Michal Vrablik

Charles University in Prague, Praha, Praha, Czech Republic

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Publications (43)108.84 Total impact

  • European Journal of Internal Medicine 03/2015; DOI:10.1016/j.ejim.2015.02.019 · 2.30 Impact Factor
  • Michal Vrablík, Richard Češka
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    ABSTRACT: Options for modification of lipoprotein metabolism and, thus, for reduction of atherothrombotic complication have widened over recent years. Apart from the development of novel approaches new pharmacological formulations of common lipid lowering drugs have been prepared- e.g. statin-containing nanoparticles, fibrate nanoparticles with a much higher bioavailability etc. Even the oldest lipid lowering agents - resins - have not been forgotten due to its once again discovered positive impact of these agents on glucose homeostasis while optimally complementing the action of statins. Clinical trials of therapies targeting HDL particle metabolism are being in progress despite we have not gathered any unambiguous evidence of positive effect of the CETP inhibitors or apoA1 mime-tics on the progression of atherosclerosis. Brand new approaches in the treatment of dyslipidemia including MTTP and PCSK9 inhibition or therapies utilizing anti-sense technologies rapidly accumulate evidence from clinical studies. We have already learned about their lipid-modifying efficacy particularly in patients with familial hypercholesterolemia, however, data from other patients´ populations can be expected quite soon.
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    ABSTRACT: The study was aimed to determine risk factors of atherosclerosis after one month lifestyle intervention in overweight/obese children and also FTO and MC4R gene variants associated with obesity. 350 non-diabetic Czech children (age 13.7 ± 2.1 years, 163 ± 10.6 cm hight) was examined. Before and after 4 weeks of lifestyle intervention (comprising a reduction of energy intake), biochemical and anthropometrical measurements were performed. The mean weight loss achieved was 6.2 ± 2.1 kg (P < 0.001). Significant associations between BMI decrease and FTO and MC4R variants were found. Carriers of the FTO GG genotype and/or MC4R CC genotype lost significantly more body weight in comparison to the non-carriers (P < 0.0009 for BMI and P < 0.002 for body weight). The differences remain significant after adjustment for sex age and baseline values (P = 0.004 for BMI and P = 0.01 for body weight). It is necessary to look for the risk individuals with wrong response to the regime intervention. This individuals is necessary early treat with drugs to prevention clinically complications.Key words: childhood obesity - components of metabolic syndrome - predisposition - response to intervention.
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    ABSTRACT: 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. Although direct statistical analysis is impossible some changes in clinical features of FH might be found over the course of the time. In fact, the basic FH characteristic has not changed dramatically. Severe isolated hypercholesterolemia with total cholesterol 9-10 mmol/l, LDL-cholesterol 7-8 mmol/l and normal values of triglycerides dominates in laboratory analysis. Interestingly, the values of triglycerides increase and almost reach the pathological range in comparison to the values from the period 50 years ago. The values of HDL-cholesterol are normal. Manifestation of CHD in male patients over 40 years of age and in female patients over 50 years of age is not exceptional (rarely occur cases of myocardial infarction in third decade of age). Typical clinical manifestation of FH is xanthomatosis. The early detection and aggressive treatment in FH patients cause that xanthoma tendinosum, xanthelesma and arcus lipoides are less frequent as decades ago. Obesity, diabetes mellitus (DM) and hypertension do not belong to typical clinical sign of FH.
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    ABSTRACT: Background Ezetimibe's mechanism of action, complementary to that of statins, makes it a useful therapeutic option in patients intolerant of lipid-lowering drugs or in those not achieving target lipid levels. Objectives To evaluate the efficacy and safety of ezetimibe in a longterm follow-up of lipid clinic patients with emphasis on motivation for use and the impact on achievement of target lipid levels. Methods Two hundred and ninety-five clinic patients who were prescribed and took ezetimibe in the 13-month period following the drug's availability in Canada were identified from our database. Patients’ history and laboratory data were collected before and at first visit after the ezetimibe therapy was started. Paired t-test and chi-square test were used for statistical comparisons of ezetimibe's effect on lipid parameters and the achievement of target lipid-levels respectively. Results Ezetimibe treatment increased significantly the proportion of patients achieving lipid targets (by 25% for LDL-C and by 21.7% for TC/HDL-C) significantly by 18% (p < 0.001) and TC/HDL-C by 15% (p < 0.011). The effect of ezetimibe in combination with other lipid-lowering therapies was similar; LDL-C decreased by 22% (p < 0.001) and TC/HDL-C by 15.4% (p < 0.011). The same lipid-lowering effect was seen in patients with diabetes. In this subgroup, addition of ezetimibe to ongoing therapy led to three- and two-fold increase in LDL-C and TC/HDL-C target levels achievement, respectively. Only 7% of patients discontinued ezetimibe treatment due to side effects. Conclusion In patients referred to the lipid clinic (typically because of side effects or failure to reach targets on other lipid-lowering therapy) treatment with ezetimibe significantly increased proportion of those achieving their target lipid levels. This was not accompanied by significant side effects.
    Cor et vasa 04/2014; DOI:10.1016/j.crvasa.2014.01.006
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    ABSTRACT: BACKGROUND: Diabetes mellitus and low levels of high-density lipoprotein cholesterol (HDL-C) are among several known risk factors for coronary artery disease. Recent research has shown potential mechanistic links between these two diseases. OBJECTIVES: The aim of our study was to characterize, by examining particular coronary artery disease risk factors, patients with extremely high and low levels of HDL-C who were referred to a prevention clinic. METHODS: We compared the phenotypes of 113 patients with HDL-C levels greater than the 90th percentile with 212 patients with levels less than the 10th percentile by using a retrospective chart review. RESULTS: The cohort with high HDL-C had a remarkable difference in the incidence of type 2 diabetes (1.8% vs 21.7%). The high HDL-C cohort also had a greater age (52.1 years vs 46.7 years), more light or moderate alcohol consumption (70.8% vs 49.4%), more healthy diet (30.1% vs 22.4%), more light or moderate exercise (90.8% vs 52.2%), and a lower body mass index (25.2 kg/m(2) vs 28.1 kg/m(2)). CONCLUSIONS: Compared with the low HDL-C group-and also the general population-the high HDL-C cohort had a remarkably low prevalence of diabetes mellitus.
    Journal of Clinical Lipidology 05/2013; 7(3):194-198. DOI:10.1016/j.jacl.2013.02.003 · 3.59 Impact Factor
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    ABSTRACT: This position statement of the Executive Committee of the Czech Society for Atherosclerosis (CSAT) summarizes the most important aspects and novelties of the latest European guidelines for the management of dyslipidemia. In particular the position statement comments on: cardiovascular risk stratification, indications for plasma lipid and lipoprotein levels assessment as well as target lipid values, evaluation of current options for both lifestyle and pharmacological treatment of lipid metabolism disorders and, also, recommendation for laboratory monitoring of patients treated with lipid lowering agents. The statement deals with actual concepts of management of dyslipiemia in everyday practice, e.g. therapy of dyslipidemia in special patients´ groups. This statement does not replace the latest guidelines but focuses on the changes from the former guidelines for dyslipidemia management, published by CSAT in 2007.Key words: dyslipidemia - risk stratification - LDL-cholesterol - statins - fibrates - niacin - ezetimibe - resins.
    Vnitr̆ní lékar̆ství 02/2013; 59(2):120-6.
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    ABSTRACT: OBJECTIVES: This study aimed to determine whether there is a relationship between common FTO (rs17817449) and MC4R (rs17782313) gene variants and body mass reduction or weight loss after a one-month lifestyle intervention in overweight/obese children. DESIGN AND METHODS: We genotyped 357 unrelated non-diabetic Czech children (age 13.7 ± 4.9 years, average BMI at baseline 30.8 ± 4.6 kg/m(2)). Biochemical and anthropometrical measurements were performed before and after 4 weeks of lifestyle interventions (comprising a reduction in energy intake to the age-matched optimum and a supervised exercise program consisting of 5 exercise units per day, 50 min each). RESULTS: The mean weight loss achieved was 6.2 ± 2.1 kg (P<0.001). Significant associations were found between a BMI decrease and the FTO and MC4R variants. Carriers of the FTO GG genotype and/or MC4R CC genotype lost significantly more body weight compared to noncarriers (P<0.0009 for BMI and P<0.002 for body weight). These differences remained significant following adjustment for sex, age and baseline values (P=0.004 for BMI and P=0.01 for body weight). CONCLUSIONS: FTO and MC4R gene variants modify the impact of an intensive lifestyle intervention on BMI decrease in overweight/obese children. Carriers of the FTO GG genotype and MC4R CC genotype benefit significantly more from the lifestyle intervention.
    Clinical biochemistry 11/2012; 46(4-5). DOI:10.1016/j.clinbiochem.2012.11.017 · 2.23 Impact Factor
  • Nutrition, metabolism, and cardiovascular diseases: NMCD 07/2012; 22(9):e22-3. DOI:10.1016/j.numecd.2012.05.001 · 3.88 Impact Factor
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    Dita Kasparova, Michal Vrablik, Tomas Fait
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    ABSTRACT: OBJECTIVE: The aim of the study was to evaluate the importance of screening for thrombophilic mutations after the first early pregnancy loss. Setting: Thrombophilic mutations were examined in a sample of 100 women with at least one miscarriage. DNA was isolated from venous blood sample. We used methods of microarray, fragmentation analysis, High Resolution Melting and PCR-ARMS with following gel electrophoresis and visualisation. Chi-square test and in cases of low expected frequencies Yates correction were used to compare relative frequencies of individual mutations. The comparison of averages was performed by t-test. Results: We detected prevalence of factor V and II mutation of 9% and 3%, respectively. Single MTHFR mutation was found in 59% and double heterozygous MTHFR mutation in 23% of cases. No mutation was present in only 6% of the study group. Heterozygous mutations of factor V occurred 1.8 times more frequently in our study group compared to the general Czech women population. Also, the frequency of factor II mutation was 1.5-3 times higher. No carrier of these mutations had overt coagulation disorder, history of thromboembolic disease or that of habitual abortions. Conclusions: The frequency of thrombophilic mutations in the group of women with early pregnancy loss is 1.5-3 times higher than in the general population.
    Neuro endocrinology letters 01/2012; 33(1):76-80. · 0.94 Impact Factor
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    ABSTRACT: Vascular erectile dysfunction (ED) predicts future development of cardiovascular diseases (CVD). We performed a study in men seeking consultant medical advice regarding vascular ED for the first time without a history of cardiovascular disease, diabetes mellitus or renal insufficiency. Our goal was to evaluate the prevalence of CVD risk factors in this cohort of patients. Furthermore, we assessed the prevalence of asymptomatic subclinical atherosclerosis. All study subjects underwent a thorough physical examination including anthropometric measurements. Laboratory analyses comprising assessment of lipid spectrum, liver and kidney function tests, glycaemia and glycated haemoglobin were measured using automated analysers. Intima-media thickness of carotid arteries was measured using SONOS machine and ankle-brachial index using a mini-duplex device. CVD risk was calculated by standard SCORE charts. Chi-square test, t-test and ANOVA were used for statistical analysis. We examined 35 men, average age 46.5 ± 9.9 years. Six (17.1%) had a positive family history of CVD, 19 (54.3%) had dyslipidemia, 10 (28.6%) were obese, 9 (25.7%) were active smokers, and 14 (40.0%) had arterial hypertension. Eighteen (51.4%) subjects had subclinical atherosclerosis as determined by ABI and CIMT assessment. Patients with vascular erectile dysfunction have similar prevalence of CVD risk factors to general population.
    Neuro endocrinology letters 11/2011; 32 Suppl 2:60-3. · 0.94 Impact Factor
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    ABSTRACT: Obesity is associated with increased inflammation which represents a link to atherosclerosis and cardiovascular disease. Lipoprotein associated phospholipase A2 (Lp-PLA2) is an independent marker of inflammation and atherosclerosis risk. To assess the impact of weight loss on metabolic markers of atherosclerosis including Lp-PLA2 we examined a group of Czech non-diabetic obese/overweight children exposed to a lifestyle intervention. Fourty unrelated overweight/obese non-diabetic Czech children (13.7 ± 2.1 years, average BMI at baseline 29.8 ± 2.6 kg/m2) underwent 4 weeks of lifestyle modification (reduction of energy intake to age matched optimum and supervised physical activity). Anthropometrical and biochemical variables were determined at baseline and after the intervention. Lp-PLA2 mass concentration was assessed using the ELISA kit. Wilcocson's rank test and Spearman's correlation were used for statistical analysis. A significant decrease of BMI and waist circumference was associated with significant changes of plasma lipoprotein and glycaemia levels. Mass concentration of Lp-PLA2 at the baseline was 402 ± 94 μg/ml, after the intervention 368 ± 105 μg/ml (p=0.008). Change in Lp-PLA2 was associated with triglyceride level decrease (p=0.009). Intensive lifestyle modification leading to body weight decrease results in significant changes of plasma lipoprotein levels and, also, a drop of Lp-PLA2 levels in paediatric obese patients. However, even after the intervention Lp-PLA2 concentrations in this patient group remain elevated suggesting possible increased atherosclerosis risk in later life.
    Neuro endocrinology letters 11/2011; 32 Suppl 2:55-9. · 0.94 Impact Factor
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    ABSTRACT: Life expectancy is determined by a combination of genetic predisposition (~25%) and environmental influences (~75%). Nevertheless a stronger genetic influence is anticipated in long-living individuals. Apolipoprotein E (APOE) gene belongs among the most studied candidate genes of longevity. We evaluated the relation of APOE polymorphism and fitness status in the elderly. We examined a total number of 128 subjects, over 80 years of age. Using a battery of functional tests their fitness status was assessed and the subjects were stratified into 5 functional categories according to Spirduso´s classification. Biochemistry analysis was performed by enzymatic method using automated analyzers. APOE gene polymorphism was analysed performed using PCR-RFLP. APOE4 allele carriers had significantly worse fitness status compared to non-carriers (p=0.025). Multiple logistic regression analysis showed the APOE4 carriers had higher risk (p=0.05) of functional unfitness compared to APOE2/E3 individuals. APOE gene polymorphism seems be an important genetic contributor to frailty development in the elderly. While APOE2 carriers tend to remain functionally fit till higher age, the functional status of APOE4 carriers deteriorates more rapidly.
    Neuro endocrinology letters 11/2011; 32 Suppl 2:51-4. · 0.94 Impact Factor
  • European Journal of Internal Medicine 10/2011; 22. DOI:10.1016/S0953-6205(11)60406-8 · 2.30 Impact Factor
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    ABSTRACT: The aim of this study was to compare HDL-cholesterol and triglyceride levels in patients with familial hypercholesterolemia (FH) with a representative sample of the Czech population. For the FH group: data of 1728 adult patients with FH (600 males and 1128 females) were taken from the MedPed CR database. The control group were 1995 individuals of the population sample of the Czech post-MONICA study (956 males and 1039 females). Compared with controls, FH males showed higher levels of HDL-cholesterol (1.35±0.35 mmol/l vs. 1.31±0.35 mmol/l; P<0.05) and triglycerides (1.98±1.00 vs. 1.81±1.45 mmol/l; P<0.01). After adjustment for age and BMI, the increase in triglycerides remained significant in the subgroup of non-FDB males only (2.22±0.06 vs. 1.74±0.04 mmol/l; P<0.001). Compared with controls, HDL-cholesterol was lower (1.55±0.40 mmol/l vs. 1.65±0.37 mmol/l; P<0.001), while triglycerides were higher (1.72±0.82 mmol/l vs. 1.28±0.75, P<0.001) in FH females. After adjustment for age and BMI, HDL-cholesterol remained lower in the subgroup of FH females without FDB (1.52±0.01 vs. 1.67±0.01 mmol/l, P<0.001) whereas triglycerides were higher in both female subgroups. A lower HDL-C in the group of FH patients compared with control subjects was demonstrated in FH females without FDB only. Elevated triglyceride levels were found in FH males and females, except for males with FDB.
    Clinica chimica acta; international journal of clinical chemistry 05/2011; 412(11-12):920-4. DOI:10.1016/j.cca.2011.01.017 · 2.76 Impact Factor
  • Jaroslav A Hubacek, Michal Vrablik
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    ABSTRACT: Hypercholesterolemia or dyslipidemia is an independent risk factor for cardiovascular disease and statins (inhibitors of a key enzyme of cholesterol synthesis, 3-hydroxymethyl glutaryl coenzyme A reductase) are the drugs of choice for decreasing plasma cholesterol. It has been estimated that genetic factors can explain 40%-60% of final cholesterol concentrations and approximately 70% of the efficacy of statin treatment. The gene most often analyzed in the context of statin efficacy is the gene for apolipoprotein E (APOE). This review summarizes evidence of the association between variations in the APOE gene locus and the response of plasma lipids to statin therapy. Although the results are not consistent, carriers of the APOE4 allele seems to be less responsive to statins than carriers of APOE2 and APOE3 alleles. This effect is partially context-dependent (gene-gender interactions; gene-nutrition and gene-smoking interactions have not yet been studied) and the absolute differences vary between different population groups.
    Drug metabolism and drug interactions 01/2011; 26(1):13-20. DOI:10.1515/DMDI.2011.107
  • Michal Vrablik, Jaroslav A Hubacek
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    ABSTRACT: High level plasma triglyceride (TG) is an independent risk factor of cardiovascular disease (CVD), and postprandial hypertriglyceridemia might be an even better predictor of TG-associated CVD risk. It has been estimated the genetic factors can explain 30-70% of final TG concentration. In the plasma, TGs can be found in all lipoprotein particles, mostly in chylomicrons and VLDL. Within lipoproteins, TGs associate with other lipids and proteins (apolipoproteins), which serve as structural components of the particles, as well as receptor ligands and cofactors for lipid-metabolizing enzymes. The polymorphisms and variants of apolipoproteins, enzymes and different regulatory and receptor genes have attracted much attention in the search for genetic basis of increased TG levels. This article summarizes the evidence of the connection between variations at different gene loci and TG levels in the plasma.
    Clinical Lipidology 08/2010; 5(4):543-554. DOI:10.2217/clp.10.38 · 0.86 Impact Factor
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    ABSTRACT: Despite the fact that statin treatment efficacy is very high, there are substantial differences in treatment effectiveness among individuals. It is supposed that genetic predisposition plays an important role in these differences, but the contribution of individual polymorphisms is poorly understood. So far, more than 30 genes have been examined with ambiguous results. Apolipoprotein A5 is an important determinant of plasma lipid concentrations and its genetic variation could account for some of the observed differences in the response to statin therapy. However, this has not been analyzed before. We examined the putative association between APOA5 SNPs (c.-1131T>C, c.56C>G and c.457G>A) and efficacy during 3 months of statin treatment in 187 adult Caucasians. Patients were treated with low-dose (10 or 20 mg per day) simvastatin (46.3%), atorvastatin (40.5%) and lovastatin (13.2%). The decrease in cholesterol was not significantly associated with the type or dose of statin. Carriers of the APOA5 genotype TT-1131 (n = 154) benefited more from statin treatment when compared with the C-1131 allele carriers (n = 33) (Delta low-density lipoprotein cholesterol: -36.3 +/- 15.1% vs Delta low-density lipoprotein cholesterol: -29.9 +/- 12.5%; p < 0.005, Mann-Whitney test). This result was independent of sex, age, BMI and APOE polymorphism. Our results suggest that the APOA5 gene variants may play an important role in the pharmacogenetics of statin treatment.
    Pharmacogenomics 07/2009; 10(6):945-50. DOI:10.2217/pgs.09.17 · 3.43 Impact Factor
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    ABSTRACT: We tested the hypothesis that the MLXIPL rs3812316 variant predicts plasma triglyceride (TG) levels. We compared three groups of adult individuals: 162 persons with TG > 10 mmol/L, 266 persons with TG < 0.65 mmol/L, and 2,043 population-based controls (range of TG concentrations 0.7-8.7 mmol/L). We found a small difference in the frequency of the Gln allele carriers between population controls (20.4%) and persons with low TG (26.3%, P = 0.033). We found no difference between individuals with high TG and population controls, and there was no association between the MLXIPL variant and plasma TG levels among the population controls.
    Human Genetics 10/2008; 124(5):553-5. DOI:10.1007/s00439-008-0577-6 · 4.52 Impact Factor
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    ABSTRACT: The purpose of this study was to identify rare APOA5 variants in 130 severe hypertriglyceridemic patients by sequencing, and to test their functionality, since no patient recall was possible. We studied the impact in vitro on LPL activity and receptor binding of 3 novel heterozygous variants, apoAV-E255G, -G271C, and -H321L, together with the previously reported -G185C, -Q139X, -Q148X, and a novel construct -Delta139 to 147. Using VLDL as a TG-source, compared to wild type, apoAV-G255, -L321 and -C185 showed reduced LPL activation (-25% [P=0.005], -36% [P<0.0001], and -23% [P=0.02]), respectively). ApoAV-C271, -X139, -X148, and Delta139 to 147 had little affect on LPL activity, but apoAV-X139, -X148, and -C271 showed no binding to LDL-family receptors, LR8 or LRP1. Although the G271C proband carried no LPL and APOC2 mutations, the H321L carrier was heterozygous for LPL P207L. The E255G carrier was homozygous for LPL W86G, yet only experienced severe hypertriglyceridemia when pregnant. The in vitro determined function of these apoAV variants only partly explains the high TG levels seen in carriers. Their occurrence in the homozygous state, coinheritance of LPL variants or common APOA5 TG-raising variant in trans, appears to be essential for their phenotypic expression.
    Arteriosclerosis Thrombosis and Vascular Biology 10/2008; 28(10):1866-71. DOI:10.1161/ATVBAHA.108.172866 · 5.53 Impact Factor

Publication Stats

225 Citations
108.84 Total Impact Points

Institutions

  • 2003–2015
    • Charles University in Prague
      • • 1st Faculty of Medicine
      • • Centrum preventivní kardiologie
      Praha, Praha, Czech Republic
  • 2011
    • University General Hospital
      Houston, Texas, United States
  • 2009–2011
    • Institute for Clinical and Experimental Medicine (IKEM)
      Praha, Praha, Czech Republic
  • 2007
    • University Hospital Olomouc
      Olmütz, Olomoucký, Czech Republic
  • 2004
    • Military University Hospital Prague
      Praha, Praha, Czech Republic