[Improvement of outcomes in patients with recent acute coronary syndrome: the place of PCSK9 inhibitors. The Resolution of National Advisory Board].

On April 9, 2018, the national advisory board "Improvement of outcomes in patients with recent ACS: the place of PCSK9 inhibitors" was held in Moscow. Leading Russian experts in the field of atherosclerosis and lipid-lowering treatment attended the board. The purpose of the Board was to determine the place of PCSK9 inhibitors in the improvement of outcomes in patients with recent (less than 1 year) acute coronary syndrome (ACS). During the Board, three major aspects of lipid-lowering treatment were discussed: 1) issues in reaching the target levels of LDL cholesterol in real clinical practice among patients with recent ACS; 2) the results of ODYSSEY OUTCOMES study and their role in the improvement of outcomes in patients with recent ACS; 3) treatment with PCSK9 inhibitors in the management of patients with recent (less than 1 year) ACS in everyday clinical practice, the role of lipid centers.

[Diagnosis and treatment of disturbances of lipid metabolism in children and adolescents].

It has been demonstrated in prospective and epidemiological studies that excessive consumption of saturated and trans-fats, refined carbohydrates, epidemic of obesity and metabolic syndrome in children and adolescents have prognostic value in relation to development of cardiovascular diseases (CVD) in adults. Pediatricians should initiate long-term prevention of CVD in early age. At present there are scientific data on safety and efficacy of drugs in the treatment of dyslipidemia in adolescent age. A review of clinical studies on detection, diagnosis, prevention, and drug correction of lipid disturbances among children and adolescents is presented in this paper. Main statements of recommendations of American Academy of Pediatrics "Cholesterol in Childhood" are analyzed in detail.

[Attitude of district internists to the problem of secondary prevention of ischemic heart disease (results of a special questionnaire survey)].

Attitude of district internists to the realization of a concept of secondary prevention (SP) of ischemic heart disease was studied in one of large cities in Russia. Among preparations most necessary for SP the following were named: b-blockers (79.5%), angiotensin converting enzyme inhibitors (49.3%), antiaggregants (43.8%), hypolipidemic drugs (13.7%), nitrates (63%), biologically active supplements, phyto-preparations, metabolic drugs, and glycosides (3-5% each). However actually prescribed drugs were b-blockers (100%), nitrates (96%), angiotensin converting enzyme inhibitors (89%), calcium antagonists (87%), antiaggregants (83%), cardiac glycosides (66%), vitamins (39%). Average doses of drugs were low: 21.7, 47.4 and 35.5% of possible maximal doses for statins, angiotensin converting enzyme inhibitors, and beta-blockers, respectively. Nondrug measures were used "rarely" and "often" by 26 and 74% of physicians, respectively. Only 18% of physicians directed their patients to corresponding specialists. Recommendations were mostly formal, without explanation of goals, methods and specific features of recommended measures. Moreover their prescription by physician was determined largely by subjective factors: availability of sufficient time (50%), cultural level of a patient (79%), patient's own initiative (33%), physician's personal attitude to a patient (21%).

[Rehabilitation of patients with ischemic heart disease at outpatient stage.].

The article is assigned to general practitioners and devoted to the outpatient combined rehabilitation of coronary heart disease patients, including those after myocardial infarction. In the part concerning the physical rehabilitation there is given the classification of patients by functional classes, the exercise programs of middle intensity for sport and home training. The formula of selection of the walking training temp according to the results of exercise stress test is given. There are presented the psychodiagnostic methods that evaluate the psychological reactions of patients on the disease, and the methods of psychological rehabilitation with use of psychopharmacotherapy. Special part is devoted to the educational program for patients.

Simvastatin and preparation of polyunsaturated phospholipids produce similar changes in the phospholipid composition of high-density lipoproteins during hypercholesterolemia.

We studied the phospholipid composition of high-density lipoproteins in patients with coronary heart disease and hypercholesterolemia treated with simvastatin (Zocor, inhibitor of the key enzyme of cholesterol synthesis) and preparation of polyunsaturated phospholipids (lipostabil forte). Simvastatin produced a hypolipidemic effect and modulates the phospholipid composition of high-density lipoproteins (similarly to lipostabil forte). These changes contribute to functional activity of high-density lipoproteins in the reverse cholesterol transport.

[Clinical efficacy of tianeptine in patients with ischemic heart disease and comorbid depression]. / Klinicheskaia éffektivnost' tianeptina u bol'nykh ishemicheskoi bolezn'iu serdtsa s komorbidnoi depressiei.

Ischemic heart disease patients (20 men, 20 women, age 36-72 years) with class II-III effort angina and depression (Beck Depression Inventory -- BDI -- score > or = 19) were randomized to standard therapy were treatment of stable ischemic heart disease (control group) or standard therapy plus tianeptine 37.5 mg/day. After 6 weeks 52% decrease of BDI score occurred in tianeptine treated patients (from 24.9+/-1.2 to 11.9+/-1.5, p<0.001). This was associated with decrease of number and severity of cardialgias, better blood pressure control in patients with hypertension, lengthening of exercise time during exercise test (by 3.3+/-0.9 min, p<0.05), and increase of overall index of quality of life (by 2.6+/-0.9 points, p<0.01). No dynamics of these parameters occurred in control group.

Effects of simvastatin on the phospholipid composition of high-density lipoproteins in patients with hypercholesterolemia.

We studied the phospholipid composition of high-density lipoproteins in patients with hypercholesterolemia before and after treatment with simvastatin. Individual phospholipids were separated by thin-layer chromatography on glass plates coated with silica gel. It was found that apart from hypolipidemic effect, simvastatin changed the concentration and phospholipid composition of high-density lipoproteins, which improved their cholesterol-accepting and cholesterol-transporting properties.

Phospholipid composition of high-density lipoproteins reflects lipolysis of triglyceride-rich lipoproteins during hyperlipidemia.

We studied phospholipid composition of high-density lipoproteins in patients with normo- and hypertriglyceridemia treated with various hypolipidemic preparations (simvastatin and fenofibrate). Both preparations changed phospholipid composition of high-density lipoproteins and improved their functional activity. The differences in the phospholipid composition of high-density lipoproteins were probably related to lipolysis of triglyceride-rich lipoproteins catalyzed by lipoprotein lipase and, in particular, hepatic lipase.

Cerivastatin modulates antiatherogenic properties of high-density lipoproteins in patients with coronary heart disease and hyperlipidemia.

The effects of cerivastatin on antiatherogenic properties of high-density lipoproteins were studied in patients with coronary heart disease and hyperlipidemia. Apart from hypolipidemic effects, cerivastatin changed the phospholipid composition of high-density lipoproteins and improved their cholesterol-acceptor properties. This effect was most pronounced in the serum from patients with low content of high-density lipoprotein cholesterol. These data indicate that cerivastatin modulates antiatherogenic properties of high-density lipoproteins.

Antiatherosclerotic and antiatherogenic effects of a calcium antagonist plus statin combination: amlodipine and lovastatin.

Recently, the Regression Growth Evaluation Statin Study (REGRESS) demonstrated the synergistic, antiatherogenic effect of lipid-lowering therapy with pravastatin in combination with calcium antagonists. This combination retarded the progression of stenosis and reduced the number of new lesions more effectively than did statin therapy alone. In the present study, our objective was to elucidate the mechanism of this more pronounced effect of the statin-calcium antagonist combination on the atherosclerotic lesion. Smooth muscle cells cultured from the subendothelial intima of the human aorta were incubated with whole blood serum or with low-density lipoprotein (LDL) taken from patients cotreated with lovastatin and amlodipine. Serum added to the cells cultured from the atherosclerotic lesion reduced cell cholesterol. Such an antiatherosclerotic effect of cotreatment with amlodipine-lovastatin was revealed in this study and was more pronounced than the effect of treatment with either amlodipine or lovastatin alone. LDL isolated from atherogenic plasma stimulated cell cholesterol accumulation. Treatment with amlodipine alone and the amlodipine-lovastatin combination ameliorated the atherogenic effect of LDL. As compared with amlodipine alone, the combination demonstrated a considerably higher antiatherogenic effect on LDL atherogenicity. Amlodipine-lovastatin cotreatment increased sialic acid and decreased the susceptibility of LDL to oxidation more effectively than amlodipine alone. In addition, combination therapy reduced the LDL negative charge, while amlodipine alone was impotent. These findings may serve as an explanation of the more pronounced antiatherogenic effect at the lipoprotein level of amlodipine-lovastatin combined therapy compared with amlodipine therapy alone.

Clinical trial of wax-matrix sustained-release niacin in a Russian population with hypercholesterolemia.

OBJECTIVE: To assess the clinical effectiveness and tolerability of wax-matrix, controlled-release nicotinic acid (CNA) in persons with hypercholesterolemia. DESIGN: Randomized, double-blind, placebo controlled, crossover trial. SETTING: Ambulatory clinic at an academic cardiology center in Moscow, Russia. PATIENTS: A volunteer sample of 135 men and women, aged 20 to 70 years, with hypercholesterolemia greater than 5.82 mmol/L (225 mg/dL) (70th-95th percentile for age and sex) who otherwise met study inclusion and exclusion criteria, were initially recruited into the study. Cholesterol levels were reduced to less than 5.82 mmol/L (225 mg/dL) in 46 subjects who participated in the initial diet intervention and were excluded from the drug intervention. Eighty-nine subjects were randomized into the clinical trial; 4 subjects (4.5%) dropped out of the study because of intolerance of CNA. INTERVENTION: Eight weeks of diet alone (American Heart Association Step I Diet) was followed by randomization to 2 treatment groups (1500 mg/d CNA [ENDURACIN] or placebo) for 2 months followed by a crossover of treatments for 2 months, followed by all subjects taking 2000 mg/d of CNA for 2 months. MAIN OUTCOME MEASURES: Significant improvements in baseline measures for total serum cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were observed after initial diet (TC, 6%; LDL-C, 6%; P < .001, t test), after 1500 mg/d CNA (TC, 14%; LDL-C, 18%; P < .001, t test), and after 2000 mg/d CNA (TC, 16%; LDL-C, 21%; P < .001, t test). Triglyceride, high-density lipoprotein cholesterol, and lipoprotein(a) levels also improved. No serious toxic reactions were encountered, and 4 subjects withdrew from the study because of intolerance of cutaneous and gastrointestinal adverse effects. CONCLUSION: Wax-matrix CNA is an effective and well-tolerated pharmacological treatment for hypercholesterolemia.

[The hypolipidemic effect of and tolerance for Lescol in treating hypercholesterolemia in hypertension patients (an analysis of the data from a multicenter study)]. / Gipolipidemicheskii éffekt i perenosimost' leskola pri lechenii giperkholesterinemii u bol'nykh gipertoniei (analiz dannykh mnogotsentrovogo issledovaniia).

Hypertensive patients with hyperlipidemia are at high risk to develop coronary heart disease (CHD). Chemotherapeutic correction of hyperlipidemia seems most reliable modality to prevent CHD. Hypolipidemic effect and tolerance of leskol (fluvastatin) in dietotherapy-resistant hypercholesterolemia were studied in 74 patients with essential hypertension treated with hypotensive drugs. The patients were included in a multicenter trial. A 12-week course reduced total cholesterol level under 6.2 mmol/l in 59% of the patients, under 5.2 mmol/l in 29% of them. LDLP cholesterol lowered to 3.5% in 34% of the patients. Mean apo B diminished by 23%. There was a 27% decrease in the proportion of atherogenic fraction apo B to antiatherogenic fraction of transport proteins apo A-I. Leskol is well tolerated and effective against hypercholesterolemia, it is safe in relation to side effects and blood biochemistry.

The GTP-binding regulatory proteins, Gs and G(i), are altered in erythrocyte membranes of patients with ischemic heart disease resulting from coronary atherosclerosis.

Acute ischemic heart disease is associated with alterations in the cardiac adenylate cyclase system response, although the specificity and mechanism of these events are unknown. We studied the characteristics of inhibitory (G(i)) and stimulatory (Gs) GTP-binding regulatory proteins (G proteins) of adenylate cyclase in erythrocyte membranes of patients (n = 16) with nonacute ischemic heart disease resulting from coronary atherosclerosis. Gs was measured by reconstitution with the resolved catalytic unit of adenylate cyclase and by cholera toxin-catalyzed ADP-ribosylation of a 42-kD protein; G(i) was tested as a 41-kD substrate of pertussis toxin-catalyzed ADP-ribosylation. Gs activity was decreased by 27 +/- 2% in the cholate extract and by 25 +/- 3% in the supernatant of guanosine 5'-(gamma-thio)triphosphate-treated membranes. The amount of cholera toxin substrate was decreased by 33 +/- 3%, and the pertussis toxin substrate was increased by 27 +/- 5% compared with healthy subjects (n = 10). All changes in G-protein characteristics appear to be specific relative to other erythrocyte membrane proteins and hemoglobin. Those patients who have a decreased Gs possess approximately normal Gi, and those with increased G(i) showed no change in Gs. Patients with increased G(i) (normal Gs) exhibited more severe deterioration of their coronary arteries than did patients with decreased Gs (normal G(i)) (P < .05), but these two groups did not differ significantly in serum lipids, hormones, drug therapy, historical data, or baseline assessment (P < 0.05).

[The use of Enduracin--a prolonged-action form of nicotinic acid--in correcting atherogenic dyslipidemias]. / Primenenie enduratsina--prolongirovannoi formy nikotinovoi kisloty--v korrektsii aterogennykh dislipidemii.

The hypolipidemic effects of induracin, a new long-acting nicotinic acid dosage form based on the waxy matrix, and its tolerance were studied in 31 patients with Types IIa and IIb hyperlipoproteinemias in a 6-month blind crossover study. There were decreases in the levels of total cholesterol by 9-13% and low density lipoprotein cholesterol by 12-22%, an increase in high density lipoprotein cholesterol by 12-15%, and a good dynamics in the ratio of blood lipid-transport proteins--a 12-16% increase to the levels of apoprotein AI to a 29% decrease in those of apoprotein B. The drug is well tolerated by patients and may be recommended for correction of atherogenic dyslipidemias.

[Esophageal diseases in patients with stenocardia and angiographically changes and little-changed coronary arteries]. / Zabolevaniia pishchevoda u bol'nykh stenokardiei i pri angiografi- cheski neizmenennykh i maloizmenennykh koronarnykh arteriiakh..

Angiography conducted in 29 anginal patients has shown that coronary arteries were intact in 23 and little affected in 6 of them. Signs of myocardial ischemia were recorded at myocardial scintigraphy, bicycle ergometry, 24-h ECG monitoring in 17 patients. Esophageal lesions confirmed by endoscopy, manometry, esophageal pH-metry with Bernstein test were revealed in 20 examinees (68%). It is suggested that patients with persistent chest pain and unaffected coronary arteries who are resistant to antianginal therapy should undergo functional study of the esophagus including endoscopy, manometry and pH-metry.