[Dyslipidemia in diabetes mellitus].
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Diabetes Complications↗
Biomedical subjects
R Ceska
Publications and source records attributed to R Ceska.
[Fluvastatin in the treatment of hyperlipoproteinemia, initial experience].
BACKGROUND: HMG CoA (beta-hydroxy-beta-methylglutaryl coenzyme A) reductase inhibitors are very effective in lowering total and low-density lipoprotein cholesterol. Since the introduction of lovastatin for clinical use in the United States in 1987, statins have become widely available and the number of patients treated with these compounds is estimated to be over 2 million. The incidence of adverse effects is very low with elevated transaminase levels and myopathy being of greatest concern. Currently, several intervention trials demonstrated the influence of HMG CoA reductase inhibitors on total and cardiovascular morbidity and mortality and on regression of atherosclerosis as well. Fluvastatin, LESCOLR, a synthetic drug, is the most recently approved HMG CoA reductase inhibitor. PATIENTS METHODS AND STUDY DESIGN: At the lipid clinic 18 patients (8 familial hypercholesterolemia heterozygotes and 10 subjects affected with familial combined hyperlipidemia) have been treated with increasing dose of fluvastatin (20 and 40 mg/day with the evening meal) for 3 months. All patients respected AHA step I diet. The basic parameters of lipid and lipoprotein metabolism have been measured, and apo A-I, apo B levels as well. RESULTS: Concentration of total cholesterol decreased after treatment with 20 and 40 mg of fluvastatin by 17% resp. 23%. The hypolipidemic effect was even more pronounced in LDL-cholesterol level, which was reduced by 21% and 29%. Decrease of LDL-cholesterol has been accompanied by reduction of apo B concentration by 16% resp. 24%. Also triglycerides levels were significantly influenced (-9%). On the other hand treatment with fluvastatin did not affect HDL-cholesterol and apo A-I concentration. DISCUSSION: Our first results correspond to results of other authors. We also compared results with fluvastatin with our previous studies in which we used lovastatin and simvastatin. From the comparision with other statins we can conclude that the efficacy of fluvastatin is similar to lovastatin and simvastatin. On the other hand we have to notice, that the percent reduction of total and LDL-cholesterol after fluvastatin was a little bit smaller. CONCLUSIONS: Fluvastatin, Lescol, seems to be a powerful hypolipidemic drug, well tolerated by the patients. In safety laboratory we did not notice any important undesirable result.
Adult↗
[Treatment of hyperlipoproteinemia in clinical practice].
There are sufficient arguments for treatment of hyperlipoproteinaemia at present and this treatment is considered not only rational but also an essential procedure in primary and in particular in secondary prevention of cardiovascular diseases. Views of scepticists as regards this treatment are, with regard to the most recent epidemiological studies with hypolipidaemic agents, not very convincing and the majority is refused. Treatment of patients with hyperlipoproteinaemia is comprehensive, its basis being dietary and lifestyle measures. The latter are, if they are not sufficiently effective, with increasing frequency supplemented with medicamentous intervention. This treatment is then as a rule very effective and leads to rapid achievement of desirable "target values" of parameters of lipid and lipoprotein metabolism. This comprehensive therapeutic algorithm is considered the modern approach to primary and secondary prevention of cardiovascular diseases. If a long-term favourable effect on the lipid spectrum is to be achieved in individual subjects and whole populations (and in particular in populations of subjects with the highest risk of manifestation of complications of atherosclerosis), it is essential to implement the mentioned therapeutic measures on a long-term basis, frequently for the rest of life. Considering contemporary prices of medicaments which are used to influence risk factors of atherosclerosis, this quite understandably worries health economists. Despite their "economic" objections it is important to give maximal support to preventive measures. Therapeutic procedures in advanced disease may be finally incomparably more expensive than soundly implemented preventive measures. On the other hand, it is a must to treat disorders of the lipid metabolism, as well as other risk factors of atherosclerosis such as hypertension or diabetes mellitus rationally, respecting recent results of basic and applied research. It is also a great advantage if we can use as a basis for the diagnostic and therapeutic algorithm international widely accepted recommendations of European and American societies. We also use their recommendations as guidelines when seeking the right patient or group of subjects on whom our greatest therapeutic effort should be focused.
Combined Modality Therapy↗
[Silent myocardial ischemia in outpatients being treated for hyperlipoproteinemia].
BACKGROUND: Hyperlipoproteinaemias, in particular those associated with hypercholesterolaemia, are in a causal relationship with the development and acceleration of atherogenesis. One of the serious forms of coronary heart disease is silent myocardial ischaemia--an asymptomatic objectively confirmed ischaemic episode. The objective of the present study was to 1. assess the prevalence of this disease in subjects with hyperlipoproteinaemia and 2. to assess the optimal diagnostic procedure to detect it. METHODS AND RESULTS: The group comprises 57 subjects selected at random (23 men and 34 women) from the out-patient department for genetics and treatment of hyperlipoproteinaemias. In all subjects an ergometric loading test was made and 24-hour ambulatory ECG monitoring. Suspected silent myocardial ischaemia (i.e. positive results of the two examinations) was confirmed by load scintigraphy of the heart muscle. Silent myocardial ischaemia was proved in 3 of 23 examined men (13%) and in 4 of 34 women (11.8%). CONCLUSIONS: Prevalence of silent myocardial ischaemia is significantly higher in high risk subjects--with hyperlipoproteinaemia than in the general asymptomatic population. The best screening test for its detection is a loading test and ambulatory ECG monitoring, supplemented by loading scintigraphy of the heart muscle.
Adult↗
[Decrease in common carotid artery intimal thickness after hypolipemic therapy].
BACKGROUND: In recent years evidence was provided that it is possible to assess sonographically the thickness of the intima of the common carotid artery, whereby an increase of the thickness of the intima is considered an early stage of atherosclerosis. In the submitted work the authors tried to assess whether it is possible to influence the thickness of the intima by therapy. METHOD AND RESULTS: In 32 patients with familial hyperlipoproteinaemia sonographic control examinations of the common carotid artery were performed after 27 months of comprehensive treatment. In 21 subjects with familial hypercholesterolaemia the thickness of the intima decreased from 0.83 mm to 0.68 mm (p < 0.01), in 8 subjects with familial combined hyperlipoproteinaemia from 0.77 mm to 0.74 mm (a decline was recorded in half the subjects). In the whole group the greatest decrease was recorded in subjects treated with statins and a smaller decrease in those treated with fibrates. CONCLUSIONS: The authors assume that the decrease of the thickness of the intima of the common carotid artery recorded in hyperlipoproteinaemic patients after hypolipidaemic treatment is a manifestation of regression of atherosclerosis.
Adult↗
[Simvastatin in the treatment of familial hypercholesterolemia].
BACKGROUND: The association between hypercholesterolemia and premature atherosclerosis is almost universally accepted. Treatment of hyperlipoproteinemias represents a reasonable approach in preventive cardiology. The aim of the study was to prove a hypolipidemic effect of simvastatin, Zocor tablets à 10 mg, produced by MSD, U:S.A. in patients with familial hypercholesterolemia. METHODS AND RESULTS: 29 familial hypercholesterolemia heterozygotes have been treated with increasing dose of simvastatin (10 and 20 mg/day with the evening meal) for three months. All patients have been on AHA step I diet. The basic parameters of lipid and lipoprotein metabolism have been measured, as well the concentrations of apolipoproteins A-I and B, and the level of lipoprotein(a). Concentration of total cholesterol decreased after treatment with 10 and 20 mg of simvastatin by 20%, resp. 26%. The hypolipidemic effect was even more pronounced in LDL-cholesterol level, which was reduced by 24% respectively 34%. On the other hand therapy with simvastatin did not influence HDL-cholesterol at all. Also triglycerides concentration did not changed very significantly after administration of simvastatin (triglycerides levels were reduced by 7% respectively by 18%). Decline of LDL-cholesterol has been accompanied by decrease of apolipoprotein B concentration by 24%, resp. 26%. The concentration of lipoprotein (a) has not been statistically significantly influenced, even its level increased slightly. The body weight of the patients did not changed during the study. Simvastatin treatment has been well tolerated by the patients. CONCLUSIONS: Simvastatin, Zocor, seems to be powerful hypolipidemic drug, which is to be used even in the treatment of familial hypercholesterolemia heterozygotes, who are usually very resistant to the therapy. The dose of 10 mg of simvastatin is usually sufficient to influence plasma lipids and lipoproteins. A double dose intensifies the hypolipidemic effect but this additional effect is not so expressive. Zocor is tolerated well by the patients and in safety laboratory we did not notice any important undesirable result.
Adult↗
[DNA analysis in heterozygotes in familial hypercholesterolemia].
BACKGROUND: Accuracy of clinical diagnosis of heterozygotes with familial hypercholesterolemia (FH) is limited. The aim of our study was to demonstrate possibilities of progressive diagnostic approach, DNA analysis, LDL receptor gene (LDLR) and apolipoprotein B (ApoB) in case of our study, and compare our results with the data obtained in other populations. METHODS AND RESULTS: The low density lipoprotein receptor (LDLR) gene RFLP frequencies for restriction endonucleases AvaII, HincII, NcoI, PvuII and StuI were determined in the sample of 52 FH patients and in the group of 37 healthy individuals. Using PCR, the LDLR gene was then tested for Pro664-Leu and Val408-Met point mutations. The first DNA diagnosis of familial defective apolipoprotein B-100 (FDB) using point mutation PCR analysis of 26. exon of ApoB gene in Czech Republic was performed. LDLR gene RFLP frequencies for restriction endonucleases AvaII, HincII, NcoI, PvuII and StuI in he sample of 52 FH patients were 0.48, 0.52, 0.73, 0.31 and 0.93 respectively. LDLR gene RFLP frequencies for enzymes AvaII, HincII, NcoI, PvuII and StuI in the group of 37 healthy individuals were 0.39, 0.50, 0.70, 0.22 and 0.99 respectively. In the group of FH patients no point mutations Pro664-Leu and Val408-Met were detected. However, there was found 110bp insertion in the 9th exon of LDLR gene in two FH patients during studies of Val408-Leu mutation. Two FDB probands in the FH group and another 7 FDB individuals in probands families were detected. FDB frequency in the sample of FH patients was 3.8%. CONCLUSIONS: LDLR gene RFLP frequencies and FDB frequency in our group of FH patients did not differ from that of FH patients in other Caucasian populations. DNA analysis is advantageous complementary method for diagnosis of FH and is irreplaceable for the detection of FDB.
Adult↗
[Pharmacotherapy of hyperlipoproteinemia in view of the newest European and American recommendations].
UNLABELLED: Hyperlipoproteinaemias, in particular types associated with elevated levels of total and LDL-cholesterol and partly triacylglycerols (in particular in combination with reduced HDL-cholesterol), are one of the most serious risk factors of early manifestation of IHD and atherosclerosis at other sites. Their effective treatment is considered a rational procedure in preventive cardiology. Who should be treated, when and how? When deciding we have to combine two basic approaches. Every patient must be considered individually, on the other hand, it is necessary to respect some general recommendations. The most comprehensive view of the given problem will be found in the innovated recommendations of the EAS of 1992 and NCEP of 1993. They contain not only values of parameters of the lipid and lipoprotein metabolism where dietetic and pharmacological intervention should be provided but also target values which should be aimed for in these patients. Treatment of hyperlipoproteinaemias is comprehensive and comprises dietary and lifestyle provisions. In indicated cases increasingly pharmacotherapy is emphasized to which most of the presented paper is devoted. Pharmacotherapy of hyperlipoproteinaemias. Hypolipidaemic agents can be divided into several groups. 1) Drugs which affect above all cholesterol; 2) Drugs which affect cholesterol and triacylglycerols (HDL-CH); 3) Drugs used only on a small scale; 4) Dietetic preparations; 5) Oestrogens? and 6) a combination of two or more hypolipidaemic agents!!! CONCLUSION: The author discusses the basic indications of different hypolipidaemic agents from the aspect of their effect, safety and tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)
Female↗
[Monitoring plasma levels of vitamin D metabolites in simvastatin (Zocor) therapy in patients with familial hypercholesterolemia].
BACKGROUND: Simvastatin is a hypolipidaemic agent, a statin which inhibits cellular cholesterol synthesis by blocking 3HMG CoA reductase. The authors present a report on levels of plasma metabolites of vitamin D after treatment with 10 and 20 mg simvastatin daily in 13 patients, heterozygotes with hypercholesterolaemia during a five-week period. METHODS AND RESULTS: During simvastatin treatment in all patients plasma levels, of the sum of hydroxylated vitamin D metabolites and 1,25-dihydroxyvitamin D after five weeks of treatment with 10 and 20 mg hypolipidaemic drug were examined. For assessment of vitamin D metabolites radioassay was used which assesses the sum of hydroxylated vitamin D metabolites, and radioimmunoanalysis for assessing the 1,25-dihydroxyvitamin D plasma level. For statistical evaluation the non-parametric Friedman test and simultaneous testing was used. CONCLUSIONS: Simvastatin raises the plasma levels of the sum of hydroxylated vitamin D metabolites and 1,25-dihydroxyvitamin D in a dose-dependent ratio. The authors recommend to monitor the plasma levels of vitamin D metabolites over a longer time period.
Adult↗
[Familial apolipoprotein B-100 defect, a newly discovered lipid metabolism disorder].
Familial defective apolipoprotein B-100 is a newly revealed genetic disorder which leads to a rise of atherogenic LDL lipoproteins. It is probably due to the replacement of a single amino acid in the huge apoliprotein B-100 molecule, i.e. substitution of glutamine by arginine in position 3,500. Thus altered LDL-lipoproteins are unable to bind with the LDL-receptor. As a result of the mentioned metabolic disorder a slightly or markedly elevated plasma cholesterol develops which very probably leads to premature manifestation of atherosclerosis. The disease is transmitted by autosomal dominant inheritance and its incidence in the population is estimated to amount to 1:500, i.e. a similar rate as familial hypercholesterolaemia. In the submitted paper some historical facts are presented which led to the detection of the disease, methods which are used for its detection, and the author presents also results of the first, so still limited clinical investigations.
Apolipoprotein B-100↗
[Therapy with fibrates and vitamin D metabolism].
The authors investigated in 29 patients with familial hyperlipoproteinaemia the effect of fibrate treatment (Duolip forte, Merckle, and Lipanthyl, Richter) on vitamin D metabolism. In 10 patients treated for 6 months with daily oral doses of 500 mg Duolip forte they did not prove changes of plasma levels of 25-hydroxyvitamin D, however, they recorded a rise of the 1,25-dihydroxyvitamin D3 plasma level. In 19 patients who were given for 6 months 300 mg Lipanthyl per day by the oral route they proved a significant decline of the 25-hydroxyvitamin D plasma levels and a rise of 1,25-dihydroxyvitamin D3 plasma levels. The authors maintain that fibrates influence plasma concentrations of vitamin D metabolites either directly or indirectly by reducing cholesterol plasma levels.
Adult↗
[Duolip Forte--experience during a 6-month period of administration].
Duolip forte (ethophylline clofibrate, tablets à 500 mg) produced by Merckle Austria was administered to 20 patients with different types of hyperlipoproteinaemia for a 6-month period in amounts of 500 mg/day. Before onset of treatment and during treatment the patients adhered to a defined hypolipidaemic diet. The total cholesterol level during administration increased from 7.71 +/- 1.71 mmol/l to 8.23 +/- 1.34 mmol/l (p = 0.05). The LDL cholesterol level rose from 4.93 +/- 1.70 mmol/l to 5.53 +/- 1.34 mmol/l (n.s.). Apolipoprotein B declined from 1.99 +/- 0.39 g/l to 1.80 +/- 0.30 g/l (n.s.). HDL cholesterol rose from 1.09 +/- 0.32 mmol/l to 1.53 +/- 0.56 mmol/l (p = 0.01). The triglyceride level declined from 5.71 +/- 5.60 mmol/1 to 3.72 +/- 4.32 mmol/1 (n.s.). The lipid metabolism parameters were evaluated already after three months of Duolip treatment but the values did not differ significantly from values assessed after 6 months of administration; therefore only the final values are given. In the course of six months of Duolip administration the body weight of the patients did not change and no serious side-effects were observed which would call for discontinuation of treatment. Duolip forte is evaluated as a safe, but as compared with other available drugs of the clofibrate series, less effective hypolipidaemic agent.
Adult↗
[Carotid artery and femoral artery disease in asymptomatic patients with various types of hyperlipoproteinemias and in healthy persons].
The authors examined by means of the sonograph Siemens Quantum 2000 the carotid and femoral arteries of 21 controls and 91 asymptomatic subjects with different types of hyperlipoproteinaemia (HLP). 46 patients suffered from familial hypercholesterolaemia, another 19 patients with hypercholesterolaemia suffered from ischaemic heart disease, 21 patients had familial combined hyperlipoproteinaemia and 5 patients had familial dysbetalipoproteinaemia. In the controls no plaques or stenoses were detected. In the different groups with HLP plaques and stenoses on the carotid artery were found in 15-36%, on the femoral artery in 24-63%. In patients with HLP on the common carotid artery in different groups a detectable intima was found more frequently, a statistically highly significantly wider intima (0.73 +/- 0.17 mm to 0.84 +/- 0.31 mm) and a lower maximum rate (79 +/- 18 cm/s to 98 +/- 24 cm/s) than in controls (0.41 +/- 0.14 mm and 121 +/- 30 cm/s resp.). On the common carotid the authors found a significant direct correlation between age and the cholesterol level and between age and the width of the intima and an indirect correlation between age and the maximal rate. The differences in the width of the intima and maximum rate were preserved even when the groups were adjusted for age. Changes of the femoral artery were less marked.
Adult↗
[Familial hypercholesterolemia from the aspect of DNA analysis].
The authors summarize their first experiences with DNA analysis of defective low density lipoprotein receptor (LDLR) gene of the familial hypercholesterolemia heterozygotes that were selected from the III. Medical Clinic of the 1st Medical Faculty in Prague patients group. First genotype studies of unrelated FH individuals were performed by restriction fragment length polymorphism (RFLP) method. Relative allele frequencies of PvuII (0.69) and StuI (0.91) restriction enzymes agree with the world literature datas, in the ApaLI (0.69) case the higher value may be caused by, for the present, small number of analyzed patients. Possibilities of DNA analysis for pedigree FH diagnosis were demonstrated on the PvuII restriction enzyme case. By the use of polymerase chain reaction (PCR) DNA diagnosis of the familial defective apolipoprotein (Apo) B-100 (exon 26) was performed. 43 unrelated FH individuals were screened and none defective ApoB-100 gene was recorded.
Apolipoprotein B-100↗
[The intima of the common carotid artery in patients with hyperlipoproteinemia].
Using sonography, the common carotid artery was examined in patients with hyperlipoproteinaemia and in controls. In 21 controls, the intima was present in 62%, intimal thickness was 0.41 +/- 0.14 mm. In patients with familial hypercholesterolaemia free of ischaemic heart disease (46 patients), the intima was demonstrable in 89%, intimal thickness was 0.74 +/- 0.21 mm. In patients with ischaemic heart disease (19 patients), the intima could be demonstrated in 100%, its thickness was 0.84 +/- 0.31 mm. In 21 patients with familial combined hyperlipoproteinaemia, the intima was present in 90%, intimal thickness was 0.73 +/- 0.17 mm. Intimal thickness was significantly greater (p < 0.001) in all groups of patients with hyperlipoproteinaemia than in the control group. A significant correlation between cholesterol levels and intimal thickness (p < 0.01) was demonstrated.
Adult↗
[Pharmacologic therapy of hyperlipoproteinemia and its pitfalls].
Hyperlipoproteinaemias, in particular those associated with hypercholesterolaemia are considered one of the most significant risk factors for the development of early atherosclerosis and ischaemic heart disease. Effective reduction of plasma lipids and lipoproteins is associated with a decline in the prevalence of ischaemic heart disease and cardiovascular mortality. Pharmacotherapy of hyperlipoproteinaemias is therefore considered a rational procedure in preventive cardiology. After a brief review of comprehensive treatment of hyperlipoproteinaemias the author discusses in particular contemporary possibilities of their medicamentous treatment. He emphasizes hypolipidaemic agents most frequently used at present, i. e. statins, resins and fibrates. When selecting hypolipidaemic agents several basic data must be taken into account: values of the lipid metabolism, the effect of the hypolipidaemic agent on individual parameters, undesirable effect of the drug, tolerance on the part of the patient, as well as whether after prolonged treatment regression of atherosclerosis or a decline in the prevalence of ischaemic heart disease was recorded. Decision taking is influenced also in a major way by the price of the preparation. The author discusses therefore also the effectiveness of hypolipidaemic agents in relation to their price. On these data the basic recommendation for pharmacotherapy of hyperlipoproteinaemias is based. The author discusses in more detail some controversial problems of treatment of hyperlipoproteinaemias, treatment of children, women and old patients. Attention is devoted also to patients with isolated low HDL-cholesterol levels and patients with elevated triglyceride levels.
Humans↗
[Recommendations for the prevention of atherosclerosis and ischemic heart disease. Detection and treatment of persons with increased lipids in adulthood].
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Humans↗
[Diseases of civilization from the aspect of evolution of the human diet].
The authors discuss contemporary views regarding the causes of diseases of civilization which developed on an epidemic scale in industrial societies during the last 60-70 years. They are due to the immense changes of lifestyle adopted by these societies. On the whole this lifestyle is a marked deviation from optimal conditions for humans. The genetic equipment of man which determines the evolutional advantages and function of different metabolic processes which ensure the homeostasis of the healthy organism is conservative and is entirely adapted to the human genome which developed in the course of hundreds of thousands of years. The aim of preventive medicine is to analyze, point out and enforce diminution of the effect of risk factors, as an important way towards improvement of the general health status of the population.
Diet↗