and 10,9 (2,1-56,7), p30 mg/dl and Th17/1 over 14% significantly increased the risk of premature CAD (OR, 28,0, 95% CI, 4,31-181,75, p=0,0005).Conclusion. We have shown for the first time that an increased Lp(a) concentration with an increased Th17/1 content is associated with the premature CAD in men.

The EAC Guidelines represent the views of the EAC, and were produced after careful consideration of the scientific and medical knowledge, and the evidence available at the time of their publication. The EAC is not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the EAC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the EAC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic, or therapeutic medical strategies; however, the EAC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient’s health condition and in consultation with that patient and, where appropriate and/or necessary, the patient’s caregiver. Nor do the EAC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient’s case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

The meeting of the expert council of cardiologists-lipidologists, organized with the support of Novartis and dedicated to the discussion of the existing system of medical care for patients with familial hypercholesterolemia / mixed dyslipidemia, the modern evidence base for lipid-lowering therapy and the practical value of the strategy of early combined lipid-lowering therapy for doctors and these categories of patients was held in Moscow on November 11, 2020.

Mortality from cardiovascular diseases (CVD) in Russian Federation (RF) remains one of the highest in the world. Compared to 2003, the mortality from CVD decreased by 37%, but when compared with most European countries, it is 3 times higher. Most deaths (53%) occur due to coronary heart disease. While analyzing reasons of mortality, total economic impact due to hypercholesterolemia in RF is estimated as 1,3 trillion RUR annually. The prevalence of hypercholesterolemia is in more than 50% of working-age population in RF. Due to AISBERG study, the prevalence of HCE in ambulatory practice in RF is 84%. When using lipid-lowering medications, the frequency of reaching of target total cholesterol level does not exceed 12%. Active actions on primary and secondary prevention are needed to low mortality rate from CVD, including active promoting of healthy lifestyle, and prescribing if necessary of lipid-lowering therapy (LLT) regimens. The paper deals with significance of target low density lipoprotein cholesterol level in accordance with the latest recommendations as the main aim for LLT. Combined LLT with one of the most potent statins rosuvastatin and ezetimibe seems to be effective and safe strategy for achieving target lipid level in different populations of patients. At present, Rosulip Plus is available in Russia - an quantitative and proven combination of rosuvastatin and ezetimibe.

Disclaimer РThe EAC/RNAS Guidelines represent the views of the EAC and RNAS, and were produced after careful consideration of the scientific and medical knowledge, and the evidence available at the time of their publication. The EAC and RNAS is not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the EAC/RNAS Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the EAC/RNAS Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic, or therapeutic medical strategies; however, the EAC/RNAS Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient’s health condition and in consultation with that patient and, where appropriate and/or necessary, the patient’s caregiver. Nor do the EAC/RNAS Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient’s case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.Members of the Working Group confirmed the lack of financial support / conflict of interest. In the event of a conflict of interest being reported, the member (s) of the Working Group was (were) excluded from the discussion of sections related to the area of conflict of interest.

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.

By the middle of 2021, the official global number of coronavirus disease 2019 (COVID-19) patients was close to 230 million, but the number accounting for asymptomatic patients was much higher. Consequences and rehabilitation after COVID-19 are of particular interest and raise many controversial and unresolved issues. On May 18, 2021, the Eurasian Association of Therapists organized an international panel of experts to analyze challenges associated with the post-COVID-19 period. This panel aimed to develop approaches to identify gaps in the discussed issues. This interdisciplinary team of leading experts reviewed the current literature and presented their data to formulate practical guidance on management of patients after COVID-19. The panel of experts also presented recommendations on how to implement the gained knowledge into health care practices.

Project of the Russian National Atherosclerosis SocietyIn 2016, Guidelines on the medical care organization to the patients with hereditary atherogenic lipid disorders in the regions of Russia were published, which described and presented the principles of routing patients with hereditary dyslipidemia and the organization of medical care for them within the current regulatory documents. In December 2018, the Russian Ministry of Health approved clinical guidelines for the diagnosis and treatment of familial hypercholesterolemia. Thus, persons with a severe hereditary dyslipidemia were able to get free medication with expensive lipid-lowering drugs and receive apheresis. Following the European ones, the Russian guidelines on the management of lipid metabolism disorders were updated: lower target low density lipoprotein cholesterol levels were adopted. In the Russian population, there is a high prevalence of hypercholesterolemia, including familial monogenic and polygenic types. Therefore, timely detection and routing to a lipid center or an office to a specialist (cardiologist, lipidologist), adequate and modern prescription of lipid-lowering therapy will make an important contribution not only to secondary, but also to primary prevention of atherosclerotic cardiovascular complications.

Experimental and clinical data indicate a significant contribution of lipoprotein(a) (Lp[a]) to the atherogenesis. However, the pathophysiological mechanisms of this relationship are not fully understood.Aim. To investigate the distribution of Lp(a) in the population of the regions participating in the Study “Epidemiology of Cardiovascular Diseases in the Regions of the Russian Federation” (ESSE-RF) and to evaluate its associations with cardiovascular risk factors.Material and methods. Representative samples of the male and female population of 7 regions of the Russian Federation, aged from 25 to 64 years, enrolled in the multi-center cross-sectional epidemiological study were analyzed. A total of 10332 people were examined, of whom 3732 were men (36.0%) and 6600 were women (64.0%), the average age was equal in both sexes.Results. The mean value of Lp(a) reached 22.4 mg/dl (standard deviation 21.3 mg/dl) and significantly differed from the median (11.1 mg/dl; interquartile range from 3.9 to 20.2 mg/dl), forming the right-skewed distribution in both male and female population. Lp(a) levels were statistically significantly correlated with the level of low-density lipoproteins cholesterol (LDL-C), ароВ/аpoAI and total cholesterol. Notably, the odds ratios were growing by quintiles, and increased along with increasing lipid values (p

The scientific basis of the selection algorithms for the management of patients with hypertension and hypercholesterolemia is presented in article. The advantages and limitations of current recommendations on the management of patients with hypercholesterolemia, which were presented by American and European experts, are discussed. Data on the narrow-mindedness of use of risk assessment scales for the development of cardiovascular complications for primary prevention in a wide population are presented. The question of the ratio of proven facts and expert opinions in clinical recommendations, as well as the validity of a flexible approach to the choice of tactics for a specific patient, considering the most acceptable approaches presented in different clinical recommendations, is being considered. The validity of recommendations for achieving lower concentrations of lowdensity lipoprotein cholesterol in patients with high and very high cardiovascular risk is discussed. The difficult problem of choosing target blood pressure levels in patients with hypertension and with some characteristics or concomitant diseases and/or risk factors is discussed. The evidence base of modern drugs for preventing the development of cardiovascular complications and/or treating patients with such complications is discussed, including new data on the benefits of longer treatment with atorvastatin for the primary prevention of cardiovascular complications in patients with hypertension are discussed. Data on the problems of the choice of drugs used for the primary or secondary prevention of cardiovascular complications in patients with hypertension and hypercholesterolemia are presented.

Tactics for the management of patients with hypertriglyceridemia (HTG) is provided in the conclusion of the Advisory Board. It is demonstrated that HTG is quite prevalent in patients with excessive body weight and is an important component of residual risk. HTG creates additional conditions for the progression of atherosclerosis, and thus it is recommended to test triglyceride in patients with high, very high and extremely high cardiovascular risk. The indication for the pharmacological treatment to reduce the triglycerides concentration is their level more than 2.3 mmol/l. Statins are drugs of choice aimed to decrease the cardiovascular risk in patients with hypercholesterinemia and HTG. Fenofibrate is used to correct HTG; in case of its intolerance or if the triglyceride target level is not reached, ethyl esters of omega-3 polyunsaturated fatty acid can be used in the dosage of 2-4 g daily. In patients with triglyceride level higher than 5.6 mmol/l, fenofibrate is the main option of treatment.

These guidelines represent all current aspects of etiology, diagnosis, and treatment of the clinical and statistical group of familial hypercholesterolemia in both adults and children in accordance with the requirements of the Ministry of Health of Russia.

Aim. To study the relationship between the concentration of lipoprotein (a) (Lp (a)) and autotaxin (ATX) in patients with and without degenerative aortic valve stenosis (AoS) in the presence of coronary artery disease (CAD).Material and methods. The study included 461 patients (mean age, 66±11 years, men, 323), 354 of whom had CAD with stenosis ≥50% in at least one coronary artery according to angiography. Degenerative AoS was diagnosed with ultrasound. The control group consisted of 107 patients without CAD and degenerative AoS. Concentrations of Lp (a), ATX, lipids and blood cells were measured for all patients.Results. CAD without degenerative AoS (group 1) was diagnosed in 307 patients, while 47 patients had CAD and degenerative AoS (group 2). Patients in both groups were older than patients in the control group (66±10, 74±8, and 61±13 years, respectively). The ATX level was lower in group 1 (median [25; 75%]: 495 [406; 583] ng/ml) than in the control group (545 [412; 654] ng/ml) or group 2 (545 [476; 605] ng/ml) (p

Familial hypercholesterolemia is the most common hereditary disease characterized by an increase in low density lipoprotein cholesterol levels and the premature development of atherosclerosis-related cardiovascular diseases. Diagnosis and treatment of such patients are associated with certain difficulties. This review presents data on the prevalence of familial hypercholesterolemia, identification of patients with such a diagnosis, prevention of adverse cardiovascular events, and also discusses the appointment of lipid-lowering therapy.

Purpose: To investigate the state of blood flow in eye vessels and brachiocephalic arteries (BCA) in patients with arterial hypertension (AH) of stages 1 and 2 and subclinical atherosclerosis (SA) using modern methods of vessel imaging. Material and methods. Doppler ultrasound methods of investigation of retrobulbar vessels and caliber measurements of eye fundus vessels were used to examine 115 patients (230 eyes) aged 40-60 (averagely 48.7 ± 7.3 yrs) with mild hypertension and subclinical atherosclerosis, for whom the parameters of choroidal and retinal circulation were determined. Results.The maximum systolic velocity of blood flow in retrobulbar vessels were found to agree with the age norm in SA while the index of peripheral vascular resistance parameters in the system of retinal and choroidal circulation exceeds the norm. In stages 1 and 2 of AH, we detected increased peripheral resistance index in the short posterior ciliary arteries and reduced caliber of retinal arteries with no significant change of retinal venular caliber. In patients with combined pathology, the changes were more pronounced. Conclusions. Ultrasound duplex scanning of BCA helps diagnose early signs of the atherosclerotic process and vascular deformations (hypertonic macroangiopathy), which testify to the need for ocular blood flow monitoring in patients with stages 1 and 2 of AH and SA // Russian Ophthalmological Journal, 2016; 3: 26-33. doi: 10.21516/2072-0076-2016-9-3-25-33.

Aim. To investigate on the relation of lipoproteide(a) (Lpa), subfractions of atherogenic lipoproteides and titers of specific autoantibodies (autoAb) with the presence and severity of carotid arteries (CA) lesion in statin-naïve patients with severe hypercholesterolemia.Material and methods. To the study, 133 statin-naïve patients included, age 18 to 75 y.o., with absent clinical signs of coronary heart disease, and with first time diagnosed severe hypercholesterolemia (total cholesterol >7,5 mM/L and/or low density lipoproteides cholesterol >4,9 mM/L) with ultrasound duplex scan data of CA. All patients underwent measurement of Lpa concentration, lipid profile, subfractional content of apoB-100-containing lipoproteides and autoAb titer against them.Results. According to the data from duplex CA scan, patients were selected to 2 groups: control group (n=76) with no CA atherosclerosis; main group — patients with CA stenosis >20% (n=57). The participants of main group were older than controls, with no other clinical or lipid profile differences. Titre of autoAb IgM specific for Lpa and its oxidized modifications was significantly lower in CA atherosclerosis comparing to controls. The grade of CA stenosis in severe hypercholesterolemia patients positively correlated with age (r=0,24, p=0,005) and negatively — with autoAb IgM to apoB100-containing lipoproteides (r=-0,28 and r=-0,26, p

Development of innovational biotechnological medications based on humanized or completely human monoclonal antibodies or antisense oligonucleotides has opened a novel epoque in lipid disorders treatment. High efficacy of such biological drugs influencing the main chains of lipid metabolism (apoprotein B100, apoprotein (a), apoprotein CIII, proprotein-convertase subtilisin-kexin type 9, antipoetin like protein 3) does open a perspective for correction of severe and statin-resistant forms of dyslipidemias, with a possibility to achieve almost complete remission of the disease. However, the evidence of safety of antisense oligonucleotides drugs demands for broader investigation. Such drugs might be used in patients with orphan diseases or serious lipid disorders, not having alternative treatment. Vice versa, the drugs based on the human monoclonal antibodies thank to evidence are started to be in clinical use at the moment.

Raised level of lipoproteide (a) (Lpa) is an independent risk factor of coronary heart disease (CHD) and is also a monogenic predictor (there is growth of prevalence) of aortic stenosis (AS) with the increase of Lpa in population. Lysophosphatide acid, secreted by an enzyme with phospholipase D activity — autotaxin (ATX) is an inflammatory mediator. Humoral immunity involvement in inflammatory processes in coronary arteries and aortic valve might present with the presence of circulating autoantibodies and shifts in the values of cellular immunity.Aim. To assess the relation of Lpa, ATX and immunity with the presence of AS in chronic CHD patients.Material and methods. To a single moment study, 210 patients were included, with chronic CHD. Patients were selected to two groups by the presence (main group, n=47) or absence (controls, n=163) of degenerative AS by echocardiography. Patients were taking standard CHD therapy. All patients underwent clinical blood count, lipids concentration and Lpa. ATX, C-reactive protein, autoantibodies to ApoB-100 lipoproteides and their Cu2+-oxidated modifications. Phenotypes of apoprotein (a) were assessed in 168 patients.Results. CHD patients with degenerative AS were older (74,2±7,8 versus 67,6±9,4 y., p=0,0007), but did not differ by the clinical and biochemical characteristics, level of Lpa and high sensitive С-reactive protein (hsCRP). Concentration of АТХ in plasma was significantly higher (554±95 and 497±105 ng/mL, p=0,001), but the level of IgM autoantibodies against the oxidated lipoproteid (а) (oxLpa) — significantly lower (10,8 [7,9;15,1] and 13,4 [11,4;16,7] relative units, p

The question of the starting point of the ascent of I.V. Stalin to unified authority is still the key in the historiography of the October Revolution of 1917, which had a great influence on the formation of I.V. Stalin as a politician. The revolution has fostered in him a sense of purpose, a will to win, a desire not to overturn a political opponent. His role in the uprising is very modest. But from the speech to the speech on the pages of the Soviet mass media, Stalin more and more clearly emphasized his closeness to the leader of the revolution — V.I. Lenin, which was important for creating the image of one of the leaders of the armed uprising. Thus, the ascent to individual power began even before 1921, when Stalin became Secretary-General of the RCP (B).

This review deals with the necessary and relevant measures for primary and secondary prevention of cardiovascular diseases in Russia. The latest European and American guidelines emphasize that statins are the main class of drugs to be used to improve prognosis. The use of rosuvastatin is justified among the categories of moderate and high risk of developing cardiovascular complications, especially in severe hypercholesterolemia. The use of acetylsalicylic acid is undoubtedly useful for the secondary and, which is more controversial, for the primary prevention of cardiovascular diseases. Over the last few years, major clinical studies on the prevention of cardiovascular, hemorrhagic and oncological complications enable to rely on the expediency of combined, safe use of rosuvastatin and acetylsalicylic acid in individuals over 50 years of age with moderate and high cardiovascular risk. The use of both drugs in one tablet (the original drug Rosulip ASA®, EGIS Pharmaceuticals PLC, Hungary) will significantly increase the compliance with the vital therapy and significantly expand the use of rosuvastatin in clinical practice, which means further reduction in morbidity and mortality from atherosclerotic cardiovascular diseases.

Despite the positive trend over the last decade, mortality from the circulatory system diseases in the Russian Federation remains high: in 2016, 616 cases per 100 thousand people were registered, with an absolute loss of about 900 thousand people, of whom nearly 50% died from coronary artery disease (CAD). Atherosclerosis plays a critical role in the development of cardiovascular disease, as the damage to the arterial bed begins early - already at a young age. The major modifiable risk factors for atherosclerosis are hyperlipidemia, hypertension, diabetes, smoking. The leading risk factor for coronary atherosclerosis is lowdensity lipoprotein cholesterol (LDL-C). According to EUROASPIRE III, in Russia, hypercholesterolemia is found in 65% of patients with CAD (LDL-C above 3 mmol/l). According to many large randomized trials and meta-analyses, there is evidence that statins which constitute the major class of lipid-lowering drugs are effective in the reduction of LDL-C in both primary and secondary prevention of cardiovascular events.

Aim. To investigate on the relation of lipoproteide (a) (Lpa), subfractions of intermediate density lipoproteides (IDL) and low density lipoproteides (LDL) with the probability of familial hypercholestrolemia diagnosis (FHE).Material and methods. Totally, 114 patients included, with severe hypercholesterolemia (LDL-C >4,9 mM/L), with no known coronary heart disease and not taking hypolipidemic therapy. For the probability assessment of FHE, Dutch Lipid Clinics Network criteria were applied. Lipid profile parameters were measured by enzymatic method; Lpa — by immune enzyme method; lipoproteides subfractions — with the Lipoprint® system (Quantimetrix, USA).Results. All patients were selected to subgroups in accordance with the Dutch criteria: I group — with low FHE probability (3-5 points, n=86) and II — with definite and porobable FHE (≥6 points, n=28). Patients from II group had higher atherogenic apoB100-containing lipoproteides (a) levels — 25,5±27,8 and 42,8±41,5 mg/dL (р=0,014), small dense subfractions of LDL — sdLDL: 2,3±3,7 and 7,1±10,1 mg/dL (р

Aim. To evaluate the influence of nicotinic acid (NA) on subfractional spectrum of proand antiatherogenic lipoproteides in hyperlipoproteidemia (a) patients.Material and methods. Totally, 78 patients included, with Lp(a) level more than 20 mg/dL, taking either combinational statin and NA therapy (n=43), or on monotherapy by statins (n=13), or monotherapy by NA (n=22). Lipid profile parameters were analyzed with the assays “Biocon/Analyticon” (Germany), quantitative subfractional contents were assessed with the system Lipoprint® (Quantimetrix,USA), Lp(a) concentriation — with immune enzyme assay.Results. Results. In combinational therapy and monotherapy groups of NA the baseline Lp(a) levels were 98,0±44,8 and 71,3±21,8 mg/dL, respectively, р

The Guidelines are designed to demonstrate possible approaches to routing patients with hereditary atherogenic lipid disorders in accordance with existing legal documents. The Guidelines define the stages of medical care of this group of patients. For each stage the possible types of medical care, conditions of its provision and hospitals, on the basis of which it can be provided, as well as ways of payment are established. Criteria for the detailed examination of patients with suspected hereditary atherogenic lipid metabolism are shown. Recommendations reassigned for health care managers, chief-hospital physicians, cardiologists, internists and other physicians.

Results of randomized clinical studies and meta-analyses on evaluation of the role of statins high dosages before and after coronary bypassing and stending are analyzed. The maximum evidence basis is provided in studies with use of atorvastatin. Considerable risk reduction of early and late cardiovascular complications is demonstrated with use of high statin dosages in patients with various forms of the ischemic heart disease.

The results of the recently completed clinical studies on the efficacy of atorvastatin in high doses are presented. In these studies high dose atorvastatin therapy was used in patients with acute coronary syndrome, chronic coronary heart disease, and percutaneous coronary interventions. Studies completed in Russia and devoted to efficacy of the high dose atorvastatin therapy are discussed specially.

Statin intake is a standard in the treatment of patients with atherosclerosis nowadays. These drugs therapy associates with 30% risk reduction in mortality and coronary events. However , the threat of recurrent events is sufficiently high in large part of patients. This can be related to low level of high density lipoprotein cholesterol as well as elevated levels of triglycerides and lipoprotein(a). Nicotinic acid intake in these patients may be necessary for the normalization of lipid profile, including lipoprotein(a), and will be able to reduce residual cardiovascular risk. Evidence-based medicine data are presented to prove an efficacy of nicotinic acid in high doses in cardiology practice. Nicotinic acid both in monotherapy and in combination with statins contributes to coronary and carotid atherosclerosis regression and reduces an incidence of cardiovascular complications. Long-acting formulation of nicotinic acid, correct receiving regime and blood bio-chemical monitoring contribute to long-term safety of the drug in patients with clinically significant atherosclerosis.

Background. Atherosclerosis is a systemic disease. That is why the damage is not restricted by one vascular area in 18-50% of patients. High serum level of lipoprotein(a) [Lp(a)] is an independent risk factor for coronary, carotid and peripheral atherosclerosis. However the correlation of apoprotein(a) [apo(a)] polymorphism with the multifocal atherosclerosis in coronary heart disease (CHD) is not sufficiently studied.Aim. To study the correlation of apo(a) phenotype with the multifocal atherosclerosis in CHD patients.Material and Methods. 220 patients aged 32- 76 y.o. with the proven coronary and carotid atherosclerosis were split into two groups depending on the presence (n=22) or absence (n=198) of peripheral atherosclerosis. Evaluation of lipid profile, Lp(a) and determination of apo(a) isoforms by SDS electrophoresis in polyacrylamide gel and immunoblotting was performed in all patients.Results. Both groups of patients were comparable by age, sex, classical cardiovascular risk factors, including frequency of hyperlipidemia and diabetes mellitus, lipid profile. The Lp(a) serum level ≥30 mg/dL and low molecular weight (LMW) apo(a) phenotype were found more often in patients with multifocal than coronary and carotid atherosclerosis: 55 and 45% (р=0.372); 73 and 44% (p

Review of large of trials that prove the positive impact of high-dose lipid-lowering therapy on the prognosis in patients with ischemic heart disease (IHD) are presented. The data on the efficacy of the lipid profile correction by lipid apheresis in patients with hypercholesterolemia that is refractory to optimal medical therapy are showed. The results of the large trials (LIPS, ARMYDA, NAPLES II, ARMYDA-RECAPTURE, Post-CABG, TNT) and meta-analyzes on the role of statins, prescribed before and after coronary artery bypass surgery and stenting, in reducing the risk of early and late cardiac events and the need for repeat myocardial revascularization are analyzed. The issue of therapeutic apheresis should be considered in cases of refractory hypercholesterolemia according to ESC/EAS Guidelines for the management of dyslipidaemias (2011). The tendency to reduction in the risk of stent restenosis and vein graft lesions after lipid apheresis is found in very high risk patients with IHD and refractory hypercholesterolemia that underwent coronary stenting or bypass surgery.

Objective: to study the association of C3256T, G13 513A, G14 846A, and G12 315A mutations in the mitochondrial genome with the presence and degree of coronary and carotid atherosclerotic lesions.Subjects and methods. The investigation enrolled 193 patients (mean age 54.6 ± 9.5 years), including 154 men, who had undergone coronary angiography. A study group consisted of 130 patients with coronary atherosclerosis. A control group comprised 63 patients without this disease. Genetic analysis consisted of 3 steps: 1) isolation of genomic deoxyribonucleic acid from whole blood leukocytes by phenol-chloroform extraction; 2) amplification of polymorphic sites in the examined mitochondrial deoxyribonucleic acid genes by polymerase chain reaction; 3) pyrosequencingfor the detection of nucleotide sequencing and the determination of the level of heteroplasmy of the examined mutations.Results. The level of heteroplasmy of G13 513A and C3256T mutations was statistically significantly higher in the patients with coronary atherosclerosis than in those without this condition (p = 0.03 and p = 0.01, respectively) whereas that of G12 315A mutation was significantly higher in the persons without coronary atherosclerosis (p = 0.004). The level of heteroplasmy of G14 846A mutation was greater in people over 45 years of age. No association was found between mutations in the mitochondrial genome and cardiovascular risk factors, such as smoking, hypertension, poor family history, and obesity. There was a direct relationship of hyperlipidemy to C3256T mutation (r = 0.18; р = 0.01) and its inverse relationship to G12 315A mutation (r = –0.2; р = 0.005), There was a positive correlation between G14 846A mutationand lipoprotein (a) levels. There was also a positive correlation between carotid atherosclerosis with С3256Т (r = 0.49; p = 0.0001)and G14 846A (r = 0.48; p = 0.0001) mutations. G12 315A mutation showed a negative correlation with carotid atherosclerosis (r = –0.32; p = 0.01). Conclusion. The case-control study gave proof to the association between the level of heteroplasmy of С3256T, G13 513A, G14 846A, and G12 315A mutations in the mitochondrial genome and coronary and carotid atherosclerosis. Measurement of the heteroplasmy of С3256T, G13 513A and G14 846A mutations in the mitochondrial gene may be proposed as potential genetic markers to improve the diagnosis of a preposition to coronary and carotid atherosclerosis.

The article concerns prevalence and efficacy of primary and secondary preventive strategies for hyperlipidemia in Russian Federation. According to the European Guidelines 2013 for Treatment of Stable Ischemic Heart Disease and the American Guidelines for Hypercholestrolemia, the article emphasizes that the main drug class that is effective in prognosis improvement, are statins, without mentioning any specific name. Among the higher cardiovascular risk categories it is possible to use high doses or intensive regimen of the two most common statins: atorvastatin and rozuvastatin. The results of the largest meta-analysis VOYAGER with 32 thousands patients, are provided, showing more success against other statins to reach target low density cholesterol levels.

Objective: to study an association of high lipoprotein(a) [Lp(a)] levels with the development of restenosis and the progression of coronaryatherosclerosis after percutaneous coronary interventions (PCI) in patients with chronic coronary heart disease (CHD).Subjects and methods. From 502 enrolled patients (mean age 54.7 ± 8.9 years), 92 underwent routine percutaneous transluminal coronary angioplasty (PTCA), 270 had PTCA with the bare metal stent (BMS) being implantation, 140 had PTCA using drug-eluting stents (DES). Functionalclasses III and IV angina have been registered in 337 (67 %) patients; history of one myocardial infarction (MI) was noted in 234 (47 %) cases, 171 (34 %) had experienced 2 or more MIs. Blood samples for lipid and Lp(a) measurements were taken in all the patients. Restenosis was defined as at least 50 % lumen narrowing of the coronary artery segment after angioplasty. Coronary atherosclerosis progression was established in cases of the new occlusion occurring, as well as identifying a 10 % decrease in lumen diameter in comparison with baseline angiograms.Results. Repeated coronary angiography revealed the signs of restenosis in 103 of 243 patients. Dividing patients into 3 groups according to the type of intervention demonstrated that the level of Lp(a) (median 25–75 % quartiles) was significantly higher in the restenosis group after implantation of BMS (33; 11–62 and 16; 6–39 mg/dl, respectively; p = 0.014) versus those who had undergone DES implantation (23; 10–30 and 20; 6–60 mg/dl; p = 0.7) or balloon angioplasty (17; 4–48 and 9; 4–36 mg/dl; p = 0.3). Patients with progression of coronary atherosclerosis had difference only in Lp(a) levels compared to the group without progression (36; 13–62 versus 12; 4–26 mg/dl, p < 0,001.Conclusion. During the first year after elective PCI Lp(a) concentration determined the severity of coronary atherosclerosis in non-culprit lesionsand associated with the risk of in-stent restenosis after BMS, independly of conventional risk factors.

Mitochondria are not only the major producers of adenosine triphosphate, but also an endogenous source of reactive oxygen species. Mitochondrialdysfunction plays a key role in the trigger and progression of atherosclerotic lesion. Impaired function in the mitochondria due to their elevated level of oxidized oxygen species, the accumulation of mitochondrial DNA damages, and the exhaustion of respiratory chains induces dysfunction and apoptosis in the endothelial cells; activation of matrix metalloproteinases; growth of vascular smooth muscle cells and their migration into the intima; expression of adhesion molecules, and oxidation of low-density lipoproteins. Mitochondrial dysfunction may be an important unifying mechanism that accounts for the atherogenic effect of major cardiovascular risk factors. Small clinical pilot studies have shown an association of different mitochondrial genome mutations with atherosclerotic lesion in the artery. Taking into account the available data on the possible role of mitochondria in atherogenesis, novel drugs are now being designed to affect mitochondrial function.