Hypercholesterolemia: Freiberger T

Vaverková H, Soska V, Rosolová H, Ceska R, Cífková R, Freiberger T, Pit'ha J, Poledne R, Stulc T, Urbanová Z, Vráblík M, Czech Atherosclerosis Society. · III. interní klinika LF UP a FN, Olomouc. · Cas Lek Cesk. · Pubmed #17650596 No free full text.

Abstract: The present guidelines are based on the recommendations published in 2005 entitled "Prevention of Cardiovascular Diseases in Adulthood" summarizing the conclusions of nine Czech medical societies and agree with them in the assessment of individual risk of mortality from cardiovascular disease (CVD) according to SCORE tables. They reflect new research data in pathophysiology of dyslipidemias (DLP) and particularly the results of recent clinical trials of lipid-lowering therapy and their meta-analyses. They establish priorities for the screening and management of DLP, present suitable diagnostic methods, additional investigations of potential use in risk assessment, including some emerging risk factors and detection of sub-clinical atherosclerosis in persons in a moderate-risk category. Major changes include a lower LDL-cholesterol treatment target (< 2.0 mmol/L for all CVD individuals) and a possible use of apolipoprotein B as a secondary target in selected persons (< 0.9 g/L in high risk without CVD, < 0.8 g/L for CVD patients) and nonHDL-cholesterol (< 3.3 mmol/L in high risk without CVD, < 2.8 mmol/L for CVD patients). Therapy of individual DLP phenotypes (monotherapy and combination therapy) as well as basic principles for control examination at lipid-lowering medication are described. Recommended therapeutic lifestyle changes are shown. Enclosed are five annexes: DLP diagnosis; causes of secondary DLP; additional investiga- tions of potential use in risk stratification; familial hypercholesterolemia; list of recommended foods; two variants of SCORE tables for risk assessment for the Czech Republic; the scheme of recommended procedures and treatment algorithm in DLP asymptomatic individuals.

Vaverková H, Soska V, Rosolová H, Ceska R, Cífková R, Freiberger T, Pit'ha J, Poledne R, Stulc T, Urbanová Z, Vráblík M, Anonymous00126. · III. interní klinika Lékarské fakulty UP a FN Olomouc. · Vnitr Lek. · Pubmed #17419181 No free full text.

Abstract: The present guidelines are based on the recommendations published in 2005 entitled "Prevention of Cardiovascular Diseases in Adulthood" summarizing the conclusions of nine Czech medical societies and agree with them in the assessment of individual risks of mortality from cardiovascular disease (CVD) according to SCORE tables. They reflect new research data in pathophysiology of dyslipidemias (DLP) and particularly the results of recent clinical trials of lipid-lowering therapy and their meta-analyses. They establish priorities for the screening and management of DLP, present suitable diagnostic methods, additional investigations of potential use in risk assessment, including some emerging risk factors and detection of sub-clinical atherosclerosis in persons in a moderate-risk category. Major changes include a lower LDL-cholesterol treatment target (< 2.0 mmol/L for all CVD individuals) and a possible use of apolipoprotein B as a secondary target in selected persons (< 0.9 g/L in high risk without CVD, < 0.8 g/L for CVD patients) and nonHDL-cholesterol (< 3.3 mmol/L in high risk without CVD, < 2.8 mmol/L for CVD patients). Therapy of individual DLP phenotypes (monotherapy and combination therapy) as well as basic principles for control examination at lipid-lowering medication are described. Recommended therapeutic lifestyle changes are shown. Enclosed are five annexes: DLP diagnosis; causes of secondary DLP; additional investigations of potential use in risk stratification; familial hypercholesterolemia; list of recommended foods; two variants of SCORE tables for risk assessment for the Czech Republic; the scheme of recommended procedures and treatment algorithm in DLP asymptomatic individuals.

Freiberger T, Ceska R. · Genetická laborator Centra kardiovaskulární a transplantacní chirurgie Brno. · Vnitr Lek. · Pubmed #17702130 No free full text.

Abstract: In 1997, the Czech Republic joined the international project MedPed (Make early diagnosis to Prevent early deaths), the principal objective of which is to dramatically reduce the number of deaths caused by the premature clinical manifestations of atherosclerosis in patients with familial hypercholesterolemia (FH). Stress has been laid on a timely diagnosis, especially in family members of patients who have already been diagnosed with the disease, and on timely application of adequate hypolipidemic therapy. A network of centres dealing with severe inborn dyslipidemias has been set up under the auspices of the Czech Society for Atherosclerosis. As many as 3,208 cases of dyslipidemia from 2377 families have been detected thanks to the network and to the contribution of cooperating doctors; this represents 16% of the estimated number of 20,000 patients with FH in this country. However, the disease is far from being under control in the Czech Republic. The principal objective for the immediate future is to dramatically increase the number of people screened within affected families; thus multiplying the current rate of diagnosed and treated patients with FH within each family from its current value of 1.3.

Kuhrová V, Francová H, Zapletalová P, Freiberger T, Fajkusová L, Hrabincová E, Slováĉková R, Kozák L, Slováková R. · Research Institute of Child Health, Department of Biochemical and Molecular Genetics, Cernopolní 9, CZ-662 62. · Hum Mutat. · Pubmed #11754108 No free full text.

Abstract: The aim of our study was to define mutations causing familial hypercholesterolemia (FH) phenotype in Czech hypercholesterolemic individuals. A combination of heteroduplex analysis, SSCP, DGGE, DNA sequencing and PCR/restriction analysis was used for this purpose. Molecular searching in the promoter region and coding sequence of the low density lipoprotein receptor (LDLR) gene in 130 patients from 68 unrelated families resulted in the identification of 37 sequence variations. Thirty of them are most likely disease causing mutations. Nineteen mutations were novel (two nonsense, five missense, six nucleotide(s) insertions and six nucleotide(s) deletions). Their pathological effect can be predicted on the basis of their position with respect to previously reported mutations with an estimated reduction of the receptor activity and/or premature termination of translation. These results expand our knowledge of mutations responsible for FH. Seven nucleotide variations were characterized as silent polymorphisms.

Kuhrová V, Francová H, Zapletalová P, Freiberger T, Fajkusová L, Hrabincová E, Slováková R, Kozák L. · Research Institute of Child Health, Department of Biochemical and Molecular Genetics, Brno, Czech Republic. · Hum Mutat. · Pubmed #11524740 No free full text.

Abstract: The aim of our study was to define mutations causing familial hypercholesterolemia (FH) phenotype in Czech hypercholesterolemic individuals. A combination of heteroduplex analysis, SSCP, DGGE, DNA sequencing and PCR/restriction analysis was used for this purpose. Molecular searching in the promoter region and coding sequence of the low density lipoprotein receptor (LDLR) gene in 130 patients from 68 unrelated families resulted in the identification of 37 sequence variations. Thirty of them are most likely disease causing mutations. Nineteen mutations were novel (two nonsense, five missense, six nucleotide(s) insertions and six nucleotide(s) deletions). Their pathological effect can be predicted on the basis of their position with respect to previously reported mutations with an estimated reduction of the receptor activity and/or premature termination of translation. These results expand our knowledge of mutations responsible for FH. Seven nucleotide variations were characterized as silent polymorphisms. Hum Mutat 18:253, 2001.

Grombiríková H, Freiberger T, Kuhrová V, Soska V, Nedomová K. · Výzkumný ústav zdraví dítĕte, Brno. · Cas Lek Cesk. · Pubmed #11242979 No free full text.

Abstract: BACKGROUND: Familial defective apolipoprotein (apo) B-100 (FDB) is a common inherited metabolic disorder. Reduced binding of the apo B-100, the major protein of LDL particles, to LDL receptor results in marked hypercholesterolemia. FDB is caused particularly by an arginine to glutamine substitution at the codon for amino acid 3500 of the apo B-100. The aim of this study was to determine mutations potentially responsible for hypercholesterolemia in the apo B gene and to estimate their frequency in the group of Czech hyperlipidemic patients. METHODS AND RESULTS: The groups of 169 unrelated patients with primary isolated hypercholesterolemia (total cholesterol > or = 6.5 mmol/l, triglycerides < or = 2.3 mmol/l) and 58 unrelated patients with combined hyperlipoproteinemia (total cholesterol > or = 6.5 mmol/l, triglycerides > 2.3 mmol/l) were screened for mutations in codon 3500 region of the apolipoprotein B gene by denaturing gradient gel electrophoresis. Mutation R3500Q was detected in 20 patients with isolated hypercholesterolemia (11.8%) and in 2 patients with combined hyperlipoproteinemia (3.4%). No other mutations were found. CONCLUSION: The frequency of FDB in our group of patients with primary isolated hypercholesterolemia is high when compared with data published in other countries. We suggest that all patients with primary isolated hypercholesterolemia (total cholesterol > or = 6.5 mmol/l) in the Czech Republic should be analysed for the presence of mutation R3500Q in the apo B gene.

Freiberger T, Soska V, Kuhrová V, Stejskal J. · Výzkumný ústav zdraví dítĕte, Brno. · Cas Lek Cesk. · Pubmed #10916204 No free full text.

Abstract: The authors present an international MedPed project (Make early diagnoses to prevent early deaths in medical pedigrees) the task of which is to increase the number of patients with familial lipid disorders identified and adequately treated all over the world. This will lead to significant decrease of premature deaths from coronary artery disease. Primary effort has been focused on familial hypercholesterolemia. The realization of MedPed program in Czech Republic is described.