Sheep polyclonal antibodies to human lipoprotein(a) were used for the development of sandwich enzyme immunoassay. These antibodies virtually do not interact with human plasminogen, apoB-100, or fibrinogen in this assay. The method permits measurements of lipoprotein(a) in a wide range of concentrations: from 2 to 500 mg/dl. The variability of analyses within the range of 5 to 180 mg/dl is approximately 4.5% in a plate and 10.5% in different tests. Correlation analysis of the results of the enzyme immunoassay modification developed in our laboratory and of its foreign analogs showed a high similarity of the methods, the correlation coefficient being 95%.Lipoprotein(a), or Lp(a), is a lipoprotein particle containing a protein apo(a) unique to the lipoprotein family; it is bound to molecule apoB-100 with a covalent disulfide bond, and this molecule is the principal protein component of a corpuscle of low-density lipoprotein (LDL). Lp(a) was discovered by Berg in 1963 as a new antigen of human plasma and as a variant of LDL corpuscles [2]. Further studies showed that Lp(a) differs from LDL not only in composition, molecular weight, and electrophoretic mobility, but also in physiological role and metabolism [12].Active studies of Lp(a) were started after it was shown to be associated with the risk of atherosclerotic involvement of the heart [4], Further investigations clearly demonstrated that a high level of Lp(a) in the blood is closely related to the appearance and development of atherosclerotic lesions in various arteries [7,12].

Липопротеид(а) (Лп(а)) представляет собой сложный надмолекулярный комплекс, принадлежащий к апоВ 100-содержащим липопротеидам. Лп(а) состоит из частицы подобной липопротеидам низкой плотности, в которой молекула апобелка В 100 ковалентно связана дисульфидной связью с уникальной полиморфной молекулой апобелка(а). Концентрация Лп(а) генетически контролируется, при этом варьирует в очень широком диапазоне. Повышенный уровень Лп(а) является независимым фактором риска атеросклероза коронарных, сонных и периферических артерий, ишемической болезни сердца и стеноза аортального клапана, сопутствующих сердечно-сосудистых осложнений, а также осложнений после операций реваскуляризации миокарда. Несмотря на это, уровень Лп(а) по-прежнему не учитывается в стратификации риска сердечно-сосудистых заболеваний. Отчасти это может быть связано с тем, что ни современная лекарственная терапия, ни новые поколения биологических гиполипидемических препаратов практически не влияют на концентрацию Лп(а), за исключением 20-30% снижения Лп(а) никотиновой кислотой и ингибиторами пропротеиновой конвертазы субтилизин-кексин 9 типа (PCSK9). Обзор освещает современные представления о Лп(а) как факторе риска сердечно-сосудистых заболеваний, возможности и целесообразности его определения, а также посвящен современным возможностям коррекции гиперлипопротеидемии(а).

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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.

We studied the composition of circulating immune complexes precipitated in the presence of various concentrations of polyethylene glycol in patients with coronary heart disease (CHD) and high concentration of lipoprotein(a) - Lp(a). Precipitation of highly purified Lp(a) preparation with polyethylene glycol was evaluated. The contents of Lp(a), autoantibodies to Lp(a), IgG, and IgM in circulating immune complexes isolated from the sera of donors and CHD patients with normal and high levels of Lp(a) were measured. Circulating immune complexes containing Lp(a) were detected in the plasma of CHD patients with high Lp(a) concentrations. The presence of high concentrations of Lp(a), autoantibodies to Lp(a), and circulating immune complexes in CHD patients suggests that immunological factor contributes to high atherothrombogenicity of Lp(a).

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.

Цель. Изучить связь концентрации липопротеида(а) [Лп(а)], подфракций липопротеидов промежуточной (ЛПП) и низкой (ЛНП) плотности у пациентов с впервые выявленной тяжелой гиперхолестеринемией (ГХС) с вероятностью диагноза семейной ГХС (СГХС). Материал и методы. В исследование включены 114 пациентов с впервые выявленной тяжелой ГХС (холестерин ЛНП >4,9 ммоль/л), без диагноза ишемической болезни сердца и не получавших гиполипидемическую терапию. Для оценки вероятности диагноза СГХС использовали голландские критерии Dutch Lipid Clinics Network. Показатели липидного спектра определяли ферментативным методом; Лп(а)-методом иммуноферментного анализа; подфракции липопротеидов с помощью системы Липопринт ® (Quantimetrix, США). Результаты. Все пациенты были разделены согласно голландским критериям на две группы: I-(n=86) с возможной СГХС (3-5 баллов) и II-(n=28) с определенной или вероятной СГХС (≥6 баллов). Пациенты II группы имели более высокие уровни атерогенных апоВ100-содержащих липопротеидов относительно пациентов I группы:

Aim.Lipoproteide (a) (Lpa) is a pathogenetic risk factor of cardiovascular atherosclerotic disease. On the role of Lpa in the development of cardiovascular complications (CVC) after lower limbs arteries revascularization, there is lack of data. The aim of the study was assessment of Lpa relation to CVC occurrence after revascularization of lower extremities during 1 year follow-up.Materialand methods.In the study, 111 patients were included (97 males, 14 females, mean age 66±9 y.o.), who had undergone revascularization of lower libms arteries due to atherosclerosis. As CVC during 1 year follow-up, the following were taken: recurrent intermittent claudication, lower extremity amputation, ischemic stroke, transient cerebral ischemia, non-fatal myocardial infarction, unstable angina, repeat revascularization and cardiovascular death. In all patients, in the blood serum, there were measured lipids and Lpa.Results.Within 1 year after revascularization there were 45 (41%) CVC. In the group with raised Lpa ≥30 mg/dL there were more CVC than in Lpa <30 mg/dL: relative risk 2,1 (95% CI 1,3-3,5; p=0,004). Hence the increased level of Lpa is an independent predictor of CVC after revascularization of lower extremities arteries.Conclusion.In prospective study, during 1 year after revascularization the level of Lpa ≥30 mg/dL is associated with double increase of the risk of CVC.