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High lipoprotein(a) (LP(a)) level contributes as an independent risk factor to the development of cardiovascular diseases of atherosclerotic origin. The article contains data on the structural features of this particle, the genetic determination of its metabolism and content in blood plasma, and the pathogenic mechanisms of its proatherogenic, proinflammatory and prothrombotic effects. The authors analyzed epidemiological data on the frequency of elevated LP(a) levels in different population groups and its association with the risk of cardiovascular diseases. The data presented concern the indicators of LP(a) as a risk factor for the development of ischemic stroke (including recurrent stroke) and its individual pathogenetic subtypes, as well as the relationship between LP(a) levels and functional outcomes after cerebral accidents. Current recommendations for the treatment of patients with elevated LP(a) levels in the context of primary and secondary prevention of cardiovascular diseases are analyzed.

An increased concentration of lipoprotein(a) (Lp(a)) is one of the main genetic residual risk factors for atherosclerotic cardiovascular diseases, as well as their complications. Lp(a) is a complex supramolecular complex in which the unique glycosylated apo(a) protein, which has a wide polymorphism, is linked by a disulfide bond to the apoB100 molecule (protein component of the low-density lipoprotein (LDL) particle). Therefore, Lp(a) is often called LDL-like particle. Unlike all other lipoproteins, Lp(a) concentration is determined genetically, almost constant throughout the life, and has wide individual and interethnic variability. As an independent risk factor, elevated Lp(a) concentrations can significantly increase global cardiovascular risk, especially in patients with other risk factors. Modern international and national guidelines recommend measuring Lp(a) concentration not only in certain categories of patients, but also in every person at least once in their life for a correct assessment of cardiovascular risk.

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.

BACKGROUND: Considering the high cardiovascular risk in patients with familial hypercholesterolemia (FH), early diagnosis and treatment are the basis for the prevention of vascular accidents. In the absence of universal screening, the results of more targeted diagnostics are of interest — the search for lipid metabolism disorders in young relatives of patients with atherosclerotic vascular diseases. OBJECTIVE: To determine the effectiveness of targeted screening for identifying patients with FH, which will justify its widespread use in clinical practice. MATERIALS AND METHODS: At the start of the observational study, 584 patients were identified from the vascular centers of the Krasnoyarsk Regional Hospital, Krasnoyarsk Interdistrict Clinical Hospital No. 20 named after. I.S. Berzon, who had lipid profile data and early cardiovascular events (all forms of coronary heart diseases), including reconstructive vascular interventions up to 55 years in men and up to 60 years in women in the case of first-degree relatives and up to 50 years in second-degree relatives. The study examined patients’ relatives aged 44 years. To diagnose FH in participants aged 16 years, the scale developed by a network of Dutch lipid clinics was used; in participants aged 16 years, the S. Broome criteria were used. Targeted screening and lipid parameters in individuals with probable, possible, and definite FH were analyzed. Data processing was performed using Microsoft Excel and Statistica v. 12.0 (USA). Parametric (calculation of the median and 25th and 75th quartiles) and nonparametric (statistical significance of differences was determined using the Mann–Whitney and χ2 tests) methods were used. RESULTS: The study examined 70 children and 104 adults aged 44 years whose first- and/or second-degree relatives suffered premature vascular events. In the general group of participants, 42 (24.14%) patients had FH (of which 18 were 17 years old) and 37 (21.2%) had hyperlipoproteinemia (a). Definite FH was documented in 16 (9.1%) patients, probable in another 16, and possible in 9. Hyperlipoproteinemia (a) was found in 37 (21.2% of general group) patients, including 12 children (17.1% of pediatric group). CONCLUSION: Not more than 30% of the population are aware of the hereditary nature of lipid metabolism disorders and atherosclerotic diseases. Targeted screening is the least expensive and most effective tool for identifying patients with FH and hyperdipoproteinemia (a).

Currently, worldwide interest in lipoprotein(a) (LP(a) as one of the most important markers of premature and aggressive atherosclerosis is steadily growing. This trend is due to both the new data on the pathogenesis of hyperlipoproteinemia (a) and the development of novel treatment methods in the near future. The variety of clinical manifestations of atherosclerosis associated with high LP(a) concentrations leads such patients to specialists of various profiles. The aim of this paper was to demonstrate, using examples from the practice of two lipid centers in Krasnodar, the diversity of clinical scenarios of atherosclerosis as a systemic disease in patients with very high LP(a) levels, as well as to highlight the current and future options for the treatment of hyperlipoproteinemia (a).

Background: The clinical phenotype of familial hypercholesterolemia (FH) combined with the classical genetic defects of this disease increase the risk of coronary artery disease (CAD) in the case of a high level of lipoprotein (a) (Lp(a)). Aim: To assess the association of hereditary disorders of lipid metabolism with a high level of Lp(a) in the case of an early manifestation of CAD in the absence of the FH phenotype. Methods: We studied 81 patients with premature CAD (at the age up to 55 years in men and up to 60 years in women). Lp(a) was measured in the blood serum by the immunoturbidimetric method. We performed the molecular genetic testing, using massively parallel sequencing, which included the following panel of genes: ABCA1, ABCG1, ABCG5, ABCG8, ANGPTL3, APOA1, APOA2, APOA4, APOA5, APOB, APOC1, APOC2, APOC3, APOE, APOH, CETP, CH25H, CIDEC, CREB3L3, GPD1, GPIHBP1, LCAT, LDLR, LDLRAP1, LIPA, LIPC, LIPE, LIPG, LMF1, LPA, LPL, MTTP, MYLIP, NPC1, NPC1L1, NPC2, PCSK9, PLTP, PPP1R17, SAR1B, SCARB1, STAP1. Results: 24 (29.6%) patients had Lp(a) 30 mg/dl and were more likely to have a family history of CAD (70.8% vs 42.1%, p=0.05). In patients with a confirmed FH phenotype, there were no pathogenic variants associated with hereditary disorders of lipid metabolism. 4 patients with Lp(a) 30 mg/dl without a confirmed FH phenotype appeared to be carriers of pathogenic variants in the genes of lipid metabolism (LDLR p.Glu763Asp, ABCA1 p.Arg1128His, APOA5 p.His321Le), as well as of a not previously registered variant in the LIPE gene NM_005357.4:c. 2312TC. Conclusions: Lp(a) can be an appropriate marker for revealing pathogenic variants in the genes of the lipid metabolism system in patients without the clinical FH phenotype with an early CAD manifestation.

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.

HMG-CoA reductase inhibitors (statins) are a key class of drugs for the treatment and prevention of atherosclerosis and its complications. This class of drugs has become firmly established in Russian and international guidelines with a high level of evidence. However, the use of these drugs in practice is not yet optimal. A significant proportion of patients at very high cardiovascular risk, taking initial doses of statins, do not achieve target levels of low-density lipoprotein cholesterol. The article is devoted to the analysis of international and Russian guidelines for statin monotherapy optimization, including their prescription in primary prevention using cardiovascular risk reclassification, coronary calcium score, carotid Doppler ultrasound and lipoprotein(a) levels.

Aim of the study: to assess the relationship between Lp(a) serum levels grading and carotid artery stenosis (CAS). The Duplex Registry database was used for this study. CAS was verified by duplex scanning in the presence of an atherosclerotic plaque (AP), stenosing the lumen of the carotid artery (CA) by 20 % or more. Patients who underwent a blood test for Lp(a) and the results were entered into the registry database were selected for this study. The immunoturbidimetric method was used to determine the serum level of Lp(a) (mg/dl). Data from 51 patients (66.6 % men) were included in the final analysis: median age 49.0 [46.0; 59], total cholesterol (TC) 5.93 [5.13; 6.56], Lp(a) 26.5 [14.2; 76.0]. Spearman rank correlation analysis showed the presence of significant relationships (p < 0.05) between Lp(a) and age (r = 0.3), gender (r = 0.3), the presence of AP in the right ICA (r = 0.5), HDL (r = 0.3). OR and 95 % CI were calculated to determine the effect of Lp(a) grades on the probability of CAS detection: Lp(a) < 30 mg/dl OR 0.36 [0.11; 1.14] p = 0.04; Lp(a) > 30 mg/dl OR 1.42 [0.44; 4.58] p = 0.27. The prevalence of CAS in the group with Lp(a) level < 30 mg/dl was 33.3 %, 30–50 mg/dl – 50 %, 50–100 mg/dl – 40 %, > 100 mg/dl – 37.5 %. The model of multiple regression analysis for Lp(a) with TC in relation to the right ICA stenosis predicting showed R = 0.51, F = 8.4, p = 0.0007. The statistics of 3M model of the logistic regression function for CAS predicting based on the Lp(a) and TC data showed: -2 • log(likelihood) = 57.16, Chi-square = 8.17 (cc = 2), p = 0.016. The present study confirmed the relationship between the Lp(a) level and the CAS detection and the presence of an additive effect of total cholesterol on this. The reference role of Lp(a) gradation at the level of 30 mg/dl was determined as significant in relation to predicting CAS detection.

Aim. To study the prevalence of elevated concentrations of lipoprotein (a) (Lp(a)) and apolipoprotein B (apoB) associated with high cardiovascular risk in a random sample of the adult Krasnoyarsk population.Material and methods. Lp(a) and apoB concentrations were determined by the immunochemiluminescent method using an automated modular Cobas 8000 platform with biochemical module c702 (Roche Diagnostic, Switzerland). We examined 263 people aged 18 to 58 who agreed to expand the standard screening by Lp(a) and apoB determination.Results. We found that high and very high levels of Lp(a) are found in 12,9% of the examined, while in women the median value was significantly higher than in men (p=0,044). In addition, 11,4% of study participants had high apoB values, regardless of sex; 3,4% of the subjects had a combination of elevated levels of ap B and Lp(a).Conclusion. Screening for Lp(a) and apoB reveals dyslipidemia associated with high cardiovascular risk in 24,3% of working-age people

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.

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

Aim of the study – in subjects without any signs of atherosclerosis to study the associations between blood serum level of lipoprotein(a) (Lp(a)) from one hand, and lipoprotein profile, insulinmediated glucose utilization parameters and pulse wave velocity (PWV), from the other. Material and methods. Totally 202 subjects (68 men, 134 women) aged 25–75 years without clinical manifestations of atherosclerosis-related diseases but with cardiovascular disease risk factors were included into the study. Blood lipid and carbohydrate parameters were measured by standard methods, serum concentration of Lp(a), apolipoproteins (apo) AI, AII, and B – immunoturbidimetrically. PWV was used as a measure of arterial stiffness. Results. Serum level of Lp(a) positively correlated with apo B concentration (R=0,143; p=0,043) and negatively with apo АII content (R=–0,286; p

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).

The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS)

Aim. Lipoprotein(a) [Lp(a)] is an independent risk factor of coronary heart disease (CHD) and myocardial infarction. Data about the role of Lp(a) in the development of peripheral artery disease (PAD) is controversial and uncertain. The aim of the study was to evaluate the association between Lp(a), apolipoprotein(a) [apo(a)] phenotypes and PAD. Materials and methods. The study included 998 patients (707 male and 291 female, average age 60±12). The patients were divided into 4 groups depending on the presence or absence PAD and CHD: group I (n=188, PAD+CHD+), group II (n=78, PAD+CHD-), group III (n=407, PAD-CHD+), group IV (n=325, PAD-CHD-). Results. The level of Lp(a) was significantly higher in groups I, II, III in comparison with patients of control group (group IV): 34 [15; 80], 30 [10; 49], 22 [8; 60] mg/dl vs. 15 [6; 35] mg/dl respectively, p

The first attempts to treat patients with homozygous familial hypercholesterolemia (HCH) were performed in the 60ies and 70ies using a total plasma exchange. Later on, more specific lipoprotein apheresis (LA) methods have been developed – the replacement with foreign proteins was no longer necessary. It could be demonstrated that LA is life-saving in these patients, lipid-lowering drugs were shown to be much less effective than in other HCH patients. A severe HCH became an accepted indication for LA when cardiovascular events appeared. An elevation of Lipoprotein(a) (Lp(a)) is an internationally accepted independent atherogenic risk factor. Thus, an increasing number of patients with high Lp(a) concentrations suffering from life-threatening cardiovascular events like a myocardial infarction or a stroke started to be treated extracorporeally. Russian specific PocardR anti-Lp(a) columns are produced, their position within the LA methods is discussed. In the future, an antisense oligonucleotide against apolipoprotein(a) will represent another therapeutic option.

Elevated lipoprotein(a) plasma concentration - [Lp(a)] is considered a risk factor for cardiovascular disease (CVD). In African Americans (AA) have 2-3 times above [Lp(a)] than in Europeans and Asians, for example, in Chinese - 7.0 mg/dl, in black Sudanese - 46 mg/dl. Some authors believe that the apo(a) gene is the main determinant of the [Lp(a)] variation in AA, while others recognize the role of variant factors. The relationship between [Lp(a)] and the risk of CVD in AA is unclear: in meta-analysis under the Collaboration Emerging Risk Factors, at Europeans [Lp(a)] is associated with coronary artery disease, in AA - no. In Novosibirsk, from 96 men with confirmed surgically expressed coronary atherosclerosis [Lp(a)] is raised only in 16 %, and the high-atherogenous phenotype of apo(a) was detected in 20 %; but in the presence of unstable plaques (UP) in coronary arteries [Lp(a)] is 1.8 times higher than in persons without UP. Average [Lp(a)]+ ([Лп(а)]>0) at Chukchi male made 28,1 mg/dl, Chukchi female have 28,4 mg/dl, at Eskimos with [Lp(a)]+ the median of the [Lp(a)] - 22,4 mg/dl, and the mode - 15,5 mg/dl. In the aboriginals of Chukotka with AH, apo(a) S1, S2 occurred a little more frequently than among those without AH. Along with lipoprotein apheresis and niacin, apolipoprotein-(B-100)-antisense mipomersen, inhibitor of PCSK9 and apolipoprotein-(a)-antisense (oligonucleotide), showed promising results in reducing [Lp(a)]. In Russia, ehvolocumab and alirocoumab have been approved.

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.

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.

Most of the recent studies demonstrate that the quantitative level of Lp(a) and especially its low-molecular apo(a) phenotypes are independent risk factors of coronary atherosclerosis and correlate directly with the appearance, progress, and severity of manifestation of ischemic heart disease (IHD). Several studies investigated the quantitative levels of Lp(a) and low-molecular apo(a) phenotypes in patients with stroke or transient ischemic attacks taking into account the presence and severity of atherosclerosis of the main arteries of the head with high risk of stroke and cerebrovascular complications of atherosclerosis. These indices appeared to be less informative for diagnostics, prognosis, and the severity of clinical course of these disorders than for the coronary atherosclerosis and IHD. On the other hand, in the retrospective studies of patients with stroke, quantitative Lp(a) levels and its low-molecular apo(a) isoforms were significantly higher than in the control group of healthy individuals (standardized odds ratio was 1.37 and 1.74, respectively). The contradiction between the results obtained in the mentioned studies and the Physicians Health Study about the risk of the development of ischemic and other types of stroke may be explained by post-stroke augmentation of Lp(a) level and by the different significance of Lp(a) level and apo(a) phenotypes in different populations. There is no common opinion about necessity to correct high levels of Lp(a). But in case of augmented Lp(a) level, one of the actual strategy to influence the established risk factors of IHD is aggressive decreasing the concentration of cholesterol of low-density lipoproteins first of all that seems to be useful and reasonable in IHD patients. There are no highly effective methods of diet and / or drug management to correct the levels of Lp(a) and/or low-molecular phenotypes of apo(a), except for using high doses of nicotine acid, neomycin and estrogen-containing drugs. However, recommended doses of these drugs are associated with a lot of side effects. All these arguments evidence the necessity for determining the apo(a) phenotype/genotype and Lp(a) concentration levels.

A connection of the level of Lp(a) with the presence and extent of atherosclerosis of main arte ries of head was proved. It was demonstrated that this level in the patients who survived stroke is reliably higher than that in the patients from reference groups. A direct connection of low-molecular phe notypes of apo(a) with the presence, extent and development of atherosclerotic affection of carotid arteries was also proved. hypertension is a significant and independent risk factor of coronary heart disease. Other factors of cardiovascular risk including disorders of lipid metabolism, added to arte rial hypertension, increase the probability of the development of coronary heart disease even to the higher extent.

Aim. To investigate the association between serum homocysteine, lipoprotein(a) (Lp(a)) and coronary atherosclerosis in young and middle-aged men.Material and methods. The study included 40 men aged 29-58 years (mean age 43,8±6,2 years), with coronary heart disease (CHD) verified by coronary angiography. The control group (CG) included 27 CHD-free men. In all participants, concentrations of homocysteine, Lp(a), total cholesterol (TCH), triglycerides (TG), high-density lipoprotein CH (HDL-CH) were assessed. Low-density lipoprotein CH (LDL-CH) level was calculated using Friedewald formula.Results. Concentrations of homocysteine, Lp(a), TCH, and LDL-CH were significantly higher in CHD patients than in CG individuals: 12,4±5,8 and 10,0±2,9 micromol/l (p

Aim. To investigate associations between coronary heart disease (CHD) and levels of lipoprotein(a), Lp(a), apolipoprotein B, apoB, as important risk factors (RF). Material and methods. The study included 661 participants: 575 patients with confirmed CHD (302 males; mean age 63.21±12.1 years; 273 females, mean age 69.57±10.85 years), and 86 individuals without cardiovascular disease (CVD) at baseline (60 males, mean age 37.41±12.26 years; 26 females, mean age 40.53±12.04 years). Lipid profile: total cholesterol (TCH), triglycerides (TG), Lp(a), apoB – was assessed. Results. Significant difference between two groups was observed in t-test: for apoB level p=0.0000; for Lp(a) p=0.0069. Lp(a) and apoB levels correlated with other standard parameters of lipid profile – TCH, TG. ApoB level (mg/dl) was significantly higher in CHD patients with arterial hypertension (AH) than in normotensive patients, as well as in participants with anterior acute myocardial infarction (MI). Conclusion. Lipid profile parameters Lp(a) and apoB are important RF of CHD. Positive correlation between Lp(a) and TCH levels was observed only in CHD patients, in comparison with CVD-free individuals. In CHD patients with normal TCH and TG levels, increased apoB concentration (>120 mg/dl) was an important RF of CHD development, especially in AH individuals. ApoB level increase significantly correlated with acute MI risk (anterior MI, in particular) in CHD patients.

Aim. To study the level of lipoprotein(a) - Lp(a) in the blood serum and incidence of isoforms of apolipoprotein(a) - apo(a) in males and females with cholelithiasis and free of it in population of Novosibirsk; to assess possible correlations between Lp(a) level in the blood, apo(a) isoforms and bile lithogenicity in females with cholesterol cholelithiasis. Material and methods. Examination of the representative samples of 870 females aged 25-64 years and 405 males aged 35-54 years has detected cholelithiasis in 91 females and 19 males. Results. Serum levels of Lp(a) are associated with cholelithiasis. Risk of the latter in males (Lp(a) > 28 mg/dl) and females (Lp(a) > 24 mg/dl) is estimated. It is confirmed that isoforms of apo(a) B, S1 and S2 in females and isoforms of apo(a) B, S2 in males with cholelithiasis occur much more frequently than in individuals free of cholelithiasis while isoform apo(a) S4 is rare. Females with cholesterol cholelithiasis have positive correlation between blood Lp(a) levels, the presence of isoforms apo(a) B, S1 and bile lithogenicity. Conclusion. Males and females with cholelithiasis have more frequent high concentrations of Lp(a) (> 30 mg.dl) while low levels (0-5 mg/dl) are rare. There is a correlation between blood levels of Lp(a), apo(a) isoforms, bile lithogenicity in females with cholesterol cholelithiasis.

Background: Hyperlipoproteinemia (a) is an independent and cause risk factor for atherosclerotic cardiovascular diseases (ASCVD). The correlation between lipoprotein (a) Lp(a) and inflammation in the vessel wall was actively studied during the past few years. C-reactive protein (CRP) plays an important role in ASCVD., Aim: To analyze the relationship between hyperlipoproteinemia (a), inflammatory markers, and the early development of stenosing atherosclerosis (AS) in several vascular pools., Materials and Methods: 76 patients, 55 men aged 18 to 55 years and 21women 18 to 60 years, with the results of instrumental examination of coronary, carotid and lower extremities vascular pools were enrolled. Three groups: with stenosing (50%) AS of only one (group 1, n=29); two or three (group 2, n=21) vascular pools. 26 patients without coronary heart disease and AS were included in the control group. All patients in groups 1 and 2 and 65% of those in the control group took statins. The concentrations of Lp(a), CRP, lipids and blood count were determined., Results: The patients of the three groups did not differ in age. In the groups with AS (79% in group 1 and 85% in group 2), there were more men (relative to 54% in the control group). Diabetes mellitus was more common only in patients with multifocal AS. The absolute number of blood monocytes and leukocytes, the neutrophil-lymphocyte ratio, as well as Lp(a) level were higher in patients of groups 1 and 2 relative to the control. The maximum Lp(a) level (median [25%; 75%]) was observed in patients with lesions of two or more vascular pools vs the control group (49 [4; 96] mg/dL, vs 10 [4; 21] mg/dL, p=0.02). The CRP level was significant elevated in patients from group 2 7.2 [4.0; 9.7] mg/L, relative to group 1 2.5 [1.0; 4.7] mg/L, and the control group 2.9 [1.2; 4.9] mg/L, p0.05. The Lp(a) and CRP concentration, or the presence of diabetes mellitus in patients, regardless of other risk factors, were associated with severe stenosing AS in young and middle age., Conclusion: An elevated concentration of Lp(a) (30 mg/dL) determines the presence of both isolated and multifocal stenosing AS in the examined patients. A simultaneous increase in the concentration of both Lp(a) and CRP, as well as the presence of diabetes mellitus, are associated with the premature development of stenosing atherosclerotic lesions in several vascular regions at once. Measurement of these predictors in young and middle-aged patients makes it possible to use them as biochemical markers to assess the likelihood of multifocal lesions of the vascular pool.

Purpose: to study relationship of lipoprotein(a) [Lp(a)], indicators of systemic inflammation and humoral immunity with severity of atherosclerotic involvement of various vascular beds in women., Materials and Methods: We included in this study 148 women aged 69±11 years with results of instrumental investigation of coronary, carotid arteries, and arteries of lower extremities. According to results of coronary angiography and ultrasound study patients were distributed into two groups: with stenosing atherosclerosis (those with hemodynamically significant [&gt;50%] atherosclerotic lesions in any of these vascular beds, n=108), and control (those without hemodynamically significant stenoses, n=40). In dependence of extent of atherosclerotic involvement patients with stenosing atherosclerosis were divided into subgroups: with lesions in one vascular bed (subgroup 1, n=44) and with lesions in two and more vascular beds (subgroup 2, n=64). All patients with stenosing atherosclerosis and 78% of control patients took statins. In all patients we measured lipid spectrum, Lp(a) concentration, C-reactive protein (CRP). Preparations of oxidized lipoproteins [oxLp(a)] were obtained by Cu2+-induced free radical oxidation at 37 °С for 3 hours. Titer of autoantibodies to Lp(a), LDL and their oxidized modifications was determined by enzyme-linked immunosorbent assay (ELISA). Concentration of low-density lipoprotein cholesterol corrected on cholesterol in Lp(a) (LDLCh corr) was calculated by Dahlen modification of Friedewald formula., Results: Stenosing atherosclerosis was diagnosed in 60 of 74 women (80%) with Lp(a) concentration above median - 33 mg/dl (in 38 multifical). Increase of blood serum Lp(a) concentration was associated with presence of isolated as well as multifocal atherosclerosis according to unifactorial, multifactorial, and logistic analysis, irrespective of other factors of risk and indicators of inflammation. According to results of logistic regression analysis increase of Lp(a) concentration by 1 mg/dl was associated with 1 % elevation of probability of appearance and development of multifocal atherosclerosis in women. Low level of class IgM autoantibodies to Lp(a) was linked with detection of stenosing atherosclerosis in any of 3 vascular beds (1st vs. 4th quartile of IgM autoantibodies concentration - OR 7.6., 95%CI 1.9-29.4; р=0.004) and had diagnostic significance. Indicators of systemic inflammation such as CRP and circulating immune complexes were high and had diagnostic significance for detection of multifocal atherosclerosis in studied women. However none of indicators was predictor of appearance of stenosing atherosclerosis according to data of logistic regression analysis., Conclusion: Elevated concentration of Lp(a) is an independent predictor of risk of development stenosing atherosclerosis in various vascular beds and appearance of multifocal irrespective of other risk factors, indicators of systemic inflammation, and factors of humoral immunity in women. Markers of inflammation, as well as IgM autoantibodies against Lp(a) have diagnostic value for detection of patients stenosing lesions ib one or several vascular beds.

Aim: Lipoprotein(a) [Lp(a)] and low molecular weight (LMW) apolipoprotein(a) [apo(a)] phenotype are risk factors of сoronary heart disease and stroke. Data about the role of Lp(a) and phenotypes apo(a) in the development of lower extremity artery disease (LEAD) is scarce. The aim of our study was to assess the association of Lp(a), apo(a) phenotypes and autoantibodies to apolipoprotein B100 (apoB100) lipoproteins with LEAD., Materials and Methods: The study included 622 patients (386 male and 236 female, average age 61±12 years), examined in the Department of Atherosclerosis of National Medical Research Center of Cardiology. Patients were divided into 2 groups: the main group included 284 patients with LEAD, 338 patients without significant atherosclerosis of coronary, carotid and lower limbs arteries formed the control group. LEAD was diagnosed as atherosclerotic lesions with at least one stenosis of low limb artery ≥50 % and ankle-brachial index ≤0.9. The concentration of Lp(a), lipids was measured in blood serum of all the patients, level of autoantibodies to apoB100 lipoproteins was measured in 247 patients, and apo(a) phenotypes were determined in 389 patients., Results: Patients with LEAD were older, were more frequently male, and had a greater prevalence of risk factors including hypertension, type 2 diabetes, smoking than the control group patients (p&lt;0.001 in all the cases). The level of Lp(a) was significantly higher in the main group compared to control group: 35 [14; 67] mg / dl vs. 14 [5; 32] mg / dl, p&lt;0,001. ROC analysis demonstrated that the level of Lp(a) ≥26 mg / dl was associated with LEAD (sensitivity 61 %, specificity 70 %). The prevalence of Lp(a) ≥26 mg / dl and LMW apo(a) phenotype were higher in the main group in comparison with the control group: 61 % vs. 30 % and 48 % vs. 26 % respectively (p&lt;0.001 in the both cases). The odds ratio of LEAD in the presence of Lp(a) ≥26 mg / dl was 3.7 (95 % confidence interval (CI), 2.6-5.1, p&lt;0.001) and in the presence of LMW apo(a) phenotype was 2.6 (95 % CI, 1.7-4.0, p&lt;0.001). In logistic regression analysis adjusted for age, sex, hypertension, smoking, diabetes, both Lp(a) and LMW apo(a) phenotype were independent predictors of LEAD when included separately. The level of IgM autoantibodies to Lp(a) was significantly higher in the control group compared to the patients with LEAD (p=0.01). Concentration of IgG autoantobodies to Lp(a) and LDL in the plasma did not differ essentially in the both groups., Conclusion: The level of Lp(a) ≥26 mg / dl and LMW apo(a) phenotype are independent predictors of LEAD, whereas the contribution of autoantobodies to Lp(a) in LEAD development is controversial.

The serum level of lipoprotein (a) (LP(a] was measured in 117 patients with coronary heart disease (CHD) angiographically documented, 22 patients with unaltered coronary arteries as evidenced by coronary angiography (Control Group 1), and 28 subjects without clinical CHD signs (Control Group 2). Total cholesterol, triglycerides, low and high density lipoprotein cholesterol, and apolipoproteins (apo) AI and B were measured in the patients and healthy subjects. They were found to be higher in CHD patients than in patients with unaltered arteries and healthy subjects. The level of LP(a) was significantly increased in patients with three-vessel disease as compared to the control groups and patients with single-vessel disease. There was no relation of LP(a) to total cholesterol, triglyceride, high density lipoprotein cholesterol, low and very low density lipoprotein cholesterol, apo-AI, apo-B, age, and sex. The findings supports the assumption that LP(a) is associated with coronary atherosclerosis.

A total of 1139 representatives of various groups of the USSR population (indigenous inhabitants of Chukotsk and the Altai, migrants to Chukotsk living there for various periods of time and citizens of Novosibirsk) was studied to determine whether the assay of Lp (a)-lipoproteins, a normal genetic marker, can be used as a novel diagnostic test for coronary heart disease. Coronary heart disease was shown to be correlated with the presence of Lp (a)-lipoprotein, with X2 being statistically significant.