Browsing by Subject "Familial hypercholesterolaemia"

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  • Task Force Members; ESC Comm Practice Guidelines CPG; ESC Natl Cardiac Societies; Mach, Francois; Baigent, Colin; Taskinen, Marja-Riitta (2019)
  • Wiegman, Albert; Gidding, Samuel S.; Watts, Gerald F.; Chapman, M. John; Ginsberg, Henry N.; Cuchel, Marina; Ose, Leiv; Averna, Maurizio; Boileau, Catherine; Boren, Jan; Bruckert, Eric; Catapano, Alberico L.; Defesche, Joep C.; Descamps, Olivier S.; Hegele, Robert A.; Hovingh, G. Kees; Humphries, Steve E.; Kovanen, Petri T.; Kuivenhoven, Jan Albert; Masana, Luis; Nordestgaard, Borge G.; Pajukanta, Paevi; Parhofer, Klaus G.; Raal, Frederick J.; Ray, Kausik K.; Santos, Raul D.; Stalenhoef, Anton F. H.; Steinhagen-Thiessen, Elisabeth; Stroes, Erik S.; Taskinen, Marja-Riitta; Tybjaerg-Hansen, Anne; Wiklund, Olov; European Atherosclerosis Soc Conse (2015)
    Familial hypercholesterolaemia (FH) is a common genetic cause of premature coronary heart disease (CHD). Globally, one baby is born with FH every minute. If diagnosed and treated early in childhood, individuals with FH can have normal life expectancy. This consensus paper aims to improve awareness of the need for early detection and management of FH children. Familial hypercholesterolaemia is diagnosed either on phenotypic criteria, i.e. an elevated low-density lipoprotein cholesterol (LDL-C) level plus a family history of elevated LDL-C, premature coronary artery disease and/or genetic diagnosis, or positive genetic testing. Childhood is the optimal period for discrimination between FH and non-FH using LDL-C screening. An LDL-C a parts per thousand yen5 mmol/L (190 mg/dL), or an LDL-C a parts per thousand yen4 mmol/L (160 mg/dL) with family history of premature CHD and/or high baseline cholesterol in one parent, make the phenotypic diagnosis. If a parent has a genetic defect, the LDL-C cut-off for the child is a parts per thousand yen3.5 mmol/L (130 mg/dL). We recommend cascade screening of families using a combined phenotypic and genotypic strategy. In children, testing is recommended from age 5 years, or earlier if homozygous FH is suspected. A healthy lifestyle and statin treatment (from age 8 to 10 years) are the cornerstones of management of heterozygous FH. Target LDL-C is <3.5 mmol/L (130 mg/dL) if > 10 years, or ideally 50% reduction from baseline if 8-10 years, especially with very high LDL-C, elevated lipoprotein(a), a family history of premature CHD or other cardiovascular risk factors, balanced against the long-term risk of treatment side effects. Identifying FH early and optimally lowering LDL-C over the lifespan reduces cumulative LDL-C burden and offers health and socioeconomic benefits. To drive policy change for timely detection and management, we call for further studies in the young. Increased awareness, early identification, and optimal treatment from childhood are critical to adding decades of healthy life for children and adolescents with FH.
  • Benedek, P.; Jiao, H.; Duvefelt, K.; Skoog, T.; Linde, M.; Kiviluoma, P.; Kere, J.; Eriksson, M.; Angelin, B. (2021)
    Aim To investigate whether genotyping could be used as a cost-effective screening step, preceding next-generation sequencing (NGS), in molecular diagnosis of familial hypercholesterolaemia (FH) in Swedish patients. Methods and results Three hundred patients of Swedish origin with clinical suspicion of heterozygous FH were analysed using a specific array genotyping panel embedding 112 FH-causing mutations in the LDLR, APOB and PCSK9 genes. The mutations had been selected from previous reports on FH patients in Scandinavia and Finland. Mutation-negative cases were further analysed by NGS. In 181 patients with probable or definite FH using the Dutch lipid clinics network (DLCN) criteria (score >= 6), a causative mutation was identified in 116 (64%). Of these, 94 (81%) were detected by genotyping. Ten mutations accounted for more than 50% of the positive cases, with APOB c.10580G>A being the most common. Mutations in LDLR predominated, with (c.2311+1_2312-1)(2514)del (FH Helsinki) and c.259T>G having the highest frequency. Two novel LDLR mutations were identified. In patients with DLCN score < 6, mutation detection rate was significantly higher at younger age. Conclusion A limited number of mutations explain a major fraction of FH cases in Sweden. Combination of selective genotyping and NGS facilitates the clinical challenge of cost-effective genetic screening in suspected FH. The frequency of APOB c.10580G>A was higher than previously reported in Sweden. The lack of demonstrable mutations in the LDLR, APOB and PCSK9 genes in similar to 1/3 of patients with probable FH strongly suggests that additional genetic mechanisms are to be found in phenotypic FH.
  • EAS Familial Hypercholestero; EAS Familial Hypercholesterolaemia (2018)
    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 similar to 2/3 countries. Lipoprotein-apheresis is offered in similar to 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.
  • Vallejo-Vaz, Antonio J.; Akram, Asif; Seshasai, Sreenivasa Rao Kondapally; Cole, Della; Watts, Gerald F.; Hovingh, G. Kees; Kastelein, John J. P.; Mata, Pedro; Raal, Frederick J.; Santos, Raul D.; Soran, Handrean; Freiberger, Tomas; Abifadel, Marianne; Aguilar-Salinas, Carlos A.; Alnouri, Fahad; Alonso, Rodrigo; Al-Rasadi, Khalid; Banach, Maciej; Bogsrud, Martin P.; Bourbon, Mafalda; Bruckert, Eric; Car, Josip; Ceska, Richard; Corral, Pablo; Descamps, Olivier; Dieplinger, Hans; Do, Can T.; Durst, Ronen; Ezhov, Marat V.; Fras, Zlatko; Gaita, Dan; Gaspar, Isabel M.; Genest, Jaques; Harada-Shiba, Mariko; Jiang, Lixin; Kayikcioglu, Meral; Lam, Carolyn S. P.; Latkovskis, Gustavs; Laufs, Ulrich; Liberopoulos, Evangelos; Lin, Jie; Lin, Nan; Maher, Vincent; Majano, Nelson; Marais, A. David; Maerz, Winfried; Mirrakhimov, Erkin; Miserez, Andre R.; Mitchenko, Olena; Widen, Elisabeth; EAS Familial Hypercholesterolaemia (2016)
    Background: The potential for global collaborations to better inform public health policy regarding major non-hypercholesterolaemia (FH), a common genetic disorder associated with premature cardiovascular disease, is yet to be reliably ascertained using similar approaches. The European Atherosclerosis Society FH Studies Collaboration (EAS FHSC) is a new initiative of international stakeholders which will help establish a global FH registry to generate large-scale, robust data on the burden of FH worldwide. Methods: The EAS FHSC will maximise the potential exploitation of currently available and future FH data (retrospective and prospective) by bringing together regional/national/international data sources with access to individuals with a clinical and/or genetic diagnosis of heterozygous or homozygous FH. A novel bespoke electronic platform and FH Data Warehouse will be developed to allow secure data sharing, validation, cleaning, pooling, harmonisation and analysis irrespective of the source or format. Standard statistical procedures will allow us to investigate cross-sectional associations, patterns of real-world practice, trends over time, and analyse risk and outcomes (e.g. cardiovascular outcomes, all-cause death), accounting for potential confounders and subgroup effects. Conclusions: The EAS FHSC represents an excellent opportunity to integrate individual efforts across the world to tackle the global burden of FH. The information garnered from the registry will help reduce gaps in knowledge, inform best practices, assist in clinical trials design, support clinical guidelines and policies development, and ultimately improve the care of FH patients. (C) 2016 Elsevier Ireland Ltd.