[Show abstract][Hide abstract] ABSTRACT: Background:
Gene SLCO1B1, encoding solute organic anionic transport polypeptide OATP1B1, belongs to the group of candidates potentially influencing statin treatment safety. OATP1B1 regulates (not only) the hepatic uptake of statins. Its genetic variation was described as an important predictor of statin-associated myopathy in a cohort of patients treated with a maximum dose of simvastatin. However, the impact of SLCO1B1 gene polymorphism on this risk in patients treated with other statins or lower doses of simvastatin needs to be assessed. Therefore, we performed the present study.
SLCO1B1 tagging rs4363657 polymorphism was analyzed in 2 groups of patients with dyslipidemia (treated with simvastatin or atorvastatin, 10 or 20 mg per day), subgroup with statin-induced myalgia (N=286), and subgroup (N=707) without myalgia/myopathy, and in 2301 population controls without lipid-lowering treatment.
Frequency of the individual genotypes in patients with myalgia/myopathy (TT=62.3%, CT=34.5%, CC=2.8%) did not significantly differ (both P values over 0.19) from that in patients without muscle symptoms (TT=61.4%, CT=32.9%, CC=5.7%) or from the population controls (TT=63.9%, CT=32.5%, CC=3.6%). Null results were also obtained for the dominant and recessive models of the analysis.
In Czech patients treated with low statin doses, there is no association between SLCO1B1 gene polymorphism and risk of myalgia/myopathy.
Medical science monitor: international medical journal of experimental and clinical research 05/2015; 21:1454-9. DOI:10.12659/MSM.893007 · 1.43 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: Cardiovascular (CV) disease belongs to the most important mortality causes worldwide. Early identification of risk factors and increased CV risk may help decrease of morbidity and mortality. An optimal age for CV risk factors screening ages of 40 in males and of 50 in females have been identified. CV risk profile of persons in these age categories has been examined by general practitioners and recorded for the purposes of this cross-sectional survey.
1812 persons, males at average age of 40 years and females at average age of 50 years, were included into the survey. In each of the examined family and personal history including pharmacological were recorded into the study protocol as well as abusus and physical activity patterns. Basic anthropometrical parameters, e.g. heart rate, blood pressure, body mass index and laboratory measures including blood lipids and glycaemia. The participating physicians recorded newly identified risk factors CV disease and determined the global CVD risk according to the SCORE charts. Percentage of those already treated for any of the main CVD risk factors and, among these, also attaining the treatment goals. The percentage of patients with a newly identified CV risk factor was calculated. We also tested the hypothesis of a relationship between positive family history of any of the followed risk factors and its risk in the examined probands using Pearson´s test.
961 males, average age of 42.9 ± 4.7 years, and 851 females , average age of 51.2 ± 3.6 years, were enrolled into the study. 49% of males and 31% of females were overweight and 32% men and 31% of women were obese. There were 36% of smokers among men and 22% among women. The prevalence of type 2 diabetes was 11% in males and also in females. Arterial hypertension was diagnosed in 43% of males and 45% of females while dyslipidemia was present in 39% of males and 41% of females. Pharmacological treatment of any of the above mentioned diseases was used in 48% of the probands, however, only 7% of them attained treatment goals of blood pressure, LDL-cholesterol and glycaemia. Type 2 diabetes was newly identified in 3% of both males and females, arterial hypertension in 8% of males and 5% of females and dyslipidemia was newly detected in 20% of probands of both genders. Non-pharmacological treatment was recommended to 62% of male and to 65% of female participants, respectively. Pharmacological treatment was initiated in 53% of males and 51% of females. In both genders this was mostly antihypertensive treatment with ACE inhibitors (29% of males and 24% of females) and lipid lowering therapy with a statin (29% of males, 27% females). The analysis of relationship between the positive family history of any of the followed diseases and their presence in the probands examined revealed significant increases of the risk for arterial hypertension, type 2 diabetes mellitus and dyslipidemia.
The survey following CV risk profile in a cohort of 40 years old men and 50 years old women showed high prevalence of CV risk factors in these age categories in the Czech probands. The high frequency of modifiable risk factors and the need to initiate pharmacological treatment in more than one half of the examined population documents the need of early detection of risk. Genetic determination of individual major risk factors for CVD mirrored in the positive family history represents an important component of the global cardiovascular risk and must be actively detected and taken into account for the risk stratification.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
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.
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.
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.
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; 56(2). DOI:10.1016/j.crvasa.2014.01.006
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: Objectives:
Statins significantly reduce CV morbidity and mortality. Unfortunately, one of the side effects of statins is myopathy, for which statins cannot be administered in sufficient doses or administered at all. The aim of this study was to demonstrate the effect of coenzyme Q10 in patients with statin myopathy.
Twenty eight patients aged 60.6±10.7 years were monitored (18 women and 10 men) and treated with different types and doses of statin. Muscle weakness and pain was monitored using a scale of one to ten, on which patients expressed the degree of their inconvenience. Examination of muscle problems was performed prior to administration of CQ10 and after 3 and 6 months of dosing. Statistical analysis was performed using Friedman test, Annova and Students t-test.
Pain decreased on average by 53.8% (p<0.0001), muscle weakness by 44.4% (p<0.0001). The CQ10 levels were increased by more than 194% (from 0,903 μg/ml to 2.66 μg/ml; p<0.0001).
After a six-month administration of coenzyme Q10, muscle pain and sensitivity statistically significantly decreased.
[Show abstract][Hide abstract] ABSTRACT: Objectives:
A significant inter-individual variability in statin treatment efficacy is likely to have a strong genetic background. A candidate gene with the potential to influence statin treatment efficacy is SLCO1B1. This gene codes for the solute carrier organic anion transporter, which has been shown to regulate the hepatic uptake of statins and some other drugs.
Materials and methods:
The SLCO1B1 rs4149056 (T>C) polymorphism was successfully analysed in a group of 253 patients with dyslipidemia (treated with simvastin or atorvastatin, 10 or 20 mg per day) and 470 healthy normolipidemic controls. The polymorphism was analysed using nested PCR-RFLP. Lipid levels (total, LDL and HDL cholesterol; triglycerides) were analysed before and after 10-13 weeks of treatment.
After treatment, as expected, there was a significant decrease both in the total cholesterol (7.60±1.36 → 5.37±1.12 mmol/L, p<0.001) and LDL cholesterol (5.04±1.34 → 3.17±0.99 mmol/L, p<0.001) levels. The distribution of the individual genotypes in the patients (TT=61.7%, CT=31.6%, CC=6.7%) was similar (p=0.35) to that of the normolipidemic controls (TT=64.4%, CT=31.3%, CC=4.3%). Homozygous CC males exhibited the lowest (Δ -21.2±7.2%) decrease of total cholesterol in contrast to the females, in whom the same genotype was associated with the highest (Δ -33.5±7.6 %) decrease (p=0.04 for gene-gender interaction).
The results of our pilot study suggest possible gender-dependent effects of the rs4149056 variant within the SLCO1B1 gene on statin treatment efficacy.
[Show abstract][Hide abstract] ABSTRACT: The aim of this work is to give summary of changes in recommendation for hormone replacement therapy (HT) and cardiovascular prevention during last decade. Conclusions from observational studies demonstrated a positive effect of HT in both the primary and secondary prevention of coronary heart disease (CHD). But large randomized trials failed to prove this positive effect; on the contrary, the cardiovascular risk was increased in the beginning of therapy. But estrogen arm of Women's Health Initiative (WHI) show neutral influence and the Estrogen in the Prevention of Atherosclerosis Trial (EPAT) indicate possible positive effects of some HT regimens. Also reanalysis of WHI in age-related groups show the window of opportunity. The prevention of CHD was excluded from possible indications of HT. Many questions regarding optimal choice in the individual treatment strategies have been raised. HT in its individualized form remains the first choice therapy for the acute climacteric syndrome, for the prevention and the therapy of urogenital atrophy and prevention of osteoporosis. Early start of HT has neutral or slightly positive effect on cardiovascular prevention.
[Show abstract][Hide abstract] 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).
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).
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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: Statins have become a cornerstone of cardiovascular prevention. However, their lipid lowering efficacy and, thus also, impact on event risk reduction, differ substantially between individuals. The major part of this inter-individual difference can be explained by genetic factors. Using the GWA approach, candidate genes that may modify the response to statin treatment have been detected. Variants rs646776 (CELSR2/PSRC1/SORT1), rs16996148 (CILP2/PBX4), rs11206510 (PCSK9) and rs693 (APOB) were analysed in 370 (146 males) dyslipidemic patients treated with statins (46.6% simvastatin, 41.5% atorvastatin, 11.9% lovastatin, 10 or 20 mg/day) and 470 normolipidemic controls (188 males). Lipid levels were available prior to and after 8-12 weeks of therapy. There was a significant decrease both in the total (7.36 +/- 1.28 -> 5.43 +/- 1.01 mmol/l) and LDL-cholesterol (4.72 +/- 1.35 -> 3.19 +/- 0.98 mmol/l) after treatment. The genotype frequencies of the three SNPs differed between patients and controls (rs646776, rs16996148, rs693). The carriers of the minor rs599838 genotype had a significantly lower response to statin treatment compared to common homozygotes (LDL-cholesterol, Delta-20.3% vs. Delta-32.0%). No other significant associations with lipid changes were detected. Together with variations of other, multiple gene loci the variant at CELSR2/PSRC1/SORT1 gene cluster may be useful for individualization of statin treatment leading to better outcomes of the treatment.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.