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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, pConclusion. HLP(a) is an independent factor of premature CAD, even with normolipidemia, which confirms the need for routine measurement of Lp(a) in clinical practice.

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, pConclusion. Every fourth patient with premature ACS has FH, while almost every second has HLP(a), and every eighth has a combination of FH and HLP(a). HLP(a) is associated with ACS up to 60 years of age and multivessel coronary artery disease in these patients.

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.

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, pConclusion.In the patients with chronic CHD, undergoing statin therapy, the levels of ATX, autoantiboides IgM against the oxLpa and relation of neutrophils to lymphocytes, but not the concentration of Lpa and low molecular phenotype of apo(a), were related to AS presence.

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.