[Effect of lovastatin on serum lipid and apolipoprotein levels after dietary fat load in patients with ischemic heart disease].
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Biomedical subjects
Publications and source records attributed to N V Perova.
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The study was undertaken to examine 34 male patients with unstable angina pectoris who underwent coronary angiography (in the period of instability and at rehospitalization) and study of protein and lipid parameters in their plasma. During a follow-up (mean 33.9-2.2 months), the patients were divided into 2 groups according to the changes occurring in the coronary bed. These included: (1) patients with progressive atherosclerotic changes and (2) those with stabilization of the process. Changes in the lipid profile in patients with unstable angina were found to appear as profound atherogenic shifts in the spectrum of lipoproteins and apolipoproteins, which suggests that coronary atherosclerosis is progressive in the late period.
Short-term maximal and long-term submaximal regimens of physical exercise had been assessed for effect on serum lipoproteins in healthy subjects, in preclinical coronary heart disease (CHD) sufferers and in manifest CHD patients having food fat-induced lipemia. Fat loading caused hypertriglyceridemia in all the examinees. In healthy subjects it was associated with a rise in apo AI, while in CHD patients with relevant fall. Maximal exercise in preexisting alimentary hyperlipidemia provoked elevation of total cholesterol, triglycerides, LDL cholesterol, being atherogenic. Apo AI grew with a decrease in apo B/apo AI ratio in healthy subjects, in coronary patients apolipoprotein changes were of atherogenic origin. Prolonged submaximal exercise at the height of food lipemia resulted in lowering of total cholesterol, triglycerides and LDL cholesterol along with elevation of HDL cholesterol and apo AI both in healthy and coronary subjects evidencing anti-atherogenicity. It is noted that the response of lipids and apolipoproteins to fat and physical exercise loads was similar in subclinical and manifest CHD patients.
A number of epidemiological surveys have recently established that in populations with the lowest levels of total cholesterol (TC) and LDL cholesterol (LDLC) death rates grow due to both malignant and cardiovascular diseases. The results of a detailed study on multifactor prevention of coronary heart disease (CHD) in an open population of Moscow males aged 40-59 to elucidate the relations between TC, HDL cholesterol, LDLC and CHD mortality demonstrated that low levels of TC are markers, but not a factor of CHD and sudden death risk in low-educated subjects free of CHD symptoms. When planning mass measures to primarily prevent CHD, subjects with low cholesterol levels should be given a special care as well as those with hypercholesterolemia.
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.
BACKGROUND: The intervention group comprised 477 children at the age of 11.8 +/- 0.11 years. The reference group comprised 528 children aged 11.9 +/- 0.12 years. Both groups were drawn on the basis of the selected examination of children from two Moscow districts. The criteria for risk factors involved the upper 5% of the distribution curve for blood pressure, the upper 10% of the distribution curve for cholesterol and triglycerides, the upper 15% of the distribution curve for the Quetelet index, and a positive response to the question on smoking, "Smoke at least once per week or more frequently?" METHODS: The intervention was carried out both among the entire sample population and more intensively among persons with risk factors. It included counseling for children and their parents on rational diet, physical activity, and smoking hazards. Relevant material on health education was disseminated. Follow-up examinations were carried out at 1 and 3 years following baseline measures. RESULTS: The examination at 1 year showed that the children of the intervention district had attained a greater reduction in their levels of total cholesterol, triglycerides, and systolic blood pressure than those of the reference district. High-density lipoprotein cholesterol levels decreased equally in both districts. After 3 years, the effect was retained for cholesterol and systolic blood pressure; the level of high-density lipoprotein cholesterol showed a greater reduction in district 2. After 1 year, the increase in the Quetelet index among the intervention sample (district 1) became less. After 3 years of intervention, the smoking accretion rate had decreased by 8.9% in district 1 (intervention) compared with that in district 2 (reference).
The dissociation of very-low-density lipoprotein (VLDL) apoproteins was studied using immunochemical approaches. The analysis of monospecific antibody binding to apo E, C-II and C-III on VLDL surface showed low apoprotein accessibility for the antibodies while the accessibility of apo C-II and C-III in solution was complete. Lipoprotein preparation dilution resulted in increasing of apo E and C-II accessibility. It was suggested that apoprotein dissociation led to apoprotein cluster dissolving on VLDL surface and higher antigen determinant accessibility. The findings confirmed previous theoretical analysis of apoprotein dissociation.
All the patients who had undergone a course of non-specific hemosorption (HS) for clinical indications showed lower plasma lipid levels and largely lower triglyceride concentrations. The patients with hypercholesterolemia alone simultaneously displayed decreased levels of cholesterol, high density lipoproteins, and apoprotein A-I. Apoprotein B levels reduced in patients having normal lipid values and in those with isolated hypercholesterolemia. The changes in the levels of lipids and apoproteins were different for 2 weeks after hemosorption in relation to the baseline lipid spectrum. The patients with coronary heart disease with hyperlipidemias had positive trends in lipid spectral changes: the parameters of atherogenic classes of lipids tended to decrease, whereas those of antiatherogenic lipid classes tended to show a slight increase. There was a negative direction in the dynamics of the studied parameters in renal patients, in those who had normal baseline lipid values, and in those with isolated hypo-alpha-cholesterolemia, i. e. higher plasma cholesterol and triglyceride, low density lipoprotein cholesterol and apoprotein B levels.
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Mean values of cholesterol contents in low- and high-density lipoproteins, and the 10% and 90% cut-off points of their distribution were determined in random samples of men aged 35-64 years and resident in three Soviet cities (Kiev, Moscow, Novosibirsk) and two Polish regions (Warsaw, and Tarnobrzeg province). Comparative analysis revealed that, while having identical mean total cholesterol levels, the studied populations differ both in the character of cholesterol distribution in atherogenic and nonatherogenic lipoproteins and in their age dynamics. The lipoprotein spectrum was also compared with data of overall mortality and that from ischaemic heart disease and stroke in the respective areas. The comparison suggested a potential association between the incidence of these diseases and the incidence of individual lipid risk factors in the population. The regional specifics of the blood lipoprotein spectrum must also be considered when developing programmes of atherosclerosis prevention.
The sera from most patients with coronary heart disease concurrent with angiographically documented coronary atherosclerosis were found to contain apolipoprotein B (Apo B), neither apolipoprotein E (Apo E) nor apolipoprotein AI (Apo AI) in the circulating immune complexes precipitated by polyethylene glycol-6000 (PEG). Low density lipoproteins are the major components of cholesterol-containing immune complexes precipitated by PEG. A correlation was established between the serum levels of total cholesterol (r = 0,74; p less than 0.01), and low density lipoprotein (LDL) cholesterol (r = 0.77; p less than 0.01) in patients with coronary heart disease and cholesterol in LDL-containing No relationship was found in healthy individuals. The in vitro increase in LDL levels in most patients with coronary heart disease concurrent with coronary atherosclerosis was not followed by an elevation in LDL-containing immune complexes.
The study was undertaken to examine 134 patients who were divided into 2 groups: 1) those with angiographically documented coronary atherosclerosis and 2) those with unaltered coronary arteries. The levels of immune complex cholesterol and the parameters of serum lipid spectrum were investigated in all the patients. The level of immune complex cholesterol and the apo B/apo AI ratio were the most informative indices in the characterization of coronary atherosclerosis. Immune complex cholesterol may be used as a marker of coronary atherosclerosis, the diagnostic accuracy is 78% with this method.
The authors provide the results of a prospective study carried out for almost 10 years among men who underwent screenings in 1975-1977 at an age of 40-59 years in Moscow and Leningrad (overall 6431 persons) with a purpose of analyzing potential causes of high risk of death from coronary heart disease in a group of subjects with hypocholesterolemia. Based on a mathematical-statistical analysis, variants of the interpretations of the indicated fact are presented.
Blood serum of most patients with coronary heart disease (CHD) caused a 2- to 5-fold increase in the lipid content of smooth muscle cells cultured from unaffected human aortic intima, i.e., possessed an atherogenic potential manifested in culture. Treatment of the CHD patients' serum with 2.5% polyethylene glycol 6000 removed the circulating immune complexes. The serum subjected to this treatment lost its atherogenic properties, i.e., failed to increase the content of lipids in cultured cells. Incubation of smooth muscle cells derived from human aortic intima with circulating immune complexes isolated from an atherogenic patient's serum caused a 1.5- to 3-fold rise in the intracellular cholesterol. Circulating immune complexes contained apolipoprotein B (apo B), but not apolipoproteins A1 and E. The apo B content strongly correlated with the total cholesterol content. The cholesterol/apo B ratio of the complexes was characteristic of low density lipoproteins (LDL), but not of very low density lipoproteins or intermediate density lipoproteins. The composition of the main lipid classes in these complexes was similar to that in LDL. Blood sera of most (90%) CHD patients was characterized by a high cholesterol and apolipoprotein B content in circulating immune complexes. The ability of these sera to induce lipid accumulation in cultured cells directly correlated with the cholesterol and apolipoprotein B level of circulating immune complexes (r = 0.91). These findings suggest that the atherogenic potential of CHD patients' blood serum is due to LDL-containing immune complexes.
The effects of omega-3 polyunsaturated fatty acids (PUSF), a 4-week fish diet--350 g of scomber a day, on the blood lipid-apolipoprotein spectrum were evaluated in 22 patients with primary angina pectoris as compared to 8 control subjects received hospital protein-, fat-, carbohydrate-, and calorie-balanced diet No. 10 differing in omega-3 PUSF content (5 and 0.03 g/day, respectively). The fish diet caused a significant reduction in total cholesterol (TC) and low density lipoprotein cholesterol (LDLC) in patients with hypercholesterolemia, however, the normal cholesterol (under 200 mg/dl) and LDLC (under 130 mg/dl) levels were reached only in a small proportion of the patients. There was a hypotriglyceridemic effect of omega-3 PUSF that was more pronounced at initially high triglyceride concentrations. Heterogeneous changes were found in LDLC levels with the fish diet. i.e. from a great decrease at initially high LDLC levels to a small increase at initially low LDLC in patients with hypertriglyceridemia and low levels of high density lipoproteins. It was concluded that a fish diet should be included into a complex of measures aimed at the secondary prevention of coronary heart disease in patients with primary angina concurrent with hypercholesterolemia (even moderate) and hypertriglyceridemia unassociated with hypoalphacholesterolemia.
In aborigines from the costal and continental areas of Chukotka who differ in dietary polyunsaturated fatty acid (PFA) n-3 intake, specific features of the composition of fatty acids in cell membranes were revealed in a model of erythrocytes: the costal inhabitants showed a higher proportion of PFA n-3 mainly through eicosapentaenic acid and lower proportion of major PFA n-6. With this, plasma lipoprotein lipids in whose composition the acids transported to the cell membranes displayed the similar regularities in changes in fatty acid composition. Only a far larger portion of eicosapentaenic acid in the cell membranes from the costal inhabitants than from the continental inhabitants was associated with greater mass of the left ventricular myocardium. It was concluded that transport of lipids containing high PFA n-3 in the composition of lipoproteins to the cell membranes caused an increase of the acids in them and, evidently, a change in physicochemical and, therefore, functional properties of cells.
Using the dynamic fluorescence quenching method, it was shown that very low density (VLDL) apoproteins (apo B, E and C) tryptophanyls exhibit a lower accessibility towards water-soluble quenchers as compared to apo B LDL chromophores. The efficiency of proteolytic degradation by trypsin of VLDL-associated apo E and apo C was much lower than that of apo B. These results may be due to the cluster arrangement of amphipatic apo E and apo C on the VLDL surface and/or to their partial shielding by apo B. Treatment of VLDL particles with sub-lytic concentrations of the detergent, Tween-20, did not change the relaxation characteristics of amphipatic apoprotein tryptophanyl microenvironment, but resulted in a reversible structural transition registered by a "red" shift of the emission spectrum maximum as well as by change of the iodine quenching pattern. The detergent-induced increase of the VLDL tryptophanyl accessibility to acrylamide and the decrease of the quenching constant at the partial and complete particle solubilization were related to a change of the apo B molecular package. Treatment of VLDL with Tween-20 or cow milk lipoprotein lipase resulted in the appearance of tryptophanyl population that was not involved in the resonance energy transfer to the lipid phase-localized fluorescent probe pyrene, which is indicative of the protein dissociation. Treatment of VLDL particles with sub-lytic concentrations of Tween-20 revealed a lower (compared to apo C) relative affinity of apo E for the VLDL lipid surface. Inhibition of the lipoprotein lipase activity by apoprotein C-III was found to be non-competitive. It was concluded that lipolysis is a self-regulatory process which involves changes in the effector apoprotein concentration on the surface of triglyceride-rich particles.
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