Aim. Russian multicenter register of familial hypercholesterolemia (FH) was transformed into Register of patients with FH and very high cardiovascular risk with insufficient effect of hypolipidemic therapy (RENESSANS Registry) in 2017 The aim of RENESSANS was maximal inclusion of patients not only with FH, but also those with atherosclerotic cardiovascular diseases (CVD), who did not achieve targeted level of low density lipoprotein cholesterol (LDL-C) using hypolipidemic drug therapy.

Material and methods. The RENESSANS Registry is an open, national, observing study that includes patients with definite and probable (according to Dutch lipid clinic network and Simon Broome Registry criteria) heterozygous and homozygous FH, as well as patients of very high cardiovascular risk. There were designed two register forms: for patients with FH and for very high cardiovascular risk patients. Doctors filled out forms in paper and electronic variants. They took into consideration the risk factors of atherosclerosis and anamnesis of CVD, adherence to diet and hypolipidemic therapy. Concentrations of total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C) were measured in blood serum in all centers. LDL-C level was defined according to Friedewald formula: LDL-C=TC-HDL-C-TG/2,2 (mmol/l).

Results. The Registry consisted of 1208 FH patients and 497 patients with very high risk (average age 54±13 and 61±8, respectively, 37% men). Baseline levels of lipids were 9,4±2,3 and 6,9±1,5 mmol/l for TC, 6,6±2,1 and 4,5±1,3 mmol/l for LDL-C, respectively. The frequency of hypolipidemic therapy in both groups is 70%, while targeted level of LDL-C was achieved extremely rarely.

Conclusion. The results show insufficient adherence and low effectiveness of standard hypolipidemic therapy both in patients with FH and very high cardiovascular risk. PCSK9 inhibitors are recommended for resistant hypercholesterolemia treatment. The RENESSANS Registry allows to improve FH diagnostics, to assess treatment effectiveness and choose patients who need treatment with PCSK9 inhibitors.

Aim. To study the prognostic significance of various markers of atherosclerosis of lower limb arteries (LLA) in patients at high and very high cardiovascular risk (CVR).

Methods. The study included 108 patients at high and very high CVR, the median age of which was 62.0 (55.7; 67.0) years. All patients underwent duplex scanning of the LLA, as well as measurement of the ankle-brachial index (ABI) by the Doppler method. The combined end point was cardiovascular death, nonfatal myocardial infarction or unstable angina, requiring hospitalization, nonfatal stroke, coronary revascularization.

Results. Atherosclerotic plaques in LLA were detected in 69.4% of cases, while a decrease in ABI was detected in 22.2% of patients, and LLA stenosis more than 50% in 36.1%. The follow-up duration was 25.0 (14.5; 35.5) months. The adverse cardiovascular events occurred in 41 (37.9%) patients. According to the Cox regression results, the following indicators had an independent predictive value in relation to the development of adverse cardiovascular events: a decrease in ABI ≤0.9 (RR 2.23; 95% CI 1.01-4.94; p=0.048), LLA stenosis ≥40% (RR 3.17; 95% CI 1.27–7.92; p=0.013) and the presence of plaque in the popliteal arteries (RR 2.49; 95% CI 1.27–7.92; p=0.013).

Conclusion. In the group of patients at high and very high CVR, among ultrasonographic markers of lower limb arteriosclerosis, independent predictive value regarding the development of adverse cardiovascular events had a decrease in ABI ≤0.9, the presence of plaque in the popliteal arteries and LLA stenosis more than 40%.

Aim. To compare the accuracy of predicting the risk of fatal and non-fatal cardiovascular events (CVE) based on SCORE scaling and ultrasound imaging of carotid atherosclerotic plaque (AP) in patients without manifested atherosclerotic cardiovascular disease (ACVD) in a multidisciplinary hospital.

Material and methods. We examined 841 patients (353 men) (avearage age 54,9±8), with at least 1 traditional cardiovascular risk factor without manifested ACVD. Ultrasound examination of the carotid arteries was performed in all patients. Patients with nonstenotic AP constituted the AP+ group, and without AP — the AP-group (356 and 485 people, respectively). Median of follow-up time was 4 years, (minimum — 2, maximum — 6 years). The endpoints included: a verified diagnosis of acute coronary syndrome, chronic coronary artery disease, planned coronary revascularization, ischemic stroke, and/or transient ischemic attack, cardiac death.

Results. Nonstenotic AP of carotid arteries was detected in 352 people (42%), including 64 (23%) in low and 182 (46%) in moderate SCORE risk. 127 CVE (178%) occurred during the follow-up, 84 (66% of the total) of them in the AP+ group. The actual frequency of development of the cumulative endpoint was significantly higher than the calculated rate (the ratio of actua predicted events was 1,6, 5,1 and 79 for high, moderate and low SCORE risk, respectively). According to the multivariate regression analysis, the OR for AP as a predictor of cardiovascular events cardiovascular events CVE was 2,54 (95% CI 1,6-4,04), and was significantly higher than the SCORE index (1,04, 95% CI 0,01-1,07). As a predictor of CVE, AP had the greatest value in the low SCORE risk group (the number of CVE in the low SCORE risk group was14 among patients with AP vs 10 among patients without AP, p=0,001).

Conclusion. The use of SCORE scale underestimates the actual risk of CVE especially in patients with low and moderate calculated SCORE risk. Ultrasound visualization of AP of the carotid arteries in these patients predicts the risk of cardiovascular disease much more accurately.

Aim. To study factors of endothelial dysfunction in order to find their associations with coagulation factors, inflammatory markers and unstable atherosclerotic plaques in the coronary arteries in men with coronary atherosclerosis.

Material and methods. The study included men with coronary atherosclerosis without acute coronary syndrome. We assessed blood concentrations of endothelial dysfunction factors (endothelin 1, monocyte chemoattractant protein-1 (MCP-1), adhesion molecules sVCAM-1, asymmetric dimethylarginine, homocysteine, plasminogen activator inhibitor-1) blood coagulation (factor II, factor VII, factor XII, antithrombin III), biomarkers of inflammation (tumor necrosis factor alpha, interleukins (IL-1-beta, IL-6, IL-8), C-reactive protein).

Results. The presence of unstable atherosclerotic plaques was associated with an increased blood level of MCP-1 (1,9 times higher; p<0,05) and a reduced concentration of sVCAM-1 (1,4 times lower; p<0,05) compared with men who withiut unstable plaques in the coronary arteries. The largest number of correlations was found between the level of MCP-1 in blood, concentrations of factor VII, antithrombin III, IL-8, C-reactive protein, IL-1 beta and the presence of unstable atherosclerotic plaques in men.

Conclusion. The results showed that the relative risk of unstable atherosclerotic plaques in the coronary arteries is associated with an increased level of MCP-1 in the blood.

Some studies have shown that the echogenicity of atherosclerotic plaques (AP) in the carotid arteries (CA) plays an important role in evaluating the risk of cardiovascular events (CVE). The method of calculating the Gray Scale Median (GSM) is currently used to quantify the echogenicity of the CA plaque.

Aim. To study GSM assessment of CA AP in patients with acute coronary syndrome (ACS) and the effect of GSM on the prognosis of CVE.

Material and methods. We examined 143 patients with ACS (32-83 years old). Duplex scanning was performed on “Philips iU 22” for 1-3 days after hospitalization, the second — in 1-1,5 years. The echogenicity of the detected APs was assessed on a gray scale using a modified GSM method at the Multivox workstation.

Results. We analyzed 378 CA AP in patients with ACS. The GSM analysis on the first and repeated surveys showed a significant increase in the average GSM by 2,2% (p<0,05). During follow-up, 23% of patients had various cardiovascular diseases (death, MI, exacerbation of coronary artery disease, repeated coronary artery revascularization, stroke). Results of GSM analysis of patients with and without CVE revealed statistically significant changes: GSM AP decrease in patients with CVE by 7,8% (p<0,05), and an increase in GSM in patients without CVE by 6,1% (p<0,05). ROC analysis showed that a relative decrease in GSM ≥6,96% with a sensitivity of 53,5% and a specificity of 71,1% determines the development of an unfavorable outcome (the area under the curve is 0,628±0,0465; 95% CI 0,55-0,7), p=0,006). The risk of CVE developing increased by 2,16 times with a decrease in GSM dynamics by more than 6,96% (RR 2,16; 95% CI 1,3-3,5; p=0,009).

Conclusion. The results of study show the importance of assessing the echogenicity of CA AP in patients with ACS. A decrease in the echogenicity of AP in such patients over time may indicate an increase in the risk of CVE developing and may be the reason to correct the therapy.

Aim. To develop a model for calculating the risk of venous thrombosis, taking into account the presence of known risk factors, comorbidity and congenital thrombophilia.

Material and methods. During the study (2015 to 2017), 79 patients with venous thrombosis were examined (36 men and 43 women, mean age — 56,76±15,570). The control group consisted of 83 patients and healthy volunteers without thrombosis at the moment and in history (35 men and 48 women, average age — 43,95±18,136). All individuals included in the study were analyzed for the presence of G1691A mutations in the factor V gene, G20210A in the prothrombin gene, C677T polymorphism in the 5,10-methylenetetrahydrofolate reductase gene, and polymorphism in the SERPINE1 gene of plasminogen activator inhibitor. Real-time polymerase chain reaction was used to identify mutations. To create a risk calculation model, a linear regression analysis was performed.

Results. We have developed a model for calculating the risk of venous thrombosis. The resulting formula showed high prognostic accuracy (the area under the ROC curve is 95,9%). For patients who do not have data on the presence of these mutations, a short version of the risk calculation model was developed (the area under the ROC curve is 94,6%).

Aim. To study the possibility of reducing the risk of intraoperative cardiac damage and 4a type myocardial infarction (MI) by administering the oral nicorandil in patients with a stable form of coronary artery disease (CAD) before planned percutaneous coronary intervention (PCI).

Material and methods. The study included 182 patients with stable CAD who were randomized to the nicorandil treatment group (n=90) and the control group with a standard treatment (n=92). Nicorandil was prescribed 2 days before PCI (30 mg/day); on the day of PCI — 2 hours before surgery (20 mg orally), 6-12 hours after PCI — 10 mg, later — 30 mg/day within 30 days. The analysis of highly sensitive troponin I (hs-troponin) and creatine kinase-MB (CK-MB) was carried out before PCI and 24, 72 hours after the procedure, the type 4a diagnosis of MI was established according to fourth universal definition.

Results. The rate of hs-troponin after 24 hours exceeded the 99th percentile from the upper limit of normal in 146 patients (80%). In the control group, there was a statistically significant more frequent increase in hs-troponin by more than 2000 ng/ml (10% of patients in the control group versus 1% of the patient in the nicorandil group, p=0,038). Type 4a MI was detected in 12% of patients in the control group, and it decreased to 3% of patients in the nicorandil group (p=0,05), and in women it was observed in 21% in the control group and in 3% in the nicorandil group. Among women (n=61), the increment of hs-troponin 24 hours after PCI was statistically significantly lower (287 versus 1135 pg/ml, p=0,04) in the nicorandil group compared to the control group.

Conclusion. Reducing the risk of cardiac damage and 4a type MI by nicorandil using before PCI, compared with standard antianginal therapy, is an effective tool in cardioprotection of patients with stable CAD before planned PCI.

Statins are currently the main group of lipid-lowering drugs used in clinical practice. However not all patients manage to achieve ‘target’ levels of LDL. A possible cause is statin-induced increase of expression of hepatocyte PCSK9 which regulates LDL uptake.

Aim. The aim of the study was to determine whether the changes of parameters of lipid spectrum depend on the changes of PCSK9 concentration in blood during treatment with rosuvastatin or atorvastatin.

Material and methods. 20 patients (9 men), median age 63 (57;72) years referred for the examination at NMRCC with coronary and carotid atherosclerosis and with the indications for statin therapy were included. In 9 patients the therapy with atorvastatin (40-80 mg/day) was initiated. 11 patients started taking rosuvastatin (10-40 mg/day). The parameters of lipid spectrum, Lp(a) and PCSK9 blood levels were determined at baseline and after 1 month after the initiation of statin therapy.

Results. Atorvastatin and rosuvastatin intake were accompanied by the decrease in the levels of total cholesterol, triglycerides, LDL. The level of Lp(a) did not change. In patients receiving rosuvastatin a significant increase in the PCSK9 serum concentration was achieved while atorvastatin therapy was associated with much less pronounced and not statistically significant increase in PCSK9 levels.

Conclusion. We suggest that the lipid-lowering activity of statins does not depend on their effect on PCSK9 expression. The limitation of this study is the small sample size and short observation time.

Aim. To study the phenotype of microvesicles circulating in the blood plasma of patients with stable coronary artery disease (CAD), carrying monomeric C-reactive protein (mCRP) on their surface, and to detect tissue accretions of mCRP in coronary artery of patients with CAD.

Material and methods. Blood samples obtained from 20 patients with stable CAD and from 7 healthy volunteers were examined. The phenotype of microvesicles of cell origin was studied by flow cytometry. Microparticles were identified by their level of binding to annexin-V, and exosomes by binding to the monoclonal antibodies to CD63. The accretion of mCRP in the coronary arteries’ walls was investigated by immunohistochemical analysis of their fragments obtained from 7 men during coronary endarterectomy surgery. Samples were stained with monoclonal antibodies to native CRP (nCRP) and mCRP.

Results. More than half of the mCRP-positive blood microparticles were CD45-positive. At the same time, the mCRP+/CD45+ microparticles were CD63 positive and annexin-V negative, which makes it possible to characterize them as exosomes secreted into the extracellular space by activated leukocytes. Microparticles of platelet and erythrocyte origin were mainly annexin-V positive. It was very weakly or not at all associated with antibodies to mCRP. The amount of blood mCRP+/CD45+ exosomes was significantly higher in patients with CAD (8749+2683 particles per μL, n=20) than in healthy people (1454+350 particles per μL, n=7 p=0,00). An analysis of coronary arteries’ material has shown that mCRP is found in atherosclerotic plaques, while intact arterial wall samples were mCRP negative.

Conclusion. An increase of exosomes carrying on their surface mCRP and characteristic leukocyte markers, as well as the appearance of mCRP in areas of atherosclerotic arterial wall lesions, in patients with CAD, may indicate the involvement of proinflammatory mCRP molecules in the pathogenesis of coronary atherosclerosis. Since exosomes are specific transporters of signaling molecules of the parent cells, it can be assumed that mCRP is transported to damaged areas by activated leukocytes.

Aim. To develope and justify the use of the abbreviated protocol of ultrasound duplex scanning (DS) of the carotid arteries (CA) to detect atherosclerotic changes in the carotid system in various groups of cardiovascular risk and to reduce the time of DS, based on solving a “narrow” task — identifying an atheroma.

Material and methods. Ultrasound CA examination was carried out in the department of ultrasound studying methods in National Medical Research Center of Cardiology. Forty three patients aged 32 to 81 years (mean 56±13 years) who are hospitalized in A. L. Myasnikov Institute of Clinical Cardiology Institute of Clinical Cardiology were examined. DS was performed with the use of the ultrasonic system “IU 22” (Philips) with a linear sensor with 3-9 MHz. Three types of DS protocol were used — standard protocol (with automatic measurement of intima-media thickness (IMT) of common carotid artery (CCA)), abbreviated protocol 2 (atheroma and IMT of CCA), abbreviated protocol 1 (atheroma).

Results. The work showed a decrease in DS time when conducting a abbreviated protocol 2 by 32,1% or 1,5 times, a shortened protocol 1 — by 72,1% or approximately 3,5 times compared with the standard DS protocol, while the efficiency of atheroma detecting has not decreased. A decision-making algorithm has been developed on the basis of conducting an ultrasound SA examination using abbreviated protocols.

Conclusion. The introduction of a abbreviated protocol of ultrasound DS will significantly reduce the time and increase the cost-effectiveness of early diagnosis of atherosclerosis.

In accordance with modern clinical guidelines, the main aim of therapy for cardiovascular risk reducing is achievement of target level of lipid parameters. Some common diseases, medications prescribed in routine clinical practice, as well as dietary disorders can cause the development of lipid metabolism disorders, called secondary hyperlipidemias. Identification and treatment (or elimination) of secondary causes of hyperlipidemia may contribute to the effectiveness of treatment of patients with lipid metabolism disorders. This review presents the underlying conditions and pathogenetic mechanisms responsible for the development of secondary hyperlipidemia.

The lipid hypothesis of atherosclerosis pathogenesis is based on lipid metabolism disorders and, in particular, hypercholesterolemia. The main participants of dyslipidemia are lipoproteins of various classes. Despite the use of modern lipidlowering drugs, the residual risk of cardiovascular complications in patients with dyslipidemia remains quite high. Modern biochemical and physico-chemical methods allowed demonstrating the high heterogeneity of the main classes of lipoproteins.

This review presents the analysis of modern ideas about the heterogeneity of lipoproteins, a brief description of existing approaches to the classification of lipoproteins, methods of their stratification, as well as the contribution of some subfractions of lipoproteins to the development of atherosclerosis.

The article presents an overview of foreign and domestic studies aimed to study the role of elemental imbalance in the development of cardiovascular pathology. The pathogenetically significant mechanisms of the influence of diselementosis on the development of atherosclerotic changes in the walls of blood vessels are discussed. Particular attention is paid to such elements as iron, copper, zinc, selenium, cadmium.

To make a decision on choice the type of myocardial revascularization in patients with coronary artery disease (CAD), an invasive coronary angiography (CAG) is necessary. However, in clinical practice, a significant number of patients during CAG fails to detect coronary obstructive disorders, there is the so-called problem of “clean” coronary arteries. Indeed, in the Russian Federation in approximately 50% of cases, CAG does not end with myocardial revascularization, and in patients with suspected CAD, non-obstructive coronary artery lesions are detected in 67% of cases. In the first part of the review, a critical analysis of the clinical evaluation of patients in the selection of patients for CAG was conducted. First stages of the diagnostic process based on clinical evaluation are considered. The review discusses the use for diagnostic purposes more complete set of routine assessment methods and the expanded use of laboratory tests using memetic algorithms.

Lipoprotein(a) (Lp(a)) is a complex supramolecular complex belonging to apoB100 lipoproteins. Lp(a) consists of a particle of similar low-density lipoprotein, in which the apolipoprotein molecule В100 is covalently linked by a disulfide bond with a unique polymorphic apolipoprotein(a) molecule. The concentration of Lp(a) is genetically controlled and varies over a very wide range. An elevated level of Lp(a) is an independent risk factor for atherosclerosis of the coronary, carotid and peripheral arteries, coronary artery disease and aortic stenosis, concomitant cardiovascular complications, and complications after myocardial revascularization. Despite this, the level of Lp(a) is still not taken into account in the stratification of the risk of cardiovascular diseases. In part, this may be due to the fact that neither modern drug therapy, nor new generations of biological lipid-lowering drugs have virtually no effect on the concentration of Lp(a), with the exception of a 20-30% decrease in Lp(a) by nicotinic acid and inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9). The lecture covers the modern understanding of Lp(a) as a risk factor for cardiovascular diseases, the possibility and feasibility of its definition, and is also devoted to the modern possibilities of correcting hyperlipoproteinemia(a).