BACKGROUND AND AIMS: Overweight and obesity are modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) in the general population, but their prevalence in individuals with heterozygous familial hypercholesterolaemia (HeFH) and whether they confer additional risk of ASCVD independent of LDL cholesterol (LDL-C) remains unclear. METHODS: Cross-sectional analysis was conducted in 35 540 patients with HeFH across 50 countries, in the EAS FH Studies Collaboration registry. Prevalence of World Health Organization-defined body mass index categories was investigated in adults (n = 29 265) and children/adolescents (n = 6275); and their association with prevalent ASCVD. RESULTS: Globally, 52% of adults and 27% of children with HeFH were overweight or obese, with the highest prevalence noted in Northern Africa/Western Asia. A higher overweight/obesity prevalence was found in non-high-income vs. high-income countries. Median age at familial hypercholesterolaemia diagnosis in adults with obesity was 9 years older than in normal weight adults. Obesity was associated with a more atherogenic lipid profile independent of lipid-lowering medication. Prevalence of coronary artery disease increased progressively across body mass index categories in both children and adults. Compared with normal weight, obesity was associated with higher odds of coronary artery disease in children (odds ratio 9.28, 95% confidence interval 1.77-48.77, adjusted for age, sex, lipids, and lipid-lowering medication) and coronary artery disease and stroke in adults (odds ratio 2.35, 95% confidence interval 2.10-2.63 and odds ratio 1.65, 95% confidence interval 1.27-2.14, respectively), but less consistently with peripheral artery disease. Adjusting for diabetes, hypertension and smoking modestly attenuated the associations. CONCLUSIONS: Overweight and obesity are common in patients with HeFH and contribute to ASCVD risk from childhood, independent of LDL-C and lipid-lowering medication. Sustained body weight management is needed to reduce the risk of ASCVD in HeFH.
- MeSH
- dítě MeSH
- dospělí MeSH
- heterozygot MeSH
- hyperlipoproteinemie typ II * epidemiologie komplikace MeSH
- index tělesné hmotnosti MeSH
- kardiovaskulární nemoci epidemiologie etiologie MeSH
- LDL-cholesterol krev metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nadváha * epidemiologie komplikace MeSH
- obezita * komplikace epidemiologie MeSH
- prevalence MeSH
- průřezové studie MeSH
- registrace * MeSH
- rizikové faktory MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
BACKGROUND: Familial dysbetalipoproteinemia (FD) is an autosomal recessive (rarely dominant) inherited disorder that is almost exclusively associated with the apolipoprotein E gene (APOE) variability. Nonetheless, only a small proportion of APOE2/E2 subjects develop the phenotype for mixed dyslipidemia; the context of other trigger metabolic or genetic factors remains unknown. METHODS: One hundred and one patients with FD and eighty controls (all APOE2/E2 homozygotes; rs429358) were screened for 18 single-nucleotide polymorphisms (SNPs) within the genes involved in triglyceride metabolism. RESULTS: Two SNPs were significantly associated with the FD phenotype (rs439401 within APOE; P < 0.0005 and rs964184 within ZPR1/APOA5/A4/C3/A1 gene cluster; P < 0.0001). Unweighted genetic risk scores - from these two SNPs (GRS2), and, also, additional 13 SNPs with P-value below 0.9 (GRS15) - were created as an additional tool to improve the risk estimation of FD development in subjects with the APOE2/E2 genotype. Both GRS2 and GRS15 were significantly (P < 0.0001) increased in patients and both GRSs discriminated almost identically between the groups (P = 0.86). Subjects with an unweighted GRS2 of three or more had an almost four-fold higher risk of FD development than other individuals (odds ratio (OR) 3.58, 95% confidence interva (CI): 1.78-7.18, P < 0.0005). CONCLUSIONS: We identified several SNPs that are individual additive factors influencing FD development. The use of unweighted GRS2 is a simple and clinically relevant tool that further improves the prediction of FD in APOE2/E2 homozygotes with corresponding biochemical characteristics.
- MeSH
- apolipoprotein E2 * genetika MeSH
- apolipoproteiny E genetika MeSH
- dospělí MeSH
- genetická predispozice k nemoci * MeSH
- genetické rizikové skóre MeSH
- genotyp * MeSH
- hyperlipoproteinemie typ III genetika MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- rizikové faktory MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Riziko onemocnění koronárních tepen nejen u dospělých, ale i u dětí především souvisí s rizikovými faktory, které vedou k akceleraci aterosklerózy. Mezi tyto faktory se tradičně řadí hypercholesterolemie, obezita, diabetes mellitus, hypertenze a kouření. Další méně známou rizikovou skupinou pro koronární onemocnění jsou jedinci se srdečními, cévními či dalšími chronickými onemocněními. Jedná se především o chronická onemocnění ledvin, chronická zánětlivá onemocnění, malignity, některé vrozené vady srdce, vrozené či získané anomálie koronárních tepen, včetně stavů po intervencích na koronárních tepnách, Kawasakiho nemoc, případně koronární vaskulopatie štěpu po transplantaci srdce. Tato onemocnění musejí proto být zohledněna při stratifikaci kardiovaskulárního rizika a u dětí s uvedenými onemocněními by měl být práh pro zahájení léčby tradičních kardiovaskulárních rizikových faktorů nižší. Článek vychází z nedávno publikovaných doporučení American Heart Association. Jeho smyslem je upozornit nejen na tradiční kardiovaskulární rizikové faktory, ale také právě na asociaci některých chronických onemocnění s akcelerací aterosklerotického postižení koronárních tepen a zároveň nabídnout doporučení ke stratifikaci a snížení tohoto rizika již od dětství.
Coronary artery disease risk not only in adults but also in children is predominantly related to risk factors associated with atherosclerosis. These traditional cardiovascular risk factors include hypercholesterolaemia, obesity, diabetes mellitus, hypertension and smoking. Another high risk group for coronary artery disease are individuals with cardiac, vascular or other chronic diseases. These include chronic kidney diseases, chronic inflammatory diseases, malignancies, certain congenital heart defects, inborn or acquired coronary anomalies including interventions on coronary arteries, Kawasaki disease and cardiac allograft vasculopathy in heart transplant recipients. The presence of these chronic conditions should modify the risk assessment and de- crease the threshold for initiation of treatment of traditional cardiovascular risk factors in this subpopulation. The presented review is based on the recently published scientific statement from the American Heart Association. Its aim is to increase awareness of traditional cardiovascular risk factors in children as well as of the association of certain chronic conditions with accelerated atherosclerosis of coronary arteries. It also offers recommendations for the assessment and reduction of coronary artery disease risk already from childhood.
- MeSH
- ateroskleróza etiologie patofyziologie MeSH
- chronická renální insuficience diagnóza komplikace terapie MeSH
- diabetes mellitus diagnóza terapie MeSH
- hodnocení rizik * MeSH
- hyperlipoproteinemie typ II diagnóza komplikace terapie MeSH
- hypertenze terapie MeSH
- Kawasakiho syndrom komplikace MeSH
- kouření tabáku patofyziologie MeSH
- lidé MeSH
- nádory komplikace MeSH
- nemoci koronárních tepen * etiologie prevence a kontrola terapie MeSH
- obezita komplikace terapie MeSH
- rizikové faktory kardiovaskulárních chorob * MeSH
- statiny terapeutické užití MeSH
- vrozené srdeční vady komplikace MeSH
- Check Tag
- lidé MeSH
BACKGROUND AND AIMS: It is well known that elevated cholesterol is associated with enhanced platelet aggregation and patients suffering from familial hypercholesterolemia (FH) have a high risk of thrombotic cardiovascular events. Although decreasing cholesterol level is associated with attenuation of platelet hyperactivity, there are currently no data on the effect of convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9ab) on platelet reactivity in FH. The aim of the study was to analyse the impact of different therapies including PCSK9ab on platelet aggregation in FH. METHODS: This study enrolled all 15 patients treated in the University Hospital Hradec Králové for FH. PCSK9ab have been administered in 12 of 15 patients while 8 patients were also undergoing lipid apheresis. Blood samples from all patients including pre- and post-apheresis period were tested for platelet aggregation triggered by 7 inducers, and the effect of 3 clinically used drugs (acetylsalicylic acid, ticagrelor and vorapaxar) was compared as well. RESULTS: Although apheresis decreased the reactivity of platelets in general, platelet responses were not different between non-apheresis patients treated with PCSK9ab and apheresis patients (post-apheresis values) with the exception of ristocetin. However, when compared to age-matched healthy population, FH patients had significantly lower platelet aggregation responses to 4 out of 7 used inducers and higher profit from 2 out of 3 used antiplatelet drugs even after exclusion of FH patients regularly receiving conventional antiplatelet treatment. CONCLUSION: This study showed for the first time the suitability of PCSK9ab treatment for reduction of platelet reactivity in FH patients.
- MeSH
- agregace trombocytů * účinky léků MeSH
- dospělí MeSH
- hyperlipoproteinemie typ II * krev terapie farmakoterapie MeSH
- inhibitory agregace trombocytů * terapeutické užití farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- monoklonální protilátky terapeutické užití farmakologie MeSH
- PCSK9 inhibitory * MeSH
- proproteinkonvertasa subtilisin/kexin typu 9 * imunologie MeSH
- senioři MeSH
- separace krevních složek * MeSH
- trombocyty účinky léků metabolismus imunologie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- časná diagnóza MeSH
- dítě MeSH
- hyperlipoproteinemie typ II * diagnóza farmakoterapie MeSH
- kongresy jako téma MeSH
- LDL-cholesterol analýza škodlivé účinky MeSH
- lidé MeSH
- náchylnost k nemoci MeSH
- plošný screening metody MeSH
- rizikové faktory MeSH
- statiny terapeutické užití MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- novinové články MeSH
- zprávy MeSH
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
- LDL-receptory genetika MeSH
- lidé MeSH
- mutace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
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
- hyperlipoproteinemie typ II * diagnóza metabolismus patofyziologie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
