[Familial hypercholesterolemia - past and present. My experiences and findings in our group of patients with familial hypercholesterolemia].

Currently, the familial hypercholesterolemia (FH) rises the interest. The reason is that this genetic disorder is targeted by newly emerged and highly effective hypolipidemic agents, PCSK-9 inhibitors, lomitapid and mipomersen. Present paper discusses 2 patient study groups, before 50 years and nowadays.

[Familial hyperlipoproteinemias--correlations between phenotypes and genotypes].

Within the grant project patients with familial hyperlipoproteinaemias have been examined. The examination was performed in the oldest lipid clinic and research laboratory in the world. The classification of lipid metabolism disorders was based upon a detailed biochemical analysis of plasma lipids including electrophoresis and assessment of apolipoprotein levels.

[Genetic predisposition for multiple metabolic syndrome. Part 1. Diabetes mellitus type 2--incidence and prevalence].

Multiple metabolic syndrome (MMS) implies a frequent coincidence of four basic serious metabolic risk factors for subsequent manifestation of cardiovascular disease. The latter include: central type obesity, arterial hypertension, dyslipoproteinaemia and diabetes mellitus type II (non-insulin-dependent diabetes mellitus--NIDDM). MMS is also described as syndrome X, Reaven's syndrome, insulin resistance syndrome, metabolic syndrome or as the "deadly quartet".

The effect of four-year hypolipidaemic treatment on the intimal thickness of the common carotid artery in patients with familiar hyperlipidaemia.

Background: Cholesterol lowering in patients with above-average cholesterol levels has been shown to reduce the progression of atherosclerosis. We assess the effects of lipid lowering therapy on the progression of early, preintrusive carotid arterial atherosclerosis in high risk patients with familial hyperlipidaemia free of symptomatic cardiovascular disease.

Methods: Fifty-two patients with familial hyperlipidaemia by were treated by diet and various hypolipidaemic drugs.

[Negative aspects of the Western life style and possibilities of intervention in patients with familial combined hyperlipidemia].

Background: Evaluation of the effect of intervention on changes in the lifestyle of patients with combined familial hyperlipidaemia (CFH).

Methods And Results: The group comprised 154 patients with CFH where changes in the lipid profile, diet, basic anthropometric data and smoking were recorded 3-6 months following intervention. In addition to little willingness to have a check-up examination the authors recorded significant shortcomings in the lifestyle of these patients with a high cardiovascular risk: a large number of smokers (51%), serious shortcomings in the composition of the diet (excessive intake of animal fats a proteins, inadequate intake of vegetable proteins, dietary fibre and vitamins, in particular E and C), overweight and a high percentage of body fat.

[Genetic predisposition for the multiple metabolic syndrome. Part 4. Apolipoprotein E and lipoprotein (a)].

Apolipoprotein E (apo E) is a genetically polymorphous glykoprotein made up of 299 amino acids. It is an important part of triacylglycerol rich lipoproteins [chylomicrons, lipoproteins with a very low density (VLDL) and their "residues"]. Apo E is a ligand of apo B, E receptors and thus regulates in a marked way the homeostasis of lipids and lipoproteins in plasma.

[Genetic predisposition in multiple metabolic syndrome. Part 3. Metabolism of lipids, lipoproteins and apolipoproteins].

The author discusses metabolic processes during exogenous and endogenous lipid transport and deviations in the metabolism of lipids, lipoproteins and apolipoproteins in multiple metabolic syndrome and in so-called diabetic dyslipidaemia. Specific phenotypic manifestations of diabetic dyslipidaemia include hypertriacylglycerolaemia, hypercholesterolaemia, elevated plasma levels of LDL-cholesterol and apolipoprotein B and reduced levels of HDL-cholesterol and apolipoprotein B and reduced levels of HDL-cholesterol and apolipoprotein A-I. Other recent findings relating to this syndrome include evidence of elevated concentrations of small and dense LDL micelles (< 25 nm), so-called LDL phenotype B, which are easily modified (e.

[Genetic predisposition in multiple metabolic syndrome. Part 2. Candidate genes in type II diabetes mellitus].

The author presents a review on candidate genes of proteins involved in the metabolism of glucose, lipids and other metabolites (glucose carriers, insulin receptors, proinsulin, glucokinase, amyline, glycogen synthase). One of the main causes of enhanced atherogenesis in patients with type II diabetes (NIDDM) are marked genetically conditioned deviations of the lipid, lipoprotein and apolipoprotein metabolism. In the metabolic dyshomeostasis of multiple metabolic syndrome participate in the process of atherogenesis also: isoforms of apolipoprotein E4, isoforms of apolipoprotein A-IV-1/1, hyperuricaemia, raised levels of the plasminogen activator inhibitor 1 (PAI-1), hyperfibrinogenaemia, hyperhomocysteinaemia and other metabolites (cytokines, endothelin etc.

[The effect of 4 years' of hypolipemic treatment on the width of the common carotid artery intima in patients with familial hyperlipidemias].

Sixty-four patients with familial hyperlipoproteinaemia were treated for almost four years by dietetic treatment and various hypolipidaemic drugs. In 25 patients with familial hypercholesterolaemia who had clinical signs of ischaemic heart disease total and LDL-cholesterol declined and the width of the intima of the common carotid artery diminished from 0.78 mm to 0.

[Screening and treatment of children and adolescents with hypercholesterolemias and dyslipidemias].

Evidence was provided that atherogenesis develops for several decades before pathological changes are manifested. It may thus be stated, that the "incubation period" of atherosclerotic pathological consequences is very long but it is reduced markedly already from childhood and adolescence in subjects with an atherogenic lipoprotein phenotype. Atherogenic lipoprotein phenotype comprises subjects suffering from one or more, frequently from a combination of several of the following metabolic indicators: hypercholesterolaemia, elevated levels of LDL-cholesterol, apolipoprotein B, lipoprotein (a), reduced levels of HDL-cholesterol and apolipoprotein A-1.

Decreasing common carotid artery intimal thickness during hypolipidemic therapy.

It has been demonstrated in recent years that ultrasound can be used to measure common carotid artery intimal thickness; an increase in intimal thickness is regarded as an early stage of atherosclerosis. This study was designed to establish whether or not intimal thickness can be modulated by therapy. Twenty-nine patients with familial hyperlipoproteinemias had follow-up ultrasound of the common carotid artery after twenty-nine months of comprehensive therapy.

[Favorable effect of treatment with statins on the intima of the common carotid artery in patients with familial hyperlipoproteinemia].

Background: In recent years evidence was provided that by measuring the width of the intima of the carotid artery, evaluated by sonography, it is possible to assess the development of arteriosclerosis. The authors used this method to evaluate hypolipidaemic treatment.

Methods And Results: The authors followed-up by clinical and laboratory methods and treated for a period of 47 months 63 patients with familial hyperlipoproteinaemia.

[Patients with familial combined hyperlipidemia and smoking].

Background: Evaluation of the negative impact of active smoking on lipid and lipoprotein serum levels and the relationship with body mass index (BMI) and waist/hip ratio (WHR).

Methods And Results: The group was formed by 178 (77 men and 101 women), mean age 54 years (SD 6.2 attending the lipid out-patient department at the Third Medical Clinic, First Medical Faculty, Charles University Prague.

[Familial hypobetalipoproteinemia].

Background: Familial hypobetalipoproteinaemia (FHBL) is a relatively rare inborn error of metabolism which must be considered in the differential diagnosis of hypocholesterolaemia which cannot be explained by secondary causes (severe malnutrition, generalization of neoplastic disease etc.).

Methods And Results: In the submitted paper the authors present the results assembled in a family with four heterozygotes with FHBL.

[The effect of micronized fenofibrate on lipid parameters and fibrinogen in heterozygous familial hypercholesterolemia and familial combined hyperlipidemia].

Background: The aim of the study was to approve the hypolipidemic potency of the new drug from the group of fibrate derivates Lipanthyl 200 M(R) (micronized fenofibrate, cps a 200 mg, Laboratoires Fournier, France) in patients with familial hyperlipoproteinemias. The drug has been administered in constant dose of 200 mg daily with the evening meal for three months. Clinical examinations and monitoring of safety laboratory have been performed in addition to complete analysis of lipids, lipoproteins and apolipoproteins during the study.

[Hyperhomocysteinemia].

Similarly as in other inborn metabolic diseases the cause of hyperhomocysteinaemia are interactions between genetically conditioned changes most frequently due to reduced cystathionine-beta synthase activities and negative factors of the external environment. Negative environmental factors include above all a high dietary animal protein consumption which is the main methionine donor and a low intake of protein of plant origin. Another negative factor is a low intake of foods of plant origin.

[Analysis of nutritional habits in patients with familial combined hyperlipidemia].

Background: Our objective was to analyze dietary habits of patients with the IIb phenotype of familial combined hyperlipidaemia. These patients were instructed on the proper composition of their diet and they thought that they adhered to these recommendations.

Methods And Results: The authors examined 41 patients with IIb phenotype of familial combined hyperlipidaemia.

[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.

[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.

[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.

[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.