BACKGROUND: In Slovakia, a mandatory national universal pediatric total cholesterol (TC) screening program is in place to identify cases of familial hypercholesterolemia (FH). However, the program's effectiveness has not been systematically assessed. OBJECTIVE: This study aimed to estimate the prevalence of FH among parents of children that had elevated TC levels identified during screening. METHODS: This prospective, non-interventional, observational study enrolled parents of 11-year-old children who underwent TC screening in 23 selected pediatric outpatient clinics between 2017 and 2018. FH was diagnosed using the Dutch Lipid Clinic Network (DLCN) criteria and targeted next-generation sequencing. The primary objective was to estimate the proportion of children with a TC level of >188 mg/dL (>4.85 mmol/L) who had a parent with a confirmed diagnosis of FH. RESULTS: A total of 112 parents of 56 children with an elevated TC level were enrolled. Five children (8.9%) had a parent in whom FH was genetically confirmed. Without genetic analysis, all five parents would only be diagnosed with "possible FH" by DLCN criteria. Of parents, 83.9% (n = 94/112) had an low-density lipoprotein cholesterol (LDL-C) level of >116 mg/dL (>3 mmol/L), but only 5.3% (n = 5/94) received lipid-lowering therapy. Among the five parents with genetically confirmed FH, all had an LDL-C level >116 mg/dL (>3 mmol/L), with a mean (±SD) of 191 (±24) mg/dL (4.94 [±0.61] mmol/L). Only two of these parents received lipid-lowering therapy. CONCLUSIONS: The present study demonstrates the significance of mandatory universal pediatric TC screening in identifying families with FH and other at-risk families in need of lipid-lowering therapy.

• MeSH
• cholesterol * krev   MeSH
• dítě MeSH
• dospělí MeSH
• hyperlipoproteinemie typ II * diagnóza   epidemiologie   krev   genetika   MeSH
• LDL-cholesterol krev   MeSH
• lidé MeSH
• plošný screening * metody   MeSH
• prospektivní studie MeSH
• rodiče MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Geografické názvy
• Slovenská republika MeSH

BACKGROUND: Large deletions and duplications within the low-density lipoprotein receptor (LDLR) gene make up approximately 10% of LDLR pathogenic variants found in Czech patients with familial hypercholesterolemia. The goal of this study was to test the hypothesis that all probands with each rearrangement share identical breakpoints inherited from a common ancestor and to determine the role of Alu repetitive elements in the generation of these rearrangements. METHODS: The breakpoint sequence was determined by PCR amplification and Sanger sequencing. To confirm the breakpoint position, an NGS analysis was performed. Haplotype analysis of common LDLR variants was performed using PCR and Sanger sequencing. RESULTS: The breakpoints of 8 rearrangements within the LDLR gene were analysed, including the four most common LDLR rearrangements in the Czech population (number of probands ranging from 8 to 28), and four less common rearrangements (1-4 probands). Probands with a specific rearrangement shared identical breakpoint positions and haplotypes associated with the rearrangement, suggesting a shared origin from a common ancestor. All breakpoints except for one were located inside an Alu element. In 6 out of 8 breakpoints, there was high homology (≥ 70%) between the two Alu repeats in which the break occurred. CONCLUSIONS: The most common rearrangements of the LDLR gene in the Czech population likely arose from one mutational event. Alu elements likely played a role in the generation of the majority of rearrangements inside the LDLR gene.

• MeSH
• genová přestavba MeSH
• hyperlipoproteinemie typ II * genetika   epidemiologie   MeSH
• lidé MeSH
• mutace MeSH
• receptory LDL genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Familial hypercholesterolaemia (FH) is under-recognized and under-treated in Europe leading to significantly higher risk for premature heart disease in those affected. As treatment beginning early in life is highly effective in preventing heart disease and cost-effective in these patients, screening for FH is crucial. It has therefore now been recognized by the European Commission Public Health Best Practice Portal as an effective strategy. Model programmes exist in Europe to identify young individuals with FH, which are based on cascade screening of first-degree relatives of affected individuals, universal screening for high cholesterol, opportunistic screening of high-risk individuals, or a combination of the above approaches. Recommendations presented herein to improve identification of FH emphasize that every country should have an FH screening programme. These programmes should be adapted from existing strategies to best fit the individual country's healthcare system, governments should provide financial support for these programmes and related care, and further research to optimize care and implementations should be conducted.

• MeSH
• dítě MeSH
• genetické testování MeSH
• hyperlipoproteinemie typ II * diagnóza   epidemiologie   genetika   MeSH
• LDL-cholesterol MeSH
• lidé MeSH
• nemoci srdce * MeSH
• plošný screening MeSH
• rizikové faktory MeSH
• veřejná politika MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

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.

• MeSH
• dítě MeSH
• hyperlipoproteinemie typ II * diagnóza   epidemiologie   genetika   MeSH
• lidé MeSH
• lipidy MeSH
• mutace MeSH
• mutační analýza DNA MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 * genetika   MeSH
• receptory LDL genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Belgie MeSH
• Česká republika MeSH
• Evropa MeSH
• Nizozemsko MeSH
• Norsko MeSH
• Portugalsko MeSH
• Rakousko MeSH
• Řecko MeSH

PURPOSE OF REVIEW: Familial hypercholesterolemia (FH) is often perceived and described as underdiagnosed and undertreated, though effective treatment of FH is available. Owing to the mentioned facts, it is ever more imperative to screen and treat FH patients. Subsequent to the identification of patients, the project focuses on the improvement of their prognoses. The ScreenPro FH project was established as a functional international network for the diagnosis, screening, and treatment of FH. Individual countries were assigned goals, e.g., to define the actual situation and available treatment. With "central support," more centers and countries participated in the project. Subsequently, individual countries reported the results at the beginning and end of the project. Collected data were statistically evaluated. RECENT FINDINGS: The increasing number of patients in databases, from 7500 in 2014 to 25,347 in 2018, demonstrates the improvement in overall effectiveness, as well as an increase in the number of centers from 70 to 252. Before all, LDL-C decreased by 41.5% and total cholesterol by 32.3%. As data from all countries and patients were not available at the time of the analysis, only those results from 10 countries and 5585 patients at the beginning of the project and at the time of writing are included. Our data are quite positive. However, our results have only limited validity. Our patients are far from the target levels of LDL-C. The situation can be improved with the introduction of new therapy, PCSK9-i, evolocumab, and alirocumab. International cooperation improved the screening of FH and finally led to an improvement in cardiovascular risk.

• MeSH
• anticholesteremika terapeutické užití   MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• hyperlipoproteinemie typ II diagnóza   farmakoterapie   epidemiologie   MeSH
• incidence MeSH
• lidé MeSH
• mezinárodní spolupráce * MeSH
• PCSK9 inhibitory MeSH
• plošný screening metody   MeSH
• poskytování zdravotní péče normy   MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Geografické názvy
• Evropa MeSH

• MeSH
• anticholesteremika terapeutické užití   MeSH
• hyperlipoproteinemie typ II * diagnostické zobrazování   epidemiologie   farmakoterapie   MeSH
• hypolipidemika terapeutické užití   MeSH
• lidé MeSH
• odběr vzorku krve metody   normy   MeSH
• registrace MeSH
• sběr dat MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

Familiární hypercholesterolemie (FH) je nejčastější vrozené metabolické onemocnění charakterizované hromaděním lipidových částic ve stěnách cév vedoucí k předčasnému rozvoji aterosklerózy. Jde o závažné onemocnění, které, není-li léčeno, může vést k předčasnému úmrtí na kardiovaskulární příhody již ve třetí nebo čtvrté dekádě života. Frekvence heterozygotů v obecné populaci je podle posledních studií 1:250, z čehož vyplývá, že se v České republice těchto pacientů může vyskytovat až 40 000. Z hlediska záchytu FH patří naše republika k nejúspěšnějším zemím na světě, nicméně většina pacientů zůstává stále nediagnostikovaná. Je nezbytné tyto jedince aktivně vyhledávat a manifestaci kardiovaskulárního onemocnění (KVO) předcházet. K dispozici je léčba, která je účinná, bezpečná a dostupná. Efektivní přístup k diagnostice a léčbě pacientů s FH představuje síť projektu MedPed (Make early diagnosis to Prevent early deaths) a velké množství lékařů, kteří jsou do projektu zapojeni. I přesto, že velká část pacientů s FH je až do manifestace KVO asymptomatická, můžeme FH diagnostikovat s pomocí biochemického vyšetření spolu s rodinnou anamnézou. U části pacientů nacházíme také tzv. klinické známky onemocnění. Mezi typické oftalmologické nálezy patří arcus lipoides corneae a xanthelasma palpebrarum. Přestože se jedná o příznaky nespecifické, měly by být, obzvláště objeví-li se u pacientů do 50 let věku, indikací k vyšetření parametrů lipidového spektra. Každý pacient s familiární hypercholesterolemií (nebo s podezřením na ni) by měl být odeslán na některé z pracovišť sítě projektu MedPed.

Familial hypercholesterolaemia (FH) is the most common congenital metabolic disorder characterised by the accumulation of lipid particles in the vascular wall thereby leading to premature development of atherosclerosis. It is a serious condition that, if left untreated, can lead to premature death in a cardiovascular event already in the third or fourth decade of life. According to recent studies, the frequency of heterozygotes in the general population is 1: 250, suggesting that there may be up to 40,000 of these patients in the Czech Republic alone. In terms of capturing FH, the Czech Republic belongs to the most successful countries in the world; however, most patients remain undiagnosed. It is essential that these individuals be actively sought for and manifestation of cardiovascular disease (CVD) prevented. There is a therapeutic option that is effective, safe and affordable. The MedPed (Make early diagnosis to Prevent early deaths) project network and a large number of physicians involved in the project represent an effective approach to the diagnosis and treatment of patients with FH. Even though a large proportion of patients with FH are asymptomatic until the manifestation of CVD, it is possible to diagnose FH using a biochemical examination together with a family history. In some patients, it is also possible to identify clinical signs of the disease. Typical ophthalmologic findings include arcus lipoides corneae and xanthelasma palpebrarum. While these are non-specific symptoms, especially if they occur in patients under 50 years of age, they should prompt examination of lipid spectrum parameters. Every patient with (or suspected) familial hypercholesterolaemia should be referred to one of the workplaces of the MedPed project network.

• Klíčová slova
• xanthelasma palpebrarum, arcus lipoides corneae, MedPed,
• MeSH
• arcus senilis diagnóza   MeSH
• ateroskleróza prevence a kontrola   MeSH
• časná diagnóza MeSH
• databáze faktografické MeSH
• hyperlipoproteinemie typ II * diagnóza   epidemiologie   farmakoterapie   komplikace   MeSH
• hypolipidemika škodlivé účinky   terapeutické užití   MeSH
• katarakta MeSH
• LDL-cholesterol účinky léků   MeSH
• lidé MeSH
• oční nemoci * diagnóza   epidemiologie   komplikace   MeSH
• plošný screening MeSH
• xantomatóza diagnóza   MeSH
• Check Tag
• lidé MeSH

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.

• MeSH
• anticholesteremika škodlivé účinky   terapeutické užití   MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• down regulace MeSH
• ezetimib terapeutické užití   MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• genetické markery MeSH
• heterozygot MeSH
• hodnocení rizik MeSH
• hyperlipoproteinemie typ II krev   farmakoterapie   epidemiologie   genetika   MeSH
• inhibitory serinových proteinas terapeutické užití   MeSH
• kardiovaskulární nemoci epidemiologie   prevence a kontrola   MeSH
• kombinovaná farmakoterapie MeSH
• LDL-cholesterol krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• PCSK9 inhibitory MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 metabolismus   MeSH
• průřezové studie MeSH
• registrace MeSH
• retrospektivní studie MeSH
• statiny terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Slovenská republika MeSH

BACKGROUND AND AIMS: Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries. METHODS: Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management. RESULTS: 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in ∼2/3 countries. Lipoprotein-apheresis is offered in ∼60% countries, although access is limited. CONCLUSIONS: FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed.

• MeSH
• anticholesteremika škodlivé účinky   terapeutické užití   MeSH
• biologické markery krev   MeSH
• celosvětové zdraví * MeSH
• disparity zdravotní péče MeSH
• dostupnost zdravotnických služeb MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• hyperlipoproteinemie typ II krev   diagnóza   epidemiologie   terapie   MeSH
• kooperační chování MeSH
• LDL-cholesterol krev   MeSH
• lidé MeSH
• mezinárodní spolupráce * MeSH
• prediktivní hodnota testů MeSH
• prevalence MeSH
• průzkumy zdravotní péče MeSH
• rizikové faktory MeSH
• separace krevních složek * škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Familial hypercholesterolemia (FH) is most frequently caused by LDLR or APOB mutations. Therefore, the aim of our study was to examine the genetic background of Slovak patients suspected of FH. Patients with clinical suspicion of FH (235 unrelated probands and 124 family relatives) were recruited throughout Slovakia during the years 2011-2015. The order of DNA analyses in probands was as follows: 1. APOB mutation p.Arg3527Gln by real-time PCR method, 2. direct sequencing of the LDLR gene 3. MLPA analysis of the LDLR gene. We have identified 14 probands and 2 relatives with an APOB mutation p.Arg3527Gln, and 89 probands and 75 relatives with 54 different LDLR mutations. Nine of LDLR mutations were novel (i.e. p.Asp90Glu, c.314-2A>G, p.Asp136Tyr, p.Ser177Pro, p.Lys225_Glu228delinsCysLys, p.Gly478Glu, p.Gly675Trpfs*42, p.Leu680Pro, p.Thr832Argfs*3). This is the first study on molecular genetics of FH in Slovakia encompassing the analysis of whole LDLR gene. Genetic etiology of FH was confirmed in 103 probands (43.8 %). Out of them, 86.4 % of probands carried the LDLR gene mutation and remaining 13.6 % probands carried the p.Arg3527Gln APOB mutation.

• MeSH
• dospělí MeSH
• hyperlipoproteinemie typ II diagnóza   epidemiologie   genetika   MeSH
• kvantitativní polymerázová řetězová reakce metody   MeSH
• lidé MeSH
• mladý dospělý MeSH
• receptory LDL genetika   MeSH
• statistika jako téma metody   MeSH
• zdravotnické přehledy * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Slovenská republika epidemiologie   MeSH