Author: "Bertrand, Cariou" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Bertrand, Cariou"' showing total 485 results

Start Over Author "Bertrand, Cariou"

485 results on '"Bertrand, Cariou"'

1. Human induced pluripotent stem cells‐derived liver organoids grown on a Biomimesys® hyaluronic acid‐based hydroscaffold as a new model for studying human lipoprotein metabolism

Author: Meryl Roudaut, Amandine Caillaud, Zied Souguir, Lise Bray, Aurore Girardeau, Antoine Rimbert, Mikaël Croyal, Gilles Lambert, Murielle Patitucci, Gaspard Delpouve, Élodie Vandenhaute, Cédric Le May, Nathalie Maubon, Bertrand Cariou, and Karim Si‐Tayeb
Subjects: cytochrome activities, hiPSC‐derived liver organoids, hyaluronic‐acid based hydroscaffold, lipid metabolism, liver steatosis, Lp(a), Chemical engineering, TP155-156, Biotechnology, TP248.13-248.65, Therapeutics. Pharmacology, RM1-950
Abstract: Abstract The liver plays a key role in the metabolism of lipoproteins, controlling both production and catabolism. To accelerate the development of new lipid‐lowering therapies in humans, it is essential to have a relevant in vitro study model available. The current hepatocyte‐like cells (HLCs) models derived from hiPSC can be used to model many genetically driven diseases but require further improvement to better recapitulate the complexity of liver functions. Here, we aimed to improve the maturation of HLCs using a three‐dimensional (3D) approach using Biomimesys®, a hyaluronic acid‐based hydroscaffold in which hiPSCs may directly form aggregates and differentiate toward a functional liver organoid model. After a 28‐day differentiation 3D protocol, we showed that many hepatic genes were upregulated in the 3D model (liver organoids) in comparison with the 2D model (HLCs). Liver organoids, grown on Biomimesys®, exhibited an autonomous cell organization, were composed of different cell types and displayed enhanced cytochromes P450 activities compared to HLCs. Regarding the functional capacities of these organoids, we showed that they were able to accumulate lipids (hepatic steatosis), internalize low‐density lipoprotein and secrete apolipoprotein B. Interestingly, we showed for the first time that this model was also able to produce apolipoprotein (a), the apolipoprotein (a) specific of Lp(a). This innovative hiPSC‐derived liver organoid model may serve as a relevant model for studying human lipopoprotein metabolism, including Lp(a).
Published: 2024
Full Text: View/download PDF

2. 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
Full Text: View/download PDF

3. Generation of an induced pluripotent stem cell line (ITXi012-A) from a patient with genetically determined high-lipoprotein(a) plasma levels

Author: Amandine Caillaud, Lise Bray, Aurore Girardeau, Zoé Begué-Racapé, Lucie Vince, Murielle Patitucci, Cédric Le May, Gilles Lambert, Bertrand Cariou, and Antoine Rimbert
Subjects: Biology (General), QH301-705.5
Abstract: Elevated circulating lipoprotein(a) (Lp(a)) is a genetically determined risk factor for coronary artery disease and aortic valve stenosis (Tsimikas, 2017). Importantly, the LPA gene, which encodes the apolipoprotein(a) (protein-component of Lp(a)), is missing in most species, and human liver cell-lines do not secrete Lp(a). There is a need for the development of human in vitro models suitable for investigating biological mechanisms involved in Lp(a) metabolism. We here generated and characterized iPSCs from a patient with extremely high Lp(a) plasma levels genetically determined (Coassin et al., 2022). This unique cellular model offers great opportunities and new perspectives for investigations on biological mechanisms involved in Lp(a) metabolism.
Published: 2023
Full Text: View/download PDF

4. Protection against stroke with glucagon-like peptide-1 receptor agonists: a comprehensive review of potential mechanisms

Author: Bruno Vergès, Victor Aboyans, Denis Angoulvant, Pierre Boutouyrie, Bertrand Cariou, Fabien Hyafil, Kamel Mohammedi, and Pierre Amarenco
Subjects: Stroke, Glucagon-like peptide-1 receptor agonists, GLP-1, Neuroprotection, Mechanisms, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Several randomized controlled trials have demonstrated the benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on ischemic stroke in patients with diabetes. In this review, we summarize and discuss the potential mechanisms of stroke protection by GLP-1RAs. GLP-1RAs exert multiple anti-atherosclerotic effects contributing to stroke prevention such as enhanced plaque stability, reduced vascular smooth muscle proliferation, increased nitric oxide, and improved endothelial function. GLP-1RAs also lower the risk of stroke by reducing traditional stroke risk factors including hyperglycemia, hypertension, and dyslipidemia. Independently of these peripheral actions, GLP-1RAs show direct cerebral effects in animal stroke models, such as reduction of infarct volume, apoptosis, oxidative stress, neuroinflammation, excitotoxicity, blood–brain barrier permeability, and increased neurogenesis, neuroplasticity, angiogenesis, and brain perfusion. Despite these encouraging findings, further research is still needed to understand more thoroughly the mechanisms by which GLP-1RAs may mediate stroke protection specifically in the human diabetic brain.
Published: 2022
Full Text: View/download PDF

5. The association between macrovascular complications and intensive care admission, invasive mechanical ventilation, and mortality in people with diabetes hospitalized for coronavirus disease-2019 (COVID-19)

Author: Gemma Llauradó, Bogdan Vlacho, Matthieu Wargny, Yue Ruan, Josep Franch-Nadal, Pere Domingo, Pierre Gourdy, Pierre-Jean Saulnier, Samy Hadjadj, Sarah H. Wild, Rustam Rea, Bertrand Cariou, Kamlesh Khunti, Dídac Mauricio, and for the CORONADO, the ABCD COVID-19 diabetes national audit, HM Hospitales investigators and the Hospital del Mar - Hospital de la Santa Creu i Sant Pau Diabetes Research Group
Subjects: Diabetes, Macrovascular disease, Mortality, COVID-19, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Background It is not clear whether pre-existing macrovascular complications (ischemic heart disease, stroke or peripheral artery disease) are associated with health outcomes in people with diabetes mellitus hospitalized for COVID-19. Methods We conducted cohort studies of adults with pre-existing diabetes hospitalized for COVID-19 infection in the UK, France, and Spain during the early phase of the pandemic (between March 2020—October 2020). Logistic regression models adjusted for demographic factors and other comorbidities were used to determine associations between previous macrovascular disease and relevant clinical outcomes: mortality, intensive care unit (ICU) admission and use of invasive mechanical ventilation (IMV) during the hospitalization. Output from individual logistic regression models for each cohort was combined in a meta-analysis. Results Complete data were available for 4,106 (60.4%) individuals. Of these, 1,652 (40.2%) had any prior macrovascular disease of whom 28.5% of patients died. Mortality was higher for people with compared to those without previous macrovascular disease (37.7% vs 22.4%). The combined crude odds ratio (OR) for previous macrovascular disease and mortality for all four cohorts was 2.12 (95% CI 1.83–2.45 with an I2 of 60%, reduced after adjustments for age, sex, type of diabetes, hypertension, microvascular disease, ethnicity, and BMI to adjusted OR 1.53 [95% CI 1.29–1.81]) for the three cohorts. Further analysis revealed that ischemic heart disease and cerebrovascular disease were the main contributors of adverse outcomes. However, proportions of people admitted to ICU (adjOR 0.48 [95% CI 0.31–0.75], I2 60%) and the use of IMV during hospitalization (adjOR 0.52 [95% CI 0.40–0.68], I2 37%) were significantly lower for people with previous macrovascular disease. Conclusions This large multinational study of people with diabetes mellitus hospitalized for COVID-19 demonstrates that previous macrovascular disease is associated with higher mortality and lower proportions admitted to ICU and treated with IMV during hospitalization suggesting selective admission criteria. Our findings highlight the importance correctly assess the prognosis and intensive monitoring in this high-risk group of patients and emphasize the need to design specific public health programs aimed to prevent SARS-CoV-2 infection in this subgroup.
Published: 2022
Full Text: View/download PDF

6. Extracellular vesicles are carriers of adiponectin with insulin-sensitizing and anti-inflammatory properties

Author: Alexia Blandin, Jérémy Amosse, Josy Froger, Grégory Hilairet, Maëva Durcin, Lionel Fizanne, Valentine Ghesquière, Xavier Prieur, Julien Chaigneau, Luisa Vergori, Cédric Dray, Jean-Philippe Pradère, Stéphanie Blandin, Joëlle Dupont, Pierre-Henri Ducluzeau, Séverine Dubois, Jérôme Boursier, Bertrand Cariou, and Soazig Le Lay
Subjects: CP: Metabolism, Biology (General), QH301-705.5
Abstract: Summary: Recent evidence supporting that adipose tissue (AT)-derived extracellular vesicles (EVs) carry an important part of the AT secretome led us to characterize the EV-adipokine profile. In addition to evidencing a high AT-derived EV secretion ability that is further increased by obesity, we identify enrichment of oligomeric forms of adiponectin in small EVs (sEVs). This adipokine is mainly distributed at the EV external surface as a result of nonspecific adsorption of soluble adiponectin. EVs also constitute stable conveyors of adiponectin in the blood circulation. Adiponectin-enriched sEVs display in vitro insulin-sensitizing effects by binding to regular adiponectin receptors. Adoptive transfer of adiponectin-enriched sEVs in high-fat-diet-fed mice prevents animals from gaining weight and ameliorated insulin resistance and tissue inflammation, with major effects observed in the AT and liver. Our results therefore provide information regarding adiponectin-related metabolic responses by highlighting EVs as delivery platforms of metabolically active forms of adiponectin molecules.
Published: 2023
Full Text: View/download PDF

7. Nutritional biomarkers and heart failure requiring hospitalization in patients with type 2 diabetes: the SURDIAGENE cohort

Author: Matthieu Wargny, Mikaël Croyal, Stéphanie Ragot, Elise Gand, David Jacobi, Jean-Noël Trochu, Xavier Prieur, Cédric Le May, Thomas Goronflot, Bertrand Cariou, Pierre-Jean Saulnier, Samy Hadjadj, and for the SURDIAGENE study group
Subjects: TMAO, Nutritional biomarkers, Diabetes mellitus, Heart failure, Cohort study, Homocysteine, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Background Heart failure (HF) is a growing complication and one of the leading causes of mortality in people living with type 2 diabetes (T2D). Among the possible causes, the excess of red meat and the insufficiency of vegetables consumption are suspected. Such an alimentation is associated with nutritional biomarkers, including trimethylamine N-oxide (TMAO) and its precursors. Here, we aimed to study these biomarkers as potential prognostic factors for HF in patients with T2D. Methods We used the SURDIAGENE (SURvival DIAbetes and GENEtics) study, a large, prospective, monocentric cohort study including 1468 patients with T2D between 2001 and 2012. TMAO and its precursors (trimethylamine [TMA], betaine, choline, and carnitine) as well as thio-amino-acids (cysteine, homocysteine and methionine) were measured by liquid chromatography-tandem mass spectrometry. The main outcome was HF requiring Hospitalization (HFrH) defined as the first occurrence of acute HF leading to hospitalization and/or death, established by an adjudication committee, based on hospital records until 31st December 2015. The secondary outcomes were the composite event HFrH and/or cardiovascular death and all-cause death. The association between the biomarkers and the outcomes was studied using cause-specific hazard-models, adjusted for age, sex, history of coronary artery disease, NT-proBNP, CKD-EPI-derived eGFR and the urine albumin/creatinine ratio. Hazard-ratios (HR) are expressed for one standard deviation. Results The data of interest were available for 1349/1468 of SURDIAGENE participants (91.9%), including 569 (42.2%) women, with a mean age of 64.3 ± 10.7 years and a median follow-up of 7.3 years [25th–75th percentile, 4.7–10.8]. HFrH was reported in 209 patients (15.5%), HFrH and/or cardiovascular death in 341 (25.3%) and all-cause death in 447 (33.1%). In unadjusted hazard-models, carnitine (HR = 1.20, 95% CI [1.05; 1.37]), betaine (HR = 1.34, [1.20; 1.50]), choline (HR = 1.35, [1.20; 1.52]), TMAO (HR = 1.32, [1.16; 1.50]), cysteine (HR = 1.38, [1.21; 1.58]) and homocysteine (HR = 1.28, [1.17; 1.39]) were associated with HFrH, but not TMA and methionine. In the fully adjusted models, none of these associations was significant, neither for HFrH nor for HFrH and/or CV death, when homocysteine only was positively associated with all-cause death (HR = 1.16, [1.06; 1.27]). Conclusions TMAO and its precursors do not appear to be substantial prognosis factors for HFrH, beyond usual cardiac- and kidney-related risk factors, whereas homocysteine is an independent risk factor for all-cause death in patients with T2D.
Published: 2022
Full Text: View/download PDF

8. Lipidomic analysis of adipose-derived extracellular vesicles reveals specific EV lipid sorting informative of the obesity metabolic state

Author: Alexia Blandin, Isabelle Dugail, Grégory Hilairet, Maharajah Ponnaiah, Valentine Ghesquière, Josy Froger, Simon Ducheix, Lionel Fizanne, Jérôme Boursier, Bertrand Cariou, Marie Lhomme, and Soazig Le Lay
Subjects: CP: Metabolism, Biology (General), QH301-705.5
Abstract: Summary: Adipose extracellular vesicles (AdEVs) transport lipids that could participate in the development of obesity-related metabolic dysfunctions. This study aims to define mouse AdEV lipid signature by a targeted LC-MS/MS approach in either healthy or obesity context. Distinct clustering of AdEV and visceral adipose tissue (VAT) lipidomes by principal component analysis reveals specific AdEV lipid sorting when compared with secreting VAT. Comprehensive analysis identifies enrichment of ceramides, sphingomyelins, and phosphatidylglycerols species in AdEVs compared with source VAT whose lipid content closely relates to the obesity status and is influenced by the diet. Obesity moreover impacts AdEV lipidome, mirroring lipid alterations retrieved in plasma and VAT. Overall, our study identifies specific lipid fingerprints for plasma, VAT, and AdEVs that are informative of the metabolic status. Lipid species enriched in AdEVs in the obesity context may constitute biomarker candidates or mediators of the obesity-associated metabolic dysfunctions.
Published: 2023
Full Text: View/download PDF

9. Plasma apolipoprotein concentrations and incident diabetes in subjects with prediabetes

Author: Mikaël Croyal, Matthieu Wargny, Kevin Chemello, Chloé Chevalier, Valentin Blanchard, Edith Bigot-Corbel, Gilles Lambert, Cédric Le May, Samy Hadjadj, and Bertrand Cariou
Subjects: New-onset diabetes, Type 2 diabetes, Apolipoproteins, Apolipoprotein E, IT-Diab study, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Background The identification of circulating biomarkers associated with the risk of type 2 diabetes (T2D) is useful for improving the current prevention strategies in the most at-risk patients. Here, we aimed to investigate the association of plasma apolipoprotein concentrations in prediabetes subjects with the incidence of new-onset T2D during follow-up. Methods In the IT-DIAB prospective study, 307 participants with impaired fasting glucose levels (fasting plasma glucose [FPG]: 110–125 mg/dL) were followed yearly for 5 years. The onset of T2D was defined as a first FPG value ≥ 126 mg/dL during follow-up. Apolipoprotein (apo)A-I, A-II, A-IV, B100, C-I, C-II, C-III, C-IV, D, E, F, H, J, L1, M, and (a) plasma concentrations were determined by mass spectrometry. Correlations between apolipoproteins and metabolic parameters at baseline were assessed by Spearman’s coefficients. Kaplan–Meier curves were drawn using a ternary approach based on terciles and incident T2D. The association between plasma apolipoproteins concentrations and the incidence of T2D was determined using Cox proportional-hazards models. Results During a median follow-up of 5-year, 115 participants (37.5%) developed T2D. After adjustment for age, sex, body mass index, FPG, HbA1c, and statin use, the plasma levels of apoC-I, apoC-II, apoC-III, apoE, apoF, apoH, apoJ, and apoL1 were positively associated with a high risk for T2D. After further adjustment for plasma triglycerides, only apoE (1 SD natural-log-transformed hazard ratio: 1.28 [95% confidence interval: 1.06; 1.54]; p = 0.010), apoF (1.22 [1.01; 1.48]; p = 0.037), apoJ (1.24 [1.03; 1.49]; p = 0.024), and apoL1 (1.26 [1.05; 1.52]; p = 0.014) remained significantly associated with the onset of T2D. Kaplan–Meier survival curves also showed that the lower third of plasma apoE levels (
Published: 2022
Full Text: View/download PDF

10. FACS-assisted CRISPR-Cas9 genome editing of human induced pluripotent stem cells

Author: Amandine Caillaud, Antoine Lévêque, Aurélie Thédrez, Aurore Girardeau, Robin Canac, Lise Bray, Manon Baudic, Julien Barc, Nathalie Gaborit, Guillaume Lamirault, Betty Gardie, Salam Idriss, Antoine Rimbert, Cédric Le May, Bertrand Cariou, and Karim Si-Tayeb
Subjects: CRISPR, Flow cytometry/Mass cytometry, Stem cells, Science (General), Q1-390
Abstract: Summary: This manuscript proposes an efficient and reproducible protocol for the generation of genetically modified human induced pluripotent stem cells (hiPSCs) by genome editing using CRISPR-Cas9 technology. Here, we describe the experimental strategy for generating knockout (KO) and knockin (KI) clonal populations of hiPSCs using single-cell sorting by flow cytometry. We efficiently achieved up to 15 kb deletions, molecular tag insertions, and single-nucleotide editing in hiPSCs. We emphasize the efficacy of this approach in terms of cell culture time.For complete details on the use and execution of this protocol, please refer to Canac et al. (2022) and Bray et al. (2022). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
Published: 2022
Full Text: View/download PDF

11. Treatment adherence and effect of concurrent statin intensity on the efficacy and safety of alirocumab in a real-life setting: results from ODYSSEY APPRISE

Author: Maciej Banach, José Luis López-Sendon, Maurizio Averna, Bertrand Cariou, Megan Loy, Garen Manvelian, Isabela Batsu, Yann Poulouin, and Daniel Gaudet
Subjects: cholesterol, low-density lipoprotein, pcsk9, treatment adherence, Medicine
Abstract: Introduction The phase IIIb open-label ODYSSEY APPRISE study prospectively assessed the safety and efficacy of alirocumab (a proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitor) in a real-life setting in high cardiovascular risk patients with heterozygous familial hypercholesterolemia or low-density lipoprotein cholesterol (LDL-C) not at goal despite maximally tolerated dose statins ± other lipid-lowering therapies (NCT02476006). This post-hoc analysis assessed patient adherence to statins and alirocumab, plus alirocumab efficacy and safety, according to concomitant statin intensity and prior ezetimibe usage. Material and methods Patients received alirocumab 75 or 150 mg (dose adjustment based on physician’s judgment) every 2 weeks (for ≥3 to ≤30 months). Results Of 994 enrolled and treated patients, 58.4% received concomitant high-intensity statins, 18.2% moderate/low-intensity statins, and 23.4% no statin; 55.9% received prior ezetimibe. Mean alirocumab adherence (percent adherence defined as injections received ÷ theoretical injections x 100) was 96.6% over 72.4 weeks’ mean treatment duration. Mean LDL-C reduction from baseline at Week 12 was similar between statin intensity subgroups (53.6–55.7%). More patients achieved LDL-C
Published: 2021
Full Text: View/download PDF

12. A high-throughput mass spectrometry-based assay for large-scale profiling of circulating human apolipoproteins[S]

Author: Valentin Blanchard, Damien Garçon, Catherine Jaunet, Kevin Chemello, Stéphanie Billon-Crossouard, Audrey Aguesse, Aya Garfa, Gilles Famchon, Amada Torres, Cédric Le May, Matthieu Pichelin, Edith Bigot-Corbel, Gilles Lambert, Bertrand Cariou, Samy Hadjadj, Michel Krempf, Kalyane Bach-Ngohou, and Mikaël Croyal
Subjects: proteomics, lipoprotein metabolism, metabolic disease, assay development, isotopic labeling, lipid metabolism, Biochemistry, QD415-436
Abstract: Apolipoproteins govern lipoprotein metabolism and are promising biomarkers of metabolic and cardiovascular diseases. Unlike immunoassays, MS enables the quantification and phenotyping of multiple apolipoproteins. Hence, here, we aimed to develop a LC-MS/MS assay that can simultaneously quantitate 18 human apolipoproteins [A-I, A-II, A-IV, A-V, B48, B100, C-I, C-II, C-III, C-IV, D, E, F, H, J, L1, M, and (a)] and determined apoE, apoL1, and apo(a) phenotypes in human plasma and serum samples. The plasma and serum apolipoproteins were trypsin digested through an optimized procedure and peptides were extracted and analyzed by LC-MS/MS. The method was validated according to standard guidelines in samples spiked with known peptide amounts. The LC-MS/MS results were compared with those obtained with other techniques, and reproducibility, dilution effects, and stabilities were also assessed. Peptide markers were successfully selected for targeted apolipoprotein quantification and phenotyping. After optimization, the assay was validated for linearity, lower limits of quantification, accuracy (biases: –14.8% to 12.1%), intra-assay variability [coefficients of variation (CVs): 1.5–14.2%], and inter-assay repeatability (CVs: 4.1–14.3%). Bland-Altman plots indicated no major statistically significant differences between LC-MS/MS and other techniques. The LC-MS/MS results were reproducible over five repeated experiments (CVs: 1.8–13.7%), and we identified marked differences among the plasma and serum samples. The LC-MS/MS assay developed here is rapid, requires only small sampling volumes, and incurs reasonable costs, thus making it amenable for a wide range of studies of apolipoprotein metabolism. We also highlight how this assay can be implemented in laboratories.
Published: 2020
Full Text: View/download PDF

13. Generation of a GPR146 knockout human induced pluripotent stem cell line (ITXi001-A-1)

Author: Lise Bray, Amandine Caillaud, Aurore Girardeau, Murielle Patitucci, Cédric Le May, Bertrand Cariou, and Antoine Rimbert
Subjects: Biology (General), QH301-705.5
Abstract: Dyslipidemia is a key modifiable causal risk factor involved in the development of atherosclerotic cardiovascular disease. Recently, the G protein-coupled receptor 146 (GPR146), a member of the G-coupled protein receptors’ family, has been shown to be a regulator of plasma cholesterol. Inhibition of hepatic GPR146 in mice displays protective effect against both hypercholesterolemia and atherosclerosis. Here, we characterize a genetically engineered human induced pluripotent stem cell (hiPSC) model invalidated for GPR146 (ITXi001-A-1) using CRISPR-Cas9 editing technology. Differentiation of ITXi001-A-1 towards hepatic fate will provide a suitable model for deciphering the molecular mechanisms sustaining the beneficial metabolic effects of GPR146 inhibition.
Published: 2022
Full Text: View/download PDF

14. Corrigendum: PCSK9 is not secreted from mature differentiated intestinal cells

Author: François Moreau, Aurélie Thédrez, Damien Garçon, Audrey Ayer, Thibaud Sotin, Wieneke Dijk, Claire Blanchard, Gilliane Chadeuf, Lucie Arnaud, Mikael Croyal, Laurianne Van Landeghem, Melissa Touvron, Xavier Prieur, Anna Roubtsova, Nabil Seidah, Annik Prat, Bertrand Cariou, and Cedric Le May
Subjects: Biochemistry, QD415-436
Published: 2022
Full Text: View/download PDF

15. Generation of human induced pluripotent stem cell lines from four unrelated healthy control donors carrying European genetic background

Author: Aurore Girardeau, Diane Atticus, Robin Canac, Bastien Cimarosti, Amandine Caillaud, Caroline Chariau, Floriane Simonet, Bertrand Cariou, Flavien Charpentier, Jean-Baptiste Gourraud, Vincent Probst, Nadjet Belbachir, Laurence Jesel, Patricia Lemarchand, Julien Barc, Richard Redon, Nathalie Gaborit, and Guillaume Lamirault
Subjects: Biology (General), QH301-705.5
Abstract: Four human induced pluripotent stem cell (hiPSC) lines have been generated from healthy control European donors, and validated. This resource represents a useful tool for stem cell-based research, as references for developmental studies and disease modeling linked to any type of human tissue and organ, in an ethnical-, sex- and age-matched context. They providea reliable in-vitro model for single cell- and tissue-based investigations, and are also a valuable tool for genome editing-based studies.
Published: 2022
Full Text: View/download PDF

16. Effect of alirocumab on individuals with type 2 diabetes, high triglycerides, and low high-density lipoprotein cholesterol

Author: Helen M. Colhoun, Lawrence A. Leiter, Dirk Müller-Wieland, Bertrand Cariou, Kausik K. Ray, Francisco J. Tinahones, Catherine Domenger, Alexia Letierce, Marc Israel, Rita Samuel, and Stefano Del Prato
Subjects: Alirocumab, PCSK9, Diabetes mellitus, Non-HDL-C, HDL-C, Triglycerides, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Background Mixed dyslipidemia [elevated non-high-density lipoprotein cholesterol (non-HDL-C) and triglycerides (TGs), and decreased HDL-C] is common in type 2 diabetes mellitus (T2DM) and is associated with increased cardiovascular risk. Non-HDL-C and apolipoprotein B (ApoB) are the preferred therapeutic targets for mixed dyslipidemia. Alirocumab is a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) that effectively reduces low-density lipoprotein cholesterol (LDL-C), non-HDL-C, ApoB, and lipoprotein(a) (Lp[a]), and is well-tolerated in individuals with T2DM. Methods The previously reported open-label ODYSSEY DM-DYSLIPIDEMIA trial data demonstrated the effects of alirocumab on individuals with non‐HDL-C ≥ 100 mg/dL and TGs ≥ 150 and
Published: 2020
Full Text: View/download PDF

17. Alirocumab therapy in individuals with type 2 diabetes mellitus and atherosclerotic cardiovascular disease: analysis of the ODYSSEY DM-DYSLIPIDEMIA and DM-INSULIN studies

Author: Kausik K. Ray, Stefano Del Prato, Dirk Müller-Wieland, Bertrand Cariou, Helen M. Colhoun, Francisco J. Tinahones, Catherine Domenger, Alexia Letierce, Jonas Mandel, Rita Samuel, Maja Bujas-Bobanovic, and Lawrence A. Leiter
Subjects: Alirocumab, Atherosclerotic cardiovascular disease, Type 2 diabetes mellitus, Low-density lipoprotein cholesterol, Dyslipidemia, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Background Individuals with diabetes often have high levels of atherogenic lipoproteins and cholesterol reflected by elevated low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and LDL particle number (LDL-PN). The presence of atherosclerotic cardiovascular disease (ASCVD) increases the risk of future cardiovascular events. We evaluated the efficacy and safety of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, alirocumab, among individuals with type 2 diabetes (T2DM), high LDL-C or non-HDL-C, and established ASCVD receiving maximally tolerated statin in ODYSSEY DM-DYSLIPIDEMIA (NCT02642159) and DM-INSULIN (NCT02585778). Methods In DM-DYSLIPIDEMIA, individuals with T2DM and mixed dyslipidemia (non-HDL-C ≥ 100 mg/dL; n = 413) were randomized to open-label alirocumab 75 mg every 2 weeks (Q2W) or usual care (UC) for 24 weeks, with UC options selected before stratified randomization. In DM-INSULIN, insulin-treated individuals with T2DM (LDL-C ≥ 70 mg/dL; n = 441) were randomized in a double-blind fashion to alirocumab 75 mg Q2W or placebo for 24 weeks. Study participants also had a glycated hemoglobin
Published: 2019
Full Text: View/download PDF

18. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Author: Amand F. Schmidt, Michael V. Holmes, David Preiss, Daniel I. Swerdlow, Spiros Denaxas, Ghazaleh Fatemifar, Rupert Faraway, Chris Finan, Dennis Valentine, Zammy Fairhurst-Hunter, Fernando Pires Hartwig, Bernardo Lessa Horta, Elina Hypponen, Christine Power, Max Moldovan, Erik van Iperen, Kees Hovingh, Ilja Demuth, Kristina Norman, Elisabeth Steinhagen-Thiessen, Juri Demuth, Lars Bertram, Christina M. Lill, Stefan Coassin, Johann Willeit, Stefan Kiechl, Karin Willeit, Dan Mason, John Wright, Richard Morris, Goya Wanamethee, Peter Whincup, Yoav Ben-Shlomo, Stela McLachlan, Jackie F. Price, Mika Kivimaki, Catherine Welch, Adelaida Sanchez-Galvez, Pedro Marques-Vidal, Andrew Nicolaides, Andrie G. Panayiotou, N. Charlotte Onland-Moret, Yvonne T. van der Schouw, Giuseppe Matullo, Giovanni Fiorito, Simonetta Guarrera, Carlotta Sacerdote, Nicholas J. Wareham, Claudia Langenberg, Robert A. Scott, Jian’an Luan, Martin Bobak, Sofia Malyutina, Andrzej Pająk, Ruzena Kubinova, Abdonas Tamosiunas, Hynek Pikhart, Niels Grarup, Oluf Pedersen, Torben Hansen, Allan Linneberg, Tine Jess, Jackie Cooper, Steve E. Humphries, Murray Brilliant, Terrie Kitchner, Hakon Hakonarson, David S. Carrell, Catherine A. McCarty, Kirchner H. Lester, Eric B. Larson, David R. Crosslin, Mariza de Andrade, Dan M. Roden, Joshua C. Denny, Cara Carty, Stephen Hancock, John Attia, Elizabeth Holliday, Rodney Scott, Peter Schofield, Martin O’Donnell, Salim Yusuf, Michael Chong, Guillaume Pare, Pim van der Harst, M. Abdullah Said, Ruben N. Eppinga, Niek Verweij, Harold Snieder, Lifelines Cohort authors, Tim Christen, D. O. Mook-Kanamori, the ICBP Consortium, Stefan Gustafsson, Lars Lind, Erik Ingelsson, Raha Pazoki, Oscar Franco, Albert Hofman, Andre Uitterlinden, Abbas Dehghan, Alexander Teumer, Sebastian Baumeister, Marcus Dörr, Markus M. Lerch, Uwe Völker, Henry Völzke, Joey Ward, Jill P. Pell, Tom Meade, Ingrid E. Christophersen, Anke H. Maitland-van der Zee, Ekaterina V. Baranova, Robin Young, Ian Ford, Archie Campbell, Sandosh Padmanabhan, Michiel L. Bots, Diederick E. Grobbee, Philippe Froguel, Dorothée Thuillier, Ronan Roussel, Amélie Bonnefond, Bertrand Cariou, Melissa Smart, Yanchun Bao, Meena Kumari, Anubha Mahajan, Jemma C. Hopewell, Sudha Seshadri, the METASTROKE Consortium of the ISGC, Caroline Dale, Rui Providencia E. Costa, Paul M. Ridker, Daniel I. Chasman, Alex P. Reiner, Marylyn D. Ritchie, Leslie A. Lange, Alex J. Cornish, Sara E. Dobbins, Kari Hemminki, Ben Kinnersley, Marc Sanson, Karim Labreche, Matthias Simon, Melissa Bondy, Philip Law, Helen Speedy, James Allan, Ni Li, Molly Went, Niels Weinhold, Gareth Morgan, Pieter Sonneveld, Björn Nilsson, Hartmut Goldschmidt, Amit Sud, Andreas Engert, Markus Hansson, Harry Hemingway, Folkert W. Asselbergs, Riyaz S. Patel, Brendan J. Keating, Naveed Sattar, Richard Houlston, Juan P. Casas, and Aroon D. Hingorani
Subjects: Genetic association studies, Mendelian randomisation, LDL-cholesterol, Phenome-wide association scan, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Background We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable. Conclusions Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
Published: 2019
Full Text: View/download PDF

19. Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex

Author: Tae Won Yi, Brendan Smyth, Gian Luca Di Tanna, Clare Arnott, Kathryn Cardoza, Amy Kang, Carol Pollock, Rajiv Agarwal, George Bakris, David M. Charytan, Dick de Zeeuw, Hiddo J.L. Heerspink, Bruce Neal, David C. Wheeler, Christopher P. Cannon, Hong Zhang, Bernard Zinman, Vlado Perkovic, Adeera Levin, Kenneth W. Mahaffey, Meg Jardine, Barry M. Brenner, Tom Greene, Meg J. Jardine, Gary Meininger, Nicole Li, Inna Kolesnyk, Diego Aizenberg, Roberto Pecoits-Filho, David Cherney, Gregorio Obrador, Glenn Chertow, Tara Chang, Carmel Hawley, Linong Ji, Takashi Wada, Vivekanand Jha, Soo Kun Lim, Mary Anne Lim-Abrahan, Florence Santos, Dong-Wan Chae, Shang-Jyh Hwang, Evgueniy Vazelov, Ivan Rychlík, Samy Hadjadj, Vera Krane, László Rosivall, Luca De Nicola, Alexander Dreval, Michał Nowicki, Adalbert Schiller, Larry Distiller, Jose L. Górriz, Mykola Kolesnyk, null David, C. Wheeler, Rodolfo Andres Ahuad Guerrero, Juan Pablo Albisu, Andres Alvarisqueta, Ines Bartolacci, Mario Alberto Berli, Anselmo Bordonava, Pedro Calella, Maria Cecilia Cantero, Luis Rodolfo Cartasegna, Esteban Cercos, Gabriela Cecilia Coloma, Hugo Colombo, Victor Commendatore, Jesus Cuadrado, Carlos Alberto Cuneo, Ana Maria Cusumano, Walter Guillermo Douthat, Ricardo Dario Dran, Eduardo Farias, Maria Florencia Fernandez, Hernan Finkelstein, Guillermo Fragale, Jose Osvaldo Fretes, Nestor Horacio Garcia, Anibal Gastaldi, Elizabeth Gelersztein, Jorge Archibaldo Glenny, Joaquin Pablo Gonzalez, Patricia del Carmen Gonzalez Colaso, Claudia Goycoa, Gustavo Cristian Greloni, Adrian Guinsburg, Sonia Hermida, Luis Isaias Juncos, Maria Isabel Klyver, Florencia Kraft, Fernando Krynski, Paulina Virginia Lanchiotti, Ricardo Alfonso Leon de la Fuente, Nora Marchetta, Pablo Mele, Silvia Nicolai, Pablo Antonio Novoa, Silvia Ines Orio, Fabian Otreras, Alejandra Oviedo, Pablo Raffaele, Jorge Hector Resk, Lucas Rista, Nelson Rodriguez Papini, Jorgelina Sala, Juan Carlos Santos, Lilia Beatriz Schiavi, Horacio Sessa, Tomas Smith Casabella, Maria Rosa Ulla, Maria Valdez, Augusto Vallejos, Adriana Villarino, Virginia Esther Visco, Alfredo Wassermann, Cesar Javier Zaidman, Ngai Wah Cheung, Carolyn Droste, Ian Fraser, David Johnson, Peak Mann Mah, Kathy Nicholls, David Packham, Joseph Proietto, Anthony Roberts, Simon Roger, Venessa Tsang, Roberto Abrão Raduan, Fernando Augusto Alves da Costa, Celso Amodeo, Luiz Alberto Andreotti Turatti, Rachel Bregman, Fernanda Cristina Camelo Sanches, Luis Henrique Canani, Antônio Roberto Chacra, João Lindolfo Cunha Borges, Sérgio Alberto Cunha Vêncio, Roberto Jorge da Silva Franco, Domingos d’Avila, Evandro de Souza Portes, Pedro de Souza, Luciane Mônica Deboni, Fadlo Fraige Filho, Bruno Geloneze Neto, Marcus Gomes, Suely Keiko Kohara, Elizete Keitel, Jose Francisco Kerr Saraiva, Hugo Roberto Kurtz Lisboa, Fabiana Loss de Carvalho Contieri, Rosângela Milagres, Renan Montenegro Junior, Claudia Moreira de Brito, Miguel Nasser Hissa, Ângela Regina Nazario Sabbag, Irene Noronha, Daniel Panarotto, Roberto Pecoits Filho, Márcio Antônio Pereira, Wladmir Saporito, Antonio Scafuto Scotton, Tiago Schuch, Roberto Simões de Almeida, Cássio Slompo Ramos, João Soares Felício, Fernando Thomé, Jean Carlo Tibes Hachmann, Sérgio Yamada, Cesar Yoiti Hayashida, Tarissa Beatrice Zanata Petry, Maria Teresa Zanella, Viktoria Andreeva, Angelina Angelova, Stefan Dimitrov, Veselka Genadieva, Gabriela Genova-Hristova, Kiril Hristozov, Zdravko Kamenov, Atanas Koundurdjiev, Lachezar Lozanov, Viktor Margaritov, Boyan Nonchev, Rangel Rangelov, Alexander Shinkov, Margarita Temelkova, Ekaterina Velichkova, Andrian Yakov, Naresh Aggarwal, Ronnie Aronson, Harpreet Bajaj, Guy Chouinard, James Conway, Serge Cournoyer, Gerald DaRoza, Sacha De Serres, François Dubé, Ronald Goldenberg, Anil Gupta, Milan Gupta, Sam Henein, Hasnain Khandwala, Lawrence Leiter, François Madore, Alan McMahon, Norman Muirhead, Vincent Pichette, Remi Rabasa-Lhoret, Andrew Steele, Navdeep Tangri, Ali Torshizi, Vincent Woo, Nadia Zalunardo, María Alicia Fernández Montenegro, Juan Gonzalo Godoy Jorquera, Marcelo Medina Fariña, Victor Saavedra Gajardo, Margarita Vejar, Nan Chen, Qinkai Chen, Shenglian Gan, Yaozhong Kong, Detian Li, Wenge Li, Xuemei Li, Hongli Lin, Jian Liu, Weiping Lu, Hong Mao, Yan Ren, Weihong Song, Jiao Sun, Lin Sun, Ping Tu, Guixia Wang, Jinkui Yang, Aiping Yin, Xueqing Yu, Minghui Zhao, Hongguang Zheng, Jose Luis Accini Mendoza, Edgar Arcos, Jorge Avendano, Jorge Ernesto Andres Diaz Ruiz, Luis Hernando Garcia Ortiz, Alexander Gonzalez, Eric Hernandez Triana, Juan Diego Higuera, Natalia Malaver, Dora Inés Molina de Salazar, Ricardo Rosero, Monica Alexandra Terront Lozano, Luis Valderrama Cometa, Alex Valenzuela, Ruben Dario Vargas Alonso, Ivan Villegas, Hernan Yupanqui, Dagmar Bartaskova, Petr Barton, Jana Belobradkova, Lenka Dohnalova, Tomas Drasnar, Richard Ferkl, Katarina Halciakova, Vera Klokocnikova, Richard Kovar, Jiri Lastuvka, Martin Lukac, Satu Pesickova, Karel Peterka, Jiri Pumprla, Ivan Rychlik, Frantisek Saudek, Vladimir Tesar, Martin Valis, Pavel Weiner, Stanislav Zemek, Eric Alamartine, Sophie Borot, Bertrand Cariou, Bertrand Dussol, Jean-Pierre Fauvel, Pierre Gourdy, Alexandre Klein, Yannick Le Meur, Alfred Penfornis, Ronan Roussel, Pierre-Jean Saulnier, Eric Thervet, Philippe Zaoui, Volker Burst, Markus Faghih, Grit Faulmann, Hermann Haller, Reinhold Jerwan-Keim, Stephan Maxeiner, Björn Paschen, Georg Plassmann, Ludger Rose, Ronaldo Arturo Gonzalez Orellana, Franklin Paul Haase, Juan Pablo Moreira Diaz, Luis Alberto Ramirez Roca, Jose Antonio Sánchez Arenales, José Vicente Sanchez Polo, Erick Turcios Juarez, Gyongyi Csecsei, Botond Csiky, Peter Danos, Laszlo Deak, Mihaly Dudas, Eleonora Harcsa, Katalin Keltai, Sandor Keresztesi, Krisztian Kiss, Laszlo Konyves, Lajos Major, Margit Mileder, Marta Molnar, Janos Mucsi, Tamas Oroszlan, Ivan Ory, Gyorgy Paragh, Eva Peterfai, Gizella Petro, Katalin Revesz, Robert Takacs, Sandor Vangel, Szilard Vasas, Marianna Zsom, Oomman Abraham, Raju Sree Bhushan, Dewan Deepak, Fernando M. Edwin, Natarajan Gopalakrishnan, Noble Gracious, Alva Hansraj, Dinesh Jain, C.B. Keshavamurthy, Dinesh Khullar, Sahay Manisha, Jayameena Peringat, Narayan Prasad, Rao K. Satyanarayana, Reddy Sreedhar, Melemadathil Sreelatha, Bhimavarapu Sudhakar, Ramesh Chandra Vyasam, Riccardo Bonadonna, Pietro Castellino, Antonio Ceriello, Luca Chiovato, Salvatore De Cosmo, Giuseppe Derosa, Alberto Di Carlo, Graziano Di Cianni, Giovanni Frascà, Giorgio Fuiano, Giovanni Gambaro, Giacomo Garibotto, Carlo Giorda, Fabio Malberti, Marcora Mandreoli, Edoardo Mannucci, Emanuela Orsi, Piermarco Piatti, Domenico Santoro, Ferdinando Carlo Sasso, Gaetano Serviddio, Andrea Stella, Roberto Trevisan, Anna Maria Veronelli, Luca Zanoli, Hitoshi Akiyama, Hiromi Aoki, Akimichi Asano, Tadashi Iitsuka, Shizuo Kajiyama, Susumu Kashine, Toshio Kawada, Takamoto Kodera, Hiroshi Kono, Kazunori Koyama, Yasuro Kumeda, Shozo Miyauchi, Kazuyuki Mizuyama, Tetsuji Niiya, Hiroko Oishi, Satoshi Ota, Terue Sakakibara, Masahiko Takai, Osamu Tomonaga, Mitsuru Tsujimoto, Masakiyo Wakasugi, Yasushi Wakida, Takayuki Watanabe, Masayo Yamada, Kazuhiro Yanagida, Toshihiko Yanase, Wataru Yumita, Egle Gaupsiene, Dalia Kozloviene, Antanas Navickas, Egle Urbanaviciene, Rohana Abdul Ghani, Khalid Abdul Kadir, Norsiah Ali, Mohd Daud Che Yusof, Chye Lee Gan, Mastura Ismail, Wei Yen Kong, Swee Win Lam, Li Yuan Lee, Chek Loong Loh, Anita Bhajan Manocha, Kee Sing Ng, Nik Nur Fatnoon Nik Ahmad, Vanassa Ratnasingam, Saiful Shahrizal Bin Shudim, Paranthaman Vengadasalam, Luis David Abraira Munoz, Melchor Alpizar Salazar, Juan Baas Cruz, Mario Burgos Soto, Jose Chevaile Ramos, Alfredo Chew Wong, Jose Ricardo Correa Rotter, Tonatiu Diaz Escalante, Favio Edmundo Enriquez Sosa, Fernando Flores Lozano, Luis Fernando Flota Cervera, Paul Frenk Baron, Cecilia Garcia Ballesteros, Jose David Gomez Rangel, Luis Enrique Herrera Jimenez, Sergio Saul Irizar Santana, Fernando Jimenez Flores, Hugo Laviada Molina, Rosa Isela Luna Ceballos, Belia Martin del Campo Blanco, Guadalupe Morales Franco, Oscar Tarsicio Moreno Loza, Cynthia Mustieles Rocha, Gregorio Obrador Vera, Ricardo Orozco Castellanos, Juan Peralta Calcaneo, Miguel Angel Reyes Rosano, Hiromi Rodriguez Pattzi, Juan Rosas Guzman, Isabel Erika Rucker Joerg, Sandra Berenice Saavedra Sanchez, Jose Hector Sanchez Mijangos, Pablo Serrano Sanson, Juan Alfredo Tamayo y Orozco, Eloisa Tellez Chavez, Alejandro Valdes Cepeda, Luis Venegas Carrillo, Juan Villagordoa Mesa, Rolando Zamarripa Escobedo, John Baker, Paul Noonan, Russell Scott, Robert Walker, Edward Watson, Michael Williams, Simon Young, Zaynab Abejuela, Jeimeen Agra, Grace Aquitania, Clodoaido Caringal, Rhea Severina Comia, Lalaine Delos Santos, Olivert Gomez, Cecilia Jimeno, Gerry Tan, Marsha Tolentino, Christy Yao, Yvette Ethel Yap, Ma. Dovie Lallaine Ygpuara, Renata Bijata-Bronisz, Lucyna Hotlos, Andrzej Januszewicz, Barbara Kaczmarek, Anna Kaminska, Lech Lazuka, Andrzej Madej, Stanislaw Mazur, Dorota Mlodawska-Choluj, Michal Nowicki, Grazyna Orlowska-Kowalik, Grazyna Popenda, Barbara Rewerska, Dariusz Sowinski, Liliana Monica Angelescu, Veronica Anghel, Rodica-Ioana Avram, Mihaela-Magdalena Busegeanu, Adriana Cif, Dana Cosma, Carmen Crisan, Luiza Despina Demian, Ioana Emilia Ferariu, Ildiko Halmagyi, Nicolae Hancu, Mircea Munteanu, Doru Negru, Adriana Gabriela Onaca, Ligia Petrica, Amorin Remus Popa, Aurelian-Emil Ranetti, Cristian Serafinceanu, Cristina Toarba, Alina Agafyina, Olga Barbarash, Olga Barysheva, Daniil Chizhov, Vladimir Dobronravov, Irina Glinkina, Elena Grineva, Vladimir Khirmanov, Elena Kolmakova, Tatiana Koroleva, Liudmila Kvitkova, Viacheslav Marasaev, Ashot Mkrtumyan, Tatiana Morugova, Galina Nagibovich, Oleg Nagibovich, Sergei Nedogoda, Irina Osipova, Tatiana Raskina, Yulia Samoylova, Olga Sazonova, Minara Shamkhalova, Elena Shutemova, Yuriy Shwartz, Oleg Uriasyev, Sergey Vorobyev, Anna Zateyshchikova, Dmitry Zateyshshikov, Tatyana Zykova, Slobodan Antic, Miodrag Djordjevic, Aleksandra Kendereski, Katarina Lalic, Nebojsa Lalic, Vesna Popovic-Radinovic, Jana Babikova, Olga Benusova, Ingrid Buganova, Jan Culak, Andrej Dzupina, Jana Dzuponova, Peter Fulop, Adriana Ilavska, Emil Martinka, Zuzana Ochodnicka, Daniel Pella, Iveta Smatanova, Fayzal Ahmed, Aysha Badat, Johannes Breedt, Lawrence Distiller, Vimladhevi Govender, Ravendran Govender, Mukesh Joshi, Jaco Jurgens, Gulam Latiff, Landman Lombard, Mohamed Mookadam, Nomangesi Ngcakani, Hendrik Nortje, Helena Oosthuizen, Larisha Pillay-Ramaya, Hans Prozesky, Jeevren Reddy, Paul Rheeder, Mary Seeber, Young Min Cho, In-Kyung Jeong, Sin Gon Kim, Yeong Hoon Kim, Hyuk-Sang Kwon, Min Jeong Kwon, Byung-Wan Lee, JungEun Lee, Moon-Kyu Lee, Moon-Suk Nam, Kook-Hwan Oh, Cheol- Young Park, Sun-Hee Park, Kun Ho Yoon, Pere Alvarez Garcia, Luis Asmarats Mercadal, Clara Barrios, Fernando Cereto Castro, Secundino Cigarran Guldris, Marta Dominguez Lopez, Jesus Egido de los Rios, Gema Fernandez Fresnedo, Antonio Galan Serrano, Isabel Garcia, Francisco Javier Gonzalez Martinez, Jose Esteban Jodar Gimeno, Manuel Lopez Mendoza, Tamara Malek Marin, Cristobal Morales Portillo, Maria Antonia Munar Vila, Manuel Muñoz Torres, Javier Nieto Iglesias, Jonay Pantoja Perez, Merce Perez Vera, Jose M. Portoles Perez, María Angustias Quesada Simón, Rafael Simo Canonge, Alfonso Soto Gonzalez, Manel Terns Riera, Francisco Jose Tinahones Madueno, Mercedes Velo Plaza, Chwen-Tzuei Chang, Lee-Ming Chuang, Te-Lin Hsia, Chang-Hsun Hsieh, Chih-Ching Lin, Yung- Chuan Lu, Wayne H-H Sheu, Olga Barna, Svitlana D. Bilyk, Volodymyr Botsyurko, Iryna Dudar, Ivan Fushtey, Olga Godlevska, Oleksandr Golovchenko, Olga Gyrina, Anatoliy Kazmirchuk, Iuliia Komisarenko, Oleksii Korzh, Nonna Kravchun, Oleg Legun, Borys Mankovskyy, Liliya Martynyuk, Yuriy Mostovoy, Nataliia Pashkovska, Larysa Pererva, Tetyana Pertseva, Oleksandr Samoylov, Ivan Smirnov, Yevgeniya Svyshchenko, Halyna Tomashkevych, Ivan Topchii, Nadiya Tryshchuk, Vira Tseluyko, Vadym Vizir, Maryna Vlasenko, Tetiana Zlova, Liliia Zub, Salah Abusnana, Mohamed Railey, Kamal Abouglila, Paul Ainsworth, Zishan Ali, Vijayaraman Arutchelvam, Maria Barnard, Srikanth Bellary, Emyr Davies, Mark Davies, Simon Davies, Alison Dawson, Mohsen El Kossi, Patrick English, Donald Fraser, Luigi Gnudi, Anthony Gunstone, Timothy Hall, Wasim Hanif, Alan Jackson, Andrew Johnson, Franklin Joseph, Singhan Krishnan, Mick Kumwenda, Iain MacDougall, Paul Nixon, Joseph O'Hare, Sam Philip, Shenaz Ramtoola, Manish Saxena, Davesh Sennik, Godwin Simon, Baldev Singh, Jeffrey Stephens, Anna Strzelecka, Rehan Symonds, Wayne Turner, Mona Wahba, John Wakeling, David Wheeler, Peter Winocour, Joseph Abdallah, Raied Abdullah, Matthew Abramowitz, Idalia Acosta, Joseph Aiello, Laura Akright, Ayim Akyea-Djamson, Rajendran Alappan, Radica Alicic, Amer Al-Karadsheh, Dale Crawford Allison, Carlos Arauz-Pacheco, Shahabul Arfeen, Ahmed Arif, Moogali Arvind, Naveen Atray, Ahmed Awad, Peggy Barnhill, Elizabeth Barranco, Carlos Barrera, Matthew Beacom, Venkata Behara, Diogo Belo, Rhonda Bentley-Lewis, Ramon Berenguer, Lidia Bermudez, Marializa Bernardo, Mihaela Biscoveanu, Cynthia Bowman-Stroud, Donald Brandon, Osvaldo Brusco, Robert Busch, Yamil Canaan, Alicia Chilito, Tom Christensen, Cynthia Christiano, Elena Christofides, Caroucel Chuateco, Kenneth Cohen, Robert Cohen, Debbie Cohen-Stein, Charles Cook, Daniel Coyne, Nizar Daboul, Riad Darwish, Adarsh Daswani, Kenneth Deck, Cyrus Desouza, Devasmita Dev, Monika Dhillon, Sohan Dua, Frank Eder, Ana Maria Elosegui, Mohamed El-Shahawy, John Ervin, Alberto Esquenazi, John Evans, Steven Fishbane, Juan Frias, Eugenia Galindo-Ramos, Claude Galphin, Adline Ghazi, Enrique Gonzalez, David Gorson, Anupama Gowda, Barbara Greco, Stephen Grubb, Rakesh Gulati, Jamal Hammoud, Stuart Handelsman, Israel Hartman, Kenneth Hershon, Daniel Hiser, George Hon, Radu Jacob, Maria Jaime, Aamir Jamal, Charles Kaupke, Gerald Keightley, Elizabeth Kern, Rakhi Khanna, Zeid Khitan, Sun Kim, Nelson Kopyt, Csaba Kovesdy, Gopal Krishna, Jeffrey (Jay) Kropp, Amrendra Kumar, Jayant Kumar, Neil Kumar, Jorge Kusnir, Wendy Lane, Mary Lawrence, Lawrence Lehrner, John Lentz, Dennis Levinson, Derek Lewis, Kenneth Liss, Andreas Maddux, Hiralal Maheshwari, Sreedhar Mandayam, Isam Marar, Bhasker Mehta, John Middleton, Jorge Mordujovich, Ramon Moreda, Moustafa Moustafa, Samuel Mujica Trenche, Mohanram Narayanan, Javier Narvarte, Tareq Nassar, George Newman, Brian Nichol, Philip Nicol, Josier Nisnisan, A. Kaldun Nossuli, Chamberlain Obialo, Sarah Olelewe, Michael Oliver, Andrew O'Shaughnessy, John Padron, Rohit Pankhaniya, Reginald Parker, Devesh Patel, Gnyandev Patel, Nina Patel, Humberto Pavon, Armando Perez, Carlos Perez, Alan Perlman, Karlton Pettis, Walter Pharr, Andrea Phillips, Raman Purighalla, Luis Quesada-Suarez, Rajiv Ranjan, Sanjeev Rastogi, Jakkidi Reddy, Marc Rendell, Lisa Rich, Michael Robinson, Hector Rodriguez, Sylvia Rosas, Fadi Saba, Rallabhandi Sankaram, Ravi Sarin, Robert Schreiman, David Scott, Mohamed Sekkarie, John Sensenbrenner, Muhammad Shakeel, Michael Shanik, Sylvia Shaw, Stephen Smith, Richard Solomon, Amy Sprague, Leslie Spry, Pusadee Suchinda, Senan Sultan, Prasanth Surampudi, Sherry Sussman, Anjanette Tan, Antonio Terrelonge, Michael Thompson, Fernando Trespalacios, Bruce Trippe, Pilar Trueba, Marcel Twahirwa, John Updegrove, Peter Van Buren, Mark Vannorsdall, Freemu Varghese, Pedro Velasquez-Mieyer, Sailaja Ventrapragada, Goga Vukotic, Khurram Wadud, Mark Warren, Henry Watson, Ronald Watts, Daniel Weiner, James Welker, Jean Welsh, Shelley Williams, and Michelle Zaniewski-Singh
Subjects: age, diabetes, Nephrology, kidney outcomes, sex, Diabetic kidney disease, canagliflozin, cardiovascular outcomes, chronic kidney disease, sodium/glucose cotransporter 2 inhibitors
Abstract: Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kidney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a randomized controlled trial.Setting & Participants: Participants in the CREDENCE trial.Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kidney failure, doubling of serum creatinine concentration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Outcomes were evaluated by age at baseline (Results: The mean age of the cohort was 63.0 ± 9.2 years, and 34% were female. Older age and female sex were independently associated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (a composite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.48-0.82], and 0.89 [0.61-1.29] for ages Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791.
Published: 2023
Full Text: View/download PDF

20. Voies thérapeutiques dans l’hépatopathie stéatosique métabolique

Author: Sarra Smati, Clémence M. Canivet, Jérôme Boursier, and Bertrand Cariou
Subjects: Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine, Cardiology and Cardiovascular Medicine
Published: 2023
Full Text: View/download PDF

21. Parathyroidectomy for primary hyperparathyroidism: effect on quality of life after 3 years – a prospective cohort study

Author: Samuel Frey, Bastien Perrot, Cécile Caillard, Maëlle Le Bras, Maxime Gérard, Claire Blanchard, Bertrand Cariou, Matthieu Wargny, and Eric Mirallié
Subjects: Surgery, General Medicine
Published: 2023
Full Text: View/download PDF

22. PCSK9 is not secreted from mature differentiated intestinal cells

Author: Moreau François, Aurélie Thédrez, Damien Garçon, Audrey Ayer, Thibaud Sotin, Wieneke Dijk, Claire Blanchard, Gilliane Chadeuf, Lucie Arnaud, Mikael Croyal, Laurianne Van Landeghem, Melissa Touvron, Xavier Prieur, Anna Roubtsova, Nabil Seidah, Annik Prat, Bertrand Cariou, and Cedric Le May
Subjects: PCSK9, intestine, cholesterol metabolism, lipoprotein metabolism, Caco-2 cell, liver-specific knockout, Biochemistry, QD415-436
Abstract: Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes lysosomal degradation of the LDL receptor and is a key regulator of cholesterol metabolism. After the liver, the small intestine is the second organ that highly expresses PCSK9. However, the small intestine's ability to secrete PCSK9 remains a matter of debate. While liver-specific PCSK9-deficient mice present no PCSK9 in systemic blood, human intestinal Caco-2 cells can actively secrete PCSK9. This raises the possibility for active intestinal secretion via the portal blood. Here, we aimed to determine whether enterocytes can secrete PCSK9 using in vitro, ex vivo, and in vivo approaches. We first observed that PCSK9 secretion from Caco-2 cells was biphasic and dependent on Caco-2 maturation status. Transcriptional analysis suggested that this transient reduction in PCSK9 secretion might be due to loss of SREBP2-mediated transcription of PCSK9. Consistently, PCSK9 secretion was not detected ex vivo in human or mouse intestinal biopsies mounted in Ussing chambers. Finally, direct comparison of systemic versus portal blood PCSK9 concentrations in WT or liver-specific PCSK9-deficient mice confirmed the inability of the small intestine to secrete PCSK9 into the portal compartment. Altogether, our data demonstrate that mature enterocytes do not secrete PCSK9 and reinforce the central role of the liver in the regulation of the concentration of circulating PCSK9 and consequently of cellular LDL receptors.
Published: 2021
Full Text: View/download PDF

23. Prevalence of hypobetalipoproteinemia and related psychiatric characteristics in a psychiatric population: results from the retrospective HYPOPSY Study

Author: Bertrand Cariou, Gaëlle Challet-Bouju, Céline Bernard, Marie Marrec, Jean-Benoit Hardouin, Charlotte Authier, Kalyane Bach-Ngohou, Christophe Leux, Matthieu Pichelin, and Marie Grall-Bronnec
Subjects: Hypobetalipoproteinemia, LDL cholesterol, Autism spectrum disorders, Hetero-aggression, Schizophrenia, Nutritional diseases. Deficiency diseases, RC620-627
Abstract: Abstract Background Hypobetalipoproteinemia (HBL) is defined by plasma concentrations of LDL-cholesterol (LDL-C) lower than the fifth percentile for age and sex. Several psychiatric symptoms have been reported in association with HBL. The objective was to assess the prevalence of primary HBL in patients hospitalized in a psychiatric population and to better characterize the related psychiatric disorders. Methods HYPOPSY is a retrospective study including 839 adults hospitalized in the Psychiatry department of Nantes University Hospital during the year 2014, except patients with eating disorders. The prevalence of primary HBL was defined by a plasma LDL-C concentration ≤ 50 mg/dL. Secondary causes of HBL were excluded after a review of medical records (n=2). Related-psychiatric disorders in patients with and without HBL were recorded using the ICD-10 classification. Results Twenty cases of primary HBL (mean [SD] LDL-C: 42 [7] mg/dL) were diagnosed, leading to a prevalence of 2.39%. In comparison, the prevalence of HBL in a healthy control population was 0.57%. Psychiatric patients with HBL were characterized by a higher frequency of schizophrenia (p=0.044), hetero-aggression (p=0.015) and pervasive and specific developmental disorders (including autism) (p=0.011). Conclusions The prevalence of HBL is 4-fold higher in psychiatric than in general population. More specifically, some statistically significant associations were found between low LDL-C concentrations and schizophrenia, autism and hetero-aggression. These data reinforce the hypothesis for a link between genetically low LDL-C levels and psychiatric disorders.
Published: 2018
Full Text: View/download PDF

24. Effects of parathyroidectomy on kidney function in patients with primary hyperparathyroidism: Results of a prospective study

Author: Samuel Frey, Matthieu Wargny, Claire Blanchard, Cécile Caillard, Samy Hadjadj, Bertrand Cariou, Lucile Figueres, and Eric Mirallié
Subjects: Surgery
Abstract: Altered glomerular filtration rate is a controversial indication for parathyroidectomy in patients with primary hyperparathyroidism. The objective of this study was to evaluate the estimated glomerular filtration rate change 12 months after parathyroidectomy for primary hyperparathyroidism according to preoperative kidney function.Patients who underwent parathyroidectomy for primary hyperparathyroidism between 2016 and 2021 (n = 381) were enrolled in a monocentric prospective cohort. Patients without 1-year follow-up or with missing data were excluded (n = 135, 35%). Patients were dichotomized according to their baseline estimated glomerular filtration rate:60 mL/min (group 1) and ≥60 mL/min (group 2). Parameters were measured before and then at 6 and 12 months after parathyroidectomy.Out of 246 included patients, 27 (11%) were assigned to group 1 and 219 (89%) to group 2. The mean baseline estimated glomerular filtration rate was 46.8 ± 11.5 and 87.3 ± 14.7 mL/min in groups 1 and 2, respectively. Group 1 patients were older (P = .0006) and had a higher median serum parathyroid hormone level (P = .021). At 6 months postoperative, 224 patients (91%) were normocalcemic. The estimated glomerular filtration rate raw change after parathyroidectomy was significantly higher in group 1 than in group 2 (4.2 ± 7.8 vs -2.2 ± 9.1 mL/min, P = .0004). In group 1, 13/27 patients (48%) improved their chronic kidney disease stage after parathyroidectomy, including 6/13 (46%) with postoperative estimated glomerular filtration rate ≥60 mL/min, whereas 2/27 (7%) worsened. The baseline estimated glomerular filtration rate60 mL/min and elevated serum calcium level were associated with postoperative estimated glomerular filtration rate improvement in multivariable analysis (P = .0023 and .039, respectively).Parathyroidectomy for primary hyperparathyroidism is more likely to improve kidney function in patients with preoperative estimated glomerular filtration rate60 mL/min. These results strengthen the current guidelines for surgery.
Published: 2023
Full Text: View/download PDF

25. Lipid-lowering efficacy and safety of alirocumab in a real-life setting in France: Insights from the ODYSSEY APPRISE study

Author: Patrick, Henry, Bertrand, Cariou, Michel, Farnier, Sarah L, Lakhdari, and Bruno, Detournay
Subjects: General Medicine, Cardiology and Cardiovascular Medicine
Abstract: Recently, a multicentre, prospective, single-arm, phase 3b, open-label trial was conducted to determine the safety and efficacy of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in a real-life setting. This study enrolled patients at high cardiovascular risk, with heterozygous familial hypercholesterolaemia (HeFH) or non-familial hypercholesterolaemia (non-FH). Results showed that alirocumab was well tolerated and resulted in a clinically signiﬁcant reduction in low-density lipoprotein cholesterol (LDL-C).This ancillary analysis aimed to describe the characteristics of the French patients enrolled in the study, the main results observed in this population according to their familial hypercholesterolaemia status, and adherence to treatment.French data were analysed separately from the original dataset of the study.Among 215 French patients in the ODYSSEY APPRISE trial, 63.7% had non-FH, with a mean LDL-C concentration of 5.0±1.8mmol/L at baseline. The mean duration of alirocumab exposure was 72.4±42.5 weeks, with only 48.4% of patients receiving statins concomitantly. At week 12, a mean reduction in LDL-C of 56.5±17.8% was observed: 51.2±22.8% in HeFH; 59.5±13.2% in non-FH. This improvement in LDL-C started from week 4 and remained stable and sustained until week 120 in both populations. The overall incidence of severe treatment-emergent adverse events (TEAEs) was 33.5%. The most frequent TEAEs were myalgia (15.8%) and asthenia (15.3%). No tolerance or efficacy differences were observed between patients with or without established coronary artery disease or other cardiovascular disease, whatever the age of these events or considering the concomitant use of other lipid-lowering therapies.In the French setting, alirocumab was well tolerated, safe and highly effective at reducing LDL-C. These findings support the use of alirocumab to manage hypercholesterolaemia in patients at high cardiovascular risk.
Published: 2023
Full Text: View/download PDF

26. The effects of basal insulin peglispro vs. insulin glargine on lipoprotein particles by NMR and liver fat content by MRI in patients with diabetes

Author: Trevor J. Orchard, Bertrand Cariou, Margery A. Connelly, James D. Otvos, Shuyu Zhang, Caryl J. Antalis, Tibor Ivanyi, and Byron J. Hoogwerf
Subjects: Diabetes, Basal insulin peglispro, Insulin glargine, Lipoproteins, NMR, Apolipoproteins, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Background In Phase 2/3 studies of basal insulin peglispro (BIL) compared to insulin glargine, patients with type 1 or type 2 diabetes previously treated with insulin and randomized to BIL had an increase in serum triglycerides (TGs). To further understand lipoprotein changes, a lipid substudy which included liver fat content was designed to assess relationships among the measured variables for each diabetes cohort and compare the hepato-preferential insulin BIL to glargine. Methods In three cohorts of patients with diabetes (type 1, type 2 insulin naïve, and type 2 previously on insulin; n = 652), liver fat content (LFC) was determined by magnetic resonance imaging (MRI) and blood lipids were analyzed by nuclear magnetic resonance (NMR) spectroscopy at baseline, 26 and 52 weeks of treatment. Apolipoproteins, adiponectin, and other lipid parameters were also measured. Descriptive statistics were done, as well as correlation analyses to look for relationships among LFC and lipoproteins or other lipid measures. Results In patients with type 1 diabetes treated with BIL, but not glargine, small LDL and medium and large VLDL subclass concentrations increased from baseline. In patients with type 2 diabetes previously on insulin and treated with BIL, large VLDL concentration increased from baseline. In insulin naïve patients with type 2 diabetes treated with BIL, there were very few changes, while in those treated with glargine, small LDL and large VLDL decreased from baseline. Baseline LFC correlated significantly in one or more cohorts with baseline large VLDL, small LDL, VLDL size, and Apo C3. Changes in LFC by treatment showed generally weak correlations with lipoprotein changes, except for positive correlations with large VLDL and VLDL size. Adiponectin was higher in patients with type 1 diabetes compared to patients with type 2 diabetes, but decreased with treatment with both BIL and glargine. Conclusions The lipoprotein changes were in line with the observed changes in serum TGs; i.e., the cohorts experiencing increased TGs and LFC with BIL treatment had decreased LDL size and increased VLDL size. These data and analyses add to the currently available information on the metabolic effects of insulins in a very carefully characterized cohort of patients with diabetes. Clinicaltrials.gov registration numbers and dates NCT01481779 (2011), NCT01435616 (2011), NCT01454284 (2011), NCT01582451 (2012)
Published: 2017
Full Text: View/download PDF

27. Design and rationale of the ODYSSEY DM-DYSLIPIDEMIA trial: lipid-lowering efficacy and safety of alirocumab in individuals with type 2 diabetes and mixed dyslipidaemia at high cardiovascular risk

Author: Dirk Müller-Wieland, Lawrence A. Leiter, Bertrand Cariou, Alexia Letierce, Helen M. Colhoun, Stefano Del Prato, Robert R. Henry, Francisco J. Tinahones, Lisa Aurand, Jaman Maroni, Kausik K. Ray, and Maja Bujas-Bobanovic
Subjects: Alirocumab, PCSK9, Diabetes, Mixed dyslipidaemia, Non-HDL-C, ODYSSEY, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Background Type 2 diabetes mellitus (T2DM) is often associated with mixed dyslipidaemia, where non-high-density lipoprotein cholesterol (non-HDL-C) levels may more closely align with cardiovascular risk than low-density lipoprotein cholesterol (LDL-C). We describe the design and rationale of the ODYSSEY DM-DYSLIPIDEMIA study that assesses the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, versus lipid-lowering usual care in individuals with T2DM and mixed dyslipidaemia at high cardiovascular risk with non-HDL-C inadequately controlled despite maximally tolerated statin therapy. For the first time, atherogenic cholesterol-lowering with a PCSK9 inhibitor will be assessed with non-HDL-C as the primary endpoint with usual care as the comparator. Methods DM-DYSLIPIDEMIA is a Phase 3b/4, randomised, open-label, parallel group, multinational study that planned to enrol 420 individuals. Main inclusion criteria were T2DM and mixed dyslipidaemia (non-HDL-C ≥100 mg/dl [≥2.59 mmol/l], and triglycerides ≥150 and
Published: 2017
Full Text: View/download PDF

28. A comment on metformin and <scp>COVID</scp> ‐19 with regard to 'Metformin use is associated with a decrease in the risk of hospitalization and mortality in <scp>COVID</scp> ‐19 patients with diabetes: A population‐based study in Lombardy'

Author: Abdallah Al‐Salameh, Nicolas Wiernsperger, Bertrand Cariou, and Jean‐Daniel Lalau
Subjects: Endocrinology, Endocrinology, Diabetes and Metabolism, Internal Medicine
Published: 2022
Full Text: View/download PDF

29. 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
Full Text: View/download PDF

30. Nocturnal hypoglycemia is underdiagnosed in older people with insulin‐treated type 2 diabetes: The <scp>HYPOAGE</scp> observational study

Author: Anne‐Sophie Boureau, Béatrice Guyomarch, Pierre Gourdy, Ingrid Allix, Cédric Annweiler, Nathalie Cervantes, Guillaume Chapelet, Isabelle Delabrière, Sophie Guyonnet, Rachel Litke, Marc Paccalin, Alfred Penfornis, Pierre‐Jean Saulnier, Matthieu Wargny, Samy Hadjadj, Laure de Decker, and Bertrand Cariou
Subjects: Geriatrics and Gerontology
Published: 2023
Full Text: View/download PDF

31. Metabolic syndrome predicts cardiovascular risk and mortality in familial hypercholesterolemia

Author: Martine Paquette, Sophie Bernard, Bertrand Cariou, Robert A. Hegele, Jacques Genest, Mark Trinder, Liam R. Brunham, Sophie Béliard, and Alexis Baass
Subjects: Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine, Cardiology and Cardiovascular Medicine
Published: 2023
Full Text: View/download PDF

32. A proposal from the Liver Forum for the management of comorbidities in nonalcoholic steatohepatitis therapeutic trials

Author: Raluca Pais, Bertrand Cariou, Mazen Noureddin, Sven Francque, Jörn M. Schattenberg, Manal F. Abdelmalek, Gadi Lalazar, Sharat Varma, Julie Dietrich, Veronica Miller, Arun Sanyal, and Vlad Ratziu
Subjects: Hepatology
Published: 2023
Full Text: View/download PDF

33. Fatty liver index is a strong predictor of changes in glycemic status in people with prediabetes: The IT-DIAB study.

Author: Matthieu Wargny, Sarra Smati, Matthieu Pichelin, Edith Bigot-Corbel, Charlotte Authier, Violette Dierry, Yassine Zaïr, Vincent Jacquin, Samy Hadjadj, Jérôme Boursier, and Bertrand Cariou
Subjects: Medicine, Science
Abstract: Background & aimsIn patients at metabolic risk, nonalcoholic fatty liver disease is a strong and highly prevalent predictor for type 2 diabetes. Its assessment in clinical practice is not easy but the fatty liver index (FLI) could be used as a surrogate. Here, we studied the association between the FLI and the conversion to new-onset diabetes (NOD) or prediabetes reversion in patients with prediabetes.MethodsThe IT-DIAB observational study included 389 individuals with prediabetes, defined as fasting plasma glucose (FPG) between 110 and 125 mg/dL. NOD conversion was defined as a first FPG value ≥ 126 mg/dL and prediabetes reversion as a first FPG value < 110 mg/dL. The associations of both events with baseline FLI were studied separately using multivariate Cox models.ResultsAfter a median follow-up of 3.9 years (range 0.1-6.1), 138 individuals (35.5%) converted to NOD. FLI was associated with a higher risk of NOD conversion (unadjusted HR per SD = 1.54, 95%CI 1.27-1.86, pConclusionsFLI is a simple, practical score to further stratify the risk of conversion to NOD or the possibility of prediabetes reversion in clinical practice, independently of classical glucose parameters.Trial registrationClincialTrials.gov number NCT01218061 and NCT01432509.
Published: 2019
Full Text: View/download PDF

34. Chronic O-GlcNAcylation and Diabetic Cardiomyopathy: The Bitterness of Glucose

Author: Simon Ducheix, Jocelyne Magré, Bertrand Cariou, and Xavier Prieur
Subjects: glucotoxicity, diabetes, metabolism, cardiomyopathy, O-GlcNAcylation, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Type 2 diabetes (T2D) is a major risk factor for heart failure. Diabetic cardiomyopathy (DC) is characterized by diastolic dysfunction and left ventricular hypertrophy. Epidemiological data suggest that hyperglycaemia contributes to the development of DC. Several cellular pathways have been implicated in the deleterious effects of high glucose concentrations in the heart: oxidative stress, accumulation of advanced glycation end products (AGE), and chronic hexosamine biosynthetic pathway (HBP) activation. In the present review, we focus on the effect of chronic activation of the HBP on diabetic heart function. The HBP supplies N-acetylglucosamine moiety (O-GlcNAc) that is O-linked by O-GlcNAc transferase (OGT) to proteins on serine or threonine residues. This post-translational protein modification modulates the activity of the targeted proteins. In the heart, acute activation of the HBP in response to ischaemia-reperfusion injury appears to be protective. Conversely, chronic activation of the HBP in the diabetic heart affects Ca2+ handling, contractile properties, and mitochondrial function and promotes stress signaling, such as left ventricular hypertrophy and endoplasmic reticulum stress. Many studies have shown that O-GlcNAc impairs the function of key protein targets involved in these pathways, such as phospholamban, calmodulin kinase II, troponin I, and FOXO1. The data show that excessive O-GlcNAcylation is a major trigger of the glucotoxic events that affect heart function under chronic hyperglycaemia. Supporting this finding, pharmacological or genetic inhibition of the HBP in the diabetic heart improves heart function. In addition, the SGLT2 inhibitor dapagliflozin, a glucose lowering agent, has recently been shown to lower cardiac HBP in a lipodystophic T2D mice model and to concomitantly improve the diastolic dysfunction of these mice. Therefore, targeting cardiac-excessive O-GlcNAcylation or specific target proteins represents a potential therapeutic option to treat glucotoxicity in the diabetic heart.
Published: 2018
Full Text: View/download PDF

35. Transintestinal cholesterol excretion in health and disease

Author: Damien Garçon, Jean-Matthieu Berger, Bertrand Cariou, and Cédric Le May
Subjects: Mice, Cholesterol, Liver, Animals, Humans, Biological Transport, Atherosclerosis, Cardiology and Cardiovascular Medicine, Rats
Abstract: The transintestinal cholesterol efflux (TICE) pathway is the second described route for plasma cholesterol fecal elimination. This article summarizes recent TICE research progresses, involving TICE inducers, molecular determinants of this pathway, and its role in lipoprotein metabolism.TICE is an active pathway in mice, rats, and humans. Kinetic measurements showed that under basal conditions, the relative contribution of TICE in fecal elimination of plasma cholesterol is quantitatively less important than the hepatobiliary pathway. However, the amplitude of TICE can be induced by numerous nutritional factors and pharmacological drugs. More importantly, by contrast with the stimulation of biliary cholesterol excretion that is associated with an increased risk of gallstone formation, TICE appears as a safer therapeutical target. Finally, several independent studies have demonstrated that TICE is actively contributing to the anti-atherogenic reverse cholesterol pathway reinforcing the interest to better understand its mode of action. The discovery of TICE and the understanding of its mode of action open new therapeutical perspectives for patients at high risk of cardiovascular diseases.
Published: 2022
Full Text: View/download PDF

36. The metabolic triad of non‐alcoholic fatty liver disease, visceral adiposity and type 2 diabetes: Implications for treatment

Author: Bertrand Cariou
Subjects: Endocrinology, Diabetes Mellitus, Type 2, Liver, Non-alcoholic Fatty Liver Disease, Obesity, Abdominal, Endocrinology, Diabetes and Metabolism, Internal Medicine, Humans, Hypoglycemic Agents, Adiposity
Abstract: Non-alcoholic fatty liver disease (NAFLD) is associated with visceral obesity, insulin resistance, type 2 diabetes (T2D) and has been often considered as the hepatic expression of the metabolic syndrome (MetS). Epidemiological studies highlight a bidirectional relationship of NAFLD with T2D in which NAFLD increases the risk of incident T2D and T2D increases the risk of severe non-alcoholic steatohepatitis (NASH) and liver fibrosis. Regarding the molecular determinants of NAFLD, we specifically focused in this review on adipocyte dysfunction as a key molecular link between visceral adipose tissue, MetS and NAFLD. Notably, the subcutaneous white adipose tissue expandability appears a critical adaptive buffering mechanism to prevent lipotoxicity and its related metabolic complications, such as NAFLD and T2D. There is a clinical challenge to consider therapeutic strategies targeting the metabolic dysfunction common to NASH and T2D pathogenesis. Strategies that promote significant and sustained weight loss (~10% of total body weight) such as metabolic and bariatric surgery or incretin-based therapies (GLP-1 receptor agonists or dual GLP-1/GIP or GLP-1/glucagon receptor co-agonists) are among the most efficient ones. In addition, insulin sensitizers such as PPARγ (pioglitazone) and pan-PPARs agonists (lanifibranor) have shown some beneficial effects on both NASH and liver fibrosis. Since NASH is a complex and multifactorial disease, it is conceivable that targeting different pathways, not only insulin resistance but also inflammation and fibrotic processes, is required to achieve NASH resolution.
Published: 2022
Full Text: View/download PDF

37. Urine-sample-derived human induced pluripotent stem cells as a model to study PCSK9-mediated autosomal dominant hypercholesterolemia

Author: Karim Si-Tayeb, Salam Idriss, Benoite Champon, Amandine Caillaud, Matthieu Pichelin, Lucie Arnaud, Patricia Lemarchand, Cédric Le May, Kazem Zibara, and Bertrand Cariou
Subjects: Urine-derived somatic cells, Human induced pluripotent stem cells, Hepatocyte differentiation, Autosomal dominant hypercholesterolemia, PCSK9, Medicine, Pathology, RB1-214
Abstract: Proprotein convertase subtilisin kexin type 9 (PCSK9) is a critical modulator of cholesterol homeostasis. Whereas PCSK9 gain-of-function (GOF) mutations are associated with autosomal dominant hypercholesterolemia (ADH) and premature atherosclerosis, PCSK9 loss-of-function (LOF) mutations have a cardio-protective effect and in some cases can lead to familial hypobetalipoproteinemia (FHBL). However, limitations of the currently available cellular models preclude deciphering the consequences of PCSK9 mutation further. We aimed to validate urine-sample-derived human induced pluripotent stem cells (UhiPSCs) as an appropriate tool to model PCSK9-mediated ADH and FHBL. To achieve our goal, urine-sample-derived somatic cells were reprogrammed into hiPSCs by using episomal vectors. UhiPSC were efficiently differentiated into hepatocyte-like cells (HLCs). Compared to control cells, cells originally derived from an individual with ADH (HLC-S127R) secreted less PCSK9 in the media (−38.5%; P=0.038) and had a 71% decrease (P
Published: 2016
Full Text: View/download PDF

38. The Added Value of Coronary Calcium Score in Predicting Cardiovascular Events in Familial Hypercholesterolemia

Author: Antonio Gallo, Leopoldo Pérez de Isla, Sybil Charrière, Alexandre Vimont, Rodrigo Alonso, Ovidio Muñiz-Grijalvo, José L. Díaz-Díaz, Daniel Zambón, Philippe Moulin, Eric Bruckert, Pedro Mata, Sophie Béliard, Denis Angoulvant, Sophie Beliard, Franck Boccara, 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, Philippe Giral, Sophie Gonbert, Regis Hankard, Jocelyn Inamo, 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, Rocío Aguado, Ma Pilar Álvarez-Baños, Rosa Argüeso, Francisco Arrieta, Miguel Ángel Barba, Marta Casañas, José María Cepeda, Raimundo De Andrés, Gonzalo Díaz-Soto, Jose Luis Díaz-Diaz, Marta Dieguez, Ceferino Faedo, Francisco Fuentes, Juan A. Garrido, Aurora González, Pablo González-Bustos, Ma Dolores Mañas, Marta Mauri, Juan Diego Mediavilla, Alfredo Michán, Pablo Miramontes, Ovidio Muñiz, Leire Pérez, Leopoldo Perez De Isla, Xavier Pintó, Manuel J. Romero, Patricia Rubio, Juan F. Sánchez Muñoz-Torrero, Jose I. Vidal-Pardo, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), 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), Public Health Expertise [Paris, France], Hospital Universitario Virgen del Rocío [Sevilla], Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), 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), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), 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], Hospital Abente y Lago, Fundación Hipercolesterolemia Familiar, and ANR-16-RHUS-0007,CHOPIN,CHOPIN(2016)
Subjects: Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Coronary Artery Disease, Disease, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Risk Assessment, Sudden death, Cohort Studies, Hyperlipoproteinemia Type II, risk prediction, 03 medical and health sciences, 0302 clinical medicine, cardiovascular disease, genetic disease, Predictive Value of Tests, Risk Factors, Interquartile range, Internal medicine, Humans, Medicine, Radiology, Nuclear Medicine and imaging, 030212 general & internal medicine, Vascular Calcification, Stroke, coronary artery calcium, ComputingMilieux_MISCELLANEOUS, familial hypercholesterolemia, business.industry, Proportional hazards model, nutritional and metabolic diseases, Middle Aged, Atherosclerosis, medicine.disease, 3. Good health, Coronary Calcium Score, Cardiology, Calcium, Cardiology and Cardiovascular Medicine, business, coronary imaging, Cohort study
Abstract: International audience; ObjectivesThis study aimed at investigating the additional contribution of coronary artery calcium (CAC) score to SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study) risk equation (SAFEHEART-RE) for cardiovascular risk prediction in heterozygous familial hypercholesterolemia (HeFH).BackgroundCommon cardiovascular risk equations are imprecise for HeFH. Because of the high phenotype variability of HeFH, CAC score could help to better stratify the risk of atherosclerotic cardiovascular disease (ASCVD).MethodsREFERCHOL (French Registry of Familial Hypercholesterolemia) and SAFEHEART are 2 ongoing national registries on HeFH. We analyzed data from primary prevention HeFH patients undergoing CAC quantification. We used probability-weighted Cox proportional hazards models to estimate HRs. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of CAC score when added to the SAFEHEART-RE for ASCVD prediction. ASCVD was defined as coronary heart disease, stroke or transient ischemic attack, peripheral artery disease, resuscitated sudden death, and cardiovascular death.ResultsWe included 1,624 patients (mean age: 48.5 ± 12.8 years; men: 45.7%) from both registries. After a median follow-up of 2.7 years (interquartile range: 0.4-5.0 years), ASCVD occurred in 81 subjects. The presence of a CAC score of >100 was associated with an HR of 32.05 (95% CI: 10.08-101.94) of developing ASCVD as compared to a CAC score of 0. Receiving-operating curve analysis showed a good performance of CAC score alone in ASCVD prediction (AUC: 0.860 [95% CI: 0.853-0.869]). The addition of log(CAC + 1) to SAFEHEART-RE resulted in a significantly improved prediction of ASCVD (AUC: 0.884 [95% CI: 0.871-0.894] for SAFEHEART-RE + log(CAC + 1) vs AUC: 0.793 [95% CI: 0.779-0.818] for SAFEHEART-RE; P < 0.001). These results were confirmed also when considering only hard cardiovascular endpoints. The addition of CAC score was associated with an estimated overall net reclassification improvement of 45.4%.ConclusionsCAC score proved its use in improving cardiovascular risk stratification and ASCVD prediction in statin-treated HeFH.
Published: 2021
Full Text: View/download PDF

39. LDL lowering effect of PCSK9 inhibition is reduced in women

Author: Veronika A Myasoedova, Antoine Rimbert, Marina Camera, Cedric Le May, Romain Capoulade, Bertrand Cariou, and Paolo Poggio
Subjects: Pharmacology (medical), Cardiology and Cardiovascular Medicine
Abstract: AimsProprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of plasma low-density lipoprotein cholesterol (LDL-C) concentration, and its inhibition reduces the risk of atherosclerotic cardiovascular disease (ASCVD). We aimed to assess the sex-differential effect of either pharmacological or genetic inhibition of PCSK9 on LDL-C levels.Methods and resultsWe meta-analyzed six real-life studies (1216 men and 641 women) that investigated the effects of PCSK9 monoclonal antibodies (mAbs) on LDL-C reduction in men and women. Despite higher LDL-C levels in women at baseline [mean difference (MD) = 17.4 mg/dL, P We tested the sex-related association of the loss-of-function variant PCSK9-R46L with LDL-C plasma levels in 382 813 individuals (219 301 women and 163 512 men) free of lipid-lowering drugs from the UK Biobank general population cohort. The magnitude of LDL-C reduction was larger in men than in women (mean LDL-C difference: –35 mg/dL vs. –26 mg/dL, when comparing homozygous carriers with non-carriers in men and women, respectively). The relationship between PCSK9-R46L and LDL-C was significantly dependent on sex (P for interaction = 7.2e–04).ConclusionThese results demonstrate by complementary approaches that the decrease in LDL-C mediated by PCSK9 inhibition is slightly, but significantly, less marked in women than in men. These data reinforce the need for specific studies to develop sex-specific recommendations for the management of ASCVD in women.
Published: 2023
Full Text: View/download PDF

40. Single-Anastomosis Duodeno-Ileal Bypass with Sleeve Gastrectomy Model in Mice

Author: Cédric Le May, Claire Blanchard, Bertrand Cariou, Victoria Lorant, Thibaud Sotin, Audrey Ayer, and Samuel Frey
Subjects: General Immunology and Microbiology, General Chemical Engineering, General Neuroscience, General Biochemistry, Genetics and Molecular Biology
Published: 2023
Full Text: View/download PDF

41. 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
Full Text: View/download PDF

42. Review for 'Effects of oral semaglutide on cardiovascular outcomes in individuals with type 2 diabetes and established atherosclerotic cardiovascular disease and/or chronic kidney disease: <scp>SOUL</scp> , a randomized trial, design and baseline characteristics'

Author: Bertrand CARIOU
Published: 2023
Full Text: View/download PDF

43. Evaluation of lipoprotein(a) in the prevention and management of atherosclerotic cardiovascular disease: A survey among the Lipid Clinics Network

Author: Catapano, Alberico L, Tokgözoğlu, Lale, Banach, Maciej, Gazzotti, Marta, Olmastroni, Elena, Casula, Manuela, Ray, Kausik K, the Lipid Clinics Network, Alaa ABDELRAZIK (University Hospital of North Midland, United Kingdom), Alberto MELLO E SILVA (Sociedade Portuguesa de Aterosclerose, Portugal), Alexander VONBANK (VIVIT Institute, Austria), Alexandros, D TSELEPIS (Dept of Chemistry, Atherothrombosis Research Center, University of Ioannina, Greece), Alper SONMEZ (Department of Endocrinology and Metabolism, Ankara Guven Hospital, Turkey), Angelina PASSARO (Department of Translational Medicine, University of Ferrara &amp, Center for the Study and Treatment of Metabolic Diseases, Atherosclerosis, and Clinical Nutrition, University Hospital of Ferrara Arcispedale Sant’Anna, Italy), Anja VOGT (Medizinische Klinik und Poliklinik IV, Klinikum der Universit¨at München, Germany), Ann MERTENS (Clinical and Experimental Endocrinology, Leuven, Ku, Leuven, Belgium), Ann VERHAEGEN (Antwerp University Hospital, Belgium), Arman, S POSTADZHIYAN (Medical University of Sofia, Saint Anna University Hospital, Departement of Cardiology, Bulgaria), BAHADIR KIRILMAZ (Canakkale Onsekiz Mart University, Medical Faculty Cardiology Dept, Baris GUNGOR (University of Health Sciences Dr. Siyami Ersek Hospital, Turkey), Berit S HEDEGAARD (Aalborg University, Denmark), Bertrand CARIOU (Nantes Universit´e, Chu, Nantes, Cnrs, Inserm, l’institut du thorax, Nantes, France), Britta OTTE (Universit¨atsklinikum Münster, Lipidambulanz, Germany), Bu˘gra ¨OZKAN (Mersin University, Turkey), of cardiology, Christ BERGE (Dept., Unversity Hopsital, Haukeland., Norway), F EBENBICHLER (Department for Internal Medicine I, Christoph, Medical University Innsbruck, Austria), Christoph J BINDER (Medical University of Vienna, Austria), Christoph OLIVIER (Department of Cardiology and Angiology, University Heart Center Freiburg-Bad Krozingen, Faculty of Medicine, University of Freiburg, Conrad AZZOPARDI (Mater Dei Hospital, Malta), Cristina SOLER (Lipid Unit, Hospital de Sta Caterina, Spain), Dan GAITA (Universitatea de Medicina si Farmacie Victor Babes din Timisoara &amp, Clinica de Cardiologie, Institutul de Boli Cardiovasculare Timisoara, Romania), Daniel WEGHUBER (Department of Pediatrics, Paracelsus Medical University, Dilek URAL (Koç University School of Medicine Department of Cardiology, Turkey), Diogo CRUZ (Hospital de Cascais - Dr. Jos´e de Almeida, Portugal), Dragos VINEREANU (University of Medicine and Pharmacy, University and Emergency Hospital, Bucharest, Romania), Elena D PENCU (Grand Hˆopital de Charleroi GHDC, Belgium), Emil HAGSTR¨OM (Dept of medical sciences, Uppsala, University, Sweden), Erik B SCHMIDT (Aalborg University, Denmark), Erik, S STROES (Dept of vascular medicine, Amsterdamumc, The, Netherlands), Evangelos LIBEROPOULOS (1st Department of Propedeutic Medicine, School of Medicine, National and Kapodistrian University of Athens, General Hospital of Athens Laiko, Fabian DEMEURE (CHU UCL Namur - Site Godinne, Belgium), Fabio FIMIANI (Azienda Ospedaliera di Rilievo Nazionale AORN Dei Colli, Monaldi', 'V., Unit of Inherited and Rare Cardiovascular Diseases, Italy, ), Fabio PELLEGATTA (Center for the Study of Atherosclerosis. Bassini Hospital. Cinisello Balsamo, Italy), Fahri BAYRAM (Erciyes University, Turkey), Finn L HENRIKSEN (Department of Cardiology Odense University Hospital, Denmark), Florian H¨OLLERL (1st Medical Department, Landstrasse, Clinic, Vienna Health Association, Francesco CIPOLLONE (Clinica Medica Institute of, Department of Medicine and Aging Sciences, d’Annunzio' University, 'G., Francisco ARAÚJO (Hospital Lusíadas, Portugal), Franck BOCCARA (Sorbonne Universit´e, Groupe de Recherche Clinique number 22, C2MV—Complications Cardiovasculaires et M´etaboliques chez les Patients Vivant avec le Virus de l’Immunod´eficience Humaine, Institut National de la Sant´e et de la Recherche M´edicale Unit´e Mixte de Recherche, S 938, Centre de Recherche Saint-Antoine, Institut Hospital Universitaire de Cardiom ´etabolisme et Nutrition Cardiologie, Hˆopital Saint Antoine Assistance Publique–Hˆopitaux de Paris, Paris, France), François PAILLARD (Cardiologie et Centre Clinico-Biologique des Lipides et Ath´eroscl´erose, Chu, Rennes, France), Imre University Teaching Hospital, Gabor SIMONYI (DBC St., Metabolic, Center, Lipid, Center, Hungary), Gabriella IANNUZZO (Department of Clinical Medicine and Surgery. University of Naples Federico II, Italy), Giuseppe MANDRAFFINO (Department of Clinical and Experimental Medicine, - Lipid Center, University of Messina, Graham BAYLY (Dept Clinical Biochemistry, University Hospitals Bristol, United, Kingdom), Gustavs LATKOVSKIS (Institute of Cardiology and Regenerative Medicine, University of Latvia &amp, Latvian Center of Cardiology, Pauls Stradins Clinical University Hospital &amp, University of Latvia, Latvia), Gy¨orgy PARAGH (Division of Metabolic Disorders, Department of Internal Medicine, University of Debrecen, Debrecen, Hungary), Hana ROSOLOVA (Charles University Prague Medical Hospital in Pilsen, Czech Republic), Handrean SORAN (Central Manchester University Hospital NHS Foundation Trust, United Kingdom), Helle KANSTRUP (Department of cardiology, Aarhus University hospital, Denmark), Hermann TOPLAK (Department of Medicine, Division of Endocrinology and Diabetology, Medical University Graz, Hülya ÇIÇEKÇIO ˘GLU (ankara bilkent city hospital, Turkey), Inanc ARTAC (Department of Cardiology, Kafkas University Hospital, Ioanna GOUNI-BERTHOLD (Center for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Irfan, V DUZEN (Gaziantep University, Cardiology, Department, Isabel M PALMA (CHUPORTO - Centro Hospitalar Universit ´ario do Porto, Portugal), Istvan REIBER (Szent Gyorgy University Teaching Hospital of Fejer County, Hungary), Iveta DZIVITE-KRISANE (Children’s University Hospital, Latvia), Jeanine, E ROETERS VAN LENNEP (Department of Internal medicine, Erasmus MC University Medical Center, Jean-Luc, J BALLIGAND (Institut de Recherche Exp´erimentale et Clinique, Universite catholique de Louvain, Bruxelles), Joao C PORTO (CHUC, Portugal), Jo˜ao, S DUARTE (Hospital Egas Moniz, Lisboa, Portugal), Johan DE SUTTER (AZ Maria Middelares Hospital Gent, Belgium), Jos´e L´OPEZ-MIRANDA (Lipid and Arteriosclerosis Unit. Department of Internal Medicine. Hospital Universitario Reina Sofia. IMIBIC. University of Cordoba. CiberOBN, Spain), Jose M MOSTAZA (Hospital La Paz-Carlos III, Spain), Jurgita PLISIENE (Lithuanian University of Health sciences, Lithuania), Kadir, U MERT (Eskis ¸ehir Osmangazi University, Department of Cardiology, Kirsten, B HOLVEN (Department of Nutrition, University of Oslo and National Advisory unit on FH, Oslo University Hospital, Kjetil RETTERSTØL (The Lipid Clinic, Oslo University Hospital and Department of Nutrition, University of Oslo, Kristian, K THOMSEN (University Hospital of South Denmark, Esbjerg, Denmark), Lale TOKGOZOGLU (Hacettepe University, Turkey), Laszlo BAJNOK (1st Department of Medicine, Medical, School, University of Pecs, Lia E BANG (Copenhagen University Hospital, Denmark), Liliana GRIGORE (IRCCS Multimedica, Italy), Lluís MASANA (Hospital Universitari Sant Joan. Universitat Rovira i Virgili. CIBERDEM. Reus, Spain), Loukianos S RALLIDIS (University General Hospital Attikon, Greece), Maciej BANACH (Department of Preventive Cardiology and Lipidology, Medical University of Lodz, Poland), Małgorzata WALU´S-MIARKA (Jagiellonian University Medical College, Of Metabolic Diseases and Diabetology, Dept., Manuel CASTRO CABEZAS (Franciscus Gasthuis &amp, Vlietland Rotterdam, The Netherlands), Marcello ARCA (Sapienza University of Rome, Italy), Margus VIIGIMAA (North Estonia Medical Centre, Tallinn University of Technology, Estonia), Martin, P BOGSRUD (Unit for Cardiac and Cardiovascular Genetics, Matej MLINARIˇC (Department of Endocrinology, Diabetes and Metabolism, University Children’s Hospital, University Medical Centre Ljubljana, Slovenia), Matteo PIRRO (Section of Internal Medicine, Angiology and Arteriosclerosis Diseases, Maurizio AVERNA (Department PROMISE-University of Palermo &amp, Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Palermo, Italy), Meral KAYIKCIOGLU (Ege University Medical School Department of Cardiology, Turkey), Merete HEITMANN (Bispebjerg-Frederiksberg University Hospital, Denmark), Mette MOURIDSEN (Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Michal VRABLIK (3rd Department of Internal Medicine, General University Hospital and 1st Medical Faculty, Charles, University, Prague, Czech, Republic), Michel FARNIER (PEC2, University of Bourgogne Franche-Comt´e, Laboratory Medicine, Michel R LANGLOIS (Dept., Jan Hospital, AZ St., Belgium), Milad KHEDR (Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospital, Muge ILDIZLI DEMIRBAS (Kartal Kosuyolu Research and Training Hospital, Turkey), Myra TILNEY (Lipid Clinic, Mater Dei Hospital &amp, Dept of Medicine, University of Malta Medical School, Malta), Nadia CITRONI (Internal Medicine, APSS Trento Hospital, Of Internal Medicine, Niels P RIKSEN (Dept., Radboud university medical center, Nikolay M RUNEV (UMHAT Alexandrovska, Bulgaria), Nora KUPSTYTEKRISTAPONE (Hospital of Lithuanian University of Health Sciences Kaunas Clinics, Lithuania), Olena MITCHENKO (NSC, Clinical and Regenerative Medicine of the NAMS of Ukraine, Ukraine), Oliver WEING¨ARTNER (Universit¨atsklinikum Jena, Department of Internal Medicine, I, Oner OZDOGAN (University of Health Sciences, Izmir Faculty of Medicine, Tepecik Training and Research Hospital, Ovidio MU˜NIZGRIJALVO (Hospital Virgen del Rocío, Spain), Ozcan BASARAN (Mugla Sitki Kocman University, Pankaj GUPTA (University Hospitals of Leicester, United Kingdom), Paolo PARINI (Cardio Metabolic Unit, Karolinska, Institutet, and Theme Inflammation and Ageing, Karolinska University Hospital Huddinge, Patrizia SUPPRESSA (Department of Internal Medicine and rare disease Centre, Bari, Italy), Paul DOWNIE (Salisbury NHS Foundation trust, United Kingdom), Pavel JESINA (Metabolic Center General University Hospital, Czech Republic), of Internal Medicine, Pavel KRAML (Dept., Third Faculty of Medicine, Charles University and Kr´alovsk´e Vinohrady University Hospital Prague, Pawel BURCHARDT (Department of Cardiology, Cardiovascular, Unit, Hospital, J. Stru´s., Pozna´n, &amp, Department of Hypertension, Angiology and Internal Medicine, Poznan University of Medical Sciences, Pozna´n, Poland), Pedro VALDIVIELSO (Hospital VIRGEN DE LA VICTORIA, Spain), Pedro VON HAFE (Instituto Cuf, Portugal), Dept, Peter FASCHING (5th Med., Clinic, Ottakring, Philippe MOULIN (Hospices civils de Lyon/INSERM/Universit ´e Lyon1, Hˆopital Louis Pradel, F´ed´eration, D’Endocrinologie, Quit´eria RATO (Sociedade Portuguesa de Aterosclerose, Portugal), Reinhold INNERHOFER (Medical University Vienna, Austria), Renata C´IFKOV´A (Center for Cardiovascular Prevention, Charles University in Prague, First Faculty of Medicine and Thomayer University Hospital, Rene VALERO (Aix Marseille Univ, Aphm, Inserm, Inrae, C2vn, University Hospital La Conception, Department of Nutrition, Metabolic Diseases and Endocrinology, Scicali, Roberto, Robin URB´ANEK (Internal medicine, Obezita-Ormiga, s. r. o., Roma KAVALIAUSKIENE (Klaip˙ eda Seamen’s Hospital, Lituania), Roman CIBULKA (Department of paramedic science, medical diagnostics studies and public health, Faculty of Health Care Studies, University of West Bohemia, Sabina ZAMBON (Department of Medicine, - DIMED, University of Padova, Sergio D’ADDATO (University of Bologna. IRCCS S. Orsola Bologna, Italy), Stanislav ZEMEK (Lipidova ambulance, Czech Republic), Stefano ROMEO (Gothenburg University, Sweden), Stephanie K¨ONEMANN (Department of Internal Medicine, B, University Medicine Greifswald, DZHK (German Centre for Cardiovascular Research), Susanne GREBER-PLATZER (Clinical Division of Pediatric Pulmonology, Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Medical University Vienna, Thomas STULNIG (Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University Vienna &amp, Third Medical Department and Karl Landsteiner Institute for Metabolic Diseases and Nephrology, Clinic, Hietzing, Vienna, Austria), Thomas MUHR (Dept of Cardiology, Link¨oping University Hospital, Tina, Z KHAN (Consultant Cardiologist, Royal Brompton and Harefield Hospitals Part of Guy’s and St Thomas’ NHS Foundation Trust, Tomas FREIBERGER (Centre of Cardiovascular Surgery and Transplantation, Brno &amp, Medical, Faculty, Masaryk, University, Brno, Tom´aˇs ˇS´ALEK (Metabolic Clinic, Tomas Bata Hospital, Zlín, Tomas VASYLIUS (Republican Panevezys hospital, Of Cardiology, Dep., Lithuania), Ulrich LAUFS (Klinik und Poliklinik für Kardiologie, Universit ¨atsklinikum Leipzig, Ulrike SCHATZ (University Hospital Carl Gustav Carus Dresden at the Technical University Dresden, Department of Internal Medicine III, Urh GROSELJ (UMC, - University Children’s Hospital Ljubljana, University of Ljubljana, Victoria MARCO-BENEDI (Hospital Universitario Miguel Servet, Iisa, Cibercv, Vincent MAHER (Advanced Lipid Management and Research ALMAR centre, Tallaght University Hospital, Ireland), Vladimír BLAHA (University Hospital Hradec Kr´alov´e and Charles University, Faculty of Medicine in Hradec Kr´alov´e, 3rd Department of Internal Medicine, - Metabolism and Gerontology, Vladimir SOSKA (Department of Clinical Biochemistry, St. Anne’s University Hospital Brno, 2nd Clinic of Internal Medicine, Masaryk University Brno, Volker JJ SCHETTLER (Centre of Nephrology G¨ottingen, Germany), Wolfgang REINHARDT (SUS Malmoe, Sweden), Xavier PINT´O (Hospital Universitari de Bellvitge-Idibell-UB-CiberObn, Spain), Yoto YOTOV (Second Cardiology Clinic, Marina, University Hospital Sv., Medical University of Varna, Zaneta PETRULIONIENE (Vilnius University Medical Faculty, Vilnius University Hospital Santaros klinikos, Lithuania), ˇZeljko REINER (Department for Metabolic Diseases, University Hospital Center Zagreb, and Croatia, ).
Subjects: Clinicians, Clinical evaluation, Cardiology and Cardiovascular Medicine, Cardiovascular risk, Lipoprotein(a)
Published: 2023

44. Les organoïdes hépatiques

Author: E. Luce, Etienne Bur, Anne Dubart-Kupperschmitt, Bertrand Cariou, Amandine Caillaud, Antonietta Messina, Jean-Charles Duclos-Vallée, and Karim Si-Tayeb
Subjects: 0303 health sciences, Cell type, Ethical issues, General Medicine, Biology, General Biochemistry, Genetics and Molecular Biology, In vitro, Cell biology, Transplantation, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Organoid, Induced pluripotent stem cell, 030304 developmental biology
Abstract: L’étude et la compréhension de l’organogenèse du foie ont permis le développement de protocoles de différenciation des cellules souches pluripotentes afin de pallier le manque de cellules primaires, offrant ainsi une source quasi illimitée de cellules hépatiques. La différenciation de ces cellules dans des systèmes de culture conventionnels en deux dimensions (2D) ayant cependant montré ses limites, des organoïdes hépatiques ont été dérivés de cellules souches pluripotentes humaines et représentent désormais une alternative prometteuse. Ces structures 3D, complexes et organisées, intégrant un ou plusieurs types cellulaires, permettent de reproduire in vitro une ou plusieurs fonctions de l’organe, et ouvrent ainsi la voie à de nombreuses applications, comme l’étude du développement du foie, la production en masse de cellules hépatiques fonctionnelles pour la transplantation ou le développement de foies bioartificiels, sans oublier la modélisation de pathologies hépatiques permettant le criblage à haut débit de médicaments ou des études de toxicité. Des enjeux économiques et éthiques doivent également être pris en considération avant une utilisation de ces organoïdes pour des applications thérapeutiques.
Published: 2021
Full Text: View/download PDF

45. Variants in the

Author: Antoine, Rimbert, Ming W, Yeung, Nawar, Dalila, Chris H L, Thio, Haojie, Yu, Natalia, Loaiza, Federico, Oldoni, Adriaan, van der Graaf, Siqi, Wang, M Abdullah, Said, Lisanne L, Blauw, Aurore, Girardeau, Lise, Bray, Amandine, Caillaud, Vincent W, Bloks, Marie, Marrec, Philippe, Moulin, Patrick C N, Rensen, Bart, van de Sluis, Harold, Snieder, Mathilde, Di Filippo, Pim, van der Harst, Anne, Tybjaerg-Hansen, Philip, Zimmerman, Bertrand, Cariou, and Jan Albert, Kuivenhoven
Subjects: Hypobetalipoproteinemias, Mice, C-Reactive Protein, Pharmaceutical Preparations, Cholesterol, HDL, Animals, Humans, Cholesterol, LDL, Atherosclerosis, Apolipoproteins B, Receptors, G-Protein-Coupled
Abstract: In mice, GPR146 (G-protein-coupled receptor 146) deficiency reduces plasma lipids and protects against atherosclerosis. Whether these findings translate to humans is unknown.Common and rare genetic variants in theIn the UK Biobank, carriers of the common rs2362529-C allele present with lower low-density lipoprotein cholesterol, apo (apolipoprotein) B, high-density lipoprotein cholesterol, apoAI, CRP (C-reactive protein), and plasma liver enzymes compared with noncarriers. Carriers of the common rs1997243-G allele, associated with higher GPR146 expression, present with the exact opposite phenotype. The associations with plasma lipids of the above alleles are allele dose-dependent. Heterozygote carriers of a rare coding variant (p.Pro62Leu; n=2615), predicted to be damaging, show a stronger reductions in the above parameters compared with carriers of the common rs2362529-C allele. The p.Pro62Leu variant is furthermore shown to segregate with low low-density lipoprotein cholesterol in a family with familial hypobetalipoproteinemia. Compared with controls, carriers of the common rs2362529-C allele show a marginally reduced risk of coronary artery disease (This study shows that carriers of new genetic
Published: 2022

46. 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
Full Text: View/download PDF

47. L’acromégalie est associée à des déformations vertébrales mais pas à des fractures vertébrales : étude monocentrique transversale

Author: Delphine Drui, Bertrand Cariou, Charlotte Plard, Pascale Guillot, Samy Hadjadj, Clarisse Hochman, Benoit Le Goff, and Yves Maugars
Subjects: 030203 arthritis & rheumatology, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, 030212 general & internal medicine
Abstract: Resume Objectifs La plupart des etudes retrouvent une majoration du risque de fractures vertebrales chez les patients acromegales, malgre une densite minerale osseuse normale. Nous avons etudie la prevalence des fractures vertebrales chez les patients acromegales de moins de 80 ans suivis au CHU de Nantes. Methode Etude transversale monocentrique realisee au CHU de Nantes de 1988 a 2018. Cinquante patients (18 femmes, 32 hommes) d’un âge median de 52,3 ans (27 -78 ans) ont ete inclus. Les fractures vertebrales etaient evaluees sur des radiographies conventionnelles des rachis lombaire et thoracique de face et de profil, selon la methode semi-quantitative de Genant. Nous avons egalement etudie les deformations vertebrales autres que les fractures, en utilisant 3 criteres : presence d’osteophytes, presence de pincement discal et aspect cuneiforme des vertebres. Nous avons analyse la densite minerale osseuse par absorptiometrie bi-photonique et le statut hormonal. Resultats Trois patients (6 %) presentaient une fracture vertebrale : une fracture de grade 1 et 2 fractures de grade 2 selon la classification de Genant, chez deux patients osteoporotiques et un patient osteopenique. Leurs deficits ante-hypophysaires etaient substitues. En considerant les deformations franches (osteophyte ou pincement discal ≥ grade 2 ou aspect cuneiforme), le rachis dorsal etait deforme chez 22 patients (44 %) et le rachis lombaire chez 21 patients (42 %). Conclusions Les patients acromegales presentaient une faible prevalence de fractures vertebrales, mais un nombre important de deformations vertebrales. Nous supposons que cette forte prevalence de deformations franches pourrait expliquer la forte prevalence de fractures vertebrales rapportee precedemment.
Published: 2021
Full Text: View/download PDF

48. Impact of parathyroidectomy on cardiovascular risk in primary hyperparathyroidism: A narrative review

Author: Claire Blanchard, Bertrand Cariou, Eric Mirallié, and S. Frey
Subjects: Parathyroidectomy, medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Decision-Making, Medicine (miscellaneous), 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Risk Assessment, Severity of Illness Index, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Humans, Endocrine system, Glucose homeostasis, Risk factor, Nutrition and Dietetics, business.industry, Hyperparathyroidism, Primary, medicine.disease, Treatment Outcome, Cardiovascular Diseases, Heart Disease Risk Factors, Narrative review, Kidney disorder, Cardiology and Cardiovascular Medicine, business, Primary hyperparathyroidism
Abstract: Aims Primary hyperparathyroidism (PHPT), one of the most frequent endocrine disorders, is not only associated with bone and kidney disorders but also with increased cardiovascular risk. This cardiovascular risk is not part of the indication for surgery owing to discordant evidence of the effects of parathyroidectomy (PTX), especially in mild PHPT which is the most common presentation of PHPT. This literature review focuses on the effects of PTX on the cardiovascular risk in PHPT. The MEDLINE database was searched via the PubMed interface, selecting relevant articles published after 1990 in English. Data synthesis In the most recent series, PTX appeared to have a positive impact on cardiovascular morbidity and mortality. Surgery improves arterial hypertension, markers of glucose homeostasis, vascular and cardiac remodeling and electrocardiographic impairments due to classical PHPT. However, the results of surgery on mild PHPT are conflicting. Conclusions PTX seems to improve cardiovascular risk in patients presenting the classical form of PHPT. This improvement is correlated with preoperative serum calcium and/or PTH level, depending on the cardiovascular risk factor. However, many aspects of this improvement are not fully understood. Future studies should assess the effects of PTX on nocturnal hypertension, cardiac morphology and functions. The results for mild PHPT are conflicting owing to the limited size of the cohorts included in studies and the lack of randomized trials. Surgery is not currently recommended for patients presenting mild PHPT based on the cardiovascular risk and more studies are needed to better understand the interest of PTX on cardiovascular outcomes.
Published: 2021
Full Text: View/download PDF

49. La vie sans tissu adipeux : les lipodystrophies généralisées congénitales ; causes, physiopathologie et prise en charge thérapeutique

Author: Xavier Prieur, Jocelyne Magré, and Bertrand Cariou
Subjects: 0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine, 030209 endocrinology & metabolism, Cardiology and Cardiovascular Medicine
Abstract: Resume Les lipodystrophies congenitales generalisees, aussi connues sous le nom de lipodystrophie congenitale de Berardinelli-Seip (BSCL), representent le phenotype le plus extreme des lipodystrophies. Elles se caracterisent par la perte quasi-totale du tissu adipeux et une predisposition a developper des complications metaboliques, telles qu’un diabete, une hypertriglyceridemie et une hepatopathie steatosique dysmetabolique. Quatre sous-types de BSCL sont distingues en fonction du gene en cause : AGPAT2 codant l’enzyme 1-acylglycerol-3-phosphate O-acyltransferase 2 et BSCL2 codant la Seipine, et plus rarement, CAV1 et PTRF codant des proteines associees aux caveoles, respectivement la caveoline-1, et la polymerase 1 et facteur de liberation de la transcription appelee aussi Cavin-1. L’etude de la physiopathologie de la BSCL, par des travaux cliniques et par la generation de modeles animaux et cellulaires originaux a permis de comprendre comment l’absence de ces proteines entraine des dysfonctions adipocytaires primaires et severes. Ces etudes soulignent l’importance cruciale du tissu adipeux dans l’homeostasie glucido-lipidique, tant par son role de stockage des molecules energetiques que par son action endocrine. Dans cette revue, nous nous concentrerons sur les caracteristiques cliniques, les mecanismes moleculaires, et le traitement des lipodystrophies congenitales. La BSCL est un phenotype extreme qui donne l’opportunite unique d’etudier les consequences physiopathologiques de la vie sans tissu adipeux.
Published: 2021
Full Text: View/download PDF

50. Associations of microvascular complications with all-cause death in patients with diabetes and COVID-19: The CORONADO, ABCD COVID-19 UK national audit and AMERICADO study groups

Author: Samy, Hadjadj, Pierre-Jean, Saulnier, Yue, Ruan, Xu, Zhu, Renee, Pekmezaris, Michel, Marre, Jean Michel, Halimi, Matthieu, Wargny, Rustam, Rea, Pierre, Gourdy, Bertrand, Cariou, Alyson K, Myers, and Kamlesh, Khunti
Abstract: To provide a detailled analysis of the microvascular burden in patients with diabetes hopitalized for COVD-19.We analysed data from the French CORONADO initiative and the UK Association of British Clinical Diabetologists (ABCD) COVID-19 audit, two nationwide multicentre studies, and the AMERICADO, a multicentre study conducted in New York area. We assessed the association between risk of all-cause death during hospital stay and the following microvascular complications in patients with diabetes hospitalized for COVID-19: diabetic retinopathy and/or diabetic kidney disease and/or history of diabetic foot ulcer.Among 2951 CORONADO, 3387 ABCD COVID-19 audit and 9327 AMERICADO participants, microvascular diabetic complications status was ascertained for 1314 (44.5%), 1809 (53.4%) and 7367 (79.0%) patients, respectively: 1010, 1059 and 1800, respectively, had ≥1 severe microvascular complication(s) and 304, 750 and 5567, respectively, were free of any complications. The patients with isolated diabetic kidney disease had an increased risk of all-cause death during hospital stay: odds ratio [OR] 2.53 (95% confidence interval [CI] 1.66-3.83), OR 1.24 (95% CI 1.00-1.56) and OR 1.66 (95% CI 1.40-1.95) in the CORONADO, the ABCD COVID-19 national audit and the AMERICADO studies, respectively. After adjustment for age, sex, hypertension and cardiovascular disease (CVD), compared to those without microvascular complications, patients with microvascular complications had an increased risk of all-cause death during hospital stay in the CORONADO, the ABCD COVID-19 diabetes national audit and the AMERICADO studies: adjusted OR (Microvascular burden is associated with an increased risk of death in patients hospitalized for COVID-19.
Published: 2022

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

485 results on '"Bertrand, Cariou"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources