Reporting LDL cholesterol results by clinical biochemistry laboratories in Czechia and Slovakia to improve the detection rate of familial hypercholesterolemia.

Introduction: This survey aims to assess the implementation of recommendations from the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) by clinical biochemistry laboratories in Czechia and Slovakia in their policies for reporting low-density lipoprotein cholesterol (LDL-C) concentrations. Materials and methods: The web-based survey was distributed to all 383 Czech and Slovak clinical biochemistry laboratories that measure lipids by external quality assessment provider SEKK. A total of 17 single-answer questions were included. The questionnaire was focused on the detection and decision points in familial hypercholesterolemia (FH). All survey answers were taken into account. The laboratories followed the EFLM and EAS guidelines when they reported an interpretative comment considering FH diagnosis in adults. Results: A total of 203 (53%) laboratories answered. Only 5% of laboratories added interpretative comments considering FH diagnosis when LDL-C concentrations are above 5.0 mmol/L in adults, and 3% of laboratories added interpretative comments considering FH diagnosis when LDL-C concentrations are above 4.0 mmol/L in children. Only 7% of laboratories reported goals for all cardiovascular risk categories (low, moderate, high, very high). Non-HDL cholesterol concentrations were calculated by 74% of responders. A significant number (51%) of participants did not measure apolipoprotein B, and 59% of laboratories did not measure lipoprotein(a). Conclusions: Only a small portion of laboratories from Czechia and Slovakia reported high LDL-C results with interpretative comments considering FH diagnosis in adults, the laboratories did not follow the guidelines.

Nutraceuticals in the Management of Dyslipidemia: Which, When, and for Whom? Could Nutraceuticals Help Low-Risk Individuals with Non-optimal Lipid Levels?

PURPOSE OF REVIEW: The aim of this review is to summarize the available clinical efficacy and safety data related to the most studied and used lipid-lowering nutraceuticals. RECENT FINDINGS: A growing number of meta-analyses of randomized clinical trials supports the effectiveness and tolerability of some lipid-lowering nutraceuticals such as red yeast rice, plant sterols and stanols, soluble fibers, berberine, artichoke extracts, bergamot polyphenol fraction, garlic, green tea, and spiruline. No significant safety concern has been raised for the use of such products. Association of more lipid-lowering nutraceuticals and of some nutraceuticals with lipid-lowering drugs has been tested as well. Current evidence suggests that some clinically tested lipid-lowering nutraceuticals could be safely used to improve plasma lipid levels in subjects affected by mild-to-moderate dyslipidaemia with low cardiovascular risk.

Comparison of the mutation spectrum and association with pre and post treatment lipid measures of children with heterozygous familial hypercholesterolaemia (FH) from eight European countries.

BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) is commonly caused by mutations in the LDLR, APOB or PCSK9 genes, with untreated mean low density lipoprotein-cholesterol (LDL-C) concentrations being elevated in APOB mutation carriers, even higher in LDLR mutation and highest in those with a PCSK9 mutation. Here we examine this in children with FH from Norway, UK, The Netherlands, Belgium, Czech Republic, Austria, Portugal and Greece. METHODS: Differences in characteristics and pre- and post-treatment lipid concentrations in those with different molecular causes were compared by standard statistical tests. RESULTS: Data were obtained from 2866 children, of whom 2531 (88%) carried a reported LDLR/APOB/PCSK9 variant. In all countries, the most common cause of FH was an LDLR mutation (79% of children, 297 different), but the prevalence of the APOB p.(Arg3527Gln) mutation varied significantly (ranging from 0% in Greece to 39% in Czech Republic, p < 2.2 × 10-16). The prevalence of a family history of premature CHD was significantly higher in children with an LDLR vs APOB mutation (16% vs 7% p=0.0005). Compared to the LDLR mutation group, mean (±SD) concentrations of pre-treatment LDL-C were significantly lower in those with an APOB mutation (n = 2260 vs n = 264, 4.96 (1.08)mmol/l vs 5.88 (1.41)mmol/l, p < 2.2 × 10-16) and lowest in those with a PCSK9 mutation (n = 7, 4.71 (1.22)mmol/l). CONCLUSIONS: The most common cause of FH in children from eight European countries was an LDLR mutation, with the prevalence of the APOB p.(Arg3527Gln) mutation varying significantly across countries. In children, LDLR-FH is associated with higher concentrations of LDL-C and family history of CHD compared to those with APOB-FH.

Safety Evaluation of α-Lipoic Acid Supplementation: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Clinical Studies.

Alpha-lipoic acid (ALA) is a natural short-chain fatty acid that has attracted great attention in recent years as an antioxidant molecule. However, some concerns have been recently raised regarding its safety profile. To address the issue, we aimed to assess ALA safety profile through a systematic review of the literature and a meta-analysis of the available randomized placebo-controlled clinical studies. The literature search included EMBASE, PubMed Medline, SCOPUS, Google Scholar, and ISI Web of Science by Clarivate databases up to 15th August 2020. Data were pooled from 71 clinical studies, comprising 155 treatment arms, which included 4749 subjects with 2558 subjects treated with ALA and 2294 assigned to placebo. A meta-analysis of extracted data suggested that supplementation with ALA was not associated with an increased risk of any treatment-emergent adverse event (all p > 0.05). ALA supplementation was safe, even in subsets of studies categorized according to smoking habit, cardiovascular disease, presence of diabetes, pregnancy status, neurological disorders, rheumatic affections, severe renal impairment, and status of children/adolescents at baseline.

Brief recommendations on the management of adult patients with familial hypercholesterolemia during the COVID-19 pandemic.

Individuals with Familial Hypercholesterolaemia (FH) are at very high risk of cardiovascular disease, which is associated with poor outcomes from coronavirus infections. COVID-19 puts strain on healthcare systems and may impair access to routine FH services. On behalf of the International Lipid Expert Panel (ILEP) and the European FH Patient Network (FH Europe), we present brief recommendations on the management of adult patients with FH during the COVID-19 pandemic. We discuss the implications of COVID-19 infections for FH patients, the importance of continuing lipid-lowering therapy where possible, issues relating to safety monitoring and service delivery. We summarise the evidence for additional benefits of statins and other lipid-lowering drugs during viral infections. The recommendations do not override in any way the individual responsibility of physicians to make appropriate and accurate decisions taking into account the condition of a given patient and the doses, rules, and regulations applicable to drugs and devices at the time of their prescription/use.

Comparison of the characteristics at diagnosis and treatment of children with heterozygous familial hypercholesterolaemia (FH) from eight European countries.

BACKGROUND AND AIMS: For children with heterozygous familial hypercholesterolaemia (HeFH), European guidelines recommend consideration of statin therapy by age 8-10 years for those with a low density lipoprotein cholesterol (LDL-C) >3.5 mmol/l, and dietary and lifestyle advice. Here we compare the characteristics and lipid levels in HeFH children from Norway, UK, Netherlands, Belgium, Czech Republic, Austria, Portugal and Greece. METHODS: Fully-anonymized data were analysed at the London centre. Differences in registration and on treatment characteristics were compared by standard statistical tests. RESULTS: Data was obtained from 3064 children. The median age at diagnosis differed significantly between countries (range 3-11 years) reflecting differences in diagnostic strategies. Mean (SD) LDL-C at diagnosis was 5.70 (±1.4) mmol/l, with 88% having LDL-C>4.0 mmol/l. The proportion of children older than 10 years at follow-up who were receiving statins varied significantly (99% in Greece, 56% in UK), as did the proportion taking Ezetimibe (0% in UK, 78% in Greece). Overall, treatment reduced LDL-C by between 28 and 57%, however, in those >10 years, 23% of on-treatment children still had LDL-C>3.5 mmol/l and 66% of those not on a statin had LDL-C>3.5 mmol/l. CONCLUSIONS: The age of HeFH diagnosis in children varies significantly across 8 countries, as does the proportion of those >10 years being treated with statin and/or ezetimibe. Approximately a quarter of the treated children and almost three quarters of the untreated children older than 10 years still have LDL-C concentrations over 3.5 mmol/l. These data suggest that many children with FH are not receiving the full potential benefit of early identification and appropriate lipid-lowering treatment according to recommendations.

Amaranth as a potential dietary adjunct of lifestyle modification to improve cardiovascular risk profile.

The aim of this review was to summarize data regarding amaranth as a potential component of lifestyle modification to improve cardiovascular risk profiles by modifying cardiovascular risk factors such as cholesterol, diabetes, and hypertension. PubMed was searched for appropriate articles. The main inclusion criteria for articles were as follows: interventions with amaranth; conducted in humans or animals or in vitro; and reported serum lipids and lipoprotein levels, and antidiabetic, antihypertensive, and antioxidant abilities. The outcome measures were changes in serum lipids and the presence of antidiabetic, antihypertensive, and antioxidant activity. A total of 33 articles were included herein. Regarding hypolipidemic activity, most studies investigated the effect of intervention with amaranth in animals, and fewer studies were performed in humans. Most studies in animal models demonstrated the ability of amaranth to decrease total cholesterol and low-density lipoprotein cholesterol. Pilot studies in humans were not convincing regarding amaranth's lipid-lowering activity. Based on this search, it is not clear which constituents are potentially responsible for the hypocholesterolemic effect of amaranth. Some authors tend to think that squalene can play a role in this effect, whereas others suggest that different components of amaranth are of greater importance (eg, sterols, oil fractions rich in fatty acids, proteins, amino acids, or fiber) for its hypocholesterolemic effect. It is possible that several constituents are jointly responsible for this action. Regarding the antidiabetic, antihypertensive, and antioxidant activities, most studies were performed in vitro and showed good potential for all three biological effects. Future research should focus on clarifying the effect of amaranth on high-density lipoprotein cholesterol, identifying the constituents responsible for these beneficial effects, and providing more data regarding its use in humans, ideally using randomized controlled trials. The antidiabetic, antihypertensive, and antioxidant activities found in vitro should be confirmed further in animal or human models.

Current and future trends in the treatment of dyslipidemias.

Lipid-lowering treatment is a part of prevention and treatment of vascular diseases caused by atherosclerosis. We need new strategies for modifying plasma lipoprotein levels in the light of new findings that reduce target lipid levels further lower, as well as the growing population of patients for whom existing treatments cannot be offered. The spectrum of existing drugs (new statins) is widening, pharmacological treatments (recombinant lipoproteins-bound statins), improved forms of established drugs (selective PPARα receptor modulators) are coming. The new procedures include fixed combinations of established drugs improving adherence and intensifying lipid modifying effects (statin + ezetimibe). The portfolio of lipid-lowering therapies today also includes monoclonal antibodies against PCSK9 (PCSK9 inhibitors). The main direction of future development is biotechnology using the principle of so-called antisense therapy, i.e. the use of specific oligonucleotide sequences blocking the translation of the selected protein. These novel therapies targeting, for example, apolipoprotein B, apolipoprotein CIII, or lipoprotein(a) are in various stages of clinical trials. A simi-lar (but not identical) principle is the use of RNA silencing - interference with gene expression using short sequences of double-stranded RNA (e.g. inclisiran siRNA against PCSK9). Innovations in the field of hypolipidemic pharmacotherapy in our country may also be inhibitors of microsomal triglyceride transfer protein (approved for use in homozygotes for familial hypercholesterolemia and experimentally also for familial chylomicronemia). The small molecule ATP citrate lyase inhibitor, bempedoic acid, decreases LDL-C by a further 20 % over and above the reduction achievable by a statin. In a broader sense, the novelty of hypolipidemic pharmacotherapy includes treatment options for some rare metabolic diseases (eg. enzyme replacement therapy for acid lysosomal lipase deficiency) manifested by lipoprotein metabolism abnormalities. All these new directions must aim at the common main goal of reducing the incidence of cardiovascular and gastrointestinal complications of dyslipidemia. Clinical research also aims to prove these effects.

Real-life LDL-C treatment goals achievement in patients with heterozygous familial hypercholesterolemia in the Czech Republic and Slovakia: Results of the PLANET registry.

BACKGROUND AND AIMS: Despite the high prevalence of familial hypercholesterolemia (FH) and available effective lipid-lowering therapy, most of the individuals with this disorder remain undiagnosed and undertreated. The aim of the PLANET registry was to assess the real-life attainment of low-density lipoprotein cholesterol (LDL-C) therapeutic target level in patients with heterozygous FH, to characterize prescribed lipid-lowering therapy with assessment of its efficiency according to the attainment of the target LDL-C level, and to characterize cardiovascular events observed in this patient population again in relation to LDL-C target level attainment. METHODS: PLANET registry was designed as a non-interventional, retrospective, cross-sectional, multicentre disease registry for adult patients with heterozygous FH in the Czech Republic and Slovakia. RESULTS: Overall, 1755 patients were enrolled at 32 sites specialized in FH treatment. 15.4% of patients attained the target LDL-C value. The proportion of patients with LDL-C goal achievement increased to 17.3% in the subgroup of patients receiving high-intensity statin therapy (54.6% of study population). Out of 55 patients receiving inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9), 61.8% reached the LDL-C treatment goal. Of all cardiovascular events reported, 14.0% occurred in patients attaining the LDL-C goal, while it was 86.0% in the not-at-target group. It was documented (p=0.004) that the longer is the patient in care at the specialized FH centre, the higher is the probability that he/she will attain the target LDL-C level. CONCLUSIONS: Although target LDL-C level attainment remains relatively low, the likelihood of LDL-C goal attainment increases with duration of specialized care.

[MedPed - the reality of familial hypercholesterolemia care at the biggest center]. / MedPed - realita péce o familiární hypercholesterolemie v nejvetsím centru.

The MedPed project (Make Early Diagnosis to Prevent Early Deaths) aiming at screening, diagnosis and treatment of patients with familial hypercholesterolemia (FH) was initiated more than 19 years ago. More than 60 cooperating centers and a large number of health care professionals have been involved. Till November 15, 2017 the nationwide database has comprised 7 567 entries of individual FH patients, 439 of these being children up to 19 years of age. Given the recently corrected estimated population frequency of FH of 1 to 250 this number represents 18.9 % of the predicted number of 40 000 FH individuals in the Czech Republic. Although the number of patients captured by the database seems to be relatively low, it is the third highest number in the world. This review describes working procedures of one of the national leading centers for FH in the Czech Republic. Additionally, a comparison of the up-to-date data set of 558 FH individuals being actively followed in the center to the original FH cohort (n = 190) as described by prof. Sobra in the late 1960 s. is being discussed.Key words: familial hypercholesterolemia - heterozygous - homozygous - project Medped.

[Cardiovascular risk in patients with rheumatic disease and its management]. / Kardiovaskulární riziko u pacientu s revmatickými chorobami a jeho management.

Cardiovascular disease (CVD) risk in patients with rheumatic diseases is increased by 50 % compared to the general population. This is a result of the increased inflammatory activity as well as modification of traditional CVD risk factors by the primary disease. So called lipid paradox, paradoxical decrease of concentrations of atherogenic plasma lipids due to increased inflammatory activity and their rise with successful anti-inflammatory treatment, is of particular importance. CVD risk in rheumatic diseases is further modified by drugs used for their treatment: while some treatment modalities increase the risk (e.g. glucocorticoids), others may act in an opposite direction (methotrexate, biological therapies). CVD risk stratification in patients with rheumatic diseases is uneasy; so far none of the specific scoring systems has been shown superior to traditional ones designed for the general population. Principles of cardiovascular risk intervention remain the same as for the general population: the management starts with lifestyle measures (healthy diet, increase in physical activity and smoking cessation) complemented with pharmacotherapy when indicated. Blood pressure as well as lipid lowering therapies should be led according to the same principles as in the general population and, also, to the same treatment goals. To improve CVD prevention outcomes in patients with rheumatic diseases it seems feasible to work in interdisciplinary teams led by a rheumatologist cooperating with a specialist in CVD prevention strategies (general practitioner, cardiologist, internist, diabetes specialist). A nutritional therapist and a physiotherapist are important members of the team, too. Interdisciplinary and complex CVD prevention in patients with rheumatic diseases decreases CVD morbidity.Key words: cardiovascular risk - intervention - lipid paradox - rheumatic diseases - risk factors - risk stratification.

COQ2 polymorphisms are not associated with increased risk of statin-induced myalgia/myopathy in the Czech population.

BACKGROUND: The gene COQ2, encoding 4-hydroxybenzoate-polyprenyltransferase (coenzyme Q2), belongs to the candidates potentially influencing statin treatment tolerability. This enzyme is involved in the biosynthesis of coenzyme Q10 (CoQ10), in which depletion induced by statin treatment is implicated in the development of statin-associated muscle symptoms (SAMS). Thus, polymorphisms in the COQ2 gene might explain susceptibility to SAMS. METHODS: Adult patients with SAMS (on low doses of atorvastatin and simvastatin)-induced myalgia/myopathy (n=278), patients on statins but without SAMS (n=293) and population (part of the post-MONICA [Multinational MONItoring of trends and determinants in CArdiovascular disease] study) controls (n=561) were genotyped (polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] assay) for rs6535454 and rs4693075 polymorphisms within the COQ2 gene loci. RESULTS: Distribution of rs6535454 in patients with SAMS (GG=51.1%, GA=40.0%, AA=8.9%) did not significantly differ (p=0.33; respectively 0.32 for codominant models of the analysis) from that in the population controls (GG=48.1%, GA=45.0%, AA=6.9%) or the SAMS-unaffected patients (GG=49.8%, GA=40.3%, AA=9.7%). Similarly, neither rs4693075 was associated with SAMS (CC=36.8%, CG=48.2%, GG=15.0% in patients suffering SAMS vs. CC=36.6%, CG=47.5%, GG=15.9 in controls and CC=35.8%, CG=48.2%, GG=15.9% in symptom-free patients, p=0.94 and 0.95 for codominant models of the analysis). Also, the haplotype distributions were not significantly different between the groups analyzed. CONCLUSIONS: The polymorphisms of the COQ2 gene do not associate with SAMS in the Czech patients treated with low doses of statins. This is another clue that the coenzyme Q10 pathway is not the most important for the development of SAMS.

[PCSK9 inhibitors - new possibilities in the treatment of hypercholesterolemia: For which patients will be indicated?Czech atherosclerosis society statement]. / PCSK9 inhibitory - nové moznosti v lécbe hypercholesterolemie: U koho budou indikovány?Stanovisko Ceské spolecnosti pro aterosklerózu.

First line drug for the treatment of hypercholesterolemia are statins, which reduce LDL-cholesterol up to 50 %; such reduction is sufficient for most patients to achieve the target values. The exceptions are patients with familial hypercholesterolemia and patients with statin intolerance. To achieve target LDL-cholesterol in these two groups of patients will be possible with new drugs - PCSK9 inhibitors, which decrease LDL-cholesterol by an additional 50-60 %. The first two PCSK9 inhibitors (alirocumab and evolocumab) already had been approved for clinical use by European regulatory authorities. The primary indication for combination statin with PCSK9 inhibitor should be undoubtedly patients with a confirmed diagnosis of familial hypercholesterolemia, who are treated in the Czech Republic primarily in specialized centers of MedPed project. Furthermore, this treatment should be available for other patients at very high risk of cardiovascular diseases, who cannot achieve target LDL-cholesterol (eg. for statins intolerance).

Rare variants in known and novel candidate genes predisposing to statin-associated myopathy.

AIM: Genetic variants affecting statin uptake, metabolism or predisposing to muscular diseases may confer susceptibility to statin-induced myopathy. Besides the SLCO1B1 rs4149056 genotype, common genetic variants do not seem to determine statin-associated myopathy. Here we aimed to address the potential role of rare variants. METHODS: We performed whole exome sequencing in 88 individuals suffering from statin-associated myopathy and assessed the burden of rare variants using candidate-gene and exome-wide association analysis. RESULTS: In the novel candidate gene CLCN1, we identified a heterozygote truncating mutation p.R894* in four patients. In addition, we detected predictably pathogenic case-specific variants in MYOT, CYP3A5, SH3TC2, FBXO32 and RBM20. CONCLUSION: These findings support the role of rare variants and nominate loci for follow-up studies.

[Severe familial hypercholesterolemia treatment]. / Lécba tezké familiární hypercholesterolemie.

Familial hypercholesterolemia (FH) represents the most frequent of inborn errors of metabolism. It is a group of disorders with a codominant mode of inheritance characterized by marked elevations of LDL-cholesterol as well as atherosclerotic cardiovascular disease risk. Clinical (phenotypic) picture of FH varies widely depending on genotype and concomitant risk factors. Identification of most seriously affected FH individuals is necessary for proper clinical management. The therapeutic approach must be complex and comprehensive. The corner stone of pharmacotherapy is high-intensity statin therapy usually combined with ezetimibe (possibly complemented with bile acid sequestrant). Even this multi-drug combination do not lead majority of patients to their treatment goals. Thus, combinations with other pharmacological (PCSK9 inhibitors, apoB-100 anti-sense therapy, MTP inhibition) and non-pharmacological (LDL-apheresis, liver transplantation) approaches is being used.Key words: ezetimibe - LDL-apheresis - lomitapide - mipomersen - PCSK9 inhibitors - severe familial hypercholesterolemia - statins.

[Familial hypercholesterolemia in the Czech Republic in 2016]. / Familiární hypercholesterolemie v Ceské republice v roce 2016.

Familial hypercholesterolemia (FH) is the most frequent autosomal dominant hereditary disease which is characterized by a decreased LDL-cholesterol catabolism and early clinical manifestation of atherosclerosis affecting blood vessels. The MedPed (Make early diagnosis to Prevent early deaths) project aims to diagnose patients with FH as early as possible, so that they can profit the most from a therapy started in a timely manner and avoid premature cardiovascular events. Currently, as of 31 October 2016, the Czech national database keeps records of 6 947 patients with FH from 5 223 families. Considering the prevalence of FH equalling 1 : 250, this represents 17.4 % of the overall expected number of patients with FH in the Czech Republic. Determining the mutation responsible for FH, now using a next generation sequencing technology in the Czech Republic, brings with it higher diagnostic accuracy, better cooperation of patients and in particular facilitation of cascade screening in families. Although we are among the most successful countries in the world with regard to FH detection, the majority of patients are still undiagnosed. Moreover, as it turns out, most FH patients do not reach the target values with the current therapeutic possibilities. In this regard the newly approved hypolipidemic drugs, PCSK9 inhibitors, to be hopefully available also in the Czech Republic in the near future for chosen patients with FH at high risk, hold great promise.Key words: cascade screening - familial hypercholesterolemia - LDL-cholesterol - MedPed.

[Atherosclerosis: from etiology to its possible influencing]. / Ateroskleróza: od etiologie po moznosti ovlivnení.

Atherosclerosis as an inflammatory process affecting vessel wall has more forms usually occurring together. Classical atherosclerotic vascular lesion characterised by lipid accumulation in the subendothelial space is frequently accompanied by changes in deeper layers of arterial wall, in which increased extracellular tissue mass and smooth muscle cells activation represent the most prominent feature. Due to a specific constellation of risk factors the first or second pathology may be more expressed. While initiation and progression of classical atherosclerosis are mostly driven by lipoproteins (especially of LDL class) the most important factor of arterial media changes seem to be different risk factors e.g. hyperactivity of renin-angiotensin-aldosterone system (RAS). Influencing these two basic pathogenic mechanisms undoubtedly slows down the course of vascular changes and impacts positively on the prognosis of the patients. It is noteworthy, that simultaneous targeting of both of these mechanisms yields synergistic effects as evidenced both by experimental and clinical works. Using the opportunities offered by intensive lowering of atherogenic plasma lipids and over activation of the RAS system reduce not only the incidence of typical atherotromobotic complications (e.g. acute coronary syndrome) but also the events caused by changes of medial part of arterial wall or left myocardial ventricle (malignant arrhythmia, heart failure). These two strategies represent necessary conditions for successful cardiovascular prevention.

[Early diagnosis of familial hypercholesterolemia in Czech Republic in pursuance of MedPed Project]. / Vcasná diagnostika familiární hypercholesterolemie v Ceské republice v rámci projektu MedPed.

Recent studies have revealed the prevalence of familial hypercholesterolemia (FH) is approximately twice higher than previously estimated and, thus, the disease affects one in 250 persons from the general population. Therefore FH remains the most frequent inherited metabolic disorder. Due to the genetic defect LDL-cholesterol accumulates both in the plasma and tissues leading to premature and accelerated atherosclerosis. Untreated patients with FH might suffer from myocardial infarction in the third or fourth decade, one third of these events being fatal. The disease is under-diagnosed and undertreated worldwide. In the Czech Republic the MedPed project focused on early diagnosis and initiation of proper treatment of FH aiming at lowering of the above mentioned risks was initiated in 1998. A crucial part of the project is so called cascade screening among the relatives of identified FH probands. There are 6,350 registered FH subjects in the nationwide registry, which represents 16% of the expected number of FH patients in the Czech Republic. This result of screening efforts ranks among the top countries in the world, however, also in spite of the recent expansion of FH treatment options early detection and initiation of treatment of FH remains in the centre of our attention.

[Position of lipoprotein apheresis in present]. / Postavení lipoproteinové aferézy v soucasnosti.

Lipoprotein apheresis (LA) is an effective treatment method the patients with severe hypercholesterolemia, resistant to the standard therapy. LA is an extracorporeal elimination technique, which specifically removes low density lipoprotein (LDL) cholesterol from the circulation. At present, lipoprotein apheresis, combined with high-dose statin and ezetimibe therapy, is the best available means of treating patients with homozygous and statin refractory heterozygous familial hypercholesterolaemia (FH). However, the extent of cholesterol-lowering achieved is often insufficient to meet the targets set by current guidelines. The recent advent of new classes of lipid-lowering agents provides new hope that the latter objective may now be achievable. These compounds act either by reducing low density lipoprotein (LDL) cholesterol production by inhibiting apolipoprotein B synthesis with an antisense oligonucleotide (mipomersen), or by inhibiting microsomal triglyceride transfer protein (lomitapid), or by enhancing LDL catabolism via monoclonal antibody-mediated inhibition of the activity of proprotein convertase subtilisin/kexin 9 (PCSK9-alirocumab, evolocumab etc). The promising is the combination of LDL-apheresis with new drugs, namely for its potential to further decrease of LDL-cholesterol between apheresis. Depending on the outcome of current trials, it seems likely that these compounds, used alone or combined with lipoprotein apheresis, will markedly improve the management of refractory FH.

SLCO1B1 polymorphism is not associated with risk of statin-induced myalgia/myopathy in a Czech population.

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. MATERIAL/METHODS: 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. RESULTS: 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. CONCLUSIONS: In Czech patients treated with low statin doses, there is no association between SLCO1B1 gene polymorphism and risk of myalgia/myopathy.