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1. Insights into medical students’ perceptions of work culture during the COVID-19 pandemic: a mixed method study

Author

Stephane Mouchabac, Vladimir Adrien, Thomas Diot, Marie-Christine Renaud, Alain Carrié, Alexis Bourla, and Florian Ferreri

Subjects
Work culture, Medical students, COVID-19, Professional identity, Coping, Special aspects of education, LC8-6691, Medicine
Abstract

Abstract Background The COVID-19 pandemic brought about profound social changes that affected students worldwide. These changes had both psychological and economic consequences, and also led to the adoption of new teaching methods. It can also have an impact on work culture, which is the collective set of values, norms, and practices within a specific profession, shaping how individuals in that field behave, communicate, and identify with their work. The aim of the study was to examine medical students’ perception of professional culture during the COVID-19 crisis when they voluntarily participated in the healthcare network established, outside of university placements, for the management of COVID patients. Methods A questionnaire study based on the vignette methodology was conducted among third-year medical students. Drawing from three scenarios in which students were variably engaged in crisis management, it included questions about their perceptions of the medical profession, their motivation, and their sense of belonging to the profession. Results 352 students responded to the survey. The pandemic had both a positive and a negative impact on students’ perceptions of the medical profession. Cluster analysis using a k-means algorithm and principal component analysis revealed three clusters of students with different perceptions of the medical profession. The first cluster, which represented the majority of students, corresponded to a relatively positive perception of the profession that was reinforced during the pandemic. In the second cluster, students’ perceptions were reinforced still further, and particular importance was attached to field experience. Students in the third cluster had the most negative perceptions, having been shaken the most by the pandemic, and they attached little importance to field experience. Conclusions The analysis highlighted the importance of students being able to adapt and draw on a range of resources during the COVID-19 pandemic. This underscores the need for work cultures that support adaptability and coping. Further research is needed to understand its long-term effects on students’ perceptions of the medical profession and to identify interventions that could support students in the aftermath of this difficult period.

Published
2024
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2. Long-term efficacy of lipoprotein apheresis and lomitapide in the treatment of homozygous familial hypercholesterolemia (HoFH): a cross-national retrospective survey

Author

Laura D’Erasmo, Antonio Gallo, Angelo Baldassare Cefalù, Alessia Di Costanzo, Samir Saheb, Antonina Giammanco, Maurizio Averna, Alessio Buonaiuto, Gabriella Iannuzzo, Giuliana Fortunato, Arturo Puja, Tiziana Montalcini, Chiara Pavanello, Laura Calabresi, Giovanni Battista Vigna, Marco Bucci, Katia Bonomo, Fabio Nota, Tiziana Sampietro, Francesco Sbrana, Patrizia Suppressa, Carlo Sabbà, Fabio Fimiani, Arturo Cesaro, Paolo Calabrò, Silvia Palmisano, Sergio D’Addato, Livia Pisciotta, Stefano Bertolini, Randa Bittar, Olga Kalmykova, Sophie Béliard, Alain Carrié, Marcello Arca, and Eric Bruckert

Subjects
Homozygous hypercholesterolemia, Lipoprotein apheresis, Lomitapide, LDL, Therapeutics, Genetic disease, Medicine
Abstract

Abstract Background Homozygous familial hypercholesterolemia (HoFH) is a rare life-threatening condition that represents a therapeutic challenge. The vast majority of HoFH patients fail to achieve LDL-C targets when treated with the standard protocol, which associates maximally tolerated dose of lipid-lowering medications with lipoprotein apheresis (LA). Lomitapide is an emerging therapy in HoFH, but its place in the treatment algorithm is disputed because a comparison of its long-term efficacy versus LA in reducing LDL-C burden is not available. We assessed changes in long-term LDL-C burden and goals achievement in two independent HoFH patients’ cohorts, one treated with lomitapide in Italy (n = 30) and the other with LA in France (n = 29). Results The two cohorts differed significantly for genotype (p = 0.004), baseline lipid profile (p

Published
2021
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3. LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients

Author

Auguste Dargent, Jean-Paul Pais de Barros, Samir Saheb, Randa Bittar, Wilfried Le Goff, Alain Carrié, Thomas Gautier, Isabelle Fournel, Anne Laure Rerole, Hélène Choubley, David Masson, Laurent Lagrost, and Jean-Pierre Quenot

Subjects
lipoproteins, low density lipoprotein, tandem mass spectroscopy, human and clinical research, inflammation, sepsis, Biochemistry, QD415-436
Abstract

Lipopolysaccharide (LPS) is a key player for innate immunity activation. It is therefore a prime target for sepsis treatment, as antibiotics are not sufficient to improve outcome during septic shock. An extracorporeal removal method by polymyxin (PMX) B direct hemoperfusion (PMX-DHP) is used in Japan, but recent trials failed to show a significant lowering of circulating LPS levels after PMX-DHP therapy. PMX-DHP has a direct effect on LPS molecules. However, LPS is not present in a free form in the circulation, as it is mainly carried by lipoproteins, including LDLs. Lipoproteins are critical for physiological LPS clearance, as LPSs are carried by LDLs to the liver for elimination. We hypothesized that LDL apheresis could be an alternate method for LPS removal. First, we demonstrated in vitro that LDL apheresis microbeads are almost as efficient as PMX beads to reduce LPS concentration in LPS-spiked human plasma, whereas it is not active in PBS. We found that PMX was also adsorbing lipoproteins, although less specifically. Then, we found that endogenous LPS of patients treated by LDL apheresis for familial hypercholesterolemia is also removed during their LDL apheresis sessions, with both electrostatic-based devices and filtration devices. Finally, LPS circulating in the plasma of septic shock and severe sepsis patients with gram-negative bacteremia was also removed in vitro by LDL adsorption. Overall, these results underline the importance of lipoproteins for LPS clearance, making them a prime target to study and treat endotoxemia-related conditions.

Published
2020
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4. Myocardial fibrosis assessed by magnetic resonance imaging in asymptomatic heterozygous familial hypercholesterolemia: the cholcoeur study

Author

Antonio Gallo, Philippe Giral, David Rosenbaum, Alessandro Mattina, Ali Kilinc, Alain Giron, Khaoula Bouazizi, Moussa Gueda Moussa, Joe-Elie Salem, Alain Carrié, Valérie Carreau, Sophie Béliard, Randa Bittar, Philippe Cluzel, Eric Bruckert, Alban Redheuil, and Nadjia Kachenoura

Subjects
Familial hypercholesterolemia, cardiovascular imaging, cardiac magnetic resonance, primary prevention, genetic dyslipidaemia, cardiovascular risk, Medicine, Medicine (General), R5-920
Abstract

Background: Familial Hypercholesterolemia (FH) is an underdiagnosed condition with an increased cardiovascular risk. It is unknown whether lipid accumulation plays a role in structural myocardial changes. Cardiovascular Magnetic Resonance (CMR) is the reference technique for the morpho-functional evaluation of heart chambers through cine sequences and for myocardial tissue characterization through late gadolinium enhancement (LGE) and T1 mapping images. We aimed to assess the prevalence of myocardial fibrosis in FH patients. Methods: Seventy-two asymptomatic subjects with genetically confirmed FH (mean age 49·24, range 40 to 60 years) were prospectively recruited along with 31 controls without dyslipidaemia matched for age, sex, BMI, and other cardiovascular risk factors. All underwent CMR including cine, LGE, pre- and post-contrast T1 mapping. Extracellular volume (ECV) and enhancement rate of the myocardium (ERM = difference between pre- and post-contrast myocardial T1, normalized by pre-contrast myocardial T1) were calculated. Findings: Five FH patients and none of the controls had intramyocardial LGE (p= 0·188). While no changes in Native T1 and ECV were found, post-contrast T1 was significantly lower (430·6 ± 55ms vs. 476·1 ± 43ms, p

Published
2021
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5. APOE Molecular Spectrum in a French Cohort with Primary Dyslipidemia

Author

Yara Abou Khalil, Oriane Marmontel, Jean Ferrières, François Paillard, Cécile Yelnik, Valérie Carreau, Sybil Charrière, Eric Bruckert, Antonio Gallo, Philippe Giral, Anne Philippi, Olivier Bluteau, Catherine Boileau, Marianne Abifadel, Mathilde Di-Filippo, Alain Carrié, Jean-Pierre Rabès, and Mathilde Varret

Subjects
hypercholesterolemia, ADH, FCHL, apolipoprotein E, APOE gene, mutation, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Primary hypercholesterolemia is characterized by elevated LDL-cholesterol (LDL-C) levels isolated in autosomal dominant hypercholesterolemia (ADH) or associated with elevated triglyceride levels in familial combined hyperlipidemia (FCHL). Rare APOE variants are known in ADH and FCHL. We explored the APOE molecular spectrum in a French ADH/FCHL cohort of 5743 unrelated probands. The sequencing of LDLR, PCSK9, APOB, and APOE revealed 76 carriers of a rare APOE variant, with no mutation in LDLR, PCSK9, or APOB. Among the 31 APOE variants identified here, 15 are described in ADH, 10 in FCHL, and 6 in both probands. Five were previously reported with dyslipidemia and 26 are novel, including 12 missense, 5 synonymous, 2 intronic, and 7 variants in regulatory regions. Sixteen variants were predicted as pathogenic or likely pathogenic, and their carriers had significantly lower polygenic risk scores (wPRS) than carriers of predicted benign variants. We observed no correlation between LDL-C levels and wPRS, suggesting a major effect of APOE variants. Carriers of p.Leu167del were associated with a severe phenotype. The analysis of 11 probands suggests that carriers of an APOE variant respond better to statins than carriers of a LDLR mutation. Altogether, we show that the APOE variants account for a significant contribution to ADH and FCHL.

Published
2022
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6. Ablation of DNA-methyltransferase 3A in skeletal muscle does not affect energy metabolism or exercise capacity.

Author

Lewin Small, Lars R Ingerslev, Eleonora Manitta, Rhianna C Laker, Ann N Hansen, Brendan Deeney, Alain Carrié, Philippe Couvert, and Romain Barrès

Subjects
Genetics, QH426-470
Abstract

In response to physical exercise and diet, skeletal muscle adapts to energetic demands through large transcriptional changes. This remodelling is associated with changes in skeletal muscle DNA methylation which may participate in the metabolic adaptation to extracellular stimuli. Yet, the mechanisms by which muscle-borne DNA methylation machinery responds to diet and exercise and impacts muscle function are unknown. Here, we investigated the function of de novo DNA methylation in fully differentiated skeletal muscle. We generated muscle-specific DNA methyltransferase 3A (DNMT3A) knockout mice (mD3AKO) and investigated the impact of DNMT3A ablation on skeletal muscle DNA methylation, exercise capacity and energy metabolism. Loss of DNMT3A reduced DNA methylation in skeletal muscle over multiple genomic contexts and altered the transcription of genes known to be influenced by DNA methylation, but did not affect exercise capacity and whole-body energy metabolism compared to wild type mice. Loss of DNMT3A did not alter skeletal muscle mitochondrial function or the transcriptional response to exercise however did influence the expression of genes involved in muscle development. These data suggest that DNMT3A does not have a large role in the function of mature skeletal muscle although a role in muscle development and differentiation is likely.

Published
2021
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7. Evaluation of a semi-automatic isoelectric focusing method for apolipoprotein E phenotyping

Author

Randa Bittar, Alain Carrié, Georges Nouadje, Corinne Cherfils, Valérie Fesel-Fouquier, Laurence Barbot-Trystram, Philippe Giral, and Dominique Bonnefont-Rousselot

Subjects
Medicine (General), R5-920, Chemistry, QD1-999
Abstract

A qualitative, semi-automatized method for apolipoprotein E (apoE) phenotyping by isoelectric focusing method has been evaluated on 40 serum samples from patients previously genotyped for apoE, especially as regards concordance with genotyping, but also repeatability and reproducibility of the method, and sample storage. Total concordance with genotyping and good precision criteria, together with its practicability and requirement of a little sample volume, lead to conclude to the usefulness of this method to help clinicians in the diagnosis of dyslipidemic and neurodegenerative diseases. Keywords: Apolipoprotein E, Isoforms, Phenotype, Isoelectric focusing

Published
2020
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8. LDL-apheresis depletes apoE-HDL and pre-β1-HDL in familial hypercholesterolemia: relevance to atheroprotection

Author

Alexina Orsoni, Samir Saheb, Johannes H.M. Levels, Geesje Dallinga-Thie, Marielle Atassi, Randa Bittar, Paul Robillard, Eric Bruckert, Anatol Kontush, Alain Carrié, and M. John Chapman

Subjects
high density lipoprotein heterogeneity, HDL proteome, low density lipoprotein receptor mutations, premature atherosclerosis, apolipoprotein E, Biochemistry, QD415-436
Abstract

Subnormal HDL-cholesterol (HDL-C) and apolipoprotein (apo)AI levels are characteristic of familial hypercholesterolemia (FH), reflecting perturbed intravascular metabolism with compositional anomalies in HDL particles, including apoE enrichment. Does LDL-apheresis, which reduces HDL-cholesterol, apoAI, and apoE by adsorption, induce selective changes in HDL subpopulations, with relevance to atheroprotection? Five HDL subpopulations were fractionated from pre- and post-LDL-apheresis plasmas of normotriglyceridemic FH subjects (n = 11) on regular LDL-apheresis (>2 years). Apheresis lowered both plasma apoE (−62%) and apoAI (−16%) levels, with preferential, genotype-independent reduction in apoE. The mass ratio of HDL2:HDL3 was lowered from ∼1:1 to 0.72:1 by apheresis, reflecting selective removal of HDL2 mass (80% of total HDL adsorbed). Pre-LDL-apheresis, HDL2 subpopulations were markedly enriched in apoE, consistent with ∼1 copy of apoE per 4 HDL particles. Large amounts (50-66%) of apoE-HDL were removed by apheresis, preferentially in the HDL2b subfraction (−50%); minor absolute amounts of apoE-HDL were removed from HDL3 subfractions. Furthermore, pre-β1-HDL particle levels were subnormal following removal (−53%) upon apheresis, suggesting that cellular cholesterol efflux may be defective in the immediate postapheresis period. In LDL-receptor (LDL-R) deficiency, LDL-apheresis may enhance flux through the reverse cholesterol transport pathway and equally attenuate potential biglycan-mediated deposition of apoE-HDL in the arterial matrix.

Published
2011
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10. Impact of COVID-19 Pandemic on Medical Students’ Work Culture: A Mixed Method Study

Author

Stéphane Mouchabac, Vladimir Adrien, Thomas Diot, Marie-Christine Renaud, Alain Carrié, Alexis Bourla, and Florian Ferreri

Abstract

Background: The COVID-19 pandemic brought about profound social changes that affected students worldwide. These changes had both psychological and economic consequences, and also led to the adoption of new teaching methods. The present study examined the pandemic’s impact on French medical students’ perceptions of their profession. Methods: A questionnaire study based on the vignette methodology was conducted among third-year medical students. It included questions about their perceptions of the medical profession, their motivation, and their sense of belonging to the profession. Results: 352 students responded to the survey . The pandemic had both a positive and a negative impact on students’ perceptions of the medical profession. Cluster analysis using a k-means algorithm and principal component analysis revealed three clusters of students with different perceptions of the medical profession. The first cluster, which represented the majority of students, corresponded to a relatively positive perception of the profession that was reinforced during the pandemic. In the second cluster, students’ perceptions were reinforced still further, and particular importance was attached to field experience. Students in the third cluster had the most negative perceptions, having been shaken the most by the pandemic, and they attached little importance to field experience. Conclusions: The analysis highlighted the importance of students being able to adapt and draw on a range of resources during the COVID-19 pandemic. This underscores the need for work cultures that support adaptability and coping. Overall, the pandemic had a profound and far-reaching impact on medical students in France, but these effects were not uniform. Further research is needed to understand its long-term effects on students' perceptions of the medical profession and to identify interventions that could support students in the aftermath of this difficult period.

Published
2023

11. Additive Effect of APOE Rare Variants on the Phenotype of Familial Hypercholesterolemia

Author

Oriane Marmontel, Yara Abou-Khalil, Olivier Bluteau, Bertrand Cariou, Valérie Carreau, Sybil Charrière, Eleonore Divry, Antonio Gallo, Philippe Moulin, François Paillard, Noel Peretti, Jean-Pierre Rabès, Mathilde Varret, Alain Carrié, and Mathilde Di Filippo

Subjects
Cardiology and Cardiovascular Medicine
Abstract

Background: Autosomal dominant hypercholesterolemia (ADH) is due to deleterious variants in LDLR , APOB , or PCSK9 genes. Double heterozygote for these genes induces a more severe phenotype. More recently, a new causative variant of heterozygous ADH was identified in APOE . Here we study the phenotype of 21 adult patients, double heterozygotes for rare LDLR and rare APOE variants ( LDLR+APOE ) in a national wide French cohort. Methods: LDLR , APOB , PCSK9 , and APOE genes were sequenced in 5743 probands addressed for ADH genotyping. The lipid profile and occurrence of premature atherosclerotic cardiovascular diseases were compared between the LDLR+APOE carriers (n=21) and the carriers of the same LDLR causative variants alone (n=22). Results: The prevalence of LDLR+APOE carriers in this French ADH cohort is 0.4%. Overall, LDL (low-density lipoprotein)-cholesterol concentrations were 23% higher in LDLR+APOE patients than in LDLR patients (9.14±2.51 versus 7.43±1.59 mmol/L, P=0 .0221). When only deleterious or probably deleterious variants were considered, the LDL-cholesterol concentrations were 46% higher in LDLR+APOE carriers than in LDLR carriers (10.83±3.45 versus 7.43±1.59 mmol/L, P=0 .0270). Two patients exhibited a homozygous familial hypercholesterolemia phenotype (LDL-cholesterol >13 mmol/L). Premature atherosclerotic cardiovascular disease was more common in LDLR+APOE patients than in LDLR carriers (70% versus 30%, P=0 .026). Conclusions: Although an incomplete penetrance should be taken into account for APOE variant classification, these results suggest an additive effect of deleterious APOE variants on ADH phenotype highlighting the relevance of APOE sequencing.

Published
2023

12. Maternal Inheritance of Familial Hypercholesterolemia Gene Mutation Predisposes to Coronary Atherosclerosis as Assessed by Calcium Score in Adulthood

Author

Florian Mourre, Roch Giorgi, Antonio Gallo, Franck Boccara, Eric Bruckert, Alain Carrié, Regis Hankard, Jocelyn Inamo, Sandrine Laboureau, Philippe Moulin, René Valéro, Sophie Béliard, Denis Angoulvant, Sophie Beliard, Bertrand Cariou, Valérie Carreau, Alain Carrie, Sybil Charrieres, Yves Cottin, Mathilde Di Filippo, Pierre Henri Ducluzeau, Sonia Dulong, Vincent Durlach, Michel Farnier, Emile Ferrari, Dorota Ferrieres, Jean Ferrieres, Olga Kalmykova, Michel Krempf, Julie Lemale, François Paillard, Noel Peretti, Agnes Perrin, Alain Pradignac, Jean Pierre Rabes, Vincent Rigalleau, François Schiele, Ariane Sultan, Patrick Tounian, René Valero, Bruno Verges, Cecile Yelnik, Olivier Ziegler, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
[SDV]Life Sciences [q-bio], hyperlipidemia, maternal inheritance, risk factors, atherosclerosis, Cardiology and Cardiovascular Medicine, cardiovascular diseases
Abstract

Background: Animal studies have demonstrated that fetal exposure to high maternal cholesterol levels during pregnancy predisposes to aortic atheroma in the offspring. In humans, little is known about the consequences of this exposure on the development of atherosclerotic cardiovascular disease later in life. We wanted to assess whether maternal/paternal inheritance of familial hypercholesterolemia (FH) gene mutation could be associated with subclinical coronary atherosclerosis. Methods: We retrospectively included 1350 patients, followed in the French registry of FH, with a documented genetic diagnosis. We selected 556 age- and sex-matched pair of patients based on the sex of the parents who transmitted the FH gene mutation, free of coronary cardiovascular event, and with a subclinical coronary atherosclerosis evaluation assessed using coronary artery calcium (CAC) score. We performed univariate and multivariate analysis to assess the individual effect of parental inheritance of the FH gene mutation on the CAC score. Results: In the whole population, patients with maternal inheritance of FH gene mutation (n=639) less frequently had a family history of premature cardiovascular events (27.7% versus 45%, P P =0.02) than those with paternal inheritance (n=711). There was no difference in the prevalence of cardiovascular events between the two groups. In the matched subgroup, maternal inheritance was significantly associated with an increase in CAC score value by 86% (95% CI, 23%–170%; P =0.003), a 1.81-fold risk of having a CAC score ≥100 Agatston units (95% CI, 1.06–3.11; P =0.03), and a 2.72-fold risk of having a CAC score ≥400 Agatston units (95% CI, 1.39–5.51; P =0.004) when compared with paternal inheritance in multivariate analysis. Conclusions: Maternal inheritance of FH gene mutation was associated with more severe subclinical coronary atherosclerosis assessed by CAC score and may be considered as a potential cardiovascular risk factor.

Published
2023

13. Effect of the LDL receptor mutation type on incident major adverse cardiovascular events in familial hypercholesterolaemia

Author

Martine Paquette, Alain Carrié, Sophie Bernard, Bertrand Cariou, Robert A Hegele, Jacques Genest, Mark Trinder, Liam R Brunham, Sophie Béliard, Alexis Baass, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and ANR-16-RHUS-0007,CHOPIN,CHOPIN(2016)

Subjects
Epidemiology, [SDV]Life Sciences [q-bio], Null, Defective, Cholesterol, LDL, Cardiovascular, Hyperlipoproteinemia Type II, Receptors, LDL, Cardiovascular Diseases, DL-C, Mutation, Humans, LDLRL, Prospective Studies, Cardiology and Cardiovascular Medicine, Familial hypercholesterolaemia
Abstract

Aims Patients with familial hypercholesterolaemia (FH) are at increased risk of cardiovascular disease (CVD) due to extremely high circulating LDL cholesterol (LDL-C) concentrations. Our objective was to study the effect of the type of LDL receptor (LDLR) mutation on the incidence of major adverse cardiovascular events (MACEs). Methods and results This was a multinational prospective cohort study, which included patients with heterozygous FH aged 18–65 years, without a prior history of CVD, and carrying a pathogenic or likely pathogenic variant in the LDLR gene. A total of 2131 patients (20 535person-years of follow-up) were included in the study, including 1234 subjects carrying a defective mutation in the LDLR and 897 subjects carrying a null mutation. During the follow-up, a first MACE occurred in 79 cases (6%) in the defective group and in 111 cases (12%) in the null group. The mean baseline LDL-C concentration was 17% higher in the null group than in the defective group (7.90 vs. 6.73 mmoL/L, P < 0.0001). In a Cox regression model corrected for traditional cardiovascular risk factors, the presence of a null mutation was associated with a hazard ratio of 2.09 (1.44–3.05), P = 0.0001. Conclusion Carriers of a null mutation have an independent ∼2-fold increased risk of incident MACE compared with patients carrying a defective mutation. This study highlights the importance of genetic screening in FH in order to improve patient care.

Published
2022

14. Corrigendum to 'Phospholipid transfer to high-density lipoprotein (HDL) upon triglyceride lipolysis is directly correlated with HDL-cholesterol levels and is not associated with cardiovascular risk' [Atherosclerosis 324C (2021) 1–8]

Author

Feng Ma, Maryam Darabi, Marie Lhomme, Emilie Tubeuf, Aurélie Canicio, Jean Brerault, Narcisse Medadje, Fabiana Rached, Sandrine Lebreton, Eric Frisdal, Fernando Brites, Carlos Serrano, Raul Santos, Emmanuel Gautier, Thierry Huby, Petra El Khoury, Alain Carrié, Marianne Abifadel, Eric Bruckert, Maryse Guerin, Philippe Couvert, Philippe Giral, Philippe Lesnik, Wilfried Le Goff, Isabelle Guillas, and Anatol Kontush

Subjects
Cardiology and Cardiovascular Medicine
Published
2023

15. Lessons from the impact of COVID-19 on medical educational continuity and practices

Author

Alexandre Hertig, Alain Carrié, Noémie Simon-Tillaux, Marie-Christine Renaud, Isabelle Jéru, and Camille Vatier

Subjects
020205 medical informatics, Physiology, Distance education, Curriculum Development and Assessment, 02 engineering and technology, Computer-assisted web interviewing, Education, Digital media, Likert scale, 03 medical and health sciences, 0302 clinical medicine, 0202 electrical engineering, electronic engineering, information engineering, ComputingMilieux_COMPUTERSANDEDUCATION, 030212 general & internal medicine, Set (psychology), Curriculum, Multiple choice, Medical education, teachers, business.industry, COVID-19, General Medicine, undergraduate student, Scale (social sciences), digital resources, business, Psychology, remote learning
Abstract

The COVID-19 crisis necessitated abrupt transition to remote learning in medical schools. We aimed to assess the impact of COVID-19 on French undergraduate students and teachers, to identify practice changes, and to evaluate successes and areas for improvement of this remote learning experience. Data from 2 online questionnaires were analyzed with 509 participants among students and 189 among teachers from Sorbonne University. Responses to multiple choice, Likert response scale, and open-ended questions were evaluated. COVID-19 had negative impact on teaching continuity. Sixty-seven percent of students were in a dropout situation, and many suffered from psychological stress, leading to set up of a psychological support unit. Although most teachers (81%) and students (72%) had limited knowledge of digital resources, distance learning was quickly implemented, with a predominant use of Zoom. The analysis of several parameters revealed that students were significantly more satisfied than teachers by remote learning. Nevertheless, both students and teachers agreed to replace classical lectures by digital media and to promote in-person teaching in small interactive groups. This paper shares tips for faculty rapidly establishing remote learning. This comparative study of the students’ and teachers’ points of view underlines that new medical curricula should include more digital contents. We make recommendations regarding general university organization, equipment, and curricular development for long-term implementation of digital resources with reinforced relationships between faculty and students.

Published
2021

16. LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients

Author

Anne Laure Rerole, Alain Carrié, Samir Saheb, David Masson, Wilfried Le Goff, Isabelle Fournel, Randa Bittar, Hélène Choubley, Thomas Gautier, Jean-Pierre Quenot, Jean-Paul Pais de Barros, Auguste Dargent, Laurent Lagrost, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de biochimie médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Réanimation Médicale (CHU de Dijon), Gestionnaire, Hal Sorbonne Université, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Laboratoire de biochimie médicale (CHU Dijon)

Subjects
Adult, Lipopolysaccharides, Male, 0301 basic medicine, Lipopolysaccharide, low density lipoprotein apheresis, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Inflammation, Familial hypercholesterolemia, QD415-436, 030204 cardiovascular system & hematology, Pharmacology, Biochemistry, Sepsis, sepsis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Humans, Medicine, Research Articles, polymyxin hemoperfusion, business.industry, Septic shock, lipopolysaccharide, Cell Biology, Hemoperfusion, medicine.disease, Healthy Volunteers, 3. Good health, [SDV] Life Sciences [q-bio], lipoproteins, 030104 developmental biology, chemistry, LDL apheresis, inflammation, Low-density lipoprotein, septic shock, Female, lipids (amino acids, peptides, and proteins), medicine.symptom, human and clinical research, business, low density lipoprotein, tandem mass spectroscopy
Abstract

International audience; Lipopolysaccharide (LPS) is a key player for innate immunity activation. It is therefore a prime target for sepsis treatment, as antibiotics are not sufficient to improve outcome during septic shock. An extracorporeal removal method by polymyxin (PMX) B direct hemoperfusion (PMX-DHP) is used in Japan, but recent trials failed to show a significant lowering of circulating LPS levels after PMX-DHP therapy. PMX-DHP has a direct effect on LPS molecules. However, LPS is not present in a free form in the circulation, as it is mainly carried by lipoproteins, including LDLs. Lipoproteins are critical for physiological LPS clearance, as LPSs are carried by LDLs to the liver for elimination. We hypothesized that LDL apheresis could be an alternate method for LPS removal. First, we demonstrated in vitro that LDL apheresis microbeads are almost as efficient as PMX beads to reduce LPS concentration in LPS-spiked human plasma, whereas it is not active in PBS. We found that PMX was also adsorbing lipoproteins, although less specifically. Then, we found that endogenous LPS of patients treated by LDL apheresis for familial hypercholesterolemia is also removed during their LDL apheresis sessions, with both electrostatic-based devices and filtration devices. Finally, LPS circulating in the plasma of septic shock and severe sepsis patients with gram-negative bacteremia was also removed in vitro by LDL adsorption. Overall, these results underline the importance of lipoproteins for LPS clearance, making them a prime target to study and treat endotoxemia-related conditions.

Published
2020

17. The Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia Variant Curation Expert Panel consensus guidelines for LDLR variant classification

Author

Joana Rita Chora, Margaret Chen, Lukáš Tichý, Sarah Leigh, Tomáš Freiberger, Michael A. Iacocca, Michal Kramarek, Robert A. Hegele, Hannah Wand, Cinthia E. Jannes, Liam R. Brunham, Heather Zimmermann, ClinGen Familial Hypercholesterolemia Expert Panel, Tami Johnston, Eric J.G. Sijbrands, Steve E. Humphries, Serra Kim, C. Lisa Kurtz, Alexandre C. Pereira, Mafalda Bourbon, Amanda J. Hooper, Jessica Chonis, Jian Wang, Mark Trinder, Joshua W. Knowles, Premysl Soucek, Maggie Williams, Annette Leon, Alain Carrié, and Internal Medicine

Subjects
ClinGen, medicine.medical_specialty, Population, Genomics, Familial hypercholesterolemia, Computational biology, 030204 cardiovascular system & hematology, Genome, Doenças Cardio e Cérebro-vasculares, Hyperlipoproteinemia Type II, 03 medical and health sciences, 0302 clinical medicine, Resource (project management), Hipercolesterolemia Familiar, medicine, Humans, ACMG/AMP, Genetic Testing, Familial Hypercholesterolemia, education, Mendelian disorders, Genetics (clinical), 030304 developmental biology, 0303 health sciences, education.field_of_study, business.industry, Genome, Human, Genetic Variation, medicine.disease, Variant Classification, 3. Good health, LDLR, Medical genetics, business, Colesterol
Abstract

The online version of this article (https://doi.org/10.1016/j. gim.2021.09.012) contains supplementary material, which is available to authorized users. Purpose: In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published consensus standardized guidelines for sequence-level variant classification in Mendelian disorders. To increase accuracy and consistency, the Clinical Genome Resource Familial Hypercholesterolemia (FH) Variant Curation Expert Panel was tasked with optimizing the existing ACMG/AMP framework for disease-specific classification in FH. In this study, we provide consensus recommendations for the most common FH-associated gene, LDLR, where >2300 unique FH-associated variants have been identified. Methods: The multidisciplinary FH Variant Curation Expert Panel met in person and through frequent emails and conference calls to develop LDLR-specific modifications of ACMG/AMP guidelines. Through iteration, pilot testing, debate, and commentary, consensus among experts was reached. Results: The consensus LDLR variant modifications to existing ACMG/AMP guidelines include (1) alteration of population frequency thresholds, (2) delineation of loss-of-function variant types, (3) functional study criteria specifications, (4) cosegregation criteria specifications, and (5) specific use and thresholds for in silico prediction tools, among others. Conclusion: Establishment of these guidelines as the new standard in the clinical laboratory setting will result in a more evidence-based, harmonized method for LDLR variant classification worldwide, thereby improving the care of patients with FH. Clinical Genome Resource (ClinGen) is primarily funded by the National Human Genome Research Institute through the following 3 grants: U41HG006834, U41HG009649, and U41HG009650. ClinGen also receives support for content curation from the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the following 3 grants: U24HD093483, U24HD093486, and U24HD093487. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. J.R.C. acknowledges her PhD fellowship funded by the Science and Technology Foundation (SFRH/BD/108503/2015). L.T. and T.F. are supported by the Ministry of Health of the Czech Republic (grant NU20-02-00261). S.E.H. is an Emeritus British Heart Foundation Professor and is funded by PG08/ 008 and by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. M.T. is supported by a Vanier Canada Graduate Scholarship. L.R.B. is a Michael Smith Foundation for Health Research scholar and a Canada Research Chair in Precision Cardiovascular Disease Prevention. R.A.H. is supported by the Jacob J. Wolfe Distinguished Medical Research Chair, the Edith Schulich Vinet Canada Research Chair in Human Genetics, the Martha G. Blackburn Chair in Cardiovascular Research, and operating grants from the Canadian Institutes of Health Research (Foundation Grant) and the Heart and Stroke Foundation of Ontario (G-18- 0022147). J.W.K. is supported by the National Institutes of Health through grants P30DK116074 (to the Stanford Diabetes Research Center), R01 DK116750, R01 DK120565, and R01 DK106236 and by the American Diabetes Association (grant #1-19-JDF-108). info:eu-repo/semantics/publishedVersion

Published
2022

18. Lipoprotein(a): Pathophysiology, measurement, indication and treatment in cardiovascular disease. A consensus statement from the Nouvelle Société Francophone d’Athérosclérose (NSFA)

Author

Sybil Charrière, M. John Chapman, Dominique Bonnefont-Rousselot, Eduardo Anglés-Cano, Sophie Béliard-Lasserre, Mathilde Di-Filippo Charcosset, René Valéro, Gilles Lambert, Xavier Collet, Bertrand Cariou, Philippe Gillery, Mathilde Varret, V. Durlach, Jean Ferrières, Alain Carrié, Philippe Moulin, Michel Farnier, Pierre Morange, Franck Boccara, Olivier Meilhac, Eric Bruckert, Université de Reims Champagne-Ardenne (URCA), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Institut de Chimie du CNRS (INC)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiopathologie et épidémiologie cérébro-cardiovasculaire [Dijon] (PEC2), Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Centre d'Investigation Clinique de La Réunion - INSERM (CIC 1410), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de Rangueil, CHU Toulouse [Toulouse], Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Innovations thérapeutiques en hémostase (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Angles-Cano, Eduardo, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140)

Subjects
medicine.medical_specialty, Antifibrinolytic, Consensus, Apolipoprotein B, medicine.drug_class, Context (language use), Atherothrombosis, Disease, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, Apolipoprotein(a), [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, 0303 health sciences, biology, business.industry, Cholesterol, Calcific aortic valve stenosis, Plasminogen, General Medicine, Lipoprotein(a), Atherosclerosis, 3. Good health, Cardiovascular diseases, chemistry, biology.protein, Cardiology, lipids (amino acids, peptides, and proteins), Cardiology and Cardiovascular Medicine, business, Lipoprotein
Abstract

International audience; Lipoprotein(a) is an apolipoprotein B100-containing low-density lipoprotein-like particle that is rich in cholesterol, and is associated with a second major protein, apolipoprotein(a). Apolipoprotein(a) possesses structural similarity to plasminogen but lacks fibrinolytic activity. As a consequence of its composite structure, lipoprotein(a) may: (1) elicit a prothrombotic/antifibrinolytic action favouring clot stability; and (2) enhance atherosclerosis progression via its propensity for retention in the arterial intima, with deposition of its cholesterol load at sites of plaque formation. Equally, lipoprotein(a) may induce inflammation and calcification in the aortic leaflet valve interstitium, leading to calcific aortic valve stenosis. Experimental, epidemiological and genetic evidence support the contention that elevated concentrations of lipoprotein(a) are causally related to atherothrombotic risk and equally to calcific aortic valve stenosis. The plasma concentration of lipoprotein(a) is principally determined by genetic factors, is not influenced by dietary habits, remains essentially constant over the lifetime of a given individual and is the most powerful variable for prediction of lipoprotein(a)-associated cardiovascular risk. However, major interindividual variations (up to 1000-fold) are characteristic of lipoprotein(a) concentrations. In this context, lipoprotein(a) assays, although currently insufficiently standardized, are of considerable interest, not only in stratifying cardiovascular risk, but equally in the clinical follow-up of patients treated with novel lipid-lowering therapies targeted at lipoprotein(a) (e.g. antiapolipoprotein(a) antisense oligonucleotides and small interfering ribonucleic acids) that markedly reduce circulating lipoprotein(a) concentrations. We recommend that lipoprotein(a) be measured once in subjects at high cardiovascular risk with premature coronary heart disease, in familial hypercholesterolaemia, in those with a family history of coronary heart disease and in those with recurrent coronary heart disease despite lipid-lowering treatment. Because of its clinical relevance, the cost of lipoprotein(a) testing should be covered by social security and health authorities.

Published
2021

19. Reply to Morje et al

Author

Camille Vatier, Marie-Christine Renaud, Isabelle Jéru, Alexandre Hertig, Alain Carrié, and Noémie Simon-Tillaux

Subjects
2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Physiology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), General Medicine, Sociology, Virology, Letter to the Editor, Education
Published
2021

20. Long-term efficacy of lipoprotein apheresis and lomitapide in the treatment of homozygous familial hypercholesterolemia (HoFH): a cross-national retrospective survey

Author

Tiziana Sampietro, Marcello Arca, Paolo Calabrò, Olga Kalmykova, Livia Pisciotta, Stefano Bertolini, Gabriella Iannuzzo, Francesco Sbrana, Fabio Nota, Antonio Gallo, Carlo Sabbà, Patrizia Suppressa, Arturo Cesaro, Giuliana Fortunato, Randa Bittar, Arturo Puja, Marco Bucci, Katia Bonomo, Angelo B. Cefalù, Samir Saheb, Maurizio Averna, Tiziana Montalcini, Alessio Buonaiuto, Sergio D'Addato, Alain Carrié, Chiara Pavanello, Sophie Béliard, Alessia Di Costanzo, S. Palmisano, Eric Bruckert, Giovanni Battista Vigna, Antonina Giammanco, Laura Calabresi, Fabio Fimiani, Laura D'Erasmo, D'Erasmo L., Gallo A., Cefalu A.B., Di Costanzo A., Saheb S., Giammanco A., Averna M., Buonaiuto A., Iannuzzo G., Fortunato G., Puja A., Montalcini T., Pavanello C., Calabresi L., Vigna G.B., Bucci M., Bonomo K., Nota F., Sampietro T., Sbrana F., Suppressa P., Sabba C., Fimiani F., Cesaro A., Calabro P., Palmisano S., D'Addato S., Pisciotta L., Bertolini S., Bittar R., Kalmykova O., Beliard S., Carrie A., Arca M., Bruckert E., D'Erasmo, L., Gallo, A., Cefalu, A. B., Di Costanzo, A., Saheb, S., Giammanco, A., Averna, M., Buonaiuto, A., Iannuzzo, G., Fortunato, G., Puja, A., Montalcini, T., Pavanello, C., Calabresi, L., Vigna, G. B., Bucci, M., Bonomo, K., Nota, F., Sampietro, T., Sbrana, F., Suppressa, P., Sabba, C., Fimiani, F., Cesaro, A., Calabro, Paolo, Palmisano, S., D'Addato, S., Pisciotta, L., Bertolini, S., Bittar, R., Kalmykova, O., Beliard, S., Carrie, A., Arca, M., Bruckert, E., Calabro, P., Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Palermo - University of Palermo, University of Naples Federico II = Università degli studi di Napoli Federico II, CEINGE - Biotecnologie Avanzate, Università degli Studi 'Magna Graecia' di Catanzaro = University of Catanzaro (UMG), Università degli Studi di Milano = University of Milan (UNIMI), Università degli Studi di Ferrara = University of Ferrara (UniFE), Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Ospedale San Luigi Gonzaga, Fondazione Toscana Gabriele Monasterio, University of the Study of Campania Luigi Vanvitelli, Policlinico S. Orsola-malpighi, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO)-Servizio sanitario regionale Emilia-Romagna, Università degli studi di Genova = University of Genoa (UniGe), Ospedale Policlinico San Martino [Genoa], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)

Subjects
medicine.medical_specialty, Settore MED/09 - Medicina Interna, [SDV]Life Sciences [q-bio], Lipoproteins, Genetic disease, Therapeutics, Familial hypercholesterolemia, Disease, Lipoprotein apheresi, LDL, Hyperlipoproteinemia Type II, chemistry.chemical_compound, Lipoprotein apheresis, Retrospective survey, Internal medicine, Cholesterol burden, Homozygous hypercholesterolemia, Lomitapide, Benzimidazoles, Homozygote, Humans, Retrospective Studies, Anticholesteremic Agents, Blood Component Removal, medicine, Pharmacology (medical), Genetics (clinical), medicine.diagnostic_test, business.industry, Research, General Medicine, medicine.disease, cholesterol burden, genetic disease, homozygous hypercholesterolemia, lipoprotein apheresis, lomitapide, therapeutics, chemistry, Cohort, Medicine, Lipid profile, business, Cross national
Abstract

Abstract Background Homozygous familial hypercholesterolemia (HoFH) is a rare life-threatening condition that represents a therapeutic challenge. The vast majority of HoFH patients fail to achieve LDL-C targets when treated with the standard protocol, which associates maximally tolerated dose of lipid-lowering medications with lipoprotein apheresis (LA). Lomitapide is an emerging therapy in HoFH, but its place in the treatment algorithm is disputed because a comparison of its long-term efficacy versus LA in reducing LDL-C burden is not available. We assessed changes in long-term LDL-C burden and goals achievement in two independent HoFH patients’ cohorts, one treated with lomitapide in Italy (n = 30) and the other with LA in France (n = 29). Results The two cohorts differed significantly for genotype (p = 0.004), baseline lipid profile (p padj = 0.004). Yearly on-treatment LDL-C padj = 0.002). A trend towards fewer total cardiovascular events was observed in the Lomitapide than in the LA cohort. Conclusions In comparison with LA, lomitapide appears to provide a better control of LDL-C in HoFH. Further studies are needed to confirm this data and establish whether this translates into a reduction of cardiovascular risk.

Published
2021

21. The Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia Variant Curation Expert Panel consensus guidelines for LDLR variant classification

Author

Tomáš Freiberger, Heather Zimmermann, Michael A. Iacocca, Lukas Tichy, Cinthia E. Jannes, Robert A. Hegele, Michal Kramarek, Alain Carrié, Alexandre C. Pereira, Sarah Leigh, Joana Rita Chora, Eric J.G. Sijbrands, Margaret Chen, Hannah Wand, Serra Kim, C. Lisa Kurtz, Tami Johnston, Amanda J. Hooper, Steve E. Humphries, Mark Trinder, Liam R. Brunham, Mafalda Bourbon, Jessica Chonis, Jian Wang, Joshua W. Knowles, Premysl Soucek, Maggie Williams, and Annette Leon

Subjects
0303 health sciences, education.field_of_study, medicine.medical_specialty, business.industry, Population, Genomics, Familial hypercholesterolemia, Computational biology, 030204 cardiovascular system & hematology, medicine.disease, Genome, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Resource (project management), medicine, Medical genetics, education, business, Mendelian disorders, 030304 developmental biology
Abstract

PurposeIn 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published consensus standardized guidelines for variant classification in Mendelian disorders. To increase accuracy and consistency, the Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia (FH) Variant Curation Expert Panel (VCEP) was tasked with optimizing the existing ACMG/AMP framework for disease-specific classification in FH. Here, we provide consensus recommendations for the most common FH-causing gene, LDLR, where >2,300 unique FH-associated variants have been identified.MethodsThe multidisciplinary FH VCEP met in person and through frequent emails and conference calls to develop LDLR-specific modifications of ACMG/AMP guidelines. Through iteration, pilot testing, debate and commentary, consensus among experts was reached.ResultsThe consensus LDLR variant modifications to existing ACMG/AMP guidelines include: 1) alteration of population frequency thresholds; 2) delineation of loss-of-function variant types; 3) functional study criteria specifications; 4) co-segregation criteria specifications; and 5) specific use and thresholds for in silico prediction tools, among others.ConclusionEstablishment of these guidelines as the new standard in the clinical laboratory setting will result in a more evidence-based, harmonized method for LDLR variant classification worldwide, thereby improving the care of FH patients.

Published
2021

22. Non-alcoholic fatty liver disease and subclinical atherosclerosis in a population affected by familial hypercholesterolemia

Author

Antonio Gallo, Alban Redheuil, Fabio Nascimbeni, A. Mondelli, Francesca Carubbi, Eric Bruckert, Philippe Giral, Valérie Carreau, D. Bonnefort-Rousselot, R. Pais, and Alain Carrié

Subjects
medicine.medical_specialty, education.field_of_study, business.industry, Fatty liver, Population, Non alcoholic, Disease, Familial hypercholesterolemia, medicine.disease, Gastroenterology, Subclinical atherosclerosis, Internal medicine, Medicine, Cardiology and Cardiovascular Medicine, business, education
Published
2021

23. Ablation of DNA-methyltransferase 3A in skeletal muscle does not affect energy metabolism or exercise capacity

Author

Brendan Deeney, Lewin Small, Rhianna C. Laker, Lars R. Ingerslev, Romain Barrès, Alain Carrié, Philippe Couvert, Ann Normann Hansen, Eleonora Manitta, Gestionnaire, Hal Sorbonne Université, IT University of Copenhagen (ITU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), IT University of Copenhagen, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Cancer Research, PROMOTER, Physiology, [SDV]Life Sciences [q-bio], QH426-470, Muscle Development, Biochemistry, DNA Methyltransferase 3A, Running, Mice, 0302 clinical medicine, Transcription (biology), Gene expression, Medicine and Health Sciences, Morphogenesis, DNA (Cytosine-5-)-Methyltransferases, Musculoskeletal System, Genetics (clinical), Mice, Knockout, 0303 health sciences, Exercise Tolerance, DNA methylation, Muscles, Cell Differentiation, Muscle Differentiation, Chromatin, Cell biology, Nucleic acids, [SDV] Life Sciences [q-bio], DIFFERENTIATION, medicine.anatomical_structure, Knockout mouse, Epigenetics, Anatomy, DNA modification, Chromatin modification, Research Article, Chromosome biology, EXPRESSION, DNA transcription, Physical exercise, Biology, 03 medical and health sciences, Physical Conditioning, Animal, medicine, Extracellular, Genetics, Animals, Humans, Muscle, Skeletal, Molecular Biology, Gene, Ecology, Evolution, Behavior and Systematics, Nutrition, 030304 developmental biology, METHYLATION PATTERNS, Biology and life sciences, Biological Locomotion, Skeletal muscle, DNA, Soleus Muscles, Diet, Skeletal Muscles, DNMT3A, OVEREXPRESSION, Energy Metabolism, 030217 neurology & neurosurgery, Developmental Biology
Abstract

In response to physical exercise and diet, skeletal muscle adapts to energetic demands through large transcriptional changes. This remodelling is associated with changes in skeletal muscle DNA methylation which may participate in the metabolic adaptation to extracellular stimuli. Yet, the mechanisms by which muscle-borne DNA methylation machinery responds to diet and exercise and impacts muscle function are unknown. Here, we investigated the function of de novo DNA methylation in fully differentiated skeletal muscle. We generated muscle-specific DNA methyltransferase 3A (DNMT3A) knockout mice (mD3AKO) and investigated the impact of DNMT3A ablation on skeletal muscle DNA methylation, exercise capacity and energy metabolism. Loss of DNMT3A reduced DNA methylation in skeletal muscle over multiple genomic contexts and altered the transcription of genes known to be influenced by DNA methylation, but did not affect exercise capacity and whole-body energy metabolism compared to wild type mice. Loss of DNMT3A did not alter skeletal muscle mitochondrial function or the transcriptional response to exercise however did influence the expression of genes involved in muscle development. These data suggest that DNMT3A does not have a large role in the function of mature skeletal muscle although a role in muscle development and differentiation is likely., Author summary Skeletal muscle is a plastic tissue able to adapt to environmental stimuli such as exercise and diet in order to respond to energetic demand. One of the ways in which skeletal muscle can rapidly react to these stimuli is DNA methylation. This is when chemical groups are attached to DNA, potentially influencing the transcription of genes. We investigated the function of DNA methylation in skeletal muscle by generating mice that lacked one of the main enzymes responsible for de novo DNA methylation, DNA methyltransferase 3A (DNMT3A), specifically in muscle. We found that loss of DNMT3A reduced DNA methylation in muscle however this did not lead to differences in exercise capacity or energy metabolism. This suggests that DNMT3a is not involved in the adaptation of skeletal muscle to diet or exercise.

Published
2021

24. Phenotypic Differences Between Polygenic and Monogenic Hypobetalipoproteinemia

Author

Sybil Charrière, Bertrand Cariou, Matthieu Pichelin, Alain Carrié, Noël Peretti, Richard Redon, Pierre Antoine Rollat-Farnier, Mathilde Di Filippo, René Valéro, Marie Marrec, Matthieu Wargny, Eléonore Divry, O. Marmontel, Edith Bigot-Corbel, X. Vanhoye, Pierre Lindenbaum, Philippe Moulin, Emmanuelle Génin, Antoine Rimbert, Dramane Coulibaly, Jean-François Deleuze, Gilles Degraef, Didier Goxe, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Hospices Civils de Lyon (HCL), Hôpital Louis Pradel [CHU - HCL], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Génomique d'Evry (IG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Caisse primaire d'assurance maladie (CPAM), Centre hospitalier universitaire de Nantes (CHU Nantes), ANR-16-RHUS-0007,CHOPIN,CHOPIN(2016), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Male, Multifactorial Inheritance, hypobetalipoproteinemias, liver diseases, [SDV]Life Sciences [q-bio], Down-Regulation, 030204 cardiovascular system & hematology, Biology, Risk Assessment, Fifth percentile, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Risk Factors, medicine, Humans, Genetic Predisposition to Disease, Retrospective Studies, 030304 developmental biology, Lipoprotein cholesterol, Genetics, 0303 health sciences, Cholesterol, cholesterol, Cholesterol, LDL, medicine.disease, Phenotype, 3. Good health, chemistry, Apolipoprotein B-100, Mutation (genetic algorithm), polygenic risk score, Female, Polygenic risk score, Hypobetalipoproteinemia, Proprotein Convertase 9, mutation, Cardiology and Cardiovascular Medicine, apolipoproteins, Biomarkers
Abstract

Objective: Primary hypobetalipoproteinemia is characterized by LDL-C (low-density lipoprotein cholesterol) concentrations below the fifth percentile. Primary hypobetalipoproteinemia mostly results from heterozygous mutations in the APOB and PCSK9 genes, and a polygenic origin is hypothesized in the remaining cases. Hypobetalipoproteinemia patients present an increased risk of nonalcoholic fatty liver disease and steatohepatitis. Here, we compared hepatic alterations between monogenic, polygenic, and primary hypobetalipoproteinemia of unknown cause. Approach and Results: Targeted next-generation sequencing was performed in a cohort of 111 patients with hypobetalipoproteinemia to assess monogenic and polygenic origins using an LDL-C-dedicated polygenic risk score. Forty patients (36%) had monogenic hypobetalipoproteinemia, 38 (34%) had polygenic hypobetalipoproteinemia, and 33 subjects (30%) had hypobetalipoproteinemia from an unknown cause. Patients with monogenic hypobetalipoproteinemia had lower LDL-C and apolipoprotein B plasma levels compared with those with polygenic hypobetalipoproteinemia. Liver function was assessed by hepatic ultrasonography and liver enzymes levels. Fifty-nine percent of patients with primary hypobetalipoproteinemia presented with liver steatosis, whereas 21% had increased alanine aminotransferase suggestive of liver injury. Monogenic hypobetalipoproteinemia was also associated with an increased prevalence of liver steatosis (81% versus 29%, P Conclusions: This study highlights the importance of genetic diagnosis in the clinical care of primary hypobetalipoproteinemia patients. It shows for the first time that a polygenic origin of hypobetalipoproteinemia is associated with a lower risk of liver steatosis and liver injury versus monogenic hypobetalipoproteinemia. Thus, polygenic risk score is a useful tool to establish a more personalized follow-up of primary hypobetalipoproteinemia patients.

Published
2021

25. Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

Author

Jie Lin, Snejana Tisheva, Ishwar C. Verma, Francesco Cipollone, Liam R. Brunham, Florentina Predica, Perla A.C. Gonzalez, Jocelyne Inamo, André R. Miserez, Belma Pojskic, Michel Farnier, Avishay Ellis, Katia Bonomo, Ibrahim Al-Zakwani, Maria Grazia Zenti, Humberto A. Lopez, Khairul Shafiq Ibrahim, Erkin M. Mirrakhimov, Alexey Meshkov, Jose P. de Moura, Muthukkaruppan Annamalai, Raul D. Santos, F. Paillard, Maria Del Ben, Jan Lacko, Miguel T. Rico, Ximena Reyes, Laura E.G. de Leon, Noor Shafina Mohd Nor, Ulrich Julius, Mohammed A. Batais, Dieter Böhm, Ta-Chen Su, Takuya Kobayashi, Magdalena Chmara, Marco Gebauer, Marcos M. Lima-Martínez, Ravshanbek D. Kurbanov, Daisaku Masuda, Amro El-Hadidy, Melanie Schüler, Francisco Fuentes, Florian J. Mayer, Helena Vaverkova, F. Ulrich Beil, Juraj Bujdak, Mario Stoll, Isabelle Ruel, Elena Dorn, Thomas M. Stulnig, Abubaker Elfatih, Rano B. Alieva, Jiri Vesely, Valérie Carreau, Cristina M. Sibaja, Sophie Béliard, Olivier Ziegler, Adriana Branchi, Daniel Schurr, G.B. John Mancini, Tai E. Shyong, Eric L.T. Siang, Mafalda Bourbon, Zerrin Yigit, Meral Kayıkçıoğlu, Jacques Genest, Wei Yu, Michal Vrablík, Shavkat U. Hoshimov, Dan Gaita, Antonio Pipolo, Ashraf H.A. AlQudaimi, Walter Speidl, Gianfranco Parati, Zaliha Ismail, Victoria M. Zubieta, René Valéro, Tomas Salek, Hana Halamkova, Gustavs Latkovskis, Nicole Allendorf-Ostwald, Agnes Perrin, Vladimir Soska, Anastasia Garoufi, Francisco Araujo, Nacu C. Portilla, Thomas Segiet, Charalambos Koumaras, Hila Knobler, Fatih Sivri, Hani Altaradi, Ivan Pećin, Long Jiang, Alexander Dressel, Marlena Woś, Jana Franekova, D. Agapakis, Quitéria Rato, Dirk J. Blom, Marcin A. Bartlomiejczyk, Krzysztof Dyrbuś, Maurizio Averna, Phivos Symeonides, Yung A. Chua, Asim Rana, András Nagy, Juan C.G. Cuellar, Alexander Jäkel, Maya Safarova, Neama Luqman, Amalia-Despoina Koutsogianni, Patrick Tounian, Jose A. Alvarez, Ada Cuevas, Corinna Richter, Sybil Charrieres, Vitaliy Zafiraki, Michalis Doumas, Angela Lux, Thanh Huong Truong, Elaine Chow, José Luis Díaz-Díaz, Jesus R.H. Almada, Sabine Füllgraf-Horst, Gustavo G. Retana, Claudio Borghi, Gianni Biolo, Ivajlo Tzvetkov, Patrícia Pais, Mehmet Akbulut, Kumiko Nagahama, Oner Ozdogan, Frank Leistikow, Jianxun He, Alexander R.M. Lyons, Poranee Ganokroj, Luis E.S. Mendia, Ann-Cathrin Koschker, Gabriela A.G. Ramirez, Dainus Gilis, Karin Balinth, José Ramiro Cruz, Paolo Calabrò, Alberico L. Catapano, Emmanouil Skalidis, Hamida Al-Barwani, Genovefa Kolovou, Carolyn S.P. Lam, Yoto Yotov, Yaacov Henkin, Gabriella Iannuzzo, Aimi Z. Razman, Alma B.M. Rodriguez, Hans Dieplinger, Darlington E. Obaseki, Ursulo J. Herrera, Arcangelo Iannuzzi, Christoph Säly, Elena Olmastroni, Francisco G. Padilla, S.A. Nazli, Ioanna Gouni-Berthold, Miriam Kozárová, Urh Groselj, Igor Shaposhnik, Lorenzo Iughetti, Nawal Rwaili, Cinthia E. Jannes, Andrea Bartuli, Mikhail Voevoda, Marat V. Ezhov, Yanyu Duan, Alper Sonmez, Mustafa Yenercag, Ariane Sultan, Natasza Gilis-Malinowska, Tavintharan Subramaniam, Mohamed Ashraf, Jing Pang, Kota Matsuki, Tao Jiang, Gerald Klose, Eduardo A.R. Rodriguez, Lucie Solcova, Riccardo Sarzani, Mahmoud Traina, Alejandra Vázquez Cárdenas, Gordon A. Francis, Adolat V. Ziyaeva, Ronen Durst, Maciej Banach, Francisco Silva, Heribert Schunkert, Børge G. Nordestgaard, Ziyou Liu, Ahmad Bakhtiar Md Radzi, Hana Rosolova, Andrea Bäßler, Abdulhalim Jamal Kinsara, Noël Peretti, Victor Gurevich, Margarita T. Tamayo, Abdullah Tuncez, Florian Höllerl, Ljubica Stosic, Jianguang Qi, Anja Kirschbaum, Jitendra P.S. Sawhney, Michael Scholl, Kausik K. Ray, Mohamed Bendary, Hapizah Nawawi, Adrienne Tarr, Barbora Nussbaumerova, B.C. Brice, Kurt Huber, Noor Alicezah Mohd Kasim, A. Rahman A. Jamal, Vaclava Palanova, Giacomo Biasucci, Pucong Ye, Eva Cubova, Roopa Mehta, Rüdiger Schweizer, Veronica Zampoleri, Jacek Jóźwiak, Alyaa Al-Khateeb, Jing Hong, Katarina Raslova, Kirsten B. Holven, Tatiana Rozkova, Reinhold Busch, Alexander Klabnik, Konrad Hein, Eloy A.Z. Carrillo, Robin Urbanek, Livia Pisciotta, Fatma Y. Coskun, Jose J.G. Garcia, Valerio Pecchioli, Azra D. Nalbantic, Weerapan Khovidhunkit, Jernej Kovac, Michaela Kadurova, Mohammed Al-Jarallah, Vita Saripo, Christos V. Rizos, Jie Peng, Ang L. Chua, Dorothee Deiss, Nor A.A. Murad, Aneta Stróżyk, See Kwok, Gökhan Alici, Gillian J. Pilcher, John J.P. Kastelein, Dmitry Duplyakov, Calin Lengher, Milena Budikova, C. Azzopardi, Christina Antza, Luis E.V. Arroyo, Khalid Al-Jumaily, Ahmad Al-Sarraf, Carlos A. Aguilar-Salinas, Erkayim Bektasheva, Arta Upena-RozeMicena, Qian Wang, Xumin Wang, Leah Leavit, Radzi Rahmat, Selim Topcu, Željko Reiner, Lorenzo Maroni, Matija Cevc, Elizabeth R. Cooremans, Masatsune Ogura, Tevfik Sabuncu, Ruy D Arjona Villicaña, Andrea Giaccari, Xuesong Fan, Auryan Szalat, Sanjaya Dissanayake, Etienne Khoury, Anja Vogt, Hermann Toplak, Alexis Baass, Isabel Palma, Gaelle Sablon, Dana A. Hay, Ya Yang, Margus Viigimaa, Erik S.G. Stroes, Dror Harats, Konstantin Krychtiuk, Zesen Liu, Aleksandra Parczewska, Yves Cottin, Yichen Qu, Mathilde Di-Fillipo, Agnieszka Konopka, Lamija Pojskic, Guadalupe J. Dominguez, Ahmet Temizhan, Roberto C. Chacon, Ibrahim E. Dural, Qiang Yong, G. Kees Hovingh, Kang Meng, Sandra Kutkiene, Julie Lemale, Reinhold Innerhofer, Alexandros D. Tselepis, Handrean Soran, Wolfgang König, Bassam Atallah, Olena Mitchenko, Jana Cepova, Eduardo M. Rodriguez, Ulrich Laufs, Norhidayah Rosman, Alena Lubasova, V. Durlach, Frederick J. Raal, Elyor Khodzhiboboev, Cristina Pederiva, Hui Yuan, Ashraf Reda, Fahad Alnouri, Konstantinos Tziomalos, Thanh T. Le, Jana Sirotiakova, Régis Hankard, Hector E.A. Cazares, Betsabel Rodriguez, Lenka Pavlickova, Assen Goudev, Julius Katzmann, Diana Boger, Wael Almahmeed, Katarina T. Podkrajsek, Sabina Zambon, Fahri Bayram, Nadia Citroni, Samir Rafla, Vincent Rigalleau, Aleksandr B. Shek, Hani Sabbour, Berenice G. Guzman, Shoshi Shpitzen, Eric Tarantino, Ahmed Bendary, Fedya Nikolov, Jean Bergeron, Stefan Kopf, Iva Rasulic, Gerald F. Watts, Muhammad I.A. Hafidz, Mehmet B. Yilmaz, Kathrin Biolik, Ira A. Haack, Robert A. Hegele, Sonia Dulong, Bartosz Wasąg, Osama Sanad, Susana Correia, Zhenjia Wang, Dana Biedermann, Christel König, Helena Podzimkova, Ihab Daoud, Mohammad Alghamdi, Dražen Perica, László Márk, Iosif Koutagiar, Volkan Dogan, Vladimir Blaha, Chandrashekhar K. Ponde, Katerina Valoskova, Amer A. Jabbar, Azhari Rosman, Sazzli Kasim, Mesut Demir, Ulugbek I. Nizamov, Aldo Ferreira-Hermosillo, Dilek Yesilbursa, Atef Elbahry, Arshad Abdulrasheed, Omer A. Elamin, Vasileios Athyros, Joanna Lewek, Gergely Nagy, Ursula Kassner, Jian Jiao, Klaus G. Parhofer, Charlotte Nzeyimana, Marcin Pajkowski, Stanislav Zemek, Jose J.C. Macías, Cornelius Müller, G. Sfikas, Leopoldo Pérez de Isla, Yulia Ragino, Fahad Al-Zadjali, Abdul Rais Sanusi, Anna Rita Roscini, Jean Ferrières, Selim Jambart, Jean Pierre Rabes, Laura Schreier, Hofit Cohen, Olivier S. Descamps, N. Lalic, Christine Stumpp, Antonio J. Vallejo-Vaz, Jutta Christmann, Manuela Casula, Mariko Harada-Shiba, Olga Lunegova, Ewa Starostecka, Nicolas D. Oca, Alain Carrié, Achilleas Attilakos, Savas Ozer, Andreea Dumitrescu, Jürgen Merke, Urte Aliosaitiene, Evangelos Liberopoulos, Manuel O. De los Rios Ibarra, Maria J. Virtuoso, Alessandro Lupi, Panagiotis Anagnostis, Ruth Agar, Dorota Ferrieres, George Liamis, José Eduardo Krieger, Mariann Harangi, Fouzia Sadiq, Francois Schiele, Saif Kamal, Mária Audikovszky, Peter Baumgartner, Marta Gazzotti, Daniel Gaudet, Ashanty F. Ortega, Marcin Gruchała, Philippe Moulin, Ljiljana Popovic, Luca Bonanni, E. Kiouri, Mika Hori, Chiara Trenti, Elena Repetti, Carlo Sabbà, Sophie Bernard, Alejandro R. Zazueta, Mirac Vural, Jesus R. Gonzalez, C. Stevens, Francesca Carubbi, Wenhui Wen, Sabri Demircan, Kanika I. Dharmayat, Anne Tybjærg-Hansen, Elizabete Terauda, Claudia Zemmrich, Alphonsus Isara, Fabiola L. Sobrevilla, Anell Hernandez Garcia, Ibrahim Sisic, Justin T. I-Shing, Yvonne Winhofer-Stöckl, Luya Wang, Manfred Mayer, Mohanad Al-ageedi, Judith Wiener, Mohammed Al-Kindi, Anis Safura Ramli, Yan Chen, Denis Angoulvant, Aytekin Oguz, K.H. Wolmarans, Claudio Ferri, Tomáš Freiberger, Lubomira Cermakova, Julieta D.M. Portano, Pierre Henri Ducluzeau, Katerina Vonaskova, Levent H. Can, Mario H.F. Andrade, György Paragh, C. Ebenbichler, Karina J.A. Rivera, Alia Khudari, Elisabeth Steinhagen-Thiessen, Ana C. Alves, Victoria Korneva, Sandra Singh, Georgia Anastasiou, Nur S. Hamzan, Massimo Federici, Lale Tokgozoglu, Hector G. Alcala, Oana Moldovan, Giuseppe Mandraffino, Swarup A.V. Shah, Lukas Burda, Ersel Onrat, Manuel de los Reyes Barrera Bustillo, Mirjana Radovic, Arman Postadzhiyan, Nien-Tzu Chang, Aylin Yildirir, Martin Mäser, Bruno Fink, Svetlana Mosteoru, Ulrike Schatz, Luis A.V. Talavera, Magdalena Dusejovska, Richard Ceska, Faisal A. Al-Allaf, T.F. Ashavaid, Gereon Böll, Sona Machacova, Gonzalo C. Vargas, Antonio Gallo, Elina Pantchechnikova, Lukas Tichy, Gersina Rega-Kaun, Moses Elisaf, Branislav Vohnout, Antonio Bossi, Suad Al-Mukhaini, Natasa Rajkovic, Ursa Sustar, Merih Kutlu, Mohamed Sobhy, Britta Otte, Ana M. Medeiros, Borut Jug, Patrick Couture, Rodrigo Alonso, Wolfgang Seeger, Guzal J. Abdullaeva, Ahmet Celik, Nasreen Al-Sayed, Béla Benczúr, Petra E. Khoury, Rafezah Razali, Ma L.R. Osorio, Ruiying Zhang, Monica M.N. Usme, Humberto Garcia Aguilar, Ceyhun Ceyhan, Antje Spens, Christoph J. Binder, Volker Schrader, Terrance C.S. Jin, Neftali E.A. Villa, Aleksandra Michalska-Grzonkowska, Francesco Purrello, Marshima M. Rosli, Vincent Maher, Dilshad Rasul, Ines Colaço, Ornella Guardamagna, Giuliana Mombelli, Khalid F. AlHabib, Fahmi Alkaf, Marianne Benn, Youmna Ghaleb, Arsenio V. Vazquez, Lakshmi L. Reddy, Salih Kilic, Siti Hamimah Sheikh Abdul Kadir, E. Bilianou, Rossella Marcucci, Sandro Muntoni, Kurt Widhalm, Evangelos A. Zacharis, Kuznetsova T. Yu, Eric Bruckert, Antonia Sonntag, Katerina Rehouskova, Josè Pablo Werba, Leobardo Sauque-Reyna, Myra Tilney, Dov Gavishv, A.M. Fiorenza, Zdenka Krejsova, Hong A. Le, Andrey V. Susekov, Isabel Klein, Mai N.T. Nguyen, Andrejs Erglis, Muge Ildizli, Diane Brisson, Salmi Razali, Winfried März, Ovidio Muñiz-Grijalvo, Justyna Borowiec-Wolna, Ingrid Buganova, Ngoc T. Kim, Yue Wu, István Reiber, Jose C.A. Martinez, Pavel Malina, Sandy Elbitar, Stephan Matthias, Ali F. Abdalsahib, Zlatko Fras, Wilson E Sadoh, Lucas Kleemann, Tayfun Sahin, Martin P. Bogsrud, Fabio Pellegatta, Mohamed A. Shafy, Yuntao Li, Martine Paquette, Zuhier Awan, Arturo Pujia, Xiantao Song, Renata Cifkova, Alexandre C. Pereira, Ioannis Skoumas, Roman Cibulka, Tadej Battelino, Mariusz Gąsior, Ghada Kazamel, Lahore S.U. Shah, Eran Leitersdorf, Niki Katsiki, Daniel Elías-López, Khalid Al-Rasadi, Grete Talviste, Sarka Mala, Rocio M. Alvarado, Pavel Kraml, Gerret Paulsen, Angelina Passaro, Zsolt Karányi, Carine Ayoub, Vera Adamkova, Ivo Petrov, Turky H. Almigbal, Rohana Abdul Ghani, Franck Boccara, Brian W. McCrindle, François Martin, Jamshed J. Dalal, Shitong Cheng, Khalid Al-Waili, Chaoyi Zhang, Ramon M. Prado, Lubica Cibickova, Lubomira Fabryova, Tobias Wiesner, Thuhairah Hasrah Abdul Rahman, Tan J. Le, Marcello Arca, Sabine Scholl-Bürgi, Juan R. Saucedo, Georgijs Nesterovics, Carla V.M. Valencia, Alexander Stadelmann, Vasileios Kotsis, Lina Badimon, Shizuya Yamashita, Jose C.M. Oyervides, Lay K. Teh, Susanne Greber-Platzer, Marianne Abifadel, Ruta Meiere, Wibke Reinhard, Pablo Corral, Nina Schmidt, Alain Pradignac, A. David Marais, Marta Jordanova, Marzena Romanowska-Kocejko, Johannes Scholl, Brian Tomlinson, Laura G.G. Herrera, Loukianos S. Rallidis, Pedro Mata, Sameh Emil, Matej Mlinaric, Emile Ferrari, Suraya Abdul Razak, Alexandra Ershova, Andrie G. Panayiotou, Alinna Y.R. Garcia, Kairat Davletov, Katarina Lalic, Doan L. Do, Krzysztof Chlebus, Ricardo A. Carrera, Daniel I.P. Vazquez, Nikolaos Sakkas, Liyuan Xu, Mays Altaey, Aysa Hacioglu, Alexandro J. Martagon, Marta Żarczyńska-Buchowiecka, Michael Schömig, Jürgen Homberger, Andrea Benso, Bertrand Cariou, Ardon Rubinstein, Omer Gedikli, Emre Durakoglugil, Mei Chong, Bahadir Kirilmaz, Suhaila Abd Muid, Jose M. Salgado, Berenice P. Aparicio, Mutaz Alkhnifsawi, Bruno Vergès, Cécile Yelnik, Goreti Lobarinhas, Zaneta Petrulioniene, Sylvia Asenjo, Aytul B. Yildirim, László Bajnok, Vallejo-Vaz A.J., Stevens C.A.T., Lyons A.R.M., Dharmayat K.I., Freiberger T., Hovingh G.K., Mata P., Raal F.J., Santos R.D., Soran H., Watts G.F., Abifadel M., Aguilar-Salinas C.A., Alhabib K.F., Alkhnifsawi M., Almahmeed W., Alnouri F., Alonso R., Al-Rasadi K., Al-Sarraf A., Al-Sayed N., Araujo F., Ashavaid T.F., Banach M., Beliard S., Benn M., Binder C.J., Bogsrud M.P., Bourbon M., Chlebus K., Corral P., Davletov K., Descamps O.S., Durst R., Ezhov M., Gaita D., Genest J., Groselj U., Harada-Shiba M., Holven K.B., Kayikcioglu M., Khovidhunkit W., Lalic K., Latkovskis G., Laufs U., Liberopoulos E., Lima-Martinez M.M., Lin J., Maher V., Marais A.D., Marz W., Mirrakhimov E., Miserez A.R., Mitchenko O., Nawawi H., Nordestgaard B.G., Panayiotou A.G., Paragh G., Petrulioniene Z., Pojskic B., Postadzhiyan A., Raslova K., Reda A., Reiner, Sadiq F., Sadoh W.E., Schunkert H., Shek A.B., Stoll M., Stroes E., Su T.-C., Subramaniam T., Susekov A.V., Tilney M., Tomlinson 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Jiao J., Wu Y., Wen W., Xu L., Zhang R., Qu Y., He J., Fan X., Wang Z., Chow E., Pecin I., Perica D., Symeonides P., Vrablik M., Ceska R., Soska V., Tichy L., Adamkova V., Franekova J., Cifkova R., Kraml P., Vonaskova K., Cepova J., Dusejovska M., Pavlickova L., Blaha V., Rosolova H., Nussbaumerova B., Cibulka R., Vaverkova H., Cibickova L., Krejsova Z., Rehouskova K., Malina P., Budikova M., Palanova V., Solcova L., Lubasova A., Podzimkova H., Bujdak J., Vesely J., Jordanova M., Salek T., Urbanek R., Zemek S., Lacko J., Halamkova H., Machacova S., Mala S., Cubova E., Valoskova K., Burda L., Bendary A., Daoud I., Emil S., Elbahry A., Rafla S., Sanad O., Kazamel G., Ashraf M., Sobhy M., El-Hadidy A., Shafy M.A., Kamal S., Bendary M., Talviste G., Angoulvant D., Boccara F., Cariou B., Carreau V., Carrie A., Charrieres S., Cottin Y., Di-Fillipo M., Ducluzeau P.H., Dulong S., Durlach V., Farnier M., Ferrari E., Ferrieres D., Ferrieres J., Gallo A., hankard R., Inamo J., Lemale J., Moulin P., Paillard F., Peretti N., Perrin A., Pradignac A., Rabes J.P., Rigalleau V., Sultan A., Schiele F., Tounian P., Valero R., Verges B., Yelnik C., Ziegler O., Haack I.A., Schmidt N., Dressel A., Klein I., Christmann J., Sonntag A., Stumpp C., Boger D., Biedermann D., Usme M.M.N., Beil F.U., Klose G., Konig C., Gouni-Berthold I., Otte B., Boll G., Kirschbaum A., Merke J., Scholl J., Segiet T., Gebauer M., Predica F., Mayer M., Leistikow F., Fullgraf-Horst S., Muller C., Schuler M., Wiener J., Hein K., Baumgartner P., Kopf S., Busch R., Schomig M., Matthias S., Allendorf-Ostwald N., Fink B., Bohm D., Jakel A., Koschker A.-C., Schweizer R., Vogt A., Parhofer K., Konig W., Reinhard W., Bassler A., Stadelmann A., Schrader V., Katzmann J., Tarr A., Steinhagen-Thiessen E., Kassner U., Paulsen G., Homberger J., Zemmrich C., Seeger W., Biolik K., Deiss D., Richter C., Pantchechnikova E., Dorn E., Schatz U., Julius U., Spens A., Wiesner T., Scholl M., Rizos C.V., Sakkas N., Elisaf M., Skoumas I., Tziomalos K., Rallidis L., Kotsis V., Doumas M., Athyros V., Skalidis E., Kolovou G., Garoufi A., Bilianou E., Koutagiar I., Agapakis D., Kiouri E., Antza C., Katsiki N., Zacharis E., Attilakos A., Sfikas G., Koumaras C., Anagnostis P., Anastasiou G., Liamis G., Koutsogianni A.-D., Karanyi Z., Harangi M., Bajnok L., Audikovszky M., Mark L., Benczur B., Reiber I., Nagy G., Nagy A., Reddy L.L., Shah S.A.V., Ponde C.K., Dalal J.J., Sawhney J.P.S., Verma I.C., Altaey M., Al-Jumaily K., Rasul D., Abdalsahib A.F., Jabbar A.A., Al-ageedi M., Agar R., Cohen H., Ellis A., Gavishv D., Harats D., Henkin Y., Knobler H., Leavit L., Leitersdorf E., Rubinstein A., Schurr D., Shpitzen S., Szalat A., Casula M., Zampoleri V., Gazzotti M., Olmastroni E., Sarzani R., Ferri C., Repetti E., Sabba C., Bossi A.C., Borghi C., Muntoni S., Cipollone F., Purrello F., Pujia A., Passaro A., Marcucci R., Pecchioli V., Pisciotta L., Mandraffino G., Pellegatta F., Mombelli G., Branchi A., Fiorenza A.M., Pederiva 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B., Stoll, M., Stroes, E., Su, T. -C., Subramaniam, T., Susekov, A. V., Tilney, M., Tomlinson, B., Truong, T. H., Tselepis, A. D., Tybjaerg-Hansen, A., Vazquez Cardenas, A., Viigimaa, M., Wang, L., Yamashita, S., Kastelein, J. J. P., Bruckert, E., Vohnout, B., Schreier, L., Pang, J., Ebenbichler, C., Dieplinger, H., Innerhofer, R., Winhofer-Stockl, Y., Greber-Platzer, S., Krychtiuk, K., Speidl, W., Toplak, H., Widhalm, K., Stulnig, T., Huber, K., Hollerl, F., Rega-Kaun, G., Kleemann, L., Maser, M., Scholl-Burgi, S., Saly, C., Mayer, F. J., Sablon, G., Tarantino, E., Nzeyimana, C., Pojskic, L., Sisic, I., Nalbantic, A. D., Jannes, C. E., Pereira, A. C., Krieger, J. E., Petrov, I., Goudev, A., Nikolov, F., Tisheva, S., Yotov, Y., Tzvetkov, I., Baass, A., Bergeron, J., Bernard, S., Brisson, D., Brunham, L. R., Cermakova, L., Couture, P., Francis, G. A., Gaudet, D., Hegele, R. A., Khoury, E., Mancini, G. B. J., Mccrindle, B. W., Paquette, M., Ruel, I., Cuevas, A., Asenjo, S., Wang, X., Meng, K., Song, X., Yong, Q., Jiang, T., Liu, Z., Duan, Y., Hong, J., Ye, P., Chen, Y., Qi, J., Li, Y., Zhang, C., Peng, J., Yang, Y., Yu, W., Wang, Q., Yuan, H., Cheng, S., Jiang, L., Chong, M., Jiao, J., Wu, Y., Wen, W., Xu, L., Zhang, R., Qu, Y., He, J., Fan, X., Wang, Z., Chow, E., Pecin, I., Perica, D., Symeonides, P., Vrablik, M., Ceska, R., Soska, V., Tichy, L., Adamkova, V., Franekova, J., Cifkova, R., Kraml, P., Vonaskova, K., Cepova, J., Dusejovska, M., Pavlickova, L., Blaha, V., Rosolova, H., Nussbaumerova, B., Cibulka, R., Vaverkova, H., Cibickova, L., Krejsova, Z., Rehouskova, K., Malina, P., Budikova, M., Palanova, V., Solcova, L., Lubasova, A., Podzimkova, H., Bujdak, J., Vesely, J., Jordanova, M., Salek, T., Urbanek, R., Zemek, S., Lacko, J., Halamkova, H., Machacova, S., Mala, S., Cubova, E., Valoskova, K., Burda, L., Bendary, A., Daoud, I., Emil, S., Elbahry, A., Rafla, S., Sanad, O., Kazamel, G., Ashraf, M., Sobhy, M., El-Hadidy, A., Shafy, M. A., Kamal, S., Bendary, M., Talviste, G., Angoulvant, D., Boccara, F., Cariou, B., Carreau, V., Carrie, A., Charrieres, S., Cottin, Y., Di-Fillipo, M., Ducluzeau, P. H., Dulong, S., Durlach, V., Farnier, M., Ferrari, E., Ferrieres, D., Ferrieres, J., Gallo, A., Hankard, R., Inamo, J., Lemale, J., Moulin, P., Paillard, F., Peretti, N., Perrin, A., Pradignac, A., Rabes, J. P., Rigalleau, V., Sultan, A., Schiele, F., Tounian, P., Valero, R., Verges, B., Yelnik, C., Ziegler, O., Haack, I. A., Schmidt, N., Dressel, A., Klein, I., Christmann, J., Sonntag, A., Stumpp, C., Boger, D., Biedermann, D., Usme, M. M. N., Beil, F. U., Klose, G., Konig, C., Gouni-Berthold, I., Otte, B., Boll, G., Kirschbaum, A., Merke, J., Scholl, J., Segiet, T., Gebauer, M., Predica, F., Mayer, M., Leistikow, F., Fullgraf-Horst, S., Muller, C., Schuler, M., Wiener, J., Hein, K., Baumgartner, P., Kopf, S., Busch, R., Schomig, M., Matthias, S., Allendorf-Ostwald, N., Fink, B., Bohm, D., Jakel, A., Koschker, A. -C., Schweizer, R., Vogt, A., Parhofer, K., Konig, W., Reinhard, W., Bassler, A., Stadelmann, A., Schrader, V., Katzmann, J., Tarr, A., Steinhagen-Thiessen, E., Kassner, U., Paulsen, G., Homberger, J., Zemmrich, C., Seeger, W., Biolik, K., Deiss, D., Richter, C., Pantchechnikova, E., Dorn, E., Schatz, U., Julius, U., Spens, A., Wiesner, T., Scholl, M., Rizos, C. V., Sakkas, N., Elisaf, M., Skoumas, I., Tziomalos, K., Rallidis, L., Kotsis, V., Doumas, M., Athyros, V., Skalidis, E., Kolovou, G., Garoufi, A., Bilianou, E., Koutagiar, I., Agapakis, D., Kiouri, E., Antza, C., Katsiki, N., Zacharis, E., Attilakos, A., Sfikas, G., Koumaras, C., Anagnostis, P., Anastasiou, G., Liamis, G., Koutsogianni, A. -D., Karanyi, Z., Harangi, M., Bajnok, L., Audikovszky, M., Mark, L., Benczur, B., Reiber, I., Nagy, G., Nagy, A., Reddy, L. L., Shah, S. A. V., Ponde, C. K., Dalal, J. J., Sawhney, J. P. S., Verma, I. C., Altaey, M., Al-Jumaily, K., Rasul, D., Abdalsahib, A. F., Jabbar, A. A., Al-ageedi, M., Agar, R., Cohen, H., Ellis, A., Gavishv, D., Harats, D., Henkin, Y., Knobler, H., Leavit, L., Leitersdorf, E., Rubinstein, A., Schurr, D., Shpitzen, S., Szalat, A., Casula, M., Zampoleri, V., Gazzotti, M., Olmastroni, E., Sarzani, R., Ferri, C., Repetti, E., Sabba, C., Bossi, A. C., Borghi, C., Muntoni, S., Cipollone, F., Purrello, F., Pujia, A., Passaro, A., Marcucci, R., Pecchioli, V., Pisciotta, L., Mandraffino, G., Pellegatta, F., Mombelli, G., Branchi, A., Fiorenza, A. M., Pederiva, C., Werba, J. P., Parati, G., Carubbi, F., Iughetti, L., Iannuzzi, A., Iannuzzo, G., Calabro, P., Averna, M., Biasucci, G., Zambon, S., Roscini, A. R., Trenti, C., Arca, M., Federici, M., Del Ben, M., Bartuli, A., Giaccari, A., Pipolo, A., Citroni, N., Guardamagna, O., Bonomo, K., Benso, A., Biolo, G., Maroni, L., Lupi, A., Bonanni, L., Zenti, M. G., Matsuki, K., Hori, M., Ogura, M., Masuda, D., Kobayashi, T., Nagahama, K., Al-Jarallah, M., Radovic, M., Lunegova, O., Bektasheva, E., Khodzhiboboev, E., Erglis, A., Gilis, D., Nesterovics, G., Saripo, V., Meiere, R., Upena-RozeMicena, A., Terauda, E., Jambart, S., Khoury, P. E., Elbitar, S., Ayoub, C., Ghaleb, Y., Aliosaitiene, U., Kutkiene, S., Kasim, N. A. M., Nor, N. S. M., Ramli, A. S., Razak, S. A., Al-Khateeb, A., Kadir, S. H. S. A., Muid, S. A., Rahman, T. A., Kasim, S. S., Radzi, A. B. M., Ibrahim, K. S., Razali, S., Ismail, Z., Ghani, R. A., Hafidz, M. I. A., Chua, A. L., Rosli, M. M., Annamalai, M., Teh, L. K., Razali, R., Chua, Y. A., Rosman, A., Sanusi, A. R., Murad, N. A. A., Jamal, A. R. A., Nazli, S. A., Razman, A. Z., Rosman, N., Rahmat, R., Hamzan, N. S., Azzopardi, C., Mehta, R., Martagon, A. J., Ramirez, G. A. G., Villa, N. E. A., Vazquez, A. V., Elias-Lopez, D., Retana, G. G., Rodriguez, B., Macias, J. J. C., Zazueta, A. R., Alvarado, R. M., Portano, J. D. M., Lopez, H. A., Sauque-Reyna, L., Herrera, L. G. G., Mendia, L. E. S., Aguilar, H. G., Cooremans, E. R., Aparicio, B. P., Zubieta, V. M., Gonzalez, P. A. C., Ferreira-Hermosillo, A., Portilla, N. C., Dominguez, G. J., Garcia, A. Y. R., Cazares, H. E. A., Gonzalez, J. R., Valencia, C. V. M., Padilla, F. G., Prado, R. M., De los Rios Ibarra, M. O., Villicana, R. D. A., Rivera, K. J. A., Carrera, R. A., Alvarez, J. A., Martinez, J. C. A., de los Reyes Barrera Bustillo, M., Vargas, G. C., Chacon, R. C., Andrade, M. H. F., Ortega, A. F., Alcala, H. G., de Leon, L. E. G., Guzman, B. G., Garcia, J. J. G., Cuellar, J. C. G., Cruz, J. R. G., Garcia, A. H., Almada, J. R. H., Herrera, U. J., Sobrevilla, F. L., Rodriguez, E. M., Sibaja, C. M., Rodriguez, A. B. M., Oyervides, J. C. M., Vazquez, D. I. P., Rodriguez, E. A. R., Osorio, M. L. R., Saucedo, J. R., Tamayo, M. T., Talavera, L. A. V., Arroyo, L. E. V., Carrillo, E. A. Z., Isara, A., Obaseki, D. E., Al-Waili, K., Al-Zadjali, F., Al-Zakwani, I., Al-Kindi, M., Al-Mukhaini, S., Al-Barwani, H., Rana, A., Shah, L. S. U., Starostecka, E., Konopka, A., Lewek, J., Bartlomiejczyk, M., Gasior, M., Dyrbus, K., Jozwiak, J., Gruchala, M., Pajkowski, M., Romanowska-Kocejko, M., Zarczynska-Buchowiecka, M., Chmara, M., Wasag, B., Parczewska, A., Gilis-Malinowska, N., Borowiec-Wolna, J., Strozyk, A., Wos, M., Michalska-Grzonkowska, A., Medeiros, A. M., Alves, A. C., Silva, F., Lobarinhas, G., Palma, I., de Moura, J. P., Rico, M. T., Rato, Q., Pais, P., Correia, S., Moldovan, O., Virtuoso, M. J., Salgado, J. M., Colaco, I., Dumitrescu, A., Lengher, C., Mosteoru, S., Meshkov, A., Ershova, A., Rozkova, T., Korneva, V., Yu, K. T., Zafiraki, V., Voevoda, M., Gurevich, V., Duplyakov, D., Ragino, Y., Safarova, M., Shaposhnik, I., Alkaf, F., Khudari, A., Rwaili, N., Al-Allaf, F., Alghamdi, M., Batais, M. A., Almigbal, T. H., Kinsara, A., Alqudaimi, A. H. A., Awan, Z., Elamin, O. A., Altaradi, H., Rajkovic, N., Popovic, L., Singh, S., Stosic, L., Rasulic, I., Lalic, N. M., Lam, C., Le, T. J., Siang, E. L. T., Dissanayake, S., I-Shing, J. T., Shyong, T. E., Jin, T. C. S., Balinth, K., Buganova, I., Fabryova, L., Kadurova, M., Klabnik, A., Kozarova, M., Sirotiakova, J., Battelino, T., Kovac, J., Mlinaric, M., Sustar, U., Podkrajsek, K. T., Fras, Z., Jug, B., Cevc, M., Pilcher, G. J., Blom, D. J., Wolmarans, K. H., Brice, B. C., Muniz-Grijalvo, O., Diaz-Diaz, J. L., de Isla, L. P., Fuentes, F., Badimon, L., Martin, F., Lux, A., Chang, N. -T., Ganokroj, P., Akbulut, M., Alici, G., Bayram, F., Can, L. H., Celik, A., Ceyhan, C., Coskun, F. Y., Demir, M., Demircan, S., Dogan, V., Durakoglugil, E., Dural, I. E., Gedikli, O., Hacioglu, A., Ildizli, M., Kilic, S., Kirilmaz, B., Kutlu, M., Oguz, A., Ozdogan, O., Onrat, E., Ozer, S., Sabuncu, T., Sahin, T., Sivri, F., Sonmez, A., Temizhan, A., Topcu, S., Tuncez, A., Vural, M., Yenercag, M., Yesilbursa, D., Yigit, Z., Yildirim, A. B., Yildirir, A., Yilmaz, M. B., Atallah, B., Traina, M., Sabbour, H., Hay, D. A., Luqman, N., Elfatih, A., Abdulrasheed, A., Kwok, S., Oca, N. D., Reyes, X., Alieva, R. B., Kurbanov, R. D., Hoshimov, S. U., Nizamov, U. I., Ziyaeva, A. V., Abdullaeva, G. J., Do, D. L., Nguyen, M. N. T., Kim, N. T., Le, T. T., Le, H. A., Tokgozoglu, L., Catapano, A. L., Ray, K. K., and EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC), Borghi C

Subjects
Male, Settore MED/09 - Medicina Interna, Arterial disease, Cross-sectional study, Adult population, Coronary Disease, Disease, Global Health, Medical and Health Sciences, Doenças Cardio e Cérebro-vasculares, Anticholesteremic Agent, Monoclonal, Prevalence, Registries, Familial Hypercholesterolemia, Humanized, Stroke, 11 Medical and Health Sciences, LS2_9, Studies Collaboration, Anticholesteremic Agents, General Medicine, Heart Disease Risk Factor, Middle Aged, FHSC global registry data, Europe, Treatment Outcome, Lower prevalence, Guidance, lipids (amino acids, peptides, and proteins), Female, Proprotein Convertase 9, Familial hypercholesterolaemia, Life Sciences & Biomedicine, Human, Adult, medicine.medical_specialty, Combination therapy, FHSC global registry, heterozygous familial hypercholesterolaemia, Cardiovascular risk factors, Antibodies, Monoclonal, Humanized, Insights, Antibodies, NO, Hyperlipoproteinemia Type II, Clinician, Medicine, General & Internal, Internal medicine, General & Internal Medicine, Health Sciences, medicine, Humans, EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC), Cross-Sectional Studie, Science & Technology, Global Perspective, business.industry, Cholesterol, LDL, medicine.disease, Cross-Sectional Studies, Heart Disease Risk Factors, Hydroxymethylglutaryl-CoA Reductase Inhibitor, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business
Abstract

Background The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally. Methods Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Data were assessed overall and by WHO regions, sex, and index versus non-index cases. Findings Of the 61 612 individuals in the registry, 42 167 adults (21 999 [53.6%] women) from 56 countries were included in the study. Of these, 31 798 (75.4%) were diagnosed with the Dutch Lipid Clinic Network criteria, and 35 490 (84.2%) were from the WHO region of Europe. Median age of participants at entry in the registry was 46.2 years (IQR 34.3-58.0); median age at diagnosis of familial hypercholesterolaemia was 44.4 years (32.5-56.5), with 40.2% of participants younger than 40 years when diagnosed. Prevalence of cardiovascular risk factors increased progressively with age and varied by WHO region. Prevalence of coronary disease was 17.4% (2.1% for stroke and 5.2% for peripheral artery disease), increasing with concentrations of untreated LDL cholesterol, and was about two times lower in women than in men. Among patients receiving lipid-lowering medications, 16 803 (81.1%) were receiving statins and 3691 (21.2%) were on combination therapy, with greater use of more potent lipid-lowering medication in men than in women. Median LDL cholesterol was 5.43 mmol/L (IQR 4.32-6.72) among patients not taking lipid-lowering medications and 4.23 mmol/L (3.20-5.66) among those taking them. Among patients taking lipid-lowering medications, 2.7% had LDL cholesterol lower than 1.8 mmol/L; the use of combination therapy, particularly with three drugs and with proprotein convertase subtilisin-kexin type 9 inhibitors, was associated with a higher proportion and greater odds of having LDL cholesterol lower than 1.8 mmol/L. Compared with index cases, patients who were non-index cases were younger, with lower LDL cholesterol and lower prevalence of cardiovascular risk factors and cardiovascular diseases (all p, Pfizer Independent Grant for Learning Change [16157823]; Amgen; Merck Sharp Dohme; Sanofi-Aventis; Daiichi Sankyo; Regeneron; National Institute for Health Research (NIHR) Imperial Biomedical Research Centre, UK; NIHR; Czech Ministry of Health [NU20-02-00261]; Canadian Institutes of Health Research; Austrian Heart Foundation; Tyrolean Regional Government; Gulf Heart Association, The EAS FHSC is an academic initiative that has received funding from a Pfizer Independent Grant for Learning & Change 2014 (16157823) and from investigator-initiated research grants to the European Atherosclerosis Society-Imperial College London from Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daiichi Sankyo, and Regeneron. KKR acknowledges support from the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre, UK. KID acknowledges support from a PhD Studentship from NIHR under the Applied Health Research programme for Northwest London, UK (the views expressed in this publication are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health). TF was supported by a grant from the Czech Ministry of Health (NU20-02-00261). JG receives support from the Canadian Institutes of Health Research. The Austrian Familial Hypercholesterolaemia registry has been supported by funds from the Austrian Heart Foundation and the Tyrolean Regional Government. The Gulf Familial Hypercholesterolaemia registry was done under the auspices of the Gulf Heart Association.

Published
2021

26. LDL-apheresis as an alternate method for plasma LPS purification in healthy volunteers, dyslipidemic and septic patients

Author

Randa Bittar, Samir Saheb, Alain Carrié, Thomas Gautier, Isabelle Fournel, Jean-Paul Pais de Barros, Wilfried Le Goff, David Masson, Anne Laure Rerole, Laurent Lagrost, Jean-Pierre Quenot, Hélène Choubley, and Auguste Dargent

Subjects
Lipopolysaccharide, business.industry, Septic shock, medicine.medical_treatment, Familial hypercholesterolemia, Pharmacology, medicine.disease, Hemoperfusion, Sepsis, chemistry.chemical_compound, chemistry, LDL apheresis, Bacteremia, medicine, lipids (amino acids, peptides, and proteins), business, Polymyxin B, medicine.drug
Abstract

Lipopolysaccharide (LPS) is a key player for innate immunity activation. It is therefore a prime target for sepsis treatment, as antibiotics are not sufficient to improve outcome during septic shock. Extracorporeal removal method by polymyxin B hemoperfusion (PMX-DHP) is used in Japan, but recent trials failed to show a significant lowering of circulating LPS levels after PMX-DHP therapy. PMX-DHP has a direct effect on LPS molecules. However, LPS is not present in a free form in the circulation, as it is mainly carried by lipoproteins, including low density lipoproteins (LDL). Lipoproteins are critical for physiological LPS clearance, as LPS are carried by low density lipoproteins (LDL) to the liver for elimination. We hypothesized that LDL-apheresis can be an alternate method for LPS removal. We demonstrated first in vitro that LDL apheresis microbeads are almost as efficient as PMX beads to reduce LPS concentration in LPS-spiked human plasma, whereas it is not active in phosphate-buffered saline. We found that PMX was also adsorbing lipoproteins, although less specifically. Then, we found that endogenous LPS of patients treated by LDL-apheresis for familial hypercholesterolemia is also removed during their LDL-apheresis sessions, both with electrostatic-based devices and filtration devices. Finally, LPS circulating in the plasma of septic shock and severe sepsis patients with gram-negative bacteremia was also removed in vitro by LDL adsorption. Overall, these results underline the importance of lipoproteins for LPS clearance, making them a prime target to study and treat endotoxemia-related conditions.

Published
2020

27. Specification of ACMG/AMP guidelines for standardized variant interpretation in familial hypercholesterolemia: On behalf of the ClinGen FH Variant Curation Expert Panel

Author

Annette Leon, Marina Cuchel, Eric J.G. Sijbrands, Heather Zimmermann, Liam R. Brunham, M. Bourbon, Jian Wang, Alain Carrié, Steve E. Humphries, A.C. Alves, Maggie Williams, Pedro Mata, Robert A. Hegele, Josh Knowles, Joep C. Defesche, Iftikhar J. Kullo, Joana Rita Chora, Raul D. Santos, Hannah Wand, C.L. Kurtz, Lukas Tichy, Michael A. Iacocca, and Tomáš Freiberger

Subjects
business.industry, Interpretation (philosophy), medicine, lipids (amino acids, peptides, and proteins), Familial hypercholesterolemia, Familial Hypercholesterolemia, Guidelines, Cardiology and Cardiovascular Medicine, Bioinformatics, medicine.disease, business, Doenças Cardio e Cérebro-vasculares
Abstract

Familial Hypercholesterolemia (FH): Lipid metabolism autosomal dominant condition; Patients present elevated low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) values since childhood → increased risk of atherosclerotic cardiovascular disease; High heterozygote prevalence (1/250); Homozygous rare (1/1 000 000); Caused by pathogenic variants in LDLR (>90%), APOB (5-10%) and PCSK9 (1-3%) genes. N/A

Published
2020

28. SAFEHEART risk-equation and cholesterol-year-score are powerful predictors of cardiovascular events in French patients with familial hypercholesterolemia

Author

Antonio Gallo, Sybil Charriere, Alexandre Vimont, M. John Chapman, Denis Angoulvant, Franck Boccara, Bertrand Cariou, Valérie Carreau, Alain Carrié, Eric Bruckert, Sophie Béliard, Sophie Beliard, Alain Carrie, Yves Cottin, Mathilde DI. Filippo, Sonia Dulong, Vincent Durlach, Michel Farnier, Emile Ferrari, Dorota Ferrieres, Jean Ferrieres, Philippe Giral, Sophie Gonbert, Regis Hankard, Jocelyn Inamo, Olga Kalmykova, Michel Krempf, Philippe Moulin, François Paillard, Noel Peretti, Agnes Perrin, Jean Pierre Rabes, Ariane Sultan, Patrick Tounian, René Valero, Bruno Verges, Cecile Yelnik, Olivier Ziegler, Inserm UMR1069, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire catalyse et spectrochimie (LCS), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Cardiologie (CHU Trousseau, Tours), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'endocrinologie-métabolisme [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), CHU Pitié-Salpêtrière [AP-HP], Station d'Amélioration Génétique des Animaux (SAGA), Institut National de la Recherche Agronomique (INRA), Centre Hospitalier Universitaire de Lyon, Service de Cardiologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Pôle Thoracique Cardiovasculaire et Neurologique, Hôpital Robert Debré, Point médical (Dijon), Hôpital Pasteur [Nice] (CHU), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Istituto di Scienze degli Alimenti e della Nutrizione, Università Cattolica del Sacro Cuore, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Centre d' investigation clinique-plurithématique du CHU de Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de cardiologie, Hôpital Pierre Zobda-Quitman [CHU de la Martinique], CHU de la Martinique [Fort de France]-CHU de la Martinique [Fort de France], Samara State Technical University, Biologie et physiopathologie intestinales. Pharmacologie nutritionnelle, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Hôpital Femme Mère Enfant, Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA (UMR_7583)), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de gastro-entérologie [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Jeanne d'Arc, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Hospices Civils de Lyon (HCL), Public Health Expertise [Paris, France], Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Service d'Endocrinologie, Métabolisme et Prévention des Maladies Cardio-vasculaires [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Cardiologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de recherche de l'institut du thorax (ITX-lab), Service d'endocrinologie, diabète, maladies métaboliques [Hôpital de la Conception - APHM], Aix Marseille Université (AMU), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), French REgistry of Familial hypERCHOLesterolemia (REFERCHOL) investigators, ANR-16-RHUS-0007,CHOPIN,CHOPIN(2016), Gestionnaire, Hal Sorbonne Université, CHOPIN - - CHOPIN2016 - ANR-16-RHUS-0007 - RHUS - VALID, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)

Subjects
cardiovascular risk, 0301 basic medicine, medicine.medical_specialty, cardiovascular risk equation, Population, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Risk Assessment, Cohort Studies, Hyperlipoproteinemia Type II, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, education, ComputingMilieux_MISCELLANEOUS, Risk equation, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Entire population, education.field_of_study, familial hypercholesterolemia, business.industry, Cholesterol, External validation, Cholesterol, LDL, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 030104 developmental biology, cholesterol-year-score, chemistry, Cardiovascular Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Clinical diagnosis, primary cardiovascular prevention, Cohort, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Cardiology and Cardiovascular Medicine, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Background and aims Patients with heterozygous familial hypercholesterolemia (HeFH) present elevated cardiovascular (CV) risk. Current CV risk stratification algorithms developed for the general population are not adapted for heFH patients. It is therefore of singular importance to develop and validate CV prediction tools, which are dedicated to the HeFH population. Methods Our first objective was to validate the Spanish SAFEHEART-risk equation (RE) in the French HeFH cohort (REFERCHOL), and the second to compare SAFEHEART-RE with the low-density-lipoprotein-cholesterol (LDL-C)-year-score for the prediction of CV events in the HeFH French population. Results We included HeFH (n = 1473) patients with a genetic or clinical diagnosis (DLCN score ≥8). Among them, 512 patients with a 5-year follow-up were included to validate the 5 year-CV-RE. A total of 152 events (10.3%) occurred in the entire population of 1473 patients during a mean follow-up of 3.9 years. Over the five-year follow-up, non-fatal CV events occurred in 103 patients (20.2%). Almost all the parameters used in the SAFEHEART-RE were confirmed as strong predictors of CV events in the REFERCHOL cohort. The C-statistic revealed a satisfactory performance of both the SAFEHEART-RE and LDL-C-year-scores in predicting CV events for all the patients (primary and secondary prevention) (C-index 0.77 and 0.70, respectively) as well as for those in primary prevention at inclusion (C-index 0.78 and 0.77, respectively). Conclusions This analysis represents the first external validation of the SAFEHEART-RE and demonstrated that both SAFEHEART-RE and the LDL-C-year-score are good predictors of CV events in primary prevention HeFH patients.

Published
2020

29. Phospholipid transfer to high-density lipoprotein (HDL) upon triglyceride lipolysis is directly correlated with HDL-cholesterol levels and is not associated with cardiovascular risk

Author

Alain Carrié, Anatol Kontush, Petra El Khoury, Jean Brerault, Emmanuel L. Gautier, F. Rached, Philippe Giral, Isabelle Guillas, Eric Bruckert, Maryam Darabi, Marie Lhomme, Maryse Guerin, Philippe Couvert, Raul D. Santos, Philippe Lesnik, Eric Frisdal, Wilfried Le Goff, Sandrine Lebreton, Feng Ma, Marianne Abifadel, Fernando Brites, Aurélie Canicio, Thierry Huby, Narcisse Medadje, Carlos V. Serrano, Emilie Tubeuf, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut d'écologie et des sciences de l'environnement de Paris (iEES Paris ), Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
0301 basic medicine, medicine.medical_specialty, HDL, Lipolysis, Phospholipid, Triglyceride-rich lipoprotein, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, High-density lipoprotein, Risk Factors, Internal medicine, medicine, Triglyceride metabolism, Humans, Risk factor, Phospholipids, Triglycerides, Lipoprotein lipase, Triglyceride, Cholesterol, nutritional and metabolic diseases, 3. Good health, Lipoprotein Lipase, 030104 developmental biology, Endocrinology, chemistry, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Heart Disease Risk Factors, lipids (amino acids, peptides, and proteins), LPL, Cardiology and Cardiovascular Medicine, Lipoproteins, HDL, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Background and aimsWhile low concentrations of high-density lipoprotein-cholesterol (HDL-C) represent a well-established cardiovascular risk factor, extremely high HDL-C is paradoxically associated with elevated cardiovascular risk, resulting in the U-shape relationship with cardiovascular disease. Free cholesterol transfer to HDL upon lipolysis of triglyceride-rich lipoproteins (TGRL) was recently reported to underlie this relationship, linking HDL-C to triglyceride metabolism and atherosclerosis. In addition to free cholesterol, other surface components of TGRL, primarily phospholipids, are transferred to HDL during lipolysis. It remains indeterminate as to whether such transfer is linked to HDL-C and cardiovascular disease.Methods and resultsWhen TGRL was labelled with fluorescent phospholipid 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI), time- and dose-dependent transfer of DiI to HDL was observed upon incubations with lipoprotein lipase (LPL). The capacity of HDL to acquire DiI was decreased by −36% (p

Published
2020

30. Evaluation of a semi-automatic isoelectric focusing method for apolipoprotein E phenotyping

Author

C. Cherfils, Laurence Barbot-Trystram, Georges Nouadje, Philippe Giral, Dominique Bonnefont-Rousselot, Randa Bittar, Valérie Fesel-Fouquier, Alain Carrié, Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], Laboratoire de Coprologie Fonctionnelle [Pitié-Salpêtrière], Sorbonne Université (SU), Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Endocrinologie, Métabolisme et Prévention des Maladies Cardio-vasculaires [CHU Pitié-Salpêtrière], and CCSD, Accord Elsevier

Subjects
Apolipoprotein E, 030213 general clinical medicine, HDL, Concordance, [SDV]Life Sciences [q-bio], Clinical Biochemistry, apolipoprotein, IDL, intermediate density lipoprotein, Computational biology, 030204 cardiovascular system & hematology, IDL, Article, LDL, low density lipoprotein, LDL, lcsh:Chemistry, 03 medical and health sciences, Sample volume, VLDL, very low density lipoprotein, 0302 clinical medicine, apo, intermediate density lipoprotein, Medicine, isoelectric focusing, apo, apolipoprotein, Genotyping, Reproducibility, lcsh:R5-920, Radiological and Ultrasound Technology, business.industry, Isoelectric focusing, IEF, Repeatability, HDL, high density lipoprotein, 3. Good health, very low density lipoprotein, [SDV] Life Sciences [q-bio], IEF, isoelectric focusing, Phenotype, lcsh:QD1-999, high density lipoprotein, lipids (amino acids, peptides, and proteins), Semi automatic, business, lcsh:Medicine (General), Isoforms, low density lipoprotein, VLDL
Abstract

A qualitative, semi-automatized method for apolipoprotein E (apoE) phenotyping by isoelectric focusing method has been evaluated on 40 serum samples from patients previously genotyped for apoE, especially as regards concordance with genotyping, but also repeatability and reproducibility of the method, and sample storage. Total concordance with genotyping and good precision criteria, together with its practicability and requirement of a little sample volume, lead to conclude to the usefulness of this method to help clinicians in the diagnosis of dyslipidemic and neurodegenerative diseases., Highlights • Semi-automatic isoelectrofocusing method for apoE phenotyping. • Total concordance with genotyping. • Good repeatability and reproducibility.

Published
2020

31. Free cholesterol transfer to high-density lipoprotein (HDL) upon triglyceride lipolysis underlies the U-shape relationship between HDL-cholesterol and cardiovascular disease

Author

Eric Bruckert, Ma Feng, Maryam Darabi, Fernando Brites, Marie Lhomme, Eric Frisdal, Wilfried Le Goff, Aurélie Canicio, Lucrèce Matheron, Sandrine Lanfranchi-Lebreton, Alain Carrié, Thierry Huby, Maryse Guerin, Emilie Tubeuf, Carlos Vicente Serrano, Anatol Kontush, Raul D. Santos, Gérard Bolbach, Philippe Couvert, F. Rached, Philippe Lesnik, Maharajah Ponnaiah, Philippe Giral, Isabelle Guillas, Emmanuel L. Gautier, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), University of São Paulo (USP), University of Buenos Aires [Argentina], Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universidade de São Paulo = University of São Paulo (USP), Universitad de Buenos Aires = University of Buenos Aires [Argentina], and Gautier, Emmanuel

Subjects
Male, Epidemiology, [SDV]Life Sciences [q-bio], Ciencias de la Salud, Aorta, Thoracic, Disease, 030204 cardiovascular system & hematology, MESH: Lipoproteins, HDL, chemistry.chemical_compound, Mice, 0302 clinical medicine, High-density lipoprotein, POSTPRANDIAL LIPID METABOLISM, MESH: Animals, CHYLOMICRONS, lipoprotein metabolism, 0303 health sciences, HDL metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Postprandial Period, 3. Good health, [SDV] Life Sciences [q-bio], Otras Ciencias de la Salud, MESH: Cholesterol Ester Transfer Proteins, Cardiovascular Diseases, postprandial lipid metabolism, MESH: Postprandial Period, purl.org/becyt/ford/3 [https], Female, lipids (amino acids, peptides, and proteins), Cardiology and Cardiovascular Medicine, Lipoproteins, HDL, MESH: Lipoprotein Lipase, MESH: Triglycerides, medicine.medical_specialty, CIENCIAS MÉDICAS Y DE LA SALUD, HDL function, MESH: Mice, Transgenic, MESH: Aorta, Thoracic, Lipolysis, LCAT, Mice, Transgenic, purl.org/becyt/ford/3.3 [https], 03 medical and health sciences, Free cholesterol, HDL METABOLISM, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, CETP, medicine, LIPOPROTEIN LIPASE, Shape relationship, Animals, Humans, MESH: Lipolysis, Risk factor, MESH: Mice, Triglycerides, 030304 developmental biology, MESH: Humans, Triglyceride, LIPOPROTEIN METABOLISM, Cholesterol, business.industry, MESH: Cardiovascular Diseases, HDL FUNCTION, nutritional and metabolic diseases, Lipoprotein lipase, MESH: Male, Cholesterol Ester Transfer Proteins, Disease Models, Animal, Endocrinology, chemistry, ATHEROSCLEROSIS, APOLIPOPROTEINS, MESH: Biomarkers, chylomicrons, MESH: Disease Models, Animal, atherosclerosis, business, MESH: Female, apolipoproteins, Biomarkers
Abstract

Background: Low concentrations of high-density lipoprotein cholesterol (HDL-C) represent a well-established cardiovascular risk factor. Paradoxically, extremely high HDL-C levels are equally associated with elevated cardiovascular risk, resulting in the U-shape relationship of HDL-C with cardiovascular disease. Mechanisms underlying this association are presently unknown. We hypothesised that the capacity of high-density lipoprotein (HDL) to acquire free cholesterol upon triglyceride-rich lipoprotein (TGRL) lipolysis by lipoprotein lipase underlies the non-linear relationship between HDL-C and cardiovascular risk. Methods: To assess our hypothesis, we developed a novel assay to evaluate the capacity of HDL to acquire free cholesterol (as fluorescent TopFluor® cholesterol) from TGRL upon in vitro lipolysis by lipoprotein lipase. Results: When the assay was applied to several populations markedly differing in plasma HDL-C levels, transfer of free cholesterol was significantly decreased in low HDL-C patients with acute myocardial infarction (−45%) and type 2 diabetes (–25%), and in subjects with extremely high HDL-C of >2.59 mmol/L (>100 mg/dL) (−20%) versus healthy normolipidaemic controls. When these data were combined and plotted against HDL-C concentrations, an inverse U-shape relationship was observed. Consistent with these findings, animal studies revealed that the capacity of HDL to acquire cholesterol upon lipolysis was reduced in low HDL-C apolipoprotein A-I knock-out mice and was negatively correlated with aortic accumulation of [3H]-cholesterol after oral gavage, attesting this functional characteristic as a negative metric of postprandial atherosclerosis. Conclusions: Free cholesterol transfer to HDL upon TGRL lipolysis may underlie the U-shape relationship between HDL-C and cardiovascular disease, linking HDL-C to triglyceride metabolism and atherosclerosis. Fil: Feng, Ma. Inserm; Francia. Université Pierre et Marie Curie; Francia Fil: Darabi, Maryam. Université Pierre et Marie Curie; Francia. Inserm; Francia Fil: Tubeuf, Emilie. Inserm; Francia. Université Pierre et Marie Curie; Francia Fil: Canicio, Aurélie. Université Pierre et Marie Curie; Francia. Inserm; Francia Fil: Lhomme, Marie. Institute Of Cardiometabolism And Nutrition; Francia Fil: Frisdal, Eric. Inserm; Francia. Université Pierre et Marie Curie; Francia Fil: Lanfranchi Lebreton, Sandrine. Université Pierre et Marie Curie; Francia Fil: Matheron, Lucrèce. Université Pierre et Marie Curie; Francia Fil: Rached, Fabiana. Université Pierre et Marie Curie; Francia. Inserm; Francia Fil: Ponnaiah, Maharajah. Institute Of Cardiometabolism And Nutrition; Francia Fil: Serrano, Carlos V.. Instituto Do Coracao Do Hospital Das Clinicas; Brasil Fil: Santos, Raul D.. Instituto Do Coracao Do Hospital Das Clinicas; Brasil Fil: Brites, Fernando Daniel. Universidad de Buenos Aires; Argentina. Instituto Do Coracao Do Hospital Das Clinicas; Brasil Fil: Bolbach, Gerard. Université Pierre et Marie Curie; Francia Fil: Gautier, Emmanuel. Université Pierre et Marie Curie; Francia. Inserm; Francia Fil: Huby, Thierry. Inserm; Francia. Université Pierre et Marie Curie; Francia Fil: Carrie, Alain. Inserm; Francia. Université Pierre et Marie Curie; Francia Fil: Bruckert, Eric. Inserm; Francia. Université Pierre et Marie Curie; Francia Fil: Guerin, Maryse. Université Pierre et Marie Curie; Francia. Inserm; Francia Fil: Couvert, Philippe. Inserm; Francia. Université Pierre et Marie Curie; Francia Fil: Giral, Philippe. Université Pierre et Marie Curie; Francia. Inserm; Francia Fil: Lesnik, Philippe. Université Pierre et Marie Curie; Francia. Inserm; Francia Fil: Le Goff, Wilfried. Université Pierre et Marie Curie; Francia. Inserm; Francia Fil: Guillas, Isabelle. Inserm; Francia. Université Pierre et Marie Curie; Francia Fil: Kontush, Anatol. Inserm; Francia. Université Pierre et Marie Curie; Francia

Published
2020

32. Corrigendum to 'Polyvascular subclinical atherosclerosis in familial hypercholesterolemia: The role of cholesterol burden and gender' [Nutr Metab Cardiovasc Dis 29 (2019) 1068–1076]

Author

Eric Bruckert, Alessandro Mattina, Philippe Cluzel, David Rosenbaum, Sophie Béliard, Angelo Quartarone, Philippe Giral, Maurizio Averna, Antonina Giammanco, Davide Noto, Alain Carrié, Alban Redheuil, Randa Bittar, Antonio Gallo, Medicina Interna, Malattie Cardiovascolari e Nefrourologiche, Università degli studi di Palermo - University of Palermo, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], Laboratoire d'Imagerie Biomédicale (LIB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie Endocrinienne et Oncologique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de radiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Centre recherche en CardioVasculaire et Nutrition (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), School of Medicine, University of Patras [Greece], Service d'endocrinologie-métabolisme [CHU Pitié-Salpêtrière], Sapienza University [Rome], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), University of Patras, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], and Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]

Subjects
Peripheral arterial atherosclerosis, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), 030209 endocrinology & metabolism, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Coronary artery calcium, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Medicine, Nutrition and Dietetics, business.industry, Cholesterol, medicine.disease, Atherosclerosis, Cardiovascular disease, Cardiovascular risk, Calcium score, 3. Good health, Familial hyper cholesterolemia, Cholesterol burden, chemistry, Subclinical atherosclerosis, Cardiology, Cardiology and Cardiovascular Medicine, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Background and aim: Heterozygous familial hypercholesterolemia (HeFH) is a genetic disease characterized by a heterogeneous phenotype. The assessment of cardiovascular (CV) risk is challenging for HeFH. Cholesterol burden (CB) allows to estimate the lifelong exposure to high levels of cholesterol. The aim of this study was to analyze the distribution of subclinical athero-sclerosis and the relationship between atherosclerosis and the CB in a sample of HeFH patients, focusing on sex-related differences. Methods and Results: 154 asymptomatic HeFH subjects underwent coronary-artery-calcium score (CACs) and Doppler ultrasound of carotid and femoral arteries. Yearly lipid profiles and HeHF history were obtained from patients' files in order to calculate total CB. Atherosclerotic burden was defined by the presence of CACs > 0 or by the presence of carotid or femoral plaque. Study population was stratified according to gender. The prevalence of CAC, carotid and femoral atheroscle-rosis was of 62%, 55% and 56%, respectively. Coronary district was the least involved in women, who had a higher prevalence in carotid atherosclerosis. When two vascular districts were affected, women had an increased prevalence of femoral and carotid atherosclerosis whereas men had a higher prevalence of coronary and femoral atherosclerosis. CB correlated to the presence of atherosclerosis in any of the three vascular districts with a significant increasing trend depending on the number of affected areas.

Published
2019

33. Usefulness of the genetic risk score to identify phenocopies in families with familial hypercholesterolemia?

Author

Gérald Luc, Harout Iliozer, Sandy Elbitar, Youmna Ghaleb, Valérie Carreau, Catherine Boileau, Eric Bruckert, Marianne Abifadel, Alain Carrié, Michel Farnier, Petra El Khoury, Sybil Charrière, Philippe Moulin, Jean-Pierre Rabès, Mathilde Varret, M. Di-Filippo, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)

Subjects
0301 basic medicine, Apolipoprotein E, Multifactorial Inheritance, Biochemistry & Molecular Biology, medicine.medical_specialty, Apolipoprotein B, [SDV]Life Sciences [q-bio], Hypercholesterolemia, prevalence, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Polymorphism, Single Nucleotide, Article, low, autosomal-dominant hypercholesterolemia, 03 medical and health sciences, Apolipoproteins E, 0302 clinical medicine, Internal medicine, Genetics, medicine, Humans, SNP, Genetic Predisposition to Disease, Genetic Testing, Genetics (clinical), Genetics & Heredity, Phenocopy, pcsk9, biology, business.industry, PCSK9, fungi, mutations, medicine.disease, ldl, 3. Good health, Phenotype, 030104 developmental biology, Endocrinology, Apolipoprotein B-100, LDL receptor, biology.protein, lipids (amino acids, peptides, and proteins), Proprotein Convertase 9, atherosclerosis, coronary-heart-disease, business, Lipoprotein
Abstract

International audience; Familial hypercholesterolemia (FH) is caused by mutations in LDLR (low-density lipoprotein receptor), APOB (apolipoprotein B), PCSK9 (proprotein convertase subtilisin/kexin type 9), or APOE (apolipoprotein E) genes in approximately 80% of the cases. Polygenic forms of hypercholesterolemia may be present among patients clinically diagnosed with FH but with no identified mutation (FH mutation-negative (FH/M-)). To address whether polygenic forms may explain phenocopies in FH families, we calculated a 6-single-nucleotide polymorphism (SNP) genetic risk score (GRS) in all members from five French FH families where a mutation was identified (FH/M+) as well as some phenocopies (FH/M-). In two families, three FH/M- patients present a high GRS suggesting a polygenic hypercholesterolemia for these phenocopies. However, a high GRS is also observed in nine FH/M+ patients and in four unaffected relatives from three families. These observations indicate that the GRS does not seem to be a good diagnostic tool at the individual level. Nevertheless, the GRS seems to be a contributor of the severity of hypercholesterolemia since patients who cumulate a mutation and a high GRS exhibit higher low-density lipoprotein cholesterol levels when compared to patients with only FH (p = 0.054) or only polygenic hypercholesterolemia (p = 0.0039). In conclusion, the GRS can be used as a marker of the severity of hypercholesterolemia but does not seem to be a reliable tool to distinguish phenocopies within FH families.

Published
2018

34. Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel

Author

Amy C, Sturm, Joshua W, Knowles, Samuel S, Gidding, Zahid S, Ahmad, Catherine D, Ahmed, Christie M, Ballantyne, Seth J, Baum, Mafalda, Bourbon, Alain, Carrié, Marina, Cuchel, Sarah D, de Ferranti, Joep C, Defesche, Tomas, Freiberger, Ray E, Hershberger, G Kees, Hovingh, Lala, Karayan, Johannes Jacob Pieter, Kastelein, Iris, Kindt, Stacey R, Lane, Sarah E, Leigh, MacRae F, Linton, Pedro, Mata, William A, Neal, Børge G, Nordestgaard, Raul D, Santos, Mariko, Harada-Shiba, Eric J, Sijbrands, Nathan O, Stitziel, Shizuya, Yamashita, Katherine A, Wilemon, David H, Ledbetter, and Daniel J, Rader

Subjects
Hyperlipoproteinemia Type II, Receptors, LDL, Humans, Genetic Counseling, Genetic Testing, Proprotein Convertase 9, Expert Testimony, Apolipoproteins B
Abstract

Although awareness of familial hypercholesterolemia (FH) is increasing, this common, potentially fatal, treatable condition remains underdiagnosed. Despite FH being a genetic disorder, genetic testing is rarely used. The Familial Hypercholesterolemia Foundation convened an international expert panel to assess the utility of FH genetic testing. The rationale includes the following: 1) facilitation of definitive diagnosis; 2) pathogenic variants indicate higher cardiovascular risk, which indicates the potential need for more aggressive lipid lowering; 3) increase in initiation of and adherence to therapy; and 4) cascade testing of at-risk relatives. The Expert Consensus Panel recommends that FH genetic testing become the standard of care for patients with definite or probable FH, as well as for their at-risk relatives. Testing should include the genes encoding the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9); other genes may also need to be considered for analysis based on patient phenotype. Expected outcomes include greater diagnoses, more effective cascade testing, initiation of therapies at earlier ages, and more accurate risk stratification.

Published
2018

35. Long-term outcome in 53 patients with homozygous familial hypercholesterolaemia in a single centre in France

Author

Babak Khoshnood, Daniel Thomas, Randa Bittar, Samir Saheb, Eric Bruckert, Sophie Béliard, Olga Kalmykova, Valérie Carreau, Dominique Bonnefont-Rousselot, David Rosenbaum, Corinne Emery, and Alain Carrié

Subjects
Male, Heredity, Time Factors, DNA Mutational Analysis, Myocardial Infarction, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Rate ratio, Angina, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, 030212 general & internal medicine, Myocardial infarction, Child, Stroke, Anticholesteremic Agents, Incidence (epidemiology), Homozygote, Pedigree, Phenotype, Treatment Outcome, Cardiovascular Diseases, Child, Preschool, Blood Component Removal, Female, lipids (amino acids, peptides, and proteins), France, Cardiology and Cardiovascular Medicine, Lipoprotein apheresis, medicine.medical_specialty, Statin, Adolescent, medicine.drug_class, Disease-Free Survival, Angina Pectoris, Hyperlipoproteinemia Type II, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Retrospective Studies, Cholesterol, business.industry, Infant, Newborn, Infant, Cholesterol, LDL, medicine.disease, Surgery, Early Diagnosis, Receptors, LDL, chemistry, Mutation, business, Biomarkers
Abstract

Background and aims Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited condition characterized by elevated plasma low-density lipoprotein-cholesterol (LDL-C) levels, severe, accelerated atherosclerosis and premature coronary heart disease. We evaluated cardiovascular complications in HoFH patients over extended follow-up and investigated their association with changes in cholesterol over time, as well as total cholesterol burden. Methods In this retrospective single-centre study, 53 patients (baseline mean ± standard deviation [SD], total cholesterol 15.5 ± 3.7 mmol/L and LDL-C 13.2 ± 2.6 mmol/L) were followed for up to 38 years (21.2 ± 10 years). The primary outcome was an adverse clinical event, defined as cardiovascular death, nonfatal myocardial infarction, or angina. Results Twenty-eight patients experienced an event, of whom 8 died due to complications of major surgery (4), myocardial infarction (3) or stroke (1). While total cholesterol levels were comparable in patients with and without an event at baseline (20 mmol/L), those who subsequently experienced an event showed a slower decline in total cholesterol. Cumulative total cholesterol (i.e. total-cholesterol year score) was highly associated with the incidence of an adverse clinical event in a linear dose-response relation. A 100 mmol/L increase in cumulative total cholesterol (i.e. an average exposure of 10 mmol/L per 10 years or 20 mmol/L per 5 years) was associated with a doubling of the risk of a cardiovascular event (age-adjusted incidence rate ratio: 1.99, 95% CI, 1.16–3.41). Conclusions Our findings reinforce the importance of early diagnosis and initiation of maximal treatment, including lipoprotein apheresis, to ensure long-term reduction in the cholesterol burden, expressed as the total-cholesterol year score, and risk of cardiovascular complications in HoFH.

Published
2017

36. Polyvascular subclinical atherosclerosis in familial hypercholesterolemia: The role of cholesterol burden and gender

Author

Angelo Quartarone, Alban Redheuil, David Rosenbaum, Antonio Gallo, Sophie Béliard, Maurizio Averna, Eric Bruckert, Philippe Giral, Alessandro Mattina, Davide Noto, Alain Carrié, Philippe Cluzel, Antonina Giammanco, Randa Bittar, Mattina A., Giammanco A., Giral P., Rosenbaum D., Carrie A., Cluzel P., Redheuil A., Bittar R., Beliard S., Noto D., Quartarone A., Averna M., Bruckert E., Gallo A., Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Università degli studi di Palermo - University of Palermo, Service d'endocrinologie-métabolisme [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Sorbonne Université (SU), Service de Biochimie Endocrinienne et Oncologique [CHU Pitié-Salpêtrière], Service d'imagerie cardiovasculaire et de radiologie interventionnelle [CHU Pitié-Salpêtrière], Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], Institut National de la Recherche Agronomique (INRA), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU), Assistance Publique - Hôpitaux de Marseille (APHM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], and Service de radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière]

Subjects
Carotid Artery Diseases, Male, Carotid atherosclerosis, Peripheral arterial atherosclerosis, Time Factors, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Coronary Artery Disease, Disease, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Severity of Illness Index, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Atherosclerosis, Calcium score, Cardiovascular disease, Cardiovascular risk, Cholesterol burden, Coronary artery calcium, Adult, Aged, Asymptomatic Diseases, Biomarkers, Cholesterol, Cross-Sectional Studies, Female, Femoral Artery, Genetic Predisposition to Disease, Humans, Hyperlipoproteinemia Type II, Middle Aged, Paris, Peripheral Arterial Disease, Phenotype, Prevalence, Prognosis, Risk Assessment, Sex Factors, Young Adult, Medicine, Nutrition and Dietetics, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, Atherosclerosi, Cardiology, Population study, medicine.symptom, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, 030209 endocrinology & metabolism, Asymptomatic, High cholesterol, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, business.industry, medicine.disease, chemistry, Subclinical atherosclerosis, business
Abstract

International audience; BACKGROUND AND AIM:Heterozygous familial hypercholesterolemia (HeFH) is a genetic disease characterized by a heterogeneous phenotype. The assessment of cardiovascular (CV) risk is challenging for HeFH. Cholesterol burden (CB) allows to estimate the lifelong exposure to high levels of cholesterol. The aim of this study was to analyze the distribution of subclinical atherosclerosis and the relationship between atherosclerosis and the CB in a sample of HeFH patients, focusing on sex-related differences.METHODS AND RESULTS:154 asymptomatic HeFH subjects underwent coronary-artery-calcium score (CACs) and Doppler ultrasound of carotid and femoral arteries. Yearly lipid profiles and HeHF history were obtained from patients' files in order to calculate total CB. Atherosclerotic burden was defined by the presence of CACs > 0 or by the presence of carotid or femoral plaque. Study population was stratified according to gender. The prevalence of CAC, carotid and femoral atherosclerosis was of 62%, 55% and 56%, respectively. Coronary district was the least involved in women, who had a higher prevalence in carotid atherosclerosis. When two vascular districts were affected, women had an increased prevalence of femoral and carotid atherosclerosis whereas men had a higher prevalence of coronary and femoral atherosclerosis. CB correlated to the presence of atherosclerosis in any of the three vascular districts with a significant increasing trend depending on the number of affected areas.CONCLUSIONS:A polyvascular atherosclerotic burden is found in asymptomatic HeFH patients. Gender differences in the territory distribution were observed. The early and lasting exposure to high cholesterol, as expressed by CB, is a major determinant of atherosclerotic burden.

Published
2019

37. Characteristics of monogenic versus polygenic familial hypobetalipoproteinemia

Author

Bertrand Cariou, X. Vanhoye, Edith Bigot-Corbel, Noël Peretti, G. Degraef, Matthieu Wargny, Antoine Rimbert, P.A. Rollat Farnier, Matthieu Pichelin, Alain Carrié, Didier Goxe, D. Coulibaly, René Valéro, Marie Marrec, Sybil Charrière, P. Moulin, and M. Di Filippo

Subjects
Genetics, business.industry, Familial Hypobetalipoproteinemia, Medicine, Cardiology and Cardiovascular Medicine, business
Published
2020

38. Small, dense high-density lipoprotein 3 particles exhibit defective antioxidative and anti-inflammatory function in familial hypercholesterolemia: Partial correction by low-density lipoprotein apheresis

Author

Paul Robillard, S. Chantepie, Alain Carrié, Alexina Orsoni, Martine Couturier, Marielle Atassi, Patrice Thérond, Eric Bruckert, M. John Chapman, Hala Hussein, Anatol Kontush, and Samir Saheb

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Free Radicals, Endocrinology, Diabetes and Metabolism, Inflammation, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, medicine.disease_cause, Antioxidants, Proinflammatory cytokine, Hyperlipoproteinemia Type II, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, High-density lipoprotein, Internal medicine, Internal Medicine, medicine, Humans, Particle Size, Nutrition and Dietetics, business.industry, Lipoproteins, HDL3, Middle Aged, medicine.disease, Lipoproteins, LDL, Oxidative Stress, 030104 developmental biology, Endocrinology, chemistry, Biochemistry, LDL apheresis, Blood Component Removal, Female, lipids (amino acids, peptides, and proteins), medicine.symptom, Cardiology and Cardiovascular Medicine, business, Oxidative stress, Lipoprotein
Abstract

Familial hypercholesterolemia (FH) features elevated oxidative stress and accelerated atherosclerosis driven by elevated levels of atherogenic lipoproteins relative to subnormal levels of atheroprotective high-density lipoprotein (HDL). Small, dense HDL3 potently protects low-density lipoprotein (LDL) against proinflammatory oxidative damage.To determine whether antioxidative and/or anti-inflammatory activities of HDL are defective in FH and whether such defects are corrected by LDL apheresis.Antioxidative and antiinflammatory activities of HDL were evaluated as protection of reference LDL from oxidative stress and capacity to prevent accumulation of proinflammatory oxidised lipids, respectively. Lipid surface rigidity of HDL was assessed using a fluorescent probe. HDL components were measured by analytical approaches. Systemic oxidative stress was characterized as plasma 8-isoprostanes.Pre-LDL-apheresis, FH patients (n = 10) exhibited elevated systemic oxidative stress (3.3-fold, P0.001) vs. sex- and age-matched normolipidemic controls (n = 10). Both antioxidative and antiinflammatory activity of HDL3 were impaired (up to -91%, P0.01) in FH. Sphingomyelin and saturated fatty acid contents were elevated in FH HDL3, resulting in enhanced lipid surface rigidity. The surface lipid content (phospholipids, free cholesterol) was reduced in FH (up to -15%, P0.001), whereas content of core lipids (cholesteryl esters, triglycerides) was elevated (up to +17%, P0.001). Molar apolipoprotein A-I content of HDL3 was subnormal in FH. A single LDL-apheresis session partially corrected (by up to 76%) deficient HDL antiatherogenic activities, attenuated systemic oxidative stress and partially normalised both the lipid composition and surface rigidity of HDL particles.FH features elevated oxidative stress and deficient antioxidative and anti-inflammatory activities of small, dense HDL3; such functional deficiency is intimately linked to anomalies in lipid and protein composition, which may impair the capacity of HDL to acquire and inactivate oxidized lipids.

Published
2016

39. Lipoprotein-apheresis in familial hypercholesterolemia: Long-term patient compliance in a French cohort

Author

Eric Bruckert, Randa Bittar, Alain Carrié, M. John Chapman, Antonio Gallo, Samir Saheb, Emilie Duchêne, Sophie Béliard, Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA), Assistance Publique - Hôpitaux de Marseille (APHM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], Service d'endocrinologie-métabolisme [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre recherche en CardioVasculaire et Nutrition (C2VN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Service de Biochimie Endocrinienne et Oncologique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP]

Subjects
Adult, Male, Heterozygote, medicine.medical_specialty, Dyslipidaemia, Time Factors, [SDV]Life Sciences [q-bio], Familial hypercholesterolemia, Disease, 030204 cardiovascular system & hematology, Hyperlipoproteinemia Type II, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Lipoprotein apheresis, Risk Factors, Internal medicine, Humans, Medicine, Genetic Predisposition to Disease, 030212 general & internal medicine, Patient compliance, Cardiovascular History, business.industry, Homozygote, Cholesterol, LDL, Middle Aged, medicine.disease, 3. Good health, Compliance (physiology), Coronary heart disease, Phenotype, Treatment Outcome, Cohort, Blood Component Removal, Patient Compliance, Female, France, Cardiology and Cardiovascular Medicine, business, Biomarkers, Compliance
Abstract

International audience; Background and aims : Lipoprotein apheresis (LA) is a complex therapeutic option and poor compliance can adversely affect treatment outcome. The aim of this study was to describe long-term compliance to treatment in patients undergoing regular LA therapy and to investigate factors related to low compliance.Methods : We analysed 11,391 prescribed procedures of LA performed between 1990 and 2007 in 51 patients with familial hypercholesterolemia. Regular LA treatment was initiated in patients presenting with either homozygous familial hypercholesterolemia (n = 21), or severe heterozygous familial hypercholesterolemia (n = 30) with elevated LDL-cholesterol levels and who did not respond adequately to diet and drug therapy; the majority of these patients (n = 30) had cardiovascular disease at initiation of therapy.Results : The overall observed compliance rate based on the number of achieved/programmed procedures was 87.5%. Neither cardiovascular history nor subtypes of hypercholesterolemia was associated with compliance. In addition, there was no impact of patient demography on compliance. Treatment frequency alone significantly impacted non-compliance (i.e. patient with weekly procedures were less compliant). Interestingly, a non-significant decrease in compliance was observed among patients aged

Published
2018

40. High burden of recurrent cardiovascular events in heterozygous familial hypercholesterolemia: The French Familial Hypercholesterolemia Registry

Author

Sophie Béliard, Franck Boccara, Bertrand Cariou, Alain Carrié, Xavier Collet, Michel Farnier, Jean Ferrières, Michael Krempf, Noël Peretti, Jean-Pierre Rabès, Mathilde Varret, Alexandre Vimont, Sybil Charrière, Eric Bruckert, D. Angoulvant, S. Béliard, P. Benlian, C. Boileau, F. Boccara, E. Bruckert, B. Cariou, V. Carreau, A. Carrié, S. Charrière, M. Di Filippo, P.H. Ducluzeau, S. Dulong, V. Durlach, M. Farnier, E. Ferrari, J. Ferrières, A. Gallo, J.P. Girardet, R. Hankard, M. Krempf, J.D. Lalau, B. Lefort, J. Lemale, P. Moulin, F. Paillard, N. Peretti, A. Pradignac, Y. Pucheu, J.P. Rabès, S. Saheb, A. Sultan, P. Tounian, R. Valéro, M. Varret, B. Vergès, C. Yelnik, O. Ziegler, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cardiologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), CHU Pitié-Salpêtrière [APHP], Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Point médical (Dijon), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Hôpital Guillaume et René Laennec - Centre Hospitalier Universitaire de Nantes, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Ambroise Paré, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'endocrinologie-métabolisme [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Tenon [APHP], Rythmes Biologiques et Cancers, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Nutrition, croissance et cancer (U 1069) (N2C), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Maladies Métaboliques et Endocrinologie, Université de la Méditerranée - Aix-Marseille 2, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), ANR: 16-RHUS-0007,CHOPIN,Recherches Hospitalo-universitaires en santé, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Epidémiologie, Economie de la Santé et Santé Publique, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Service d' Endocrinologie, Centre Hospitalier Universitaire de Grenoble, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Hôpital Ambroise Paré [AP-HP], Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Tenon [AP-HP], SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), ANR-16-RHUS-0007, ANR-16-RHUS-0007,CHOPIN,CHOPIN(2016), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Fattouma Bourguiba [Monastir] (HFB), Unité de recherche de l'institut du thorax (ITX-lab), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Service d'Endocrinologie, Métabolisme et Prévention des Maladies Cardio-vasculaires [CHU Pitié-Salpêtrière]

Subjects
Male, coronary-artery-disease, Heredity, Time Factors, Heart disease, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Coronary artery disease, 0302 clinical medicine, Interquartile range, Recurrence, Risk Factors, Secondary Prevention, 030212 general & internal medicine, Myocardial infarction, Registries, panel, risk, education.field_of_study, Anticholesteremic Agents, PCSK9 Inhibitors, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Cardiovascular disease, myocardial-infarction, 3. Good health, Pedigree, Phenotype, Treatment Outcome, Cardiovascular Diseases, Drug Therapy, Combination, Female, France, Proprotein Convertase 9, Cardiology and Cardiovascular Medicine, guidance, management, Adult, medicine.medical_specialty, Heterozygote, Registry, Serine Proteinase Inhibitors, european atherosclerosis society, Population, Down-Regulation, Risk Assessment, Hyperlipoproteinemia Type II, Cardiovascular events, 03 medical and health sciences, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, education, Retrospective Studies, Cardiovascular recurrences, esc/eas guidelines, Unstable angina, business.industry, cholesterol, Percutaneous coronary intervention, Cholesterol, LDL, medicine.disease, heart-disease, Cardiovascular System & Cardiology, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Biomarkers
Abstract

International audience; Background and aims: Cardiovascular risk is high in heterozygous familial hypercholesterolemia (HeFH). The objective of this study was to describe recurrent cardiovascular events in selected patients with HeFH attending lipid clinics in France. Methods: We included 781 patients with a clinical (Dutch Lipid Clinic Network score \textgreater= 6) or genetic diagnosis of HeFH who had experienced a first cardiovascular event (myocardial infarction, percutaneous coronary intervention or coronary bypass, unstable angina, stroke, peripheral arterial revascularization or cardiovascular death) and were enrolled in the French Familial Hypercholesterolemia Registry (November 2015 to March 2018). Results: The first cardiovascular event occurred at the mean age of 47 years (interquartile range 39-55) in a predominantly male population (72%); 48% of patients were on statin therapy. Overall, 37% of patients had at least one recurrent cardiovascular event (mean of 1.8 events per patient), of which 32% occurred in the 12 months after the index event; 55% of events occurred \textgreater 3 years after the first event. Mean LDL-C at the last clinic visit was 144 +/- 75 mg/dL (132 +/- 69 mg/dL for patients on high-potency statin therapy and 223 +/- 85 mg/dL for untreated patients). Conclusions: The rate of recurrent cardiovascular events was high in French patients with HeFH in secondary prevention. The detection of FH during childhood is crucial to prevent CV events at a young age by early initiating statin therapy. There is a clear urgent need to expand the actual very small target population which can be treated with the PCSK9 inhibitor in France.

Published
2018

41. Identification of the first Tangier disease patient in Lebanon carrying a new pathogenic variant in ABCA1

Author

Petra El Khoury, Carine Ayoub, Philippe Giral, Catherine Boileau, Maryse Guerin, Yara Abou-Khalil, Mathilde Varret, Alexandre Superville, Jean-Pierre Rabès, Marianne Abifadel, Selim Jambart, Sandy Elbitar, Yara Azar, Alain Carrié, Wilfried Le Goff, Youmna Ghaleb, and Philippe Couvert

Subjects
0301 basic medicine, Proband, Adult, Male, Apolipoprotein B, Endocrinology, Diabetes and Metabolism, Population, Consanguinity, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Tangier disease, Internal Medicine, medicine, Humans, Lebanon, education, Hypoalphalipoproteinemia, Tangier Disease, Aged, Aged, 80 and over, education.field_of_study, Nutrition and Dietetics, biology, business.industry, Cholesterol, HDL, Genetic Variation, Exons, Middle Aged, medicine.disease, Pedigree, 030104 developmental biology, ABCA1, Immunology, biology.protein, lipids (amino acids, peptides, and proteins), Female, Cardiology and Cardiovascular Medicine, business, Dyslipidemia, ATP Binding Cassette Transporter 1
Abstract

Background The Middle East region is characterized by low levels of high-density lipoprotein cholesterol (HDL-C). To date, no genetic study has investigated the cause of low HDL-C in the Lebanese population. Objective Our objective was to study the genetic causes for hypoalphalipoproteinemia in a Lebanese family with extremely low HDL-C levels. Methods We sequenced the ABCA1 gene and evaluated cholesterol efflux, inflammatory, and metabolic profiles in the proband and his family. Results We identified the first Lebanese pathogenic variant in ABCA1 gene causing Tangier disease in a consanguineous family. The proband carried a novel homozygous pathogenic variant p.Gly592Asp in exon 14 of ABCA1, which segregated with the disease in the family. Functional study of the p.Gly592Asp pathogenic variant revealed that lipid-free apolipoprotein A-I–dependent cholesterol efflux was completely abolished in cholesterol-loaded human monocytes-derived macrophages isolated from the proband when compared to controls. Systemic inflammatory and metabolic assessments showed that plasma cytokines (MCP-1, MIP-1α, IL-6, CRP, TNF-α), adhesion molecules (ICAM-1, VCAM-1, E-selectin), inflammatory soluble receptors (sIL-6r, sTNFRI, sTNFRII), and metabolic markers (Insulin, C-peptide) were elevated in the proband when compared to controls. Noninvasive cardiovascular investigation revealed the presence of premature artery lesions in the proband. Conclusions It is the first case of Tangier disease reported in Lebanon harboring a novel pathogenic variant in ABCA1. Further genetic research is needed in the Middle East where the consanguinity rate is elevated, to understand the cause of the highly prevalent dyslipidemia. This will help guiding the early diagnosis, management, and prevention of cardiovascular complications.

Published
2018

42. ClinVar database of global familial hypercholesterolemia-associated DNA variants

Author

Robert A. Hegele, Joep C. Defesche, Pascale Benlian, Lukas Tichy, Steve E. Humphries, Robert O'Connor, Tomáš Freiberger, John Garcia, Sarah Leigh, Joshua W. Knowles, C. Lisa Kurtz, Joana Rita Chora, Pedro Mata, Alain Carrié, Michael A. Iacocca, Mafalda Bourbon, Raul D. Santos, Eric J.G. Sijbrands, Hannah Wand, Cinthia E. Jannes, Amanda J. Hooper, Marina T. DiStefano, Katherine Wilemon, ACS - Atherosclerosis & ischemic syndromes, Human Genetics, and Internal Medicine

Subjects
0301 basic medicine, MEDLINE, Genomics, Clinical Genome Resource, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Biology, Dna variants, Mendelian disease, computer.software_genre, Article, Doenças Cardio e Cérebro-vasculares, Hyperlipoproteinemia Type II, 03 medical and health sciences, 0302 clinical medicine, Databases, Genetic, Genetics, medicine, Genomic medicine, Humans, Familial Hypercholesterolemia, Genetics (clinical), Database, Genome, Human, MUTAÇÃO GENÉTICA, Genetic Variation, ClinVar, DNA, medicine.disease, Human genetics, 3. Good health, Data sharing, 030104 developmental biology, Variant Interpretation, computer
Abstract

Accurate and consistent variant classification is imperative for incorporation of rapidly developing sequencing technologies into genomic medicine for improved patient care. An essential requirement for achieving standardized and reliable variant interpretation is data sharing, facilitated by a centralized open-source database. Familial hypercholesterolemia (FH) is an exemplar of the utility of such a resource: it has a high incidence, a favorable prognosis with early intervention and treatment, and cascade screening can be offered to families if a causative variant is identified. ClinVar, an NCBI-funded resource, has become the primary repository for clinically relevant variants in Mendelian disease, including FH. Here, we present the concerted efforts made by the Clinical Genome Resource, through the FH Variant Curation Expert Panel and global FH community, to increase submission of FH-associated variants into ClinVar. Variant-level data was categorized by submitter, variant characteristics, classification method, and available supporting data. To further reform interpretation of FH-associated variants, areas for improvement in variant submissions were identified; these include a need for more detailed submissions and submission of supporting variant-level data, both retrospectively and prospectively. Collaborating to provide thorough, reliable evidence-based variant interpretation will ultimately improve the care of FH patients. The ClinGen consortium is funded by the National Human Genome Research Institute of the National Institutes of Health through the following grants and contracts: U41HG006834, U41HG009649, U41HG009650, U01HG007436, and U01HG007437. info:eu-repo/semantics/publishedVersion

Published
2018

43. The usefulness of advanced lipid and oxidative stress testing for diagnosis and management of low HDL-cholesterol phenotype: A case report

Author

Jovan Kosutic, Philippe Couvert, Jelena Vekic, Dragana Bojanin, Jelena Kotur-Stevuljevic, Aleksandra Zeljkovic, Vesna Spasojevic-Kalimanovska, Alain Carrié, Vladimir Kuburovic, Nina Kuburovic, and Milica Miljković

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Clinical Biochemistry, Small, dense LDL, Tangier disease, 030204 cardiovascular system & hematology, medicine.disease_cause, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, HDL subclasses, Internal medicine, medicine, Humans, Child, Tangier Disease, biology, Aryldialkylphosphatase, Cholesterol, HDL, Paraoxonase, PON1 status, nutritional and metabolic diseases, General Medicine, medicine.disease, Malondialdehyde, PON1, 3. Good health, Oxidative Stress, 030104 developmental biology, Endocrinology, chemistry, Oxidative stress, ABCA1, biology.protein, lipids (amino acids, peptides, and proteins), Lipid Peroxidation, ATP Binding Cassette Transporter 1, Lipoprotein
Abstract

Objective Plasma high-density lipoprotein cholesterol (HDL-C) level is a strong inverse predictor of cardiovascular disease (CVD) development. Tangier disease, a consequence of mutations in the ATP binding cassette transporter 1 (ABCA1) gene, is associated with very low HDL-C levels. Still, the relationship between Tangier disease and CVD is not always evident. The study investigates usefulness of lipoprotein subfractions, oxidative stress and paraoxonase 1 (PON1) status assessment for evaluation and management of patient with low HDL-C phenotype. Patient and methods A 12-year-old boy was hospitalised due to hypertension. Laboratory evaluation revealed low HDL-C level, and subsequent molecular diagnostic confirmed Tangier disease. Lipoprotein subfractions were assessed by gradient-gel electrophoresis. Oxidative stress status was estimated by measuring total antioxidative status, total oxidative status, prooxidative-antioxidative balance, malondialdehyde and advanced oxidation protein products levels. Activity of paraoxonase 1 in serum and its distribution within HDL subclasses was also determined (ten healthy boys aged 13.1 ± 3.4 years served as the reference group). Results Analysis of oxidative stress status biomarkers revealed a state of prolonged prooxidants activity. In turn, serum PON1 activity was substantially reduced. The majority of PON1 activity was present on HDL 2 particles. Conclusion Impaired antioxidative potential of HDL may point toward hidden cardiovascular risk in isolated low HDL-phenotype.

Published
2017

44. Early Coronary Calcifications are Related to Cholesterol Burden in Heterozygous Familial Hypercholesterolemia

Author

Valérie Carreau, Eric Bruckert, Alain Carrié, Philippe Giral, Randa Bittar, Sophie Béliard, Marianna Maranghi, Philippe Cluzel, Antonio Gallo, David Rosenbaum, Alban Redheuil, Marcello Arca, HAL-UPMC, Gestionnaire, Service d'Endocrinologie, Métabolisme et Prévention des Maladies Cardio-vasculaires [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Policlinico 'Umberto I', Universita' 'La Sapienza', Université Pierre et Marie Curie - Paris 6 (UPMC), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Dyslipidémies, inflammation et athérosclérose dans les maladies métaboliques, Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière], Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Service de radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière], and Laboratoire d'Imagerie Biomédicale [Paris] (LIB)

Subjects
Male, Multivariate analysis, Endocrinology, Diabetes and Metabolism, Familial hypercholesterolemia, Coronary Artery Disease, 030204 cardiovascular system & hematology, Cardiovascular disease prevention, Gastroenterology, Calcium Score, chemistry.chemical_compound, 0302 clinical medicine, 030212 general & internal medicine, Familial Hypercholesterolemia, education.field_of_study, Nutrition and Dietetics, Calcinosis, Middle Aged, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cholesterol burden, Cholesterol, Coronary Artery Calcification, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, Adult, medicine.medical_specialty, Heterozygote, Population, Asymptomatic, Hyperlipoproteinemia Type II, 03 medical and health sciences, Young Adult, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Internal Medicine, medicine, Humans, In patient, education, Coronary atherosclerosis, business.industry, nutritional and metabolic diseases, medicine.disease, Surgery, chemistry, Coronary artery calcification, business, Calcium score
Abstract

Background The identification of high-risk patients with Heterozygous Familial Hypercholesterolemia (HeFH) that may benefit from early treatment is challenging. Coronary Artery Calcification (CAC) score accounts for coronary atherosclerotic burden. It has proven its accuracy in cardiovascular risk (CVR) assessment in the general population but data in HeFH are lacking. Objective The aim of our study was to assess CAC prevalence and its relationship with lifelong cholesterol exposure, calculated by Total Cholesterol Burden (TCB) in patients with HeFH. Methods 112 HeFH patients (50% males, median age 45) regularly followed-up since diagnosis were prospectively recruited at Pitie-Salpetriere Hospital, Paris, France. CAC score was assessed using non contrast multi-detector computed tomography. TCB was calculated as total cholesterol (TC) x age at diagnosis plus annually assessed TC. Results The prevalence of CAC was 58%. Patients without CAC showed lower TCB than patients with CAC (298±110 vs 417.9±89 mmol-years/l, p

Published
2017

45. Genetic Testing of Familial Hypercholesterolemia: Monogenic Form and Polygenic Contribution to Cardiovascular Risk

Author

F. Paillard, Valérie Carreau, Jean Marc Lacorte, Philippe Giral, Pierre-Yves Boëlle, Eric Bruckert, Philippe Lesnik, Annelies Rotthier, Alain Carrié, Sophie Béliard, Philippe Couvert, René Valéro, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Multiplicom NV Galileilaan, and Partenaires INRAE

Subjects
Genetics, medicine.diagnostic_test, business.industry, [SDV]Life Sciences [q-bio], medicine, Familial hypercholesterolemia, Cardiology and Cardiovascular Medicine, medicine.disease, business, Genetic testing
Published
2017

46. Physiopathology of necrobiotic xanthogranuloma with monoclonal gammopathy

Author

Eric Bruckert, Jean Paul Fermand, P. Cathébras, Alain Carrié, Elise F. Villard, Paul Robillard, W. Le Goff, P. Lesnik, Maryse Guerin, F. Saint-Charles, Pedro J. Giral, J. Pirault, John Chapman, Raphael Szalat, Eric Frisdal, and M. Olivier

Subjects
Male, medicine.medical_specialty, HDL, immune complex, medicine.medical_treatment, Paraproteinemias, Enzyme-Linked Immunosorbent Assay, Inflammation, Xanthoma, chemistry.chemical_compound, Internal medicine, Internal Medicine, medicine, Humans, Necrobiotic xanthogranuloma, Aged, Aged, 80 and over, monoclonal immunoglobulin, medicine.diagnostic_test, Cholesterol, business.industry, Macrophages, Cholesterol, HDL, Original Articles, Middle Aged, Lipid Metabolism, Necrobiotic Xanthogranuloma, medicine.disease, Immune complex, Phenotype, Cytokine, Endocrinology, histiocytes, chemistry, Case-Control Studies, Immunoglobulin G, monocyte, Leukocytes, Mononuclear, Cytokines, Female, Tumor necrosis factor alpha, medicine.symptom, business, Lipid profile
Abstract

Rationale Xanthomatosis associated with monoclonal gammopathy includes hyperlipidaemic xanthoma (HX), normolipidaemic xanthoma (NX) and necrobiotic xanthogranuloma (NXG). All three pathologies are characterized by skin or visceral lesions related to cholesterol accumulation, monoclonal immunoglobulin (MIg) and hypocomplementemia. The pathophysiology underlying NXG remains unknown although the involvement of MIg is suspected. Objective To provide further insights into the pathophysiology of NXG, we evaluated the plasma lipid phenotype, mechanisms involved in cellular cholesterol accumulation and role of MIg in an analysis of blood and plasma markers of inflammation in 16 patients with xanthomatosis [NXG (n = 8) and NX (n = 8)] associated with monoclonal IgG relative to the relevant controls. Results The lipid profile of patients with NXG was characterized by a low HDL-C phenotype and an abnormal distribution of HDL particles. Sera from patients with NXG induced cholesterol accumulation in human macrophages. This accumulation was due in part to a significant reduction in the HDL capacity to promote cholesterol efflux from macrophages, which was not found in the case of NX. The MIg of NXG and NX patients was tested positively by ELISA to recognize a large spectrum of lipoproteins. High plasma levels of pro-inflammatory cytokines (TNFα and IL-6), soluble cytokine receptors (sIL-6R, sTNFRI and sTNFRII), adhesion molecules (VCAM-1 and ICAM-1) and chemokines (MCP-1, IL-8 and MIP-1α) were observed in both patients with NXG and NX, revealing a specific xanthoma inflammatory signature which was inversely correlated with plasma levels of anti-inflammatory HDL. However, patients with NXG were distinguished by elevated levels of IL-15 and a marked increase in the rate of intermediate CD14++CD16+ monocytes. Conclusion This study revealed that NXG is characterized by impaired macrophage lipid homeostasis associated with a systemic inflammatory profile that may result from the interaction of MIg and lipoproteins.

Published
2014

47. Burden of cardiovascular disease in a large contemporary cohort of patients with heterozygous familial hypercholesterolemia

Author

Jean Ferrières, Michel Farnier, Eric Bruckert, Alexandre Vimont, Vincent Durlach, Emile Ferrari, Antonio Gallo, Franck Boccara, Dorota Ferrières, Sophie Béliard, Denis Angoulvant, Karine Aouchiche, Sophie Beliard, Bertrand Cariou, Valérie Carreau, Alain Carrie, Sybil Charrieres, Yves Cottin, Mathilde Di Filippo, Caroline Dourmap, Pierre-Henri Ducluzeau, Dorota Ferrieres, Jean Ferrieres, Regis Hankard, Jocelyn Inamo, Olga Kalmykova, Michel Krempf, Julie Lemale, Philippe Moulin, François Paillard, Noel Peretti, Agnes Perrin, Alain Pradignac, Yann Pucheu, Jean Pierre Rabes, Rachel Reynaud, Vincent Rigalleau, François Schiele, Ariane Sultan, Patrick Tounian, René Valero, Bruno Verges, Cecile Yelnik, and Olivier Ziegler

Subjects
Heterozygous familial hypercholesterolemia, Registry, Incidence, Recurrence, Lipid-lowering treatment, Prognosis, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background and aims: Heterozygous familial hypercholesterolemia (HeFH) is increasingly better diagnosed and treatments can improve the cardiovascular prognosis. We evaluated the long-term cardiovascular risk of HeFH using the French REgistry of Familial hypERCHOLesterolemia (REFERCHOL). Methods: We studied HeFH patients diagnosed genetically and clinically by the Dutch Lipid Clinic Network (DLCN) criteria in all lipid clinics across the country and their 5-year risk of cardiovascular events (all fatal and non-fatal acute coronary, cerebral and peripheral arterial disease events, aortic valve replacement surgery) using the French national health data system. Results: The database comprised 3202 individuals, 2010 (62.8%) with genetically verified HeFH and 1192 (37.2%) a DLCN score ≥6. Of these individuals, 2485 (77.6%) were in primary prevention and 717 (22.4%) in secondary prevention. The incidence of cardiovascular events was 24.58 per 1000 person-years for the overall sample, 19.15 in primary prevention and 43.40 in secondary prevention. The incidence of myocardial infarction, cerebral infarction and death was 16.32 per 1000 person-years for the overall sample, 12.93 in primary prevention and 28.08 in secondary prevention. The incidence of aortic valve replacement was 1.78 per 1000 person-years. In the overall sample, at inclusion, 41% were not treated for LDL cholesterol, 48% of these in primary prevention and 20% in secondary prevention and high-dose statins were used by only 24% of individuals, 15% of these in primary prevention and 45% in secondary prevention. Conclusions: The incidence of cardiovascular events in HeFH is high and lipid-lowering treatment is far from optimal. The cardiovascular risk of HeFH is underestimated and patients are inadequately treated.

Published
2022
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49. Specification Of Acmg/Amp Guidelines For Variant Interpretation In Familial Hypercholesterolemia

Author

Joana Rita Chora, Alain Carrié, Eric J.G. Sijbrands, Mafalda Bourbon, Lukáš Tichý, Joshua W. Knowles, Sarah Leigh, Michael A. Lacocca, Robert A. Hegele, Tomáš Freiberger, and C. Lisa Kurtz

Subjects
Interpretation (philosophy), medicine, Library science, Familial hypercholesterolemia, Familial Hypercholesterolemia, Guidelines, Cardiology and Cardiovascular Medicine, medicine.disease, Psychology, Child health, Human development (humanity), Doenças Cardio e Cérebro-vasculares
Abstract

Background and Aims: the general ACMG/AMP guidelines for standardized variant interpretation in Mendelian disorders are a great asset in determining variants’ pathogenicity, but need to be adapted to each specific gene and disease. With thanks to the EAS for support in the form of a Young Investigator Fellowship. The contents of this poster are presented on behalf of the ClinGen FH Variant Curation Committee. JR Chora is funded by SFRH/BD/108503/2015. ClinGen is primarily funded by the National Human Genome Research Institute (NHGRI) (grants U41HG006834, U41HG009649, U41HG009650). ClinGen also receives support for content curation from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (grants U24HD093483, U24HD093486, U24HD093487). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. N/A

Published
2019

50. The very high cardiovascular risk in heterozygous familial hypercholesterolemia: Analysis of 734 French patients

Author

Olivier Ziegler, Philippe Moulin, J.D. Lalau, Franck Boccara, Michel Farnier, B. Vergès, Michel Krempf, Sophie Béliard, Mondher Toumi, Noël Peretti, Régis Hankard, Valérie Carreau, V. Durlach, Alain Carrié, David Rosenbaum, Gérald Luc, F. Paillard, P. Moulin, Patrick Tounian, Aurélie Millier, Denis Angoulvant, Jean Ferrières, G. Luc, E. Bruckert, Eric Bruckert, A. Pradignac, S. Béliard, Y. Pucheu, Alexandre Fredenrich, Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and W.V. Brown

Subjects
Male, Endocrinology, Diabetes and Metabolism, Disease, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Body Mass Index, 0302 clinical medicine, Risk Factors, Hyperlipidemia, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, education.field_of_study, Nutrition and Dietetics, Anticholesteremic Agents, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Plaque, Atherosclerotic, 3. Good health, Carotid Arteries, Cholesterol, Cardiovascular Diseases, LDL cholesterol, Female, France, Cardiology and Cardiovascular Medicine, Adult, medicine.medical_specialty, Population, Hypercholesterolemia, Hyperlipoproteinemia Type II, 03 medical and health sciences, Internal medicine, Internal Medicine, medicine, Humans, Risk factor, education, Aged, Retrospective Studies, business.industry, Maximum level, Cholesterol, LDL, medicine.disease, Cardiovascular risk, Cross-Sectional Studies, Physical therapy, Heterozygous familial hypercholesterolemia, business, Very high risk, Body mass index
Abstract

International audience; BACKGROUND: Heterozygous familial hypercholesterolemia (heFH) is a genetic disease causing high levels of low-density lipoprotein cholesterol (LDL-C). Although this population is at high cardiovascular (CV) risk, the risk is variable within patients depending on additional risk factors. CV disease risk groups have been defined by the Nouvelle Societe Francophone d'Atherosclerose (NSFA) and by the National Lipid Association recommendations. OBJECTIVES: The study aimed to describe a sample of French heFH patients, comparing patients at very high risk (VHR) and patients at high risk in terms of demographic and clinical characteristics as well as biological measurements and disease management. METHODS: Cross-sectional retrospective analysis on 734 patients hospitalized after 2005 in 5 academic centers. RESULTS: When considering NSFA classification, 550 (74.9%) patients belonged to the VHR group. Most patients in the VHR group presented more than 1 risk factor, the most prevalent ones being Lp(a) > 50 mg/dL and smoking. Patients in the VHR group were older (50.6 vs 45.0 years old, P =.0002), and presented a higher body mass index (25.5 kg/m(2) vs 23.3 kg/m(2), P

Published
2016

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