This 2023 statement updates clinical guidance for homozygous familial hypercholesterolaemia (HoFH), explains the genetic complexity, and provides pragmatic recommendations to address inequities in HoFH care worldwide. Key strengths include updated criteria for the clinical diagnosis of HoFH and the recommendation to prioritize phenotypic features over genotype. Thus, a low-density lipoprotein cholesterol (LDL-C) >10 mmol/L (>400 mg/dL) is suggestive of HoFH and warrants further evaluation. The statement also provides state-of-the art discussion and guidance to clinicians for interpreting the results of genetic testing and for family planning and pregnancy. Therapeutic decisions are based on the LDL-C level. Combination LDL-C-lowering therapy-both pharmacologic intervention and lipoprotein apheresis (LA)-is foundational. Addition of novel, efficacious therapies (i.e. inhibitors of proprotein convertase subtilisin/kexin type 9, followed by evinacumab and/or lomitapide) offers potential to attain LDL-C goal or reduce the need for LA. To improve HoFH care around the world, the statement recommends the creation of national screening programmes, education to improve awareness, and management guidelines that account for the local realities of care, including access to specialist centres, treatments, and cost. This updated statement provides guidance that is crucial to early diagnosis, better care, and improved cardiovascular health for patients with HoFH worldwide.
- MeSH
- anticholesteremika * terapeutické užití MeSH
- ateroskleróza * farmakoterapie MeSH
- homozygot MeSH
- homozygotní familiární hypercholesterolemie * MeSH
- hyperlipoproteinemie typ II * diagnóza genetika terapie MeSH
- LDL-cholesterol genetika MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- infarkt myokardu genetika mortalita patologie MeSH
- kardiovaskulární nemoci * genetika mortalita patologie MeSH
- LDL-cholesterol genetika MeSH
- lidé MeSH
- lipoprotein (a) * genetika MeSH
- lipoproteiny LDL genetika MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Familiární hypercholesterolemie (FH) je dědičné onemocnění, které prokazatelně zvyšuje riziko aterosklerotických komplikací. Prevalence FH mezi kardiologickými pacienty je vyšší než v běžné populaci. Vzhledem k dosažitelné a velmi účinné léčbě je vhodné, aby byli pacienti diagnostikováni a adekvátně léčeni dle výše kardiovaskulárního rizika. Tím lze předejít kardiovaskulárním komplikacím progredující aterosklerózy. Základem léčby je vysoko dávkovaný vysoce účinný statin v kombinaci s ezetimibem a při splnění úhradových kritérií i s inhibitory PCSK9. Pacientům s FH poskytuje péči síť pracovišť projektu MedPed (Make early dia gnoses to Prevent early deaths in Medical Pedigrees).
Familial hypercholesterolaemia (FH) is an hereditary disease that has been shown to increase the risk of atherosclerotic complications. The prevalence of FH among cardiac patients is higher than in the general population. Due to achievable and very eff ective treatment, it is advisable that patients be diagnosed and adequately treated according to the level of cardiovascular risk. This can prevent cardiovascular complications due to progressing atherosclerosis. The basis of the treatment is a highly dosed high-potency statin in combination with ezetimibe, and with PCSK-9 inhibitors if the payment criteria are met. Project MedPed (Make early diagnoses to Prevent early deaths in Medical Pedigrees) provides a care network for patients with FH.
- Klíčová slova
- projekt MedPed,
- MeSH
- anticholesteremika MeSH
- ezetimib terapeutické užití MeSH
- genetické testování MeSH
- hyperlipoproteinemie typ II * diagnóza farmakoterapie MeSH
- kardiovaskulární nemoci * prevence a kontrola MeSH
- kombinovaná farmakoterapie MeSH
- LDL-cholesterol genetika MeSH
- lidé MeSH
- PCSK9 inhibitory MeSH
- proproteinkonvertasa subtilisin/kexin typu 9 terapeutické užití MeSH
- sekundární prevence MeSH
- statiny terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
BACKGROUND: Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk. METHODS: In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. FINDINGS: Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0·09 mmol/L, 95% CI 0·02 to 0·15), bodyweight (1·03 kg, 0·24 to 1·82), waist-to-hip ratio (0·006, 0·003 to 0·010), and an odds ratio for type diabetes of 1·29 (1·11 to 1·50). Based on the collected data, we did not identify associations with HbA1c (0·03%, -0·01 to 0·08), fasting insulin (0·00%, -0·06 to 0·07), and BMI (0·11 kg/m2, -0·09 to 0·30). INTERPRETATION: PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefits of PCSK9 inhibitor treatment, as was previously done for statins. FUNDING: British Heart Foundation, and University College London Hospitals NHS Foundation Trust (UCLH) National Institute for Health Research (NIHR) Biomedical Research Centre.
- MeSH
- diabetes mellitus 2. typu krev diagnóza genetika MeSH
- genetická predispozice k nemoci genetika MeSH
- genetická variace genetika MeSH
- kohortové studie MeSH
- krevní glukóza metabolismus MeSH
- LDL-cholesterol krev genetika MeSH
- lidé MeSH
- mendelovská randomizace metody MeSH
- proproteinkonvertasa subtilisin/kexin typu 9 genetika MeSH
- randomizované kontrolované studie jako téma metody MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- časná diagnóza MeSH
- fenotyp MeSH
- genetické testování MeSH
- hodnocení rizik MeSH
- hyperlipoproteinemie typ II * diagnóza epidemiologie genetika prevence a kontrola MeSH
- kardiovaskulární nemoci prevence a kontrola MeSH
- LDL-cholesterol genetika metabolismus MeSH
- lidé MeSH
- mutace genetika MeSH
- plošný screening * MeSH
- programy Healthy People MeSH
- registrace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- úvodní články MeSH
- Geografické názvy
- Česká republika MeSH
Familiární hypercholesterolemie (FH) představuje nejzávažnější formu primární dyslipidemie. Pacienti s FH jsou ve vysokém riziku vzniku kardiovaskulárních onemocnění. FH probíhá často asymptomaticky, první manifestací tak může být fatální infarkt myokardu, a to již v časném věku. Recentní studie ukázaly, že výskyt FH v populaci je daleko vyšší, než se dříve předpokládalo. Diagnostikována a léčena je však stále jen malá část těchto pacientů. V roce 1998 byl v České republice spuštěn projekt MedPed (Make early diagnosis to Prevent early deaths in Medical Pedigrees). Jeho cílem je aktivní vyhledávání osob s FH a jejich pokrevních příbuzných, aby jejich léčba mohla být zahájena co nejdříve.
Familial hypercholesterolemia (FH) is the most serious type of hereditary dyslipidemia. Patients with FH may develop cardiovascular event (primarily heart attack) in young age. Recent studies showed that FH prevalence is higher than previously estimated and FH in general population is still underdiagnosed and undertreated. The MedPed project (Make early diagnosis to Prevent early deaths in Medical Pedigrees) in Czech Republic started in 1998. Its aim is to search actively for both FH patients and their relatives, so that their aggressive hypolipidemic treatment can be initiated as soon as possible.
- MeSH
- časná diagnóza MeSH
- fenotyp MeSH
- genetické testování MeSH
- hodnocení rizik MeSH
- hyperlipoproteinemie typ II * diagnóza epidemiologie genetika prevence a kontrola MeSH
- kardiovaskulární nemoci prevence a kontrola MeSH
- LDL-cholesterol genetika metabolismus MeSH
- lidé MeSH
- mutace genetika MeSH
- plošný screening * MeSH
- programy Healthy People MeSH
- registrace MeSH
- rodina MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Česká republika MeSH
Since 2007, the year of their first widespread use, genome-wide association studies (GWAS) have become the "gold standard" for the detection of causal genes and polymorphisms in all fields of human medicine. Cardiovascular disease (CVD), one of the major causes of morbidity and mortality, is no exception. The first GWAS focused on hypercholesterolemia and dyslipidemia as the major CVD determinants. GWAS confirm the importance of most of the previously identified genes (e.g. APOE, APOB, LDL-R) and recognize the importance of new genetic determinants (e.g. within the CILP2 or SORT1 gene clusters). Nevertheless, the results of GWAS still require confirmation by independent studies, as interethnic and interpopulation variability of SNP effects have been reported. We analyzed an association between eight variants within seven through GWAs detected loci and plasma lipid values in the Czech post-MONICA population sample (N=2,559). We confirmed an association (all P<0.01) between plasma LDL-cholesterol values and variants within the CILP2 (rs16996148), SORT1 (rs646776), APOB (rs693), APOE (rs4420638) and LDL-R (rs6511720) genes in both males (N=1,194) and females (N=1,368). In contrast, variants within the APOB (rs515135), PCSK9 (rs11206510) and HMGCoAR (rs12654264) genes did not significantly affect plasma lipid values in Czech males or females. Unweighted gene score values were linearly associated with LDL-cholesterol values both in males (P<0.0005) and females (P<0.00005). We confirmed the effects of some, but not all analyzed SNPs on LDL-cholesterol levels, reinforcing the necessity for replication studies of GWA-detected gene variants.
- MeSH
- celogenomová asociační studie metody MeSH
- dospělí MeSH
- hypercholesterolemie krev epidemiologie genetika MeSH
- jednonukleotidový polymorfismus genetika MeSH
- LDL-cholesterol krev genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- multifaktoriální dědičnost genetika MeSH
- surveillance populace * metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Slovenská republika epidemiologie MeSH
Autosomal dominant hypercholesterolemia (ADH), more known as familial hypercholesterolemia (FH), is a lipid metabolism disorder characterized by an elevation in low-density lipoprotein cholesterol (LDL-C) and increased risk for cardiovascular disease. In this study, we assessed a spectrum of mutations causing ADH in 3914 unrelated Czech patients with clinical diagnosis of hypercholesterolemia. Samples have been collected within the framework of the MedPed project running in the Czech Republic since 1998. So far we have found 432 patients (11.0 %) with the APOB gene mutation p.(Arg3527Gln) and 864 patients (22.1 %) with the LDLR gene mutation. In 864 probands carrying the LDLR gene mutation, 182 unique allelic variants were detected. We have identified 14 patients homozygous for mutations in the LDLR or APOB genes. We performed function analyses of p.(Leu15Pro) and p.(Gly20Arg) sequence variations.
- MeSH
- apolipoprotein B-100 genetika MeSH
- genetická variace genetika MeSH
- genetické pozadí * MeSH
- hyperlipoproteinemie typ II krev epidemiologie genetika MeSH
- LDL-cholesterol krev genetika MeSH
- LDL-receptory genetika MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Česká republika MeSH
Přinášíme souhrn novinek z odborných doporučení pro prevenci aterosklerotických vaskulárních nemocí publikovaných v ČR v letech 2014–2015 a informace o nových lécích ze skupiny hypolipidemik.
The article presents a summary of news from the guidelines for prevention of atherosclerotic vascular diseases published in 2014–2015 in the Czech Republic and some news on hypolipidemic treatment.
- MeSH
- anticholesteremika aplikace a dávkování MeSH
- antihypertenziva aplikace a dávkování MeSH
- ateroskleróza etiologie patofyziologie prevence a kontrola MeSH
- diabetes mellitus 2. typu farmakoterapie komplikace MeSH
- dyslipidemie diagnóza farmakoterapie MeSH
- hodnocení rizik MeSH
- hyperlipoproteinemie typ II diagnóza farmakoterapie genetika MeSH
- hypertenze diagnóza farmakoterapie MeSH
- hypolipidemika aplikace a dávkování MeSH
- kardiovaskulární nemoci * etiologie prevence a kontrola MeSH
- kouření škodlivé účinky MeSH
- LDL-cholesterol genetika normy účinky léků MeSH
- lidé MeSH
- prevence kouření MeSH
- rizikové faktory MeSH
- sekundární prevence MeSH
- statiny aplikace a dávkování škodlivé účinky MeSH
- Check Tag
- lidé MeSH
