[Association of polyunsaturated fatty acids treatment with coronary mortality. A meta-analysis].

AIM: A meta-analysis was undertaken to sum up data on long-chain polyunsaturated fatty acids treatment and coronary deaths. METHODS: Only studies with no less than 500 participants and length of follow-up no less than one year were included. Total number of studies was 13 with 127455 participants. RESULTS: Fixed factor (Peto) model demonstrated significant decrease in cardiac deaths in polyunsaturated fatty acids -treated group. (OR=0,89, 95%CI: 0,83-0,95, р=0,001). Random factor model confidence interval also does not included one (OR=0,88, 95%CI: 0,80-0,97, p=0.008). Subgroup analysis of studies that used therapy with 460 mg eicosapentaenoic acid and 380 docosahexaenoic acid per day demonstrated significant reduction in cardiac deaths (OR=0,84, 95%CI: 0,77-0,92) in both fixed factor and random factor models. CONCLUSION: Correspondingly supplementation with polyunsaturated fatty acids associated with lower coronary mortality.

[Use of Highly Concentrated Polyunsaturated Fatty Acids for Prevention of Complications After Myocardial Infarction. Cost-Utility Analysis].

Use of highly concentrated ethyl esters of polyunsaturated fatty acids after myocardial infarction (MI) and in patients with heart failure was associated with lower mortality. The goal of this analysis was to perform cost-utility analysis of the use of highly concentrated ethyl esters of polyunsaturated fatty acids after MI (with help of a Markov model) and to find whether its use in some group of patients led to decrease in budget costs. As a result, we have shown that use of highly concentrated ethyl esters of polyunsaturated fatty acids after MI leads to increase in quality-adjusted life expectancy on 0.5 QALY, with incremental cost-effectiveness ratio of 105 thousand rubles per QALY, and net monetary benefit of 780.5 thousand rubles. In the patient subpopulation that receives highly concentrated ethyl esters of polyunsaturated fatty acids for arrhythmia prevention after coronary artery bypass the estimated decrease of budget cost varies between 6 and 50% depending on denominator used.

[Economic assessment of drugs for rare diseases: Must it be done, if yes, which are its features?]

The orphan drug laws enacted firstly in the USA and then in some other countries have given rise to a specific market of drugs for rare diseases and to a drastic increase in the number of proposed drugs. At the same time, the prices for innovative drugs are frequently high, have resulted in debates about their cost effectiveness and the drugs for rare diseases being frequently difficult to be tested for their efficacy due to disease rarity. The article discusses the designs of clinical trials that could enhance their effectiveness, gives examples of standard-design trials, and notes that effectiveness evaluations can be obtained for most diseases, but with a small sample, they will not be very precise, which makes cost-effectiveness analysis difficult. In this connection, a number of mechanisms proposed worldwide to solve the existing situation are discussed.

[Efficacy of nondrug correction of hypertension in general medical practice]. / Effektivnost' nemedikamentoznoi korrektsii arterial'noi gipertenzii v obshchei vrachebnoi praktike.

Effectiveness of nondrug correction of elevated blood pressure was assessed in a group of hypertensives selected from participants of a study of prevalence of cardiovascular risk factors conducted in one of Saint Petersburg districts. Patients were divided into 3 subgroups in which the following interventions were used: diet with decreased sodium content, aerobic physical exercise, or combination of these methods. Blood pressure lowering achieved with these methods (-11 mm Hg systolic and -6.8 mm Hg diastolic) was maintained throughout 2 years of observation.

[Status of lipid metabolism in rabbits, delivered from females with moderate alimentary hypercholesterolemia]. / Sostoianie lipidnogo obmena u krolikov, rodivshikhsia ot samok s umerennoi alimentarnoi giperkholesteinemiei.

Offspring of rabbits fed with cholesterol diet during pregnancy and/or lactation was more sensitive to fat load versus the offspring of rabbits fed with standard diet. Such enhancement of hyperlipidemic reaction is predominantly due to the enhanced rate of blood cholesterol increase (i.e., secretion of cholesterol-containing lipoproteins) but not to the decreased rate of cholesterol elimination from the blood stream. This was confirmed by monitoring the fate of human low-density lipoproteins intravenously injected in rabbits. The data indicate certain alterations of cholesterol metabolism regulation in the offspring of rabbits with alimentary hypercholesterolemia. Hypercholesterolemia of pregnant and lactating rabbits is important for the formation of the lipid metabolism in their offspring because cholesterol levels in the serum of female rabbits positively correlate with the expression of hypercholesterolemic and hypertriglyceridemia reactions of their offspring in response to fat load and with kinetic parameters which characterize the increase in cholesterol and its elimination from the blood stream during fat load.

[The relation of a number of hormonal indices to risk factors for IHD and its prevalence based on the data from a large population study]. / Sviaz' riada gormonal'nykh pokazatelei s faktorami riska IBS i ee rasprostranennost'iu po dannym krupnogo populiatsionnogo issledovaniia.

Relevance of IHD risk factors and hormone concentrations (insulin, estradiol, testosterone, prolactin, LH, FSH, TTH and hydrocortisone) to IHD incidence was studied in 1200 men. Multivariate statistical analysis demonstrated that only a small number of hormonal indices are associated with main lipid and nonlipid risk factors. The relationships exist between systolic arterial pressure (SAP) and hydrocortisone, between TTH and total cholesterol, SAP and age, estradiol, testosterone and age. Significant independent associations were found between IHD prevalence and age (R = 0.140, 3 = 0.000), SAP (R = 0.130, P.0.001), HDLP cholesterol (R = -0.082, P = 0.007), height (R = -0.078, P = 0.010), insulin (R = 0.067, P = 0.035), standard deviation of estradiol from median value (R = 0.083, P = 0.017). The findings confirm a great role of high SAP in the development of IHD, a significant and independent association of high insulin levels with IHD prevalence, the presence of nonlinear relation of estradiol concentration to IHD occurrence in males.

[Isoelectric focusing of high density lipoproteins in the wall of the human aorta]. / Izoélektricheskoe fokusirovanie lipoproteinov vysokoi plotnosti stenki aorty cheloveka.

Charge distribution of high density lipoproteins (HDL) from the human aorta intima has been studied using the method of isoelectric focusing in the polyacrylamide gel. Four groups of aortal HDL (A-HDL) were identified by focusing in the pH range 4.6-6.0: 1) the prevailing group (pH 4.7-4.9); 2) the intermediate, the most heterogeneous group (pI 5.0-5.9), including to 15-17 subfractions (these two groups are also present in the plasma); 3) the cathodic group (pI 6.0) practically absent in the plasma and one of the main groups among A-HDL (22% of all A-HDL), certain subfractions of this group have pI about 6.9; 4) the anodic group (pI 3.75), a minor group (5% of all A-HDL), also absent in the plasma. No differences are found between charge distribution of HDL from the normal aorta intima and atherosclerosis-affected intima. The data obtained confirm that plasmic HDL penetrating to the arterial intima are subjected to considerable changes in it.

[Antioxidant activity of high density lipoproteins in vivo]. / Antioksidantnaia aktivnost' lipoproteidov vysokoi plotnosti in vivo.

The paper deals with antioxidant effect of high density lipoproteins (HDL) in vivo. The effect of intravenous injection of large-dose HDL3 (200 mg protein), isolated from human plasma to rabbits with experimental hypercholesterolemia, on the content of primary products of lipid peroxidation in rabbit blood, the correlation between HDL cholesterol level and the content of lipid peroxide products in blood plasma of healthy persons and patients with IHD were studied. Intravenous injection of HDL3 to rabbits with experimental hypercholesterolemia has been shown to lead in 6 hr to a 24-hr significant (p < 0.01) decrease of conjugated dienes and trienes. The existence of negative correlation between HDL-cholesterol level and the content of conjugated dienes in blood plasma of healthy persons (N = 47) and patients with IHD (n = 64) is revealed. Basing on the data obtained conclusion of universal character of protective antiatherogenic effect of HDL is drawn.

[High density lipoproteins of the human aortic wall; size distribution]. / Lipoproteiny vysokoi plotnosti stenki aorty cheloveka: raspredelenie po razmeram.

The paper presents data on distribution of human aortic high density lipoproteins (A-HDL) according to their size. A-HDL were isolated from the aortic intima (autopsy material) and analyzed by the gradient gel electrophoresis method. The obtained data show that the clear-cut difference exists between size distribution of A-HDL from patients whose death was connected with atherosclerosis and those who died from the diseases not connected with atherosclerosis. In the first case small particles (HDL3B and HDL3C) were predominant. A-HDL with size corresponding to plasma HDL2A and HDL2B slightly predominated in normal intima and A-HDL with size of plasma HDL3A and HDL3C predominated in affected parts of intima. The principal component analysis of data permits suggesting that one of the factors responsible for the accumulation of small A-HDL is a decreased permeability of the affected parts of the vessel wall for the larger HDL particles. Besides, changes of the normal HDL metabolism can also be responsible for the presence of small HDL particles in the intima.

[Hypoalphacholesterolemia and coronary disease (an approach using a factor analysis)]. / Gipoal'fakholesterinemiia i ishemicheskaia bolezn' serdtsa (podkhod s ispol'zovaniem faktornogo analiza).

The data obtained from a screening of 1,467 males aged 40-59 years made it possible to characterize the relation of dyslipoproteinemias, primarily hypoalphacholesterolemia, to the incidence of coronary heart disease and risk factors in males, by using factorial and multivariate analyses. The findings suggest that hypoalphacholesterolemia is closely associated with hypertriglyceridemia in its atherogenicity, thus from the clinical point of view low levels of HDL cholesterol should be used as a ground for thorough examination of lipid metabolism, with great emphasis on metabolic disturbances of triglyceride-rich lipoproteins.

[Chromato-focussing of plasma low density proteins]. / Khromatofokusirovanie plazmennykh lipoproteidov nizkoi plotnosti.

A few alternatives of the binding of healthy patients plasma low density lipoproteins (LDL) with anion exchanger PBE-94 were revealed. In the first case the main part of LDL did not bind to the gel and the isoelectric points of the minor subfractions were 5.8 and 5.3, and pI 4.1. In the second case about half of lipoproteins did not bind to the gel, and the isoelectric points of subfractions were 5.7 and 5.0; and pI 4.1. In the third case when all lipoproteins bound to the PBE-94, there were much more subfractions and their isoelectric points were 6.2, 5.8, 5.2, 4.9, 4.5 and pI 4.1. All LDL of the patients with ischemic heart disease bound to anion exchanger, and the part of subfraction with pI 4.1 was three or five times as great as the one of the healthy person. Increasing of the LDL subfraction with pI 4.1 was observed at prolonged keeping of the LDL obtained from the healthy person plasma. LDL isoelectric point distribution of the persons with carcinoma uterine cervix did not differ from the one of the healthy persons. Acetylation and hexanol modification resulted in the isoelectric point shift from 5.7 to 4.6 and to 4.3 in the case of LDL subfraction to be obtained preparatively using the chromatofocusing.