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The evidences for statin use in cardiology are presented. Especially hypolipidemic efficacy of atorvastatin is demonstrated in according to comparative studies. Results of clinical studies on atorvastatin efficacy and safety in different groups of patients are also presented.

Aim. To evaluate quality of life changes and compliance to therapy in patients following successful transluminal angioplasty, who have indications for fluvastatin extended release in addition to standard treatment. Material and methods. This is a national observational multicenter study. An inclusion of 60 investigator centers is planned (out-patient medical centers), the total number of patients to be included is 600. Patients (men and women) with coronary heart disease following successful transluminal coronary angioplasty, who were prescribed fluvastatinextended release (Lescol Forte, Novartis) 80 mg once daily will be included in the observation. The following efficacy and safety parameters will be evaluated: quality of life assessed with SF-36 scale before and during treatment; compliance to therapy; adverse events and serious adverse events. Observation period is planned for 6 months. During this period patient is expected to make 4 visits to treating physician. According to the physician’s decision, observation period can be extended to 12 months. Present study status. The study is completed. 524 patients completed the observation, including 116 patients who were followed up for 12 months. There are 414 men (79%) and 110 women (21%) among patients enrolled into the study.

Familial Hypercholesterolaemia (FH) is the commonest autosomal co-dominantly inherited condition affecting man. It is caused by mutation in one of three genes, encoding the low-density lipoprotein (LDL) receptor, or the gene for apolipoprotein B (which is the major protein component of the LDL particle), or in the gene coding for PCSK9 (which is involved in the degradation of the LDL-receptor during its cellular recycling). These mutations result in impaired LDL metabolism, leading to life-long elevations in LDL-cholesterol (LDL-C) and development of premature atherosclerotic cardiovascular disease (ASCVD) [1], [2] and [3]. If left untreated, the relative risk of premature coronary artery disease is significantly higher in heterozygous patients than unaffected individuals, with most untreated homozygotes developing ASCVD before the age of 20 and generally not surviving past 30 years [2], [3], [4] and [5]. Although early detection and treatment with statins and other LDL-C lowering therapies can improve survival, FH remains widely underdiagnosed and undertreated [1], thereby representing a major global public health challenge.

Objective: To examine the association between the kinetics of very-low-density-lipoprotein (VLDL)-apolipoprotein B-100 (apoB) and intraperitoneal, retroperitoneal, subcutaneous abdominal, and total adipose tissue masses (IPATM, RPATM, SAATM, and TATM, respectively) in overweight/obese men. Research Methods and Procedures: Hepatic secretion of VLDL was measured using an intravenous infusion of 1-[13C]-leucine in 51 men with a wide range of body mass index (25.1 to 42.2 kg/m2). Isotopic enrichment of VLDL-apoB was measured using gas chromatography-mass spectrometry and a multicompartmental model used to estimate VLDL-apoB metabolic parameters. IPATM, RPATM, and SAATM (kilograms) were quantified between T11 and S1 using magnetic resonance imaging; TATM (kilograms) was determined using bioelectrical impedance. Insulin resistance was estimated by homeostasis model assessment (HOMA) score. Results: In stepwise regression, IPATM was the best predictor of hepatic secretion of VLDL-apoB (r = 0.390, p < 0.005) and TATM was the best predictor of VLDL-apoB fractional catabolic rate (r = 0.282, p < 0.05). IPATM remained significantly associated with VLDL-apoB secretion after adjusting for TATM or HOMA score (r = 0.360, p < 0.01 and r = 0.310, p < 0.05, respectively). This association was also independent of age, dietary intake, and body mass index. None of the fat compartments were significantly associated with the fractional catabolic rate of VLDL-apoB after adjusting for HOMA score. Discussion: In overweight/obese men, the quantity of both IPATM and TATM determine the kinetics of VLDL-apoB. The effect of IPATM on VLDL-apoB secretion is independent of both total fat mass and the degree of insulin resistance.

An international panel of the International Atherosclerosis Society has developed a new set of recommendations for the management of dyslipidemia. The panel identifies non high-density lipoprotein cholesterol as the major atherogenic lipoprotein. Primary and secondary prevention are considered separately. Optimal levels for atherogenic lipoproteins are derived for the two forms of prevention. For primary prevention, the recommendations emphasize lifestyle therapies to reduce atherogenic lipoproteins; drug therapy is reserved for subjects at greater risk. Risk assessment is based on estimation of lifetime risk according to differences in baseline population risk in different nations or regions. Secondary prevention emphasizes use of cholesterol-lowering drugs to attain optimal levels of atherogenic lipoproteins. Published by Elsevier Inc. on behalf of National Lipid Association.

An international panel of the International Atherosclerosis Society has developed a new set of recommendations for management of dyslipidemia. The panel identifies non-high density lipoprotein cholesterol (non-HDL-C) as the major atherogenic lipoprotein. Primary and secondary prevention are considered separately. Optimal levels for atherogenic lipoproteins are derived for the two forms of prevention. For primary prevention, the recommendations emphasize lifestyle therapies to reduce atherogenic lipoproteins; drug therapy is reserved for higher risk subjects. Risk assessment is based on estimation of lifetime risk according to differences in baseline population risk in different nations or regions. Secondary prevention emphasizes use of cholesterol-lowering drugs to attain optimal levels of atherogenic lipoproteins.

The review describes the history of hypolipidemic therapy with statins. It gives the results of studies of the primary prevention of atherosclerosis and the treatment of hyperlipidemias with lovastatin, pravastatin, and fluvastatin. Emphasis is laid on trial data on the efficacy, tolerability, and safety of simvastatin (zocor). The results of studies, including regression ones, of this drug in different doses, controlled by biochemical, clinical, magnet resonance imaging, and ultrasonic data are summarized. There is a significant reduction in the risk of cardiovascular, coronary, and overall deaths and in that of stroke. There is evidence for the successful use of simvastatin (zocor) in combined therapy with fibrates, nicotinic acid, and ezetrol.

Substantial residual risk of development of macro- and microvascular complications is retained in most patients despite contemporary standards of therapy. The search for the solution of actual problem of lowering of residual risk of vascular complications is the aim of multiple current scientific studies conducted in medical practice of the world. The program Residual Vascular Risk Reduction Initiative (R3i) was called upon to join efforts of medical professionals and patients from different countries for solution of the global problem of residual risk of development of vascular complications. In the review we describe objective and main directions of activity of this project. We also give characteristics of individual component factors of residual risk of development of vascular complications investigated in the framework of the R3i program as well as possible methods of improvement of their correction.

To elucidate effect of two doses of atorvastatin (10 and 20 mg/day) on endothelial function, distensibility and stiffness of vascular wall.Patients (n=50) with documented ischemic heart disease and hyperlipidemia were randomized to 10 or 20 mg/day of atorvastatin (Atoris, KRKA). Endothelial function and common carotid artery wall distensibility and stiffness were assessed at baseline and after 12 and 24 weeks of treatment.Administration of both 10 and 20 mg/day doses of atorvastatin for 6 weeks was associated with significant lowering of total cholesterol (CH), triglycerides (TG) and low density lipoprotein (LDL) CH (24.5, 18.4, 34.9% and 29.1, 28.2, 40.9%, respectively). After 24 weeks LDL CH lowering from baseline reached 34.9 and 43.9% (p0.001) and that of TG - 22 and 15%, in 10 and 20 mg/day groups, respectively. There were no significant differences between 10 and 20 mg/day groups in baseline values of endothelium dependent vasodilation (EDV), carotid artery distensibility and stiffness (7.28 and 6.64%, 21.60 and 20.15, 8.04 and 9.19 U, in 10 and 20 mg/day groups, respectively). After 3 months of treatment there occurred significant 38.4% (10 mg/day) and 45.4% (20 mg/day) increases of EDV. Significant 27.6% (10 mg/day) and 28.8% (20 mg/day) enhancement of vascular distensibility was noted after 24 weeks. Vascular wall stiffness decreased 33.4% (p=0.008) and 31.3% (p=0.002) in 10 and 20 mg/day groups, respectively.

Main aim of the clinical study FARVATER was comparison of effects of 10 and 20 mg/day of atorvastatin on levels of lipids, high-sensitivity C-reactive protein (CRP), fibrinogen (F), and structural-functional state of vascular wall in patients with documented and primary hyperlipidemia (HLP). Fifty patients (mean age 60.8 years) with documented ischemic heart disease and HLP were randomized to continuous administration of 10 and 20 mg/day atorvastatin for 24 weeks. Initial levels of total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDLCH), high density lipoprotein cholesterol (HDL CH), CRP and F were 6.22, 1.86, 4.15, 1.24 mmol/l, 1.46 and 2.93 g/l, respectively. After 6 weeks lowering of TCH, TG and LDLCH was significant both in 10 (24.5, 18.4, and 34.9%, respectively) and 20 mg (29.1, 28.2, and 40.9%, respectively) groups. After 24 weeks TG levels decreased by 22 and 15% in 10 and 20 mg subgroups, respectively. Changes of HDLCH (+11 and +12% in patients treated with 10 and 20 mg, respectively) were not significant. There were no significant changes of CRP and F levels. Seven side effects (4%) were registered during 24 weeks; 2 were related to study drug (allergy and symptomless elevation of creatine kinase).

Efficacy and tolerability of atorvastatin (20 mg/day) were assessed in a 3 month study on 19 patients (5 men, 14 women, mean age 52.3 years) with familial hypercholesterolemia. Average baseline levels of total cholesterol (CH) and low density lipoprotein (LDL) CH were 10.7 and 8.6 mmol/l, respectively. By the end of 3 months levels of CH, LDL CH, triglycerides and atherogeneity index decreased by 32, 41, 16 and 45%, respectively. This was accompanied by 21% increase of high density lipoprotein CH level. There were no cases of AST or ALT activity elevation above 3 upper limits of normal values. However 1 patient had asymptomatic elevation of ALT activity up to 53 U/l which did not cause interruption of therapy. Creatine kinase remained normal throughout the study period. Three patients (16%) stopped taking atorvastatin because of side effects. Thus in patients with familial hypercholesterolemia the dose of atorvastatin 20 mg/day was sufficiently well tolerated and provided effective control of lipid levels.

To study the influence of treatment with HMG-CoA reductase inhibitor atorvastatin on endothelial function in patients with familial hypercholesterolemia type IIa.Sixteen patients (5m/11w, 51-/+3 years) with familial hypercholesterolemia were studied before and after 3 months of therapy with atorvastatin 20 mg/day. EDRF release test (D.Celermajer, 1992) was used to assess flow-mediated endothelium-dependent vasodilatation (FMD) of the brachial artery in response to reactive hyperemia. Plasma nitrite/nitrate (NOx) levels were measured as an indirect index of nitric oxide (NO) production in vivo using HPLC.Atorvastatin treatment resulted in a 32% reduction in total serum cholesterol (CH), 41% reduction in low density lipoprotein (LDL) CH, 16% reduction in triglycerides and a 21% increase in high density lipoprotein CH. Flow mediated dilatation (FMD) was impaired at baseline (5.8-/+0.9%) and significantly improved up to 9.5-/+0.9% after 3 month atorvastatin therapy (p0.002). Change in FMD inversely correlated with baseline FMD (r = -0.58, p0.05). There was no significant correlation between FMD and neither total serum CH nor LDL CH levels at baseline. During atorvastatin therapy significant reduction of plasma NOx levels occurred from 53.4-/+5.1 mcmol/l at baseline (range 42.6-86.2 mcmol/l) to 35.5-/+5.1 mcmol/l (18.4-46.0 mcmol/l) after treatment (p0.02, n=7).In patients with familial hypercholesterolemia atorvastatin produced beneficial effect on endothelial function (increase in flow-mediated dilatation, decrease in NOx).

To analyze retrospectively data on lipid lowering efficacy, tolerability and safety of different doses of simvastatin in patients with primary hyperlipidemia.Thirty five patients (mean age 54.9-/+8.5 years, 15 men, 20 women) received simvastatin for 3-6 months in doses 10 (n=12), 20 (n=8), 40 (n=10) and 80 (n=5) mg/day. Average lowering of low density lipoprotein cholesterol was 28.9, 37.6, 39.7, and 46.2% on doses 10, 20, 40 and 80 mg/day, respectively. Elevation of activity of transaminases (AST and ALT) above 3 upper limits of normal (ULN) accompanied by right upper quadrant pain occurred in 1 patient and the drug (10 mg/day) was stopped. Symptomless elevation of AST and ALT activities above 2 ULN was registered in 2 other patients receiving 10 and 20 mg/day. The dose of 80 mg/day was well tolerated - none of 5 patients had symptoms of myopathy or elevated creatinekinase activity.

To study effect of simvastatin of the level of high density lipoprotein (HDL) cholesterol (CH).Simvastatin (40 mg/day) was given for 3 months to 15 patients (3 men, 12 women, mean age 56-/+10.3 years) with hereditary type II hypercholesterolemia after washout from lipid lowering therapy. Initial level of HDL CH was below and above 1.0 mmol/l in 7 and 8 patients, respectively. Blood lipids, activity of liver enzymes and creatine kinase were determined after 1 and 3 months of therapy with simvastatin. Safety and tolerability of simvastatin were also studied.Simvastatin was well tolerated. In 1 patient the drug was stopped because of pain in the liver and nausea. In patients with initially low HDL CH levels of total and low density lipoprotein (LDL) CH significantly decreased by 29.6 and 36.8%, respectively, after 3 months, while level of HDL CH increased by 20% after 1 month of therapy. In patients with initially normal HDL CH levels of total and LDL CH significantly decreased by 31.1 and 32.6%, respectively, while those of triglycerides and HDL CH did not change.In patients with hereditary hypercholesterolemia 40 mg/day of simvastatin besides pronounced lowering of LDL CH level caused significant increase of HDL CH (up to 20% in 1 month) in patients with initially low level of this parameter.

To reveal the metabolic parameters of lipoproteins (L), which determine the benefits of hypolipidemic effects of simvastatin (S) and fluvastatin (F); to trace changes in the activity of lecithin-cholesterol acyltransferase (LCA) and cholesterol (C) ester transfer (CET) from high density lipoproteins to very low density lipoproteins (VLDL) and low density lipoproteins (LDL) and the levels of apoE in the blood and in some L classes during therapy with the above drugs.Thirty six patients took S, 10 mg/day, and 25 received F, 20 mg/day, for 3 months. The levels of lipids were measured by enzyme assays, apoprotein (apo) was determined by immunoturbidimetry and immunodiffusion.The hypocholesterolemic and hypotriglyceridemic effect of S (19.6 and 25.5, respectively) and F (19.0 and 30.5%) were similar. With S, the reduction in the blood levels of C and LDL C positively correlated with the baseline apoE levels. With F, it did with C and LDL C before treatment. Lower blood apoE was found with S and F and lower HDL apoE/(VLDL + LDL) ratio was detected only with F. F treatment significantly lowered the activity of CET and LCA; before and after S treatment, they did not differ significantly.Analyzing the relationship between the benefits of the hypolipidemic effect and the baseline parameters of L metabolism indicates that the changes in serum C, LDL C and HDL C are due to the composition of HDL particles and the distribution of apoE among different L classes in the patient to a greater degree.

The study of the hypolipidemic efficiency, safety and tolerance of ciprofibrate (lipanor) in therapy of atherogenic hyperlipoproteinemia.The trial included 14 hypertensive postmenopausal females, 14 patients with diabetes mellitus type II, 14 males with coronary heart disease and primary hyperlipoproteinemia (total cholesterol6.5 mmol/l, triglycerides4.5 mmol/l under low-cholesterol diet). Lipanor was given for 12 weeks in a daily single dose 100 mg in the morning. Lipids and other biochemical indices were measured in a fasting state after 1 and 3 months of lipanor treatment.After 1 month of lipanor treatment there was a 22-30%, 24-49% decrease in the level of low-density lipoprotein cholesterol, triglycerides, respectively. High-density lipoprotein cholesterol increased by 16%. The hypolipidemic effect of lipanor persisted for 3 months during which triglycerides continued to fall (up to 38.5%). Lipanor was well tolerated, only one patient with diabetes mellitus had hyperactivity of creatine phosphokinase manifesting with clinical symptoms (the drug was discontinued). 3 patients developed mild side effects. Alkaline phosphatase activity inhibited in all the groups by 25-41%.Lipanor is a highly effective, safe hypolipidemic drug with good tolerance. It can be recommended for correction of atherogenic hyperlipoproteinemia in patients at high risk of atherosclerosis progression.

The study was undertaken to enhance the effectiveness of a low-density lipoprotein apheresis procedure by using the mathematical approach to choosing an individual sorption regimen for each patient when the cholesterol concentration given by a physician was achieved in the shortest time. The experimental estimation of time course of changes in plasma cholesterol levels at the column inlet and outlet during low-density lipoprotein apheresis allowed the optimal parameters of the procedure to be calculated. The adequacy of the proposed methods to the real data was examined by the paired t-test (p0.0001). The optimal regimen was chosen for 5 patients with familial hypercholesterolemia. It is shown that the optimization of the regime will reduce the time of the procedure to 47 min, by removing the same amount of a substance.

Lipoprotein (a) [L(a)] is an atherogenic lipoprotein, its human plasma concentration correlates with the occurrence of coronary heart disease. The procedure for selectively removing L(a) with an anti-L(a) immunosorbent was performed to treat 3 patients who had high L(a), normal total cholesterol and other lipoprotein levels. All the patients had coronary stenosis as documented by angiography. After L(a)-apheresis, the level of L(a) decreased by 72%, while that of other plasma components, including low density lipoproteins virtually unchanged. Thus, the procedure of L(a)-apheresis is an effective and safe method for lowering human blood L(a) concentrations. In addition, this in vivo model allows information on L(a) metabolism to be obtained.

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.