Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Noninvasive detection of the vulnerable plaque : the quest of the Grail

In clinical routine, our ability to identify patients at high risk for presenting acute cardiovascular events such as myocardial infarction or stroke is poor. Recently, promising imaging techniques have been developed for identifying "vulnerable" plaques, ie those that are at high risk for precipitating fatal clinical events. Inflammation and neoangiogenesis are typical features of "vulnerability". Among the non-invasive imaging techniques, nuclear imaging (PET-CT) and contrast ultrasound allow the analysis of these characteristics. Our work allowed us to optimize the patient's preparation in order to perform a cardiac PET-CT in order to visualize the "vulnerable" plaques. Another part of our work shows that these two characteristics of vulnerability are not systematically associated in the carotid plaques and that the inflammation seems to be more pronounced in patients with an history of an acute event.Notre capacité à identifier en routine clinique, des patients à haut risque de présenter un évènement cardiovasculaire aigu, tels qu’un infarctus du myocarde ou un accident vasculaire cérébral est médiocre. Récemment, se sont développées des techniques d’imagerie prometteuses qui permettraient d’identifier les plaques dites «vulnérables», autrement dit celles qui sont à risque de précipiter ces évènements cliniques potentiellement fatals. L’inflammation et la néo-angiogénèse font partie de ces caractéristiques de « vulnérabilité ». Parmi les techniques d’imagerie non-invasives, l’imagerie nucléaire (PET-scanner) et l’échographie de contraste permettent l’analyse de ces caractéristiques. Nos travaux nous ont permis d’optimaliser la préparation du patient en vue de réaliser un PET-scanner cardiaque dans le but de visualiser les plaques « vulnérables ». Une autre partie de nos travaux démontre que ces deux caractéristiques de vulnérabilité ne sont pas systématiquement associés dans les plaques carotidiennes et que l’inflammation semble plus importante chez le patient ayant présenté un évènement aigu.(MED - Sciences médicales) -- UCL, 201

High 18F-FDG uptake in a systemic right ventricle after atrial switch

A 21-year-old patient with a D-transposition of the great arteries and a single coronary ostium underwent an atrial switch operation as newborn (Senning correction at 6 days of life in 1992). For an unrelated oncological evaluation, she underwent a recent F-FDG PET/CT. The myocardial uptake was clearly more intense in the morphological right ventricle, as this ventricle has become the systemic ventricle. On the contrary, the morphological left ventricle showed a very faint FDG uptake. This case illustrates the physiological changes related to a previous cardiac surgery

Erratum to: A new F-18 labeled PET tracer for fatty acid imaging

Erratum to J NUCL CARDIOL, 10.1007/S12350-014-0012-

Automatic external defibrillators in Belgian fitness centres

BACKGROUND: The number of fitness centres has increased in Western countries, some proposing specific training programmes (cardiac patients, weight loss or seniors).There is a real risk of cardiovascular events for individuals without cardiovascular evaluation. Fitness centres could represent a place at particularly high risk for sudden cardiac arrest (SCA). OBJECTIVE AND METHODS: In this observational study, we evaluated the number of fitness centres with automatic external defibrillators (AEDs) throughout the French-speaking part of Belgium, their geographic localization, the number of attendees, and the number of SCA reported. Details of AED and SCA were obtained by telephone survey. RESUITS: A total of 51 centres were surveyed. Only 5 (9.8%) had an AED and 68.8% (35/51) of centres had > 1 staff members specifically trained in CPR. Since the opening of these facilities, 5 SCA were reported from 3 centres (5.9%). Only 2 fitness centres had an AED present at the time of the SCA.Two SCA were unwitnessed, and for another 2 victims AED was used without success. Well-conducted CPR (no AED available) resulted in the only survivor of SCA. CONCLUSION: The rate of SCA in fitness centres in French-speaking Belgium is comparable to that reported in other countries. AED were available in less than 10% of centres and no CPR trained staff was available in almost one third of the centres

Diagnostiquer l’hypercholestérolémie familiale chez un patient et les membres de sa famille

L’hypercholestérolémie familiale est une maladie génétique fréquente mais souvent sous-diagnostiquée. Elle est pourtant facile à prendre en charge à condition de la dépister suffisamment précocement et de la traiter de manière appropriée. Nous présentons quelques outils pour la diagnostiquer. Chez un premier patient d'une famille encore inexplorée (patient-index), on utilisera le score DLCN (Dutch Lipid Clinic Network), suivi selon le cas d'une analyse génétique. Une fois le diagnostic confirmé chez ce patient, il sera facile de suspecter la maladie chez d'autres membres du 1er degré à partir d'une table de référence que nous présentons dans cet article. Cette table donne les seuils de concentrations de cholestérol LDL (selon l'âge et le sexe) à partir desquels il faut suspecter l’existence d’une hypercholestérolémie familiale chez un parent au 1er degré. Nous joignons également à cet article un modèle de lettre qui peut être adressé aux membres de cette famille pour éveiller leur attention sur l’existence de cette maladie et faciliter le travail de leur médecin généraliste. Familial hypercholesterolemia is a common, yet often underdiagnosed, genetic disease. Nevertheless, this condition is easily manageable provided that the disease is detected early enough and appropriately treated. Our article presents some diagnostic tools for this condition. In a first patient of an as yet unexplored family, referred to as the index patient, we propose to use the DLCN (Dutch Lipid Clinic Network) score, which should be followed by genetic analysis, depending on the case. Once the diagnosis has been confirmed in this index patient, the disease can easily be identified in other firstdegree relatives based on a reference table that has presented in this article. This table provides the threshold values of LDL cholesterol concentrations, according to age and gender, at which the existence of familial hypercholesterolemia in a first-degree relative should be suspected. To this article, we have attached a sample letter that can be addressed to family members, designed to alert them on this disease and facilitate the work-up of their general practitioners

Characterization of the role of the receptors PEX5 and PEX7 in the import of proteins into glycosomes of Trypanosoma brucei.

Peroxins 5 and 7 are receptors for protein import into the peroxisomal matrix. We studied the involvement of these peroxins in the biogenesis of glycosomes in the protozoan parasite Trypanosoma brucei. Glycosomes are peroxisome-like organelles in which a major part of the glycolytic pathway is sequestered. We here report the characterization of the T. brucei homologue of PEX7 and provide several data strongly suggesting that it can bind to PEX5. Depletion of PEX5 or PEX7 by RNA interference had a severe effect on the growth of both the bloodstream-form of the parasite, that relies entirely on glycolysis for its ATP supply, and the procyclic form representative of the parasite living in the tsetse-fly midgut and in which also other metabolic pathways play a prominent role. The role of the two receptors in import of glycosomal matrix proteins with different types of peroxisome/glycosome-targeting signals (PTS) was analyzed by immunofluorescence and subcellular fractionation studies. Knocking down the expression of either receptor gene resulted, in procyclic cells, in the mislocalization of proteins with both a type 1 or 2 targeting motif (PTS1, PTS2) located at the C- and N-termini, respectively, and proteins with a sequence-internal signal (I-PTS) to the cytosol. Electron microscopy confirmed the apparent integrity of glycosomes in these procyclic cells. In bloodstream-form trypanosomes, PEX7 depletion seemed to affect only the subcellular distribution of PTS2-proteins. Western blot analysis suggested that, in both life-cycle stages of the trypanosome, the levels of both receptors are controlled in a coordinated fashion, by a mechanism that remains to be determined. The observation that both PEX5 and PEX7 are essential for the viability of the parasite indicates that the respective branches of the glycosome-import pathway in which each receptor acts might be interesting drug targets