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During soccer matches, performance decrements have been reported that relate to both physical abilities and technical skills. To investigate the effects of low-frequency electrical stimulation LFES (VeinoplusSport®, Ad Rem Technology, France) administered during half-time recovery on performance alterations during the second half. Twenty-two highly trained young players undertook a soccer-match simulation (SAFT90). During half-time, they were randomly assigned to LFES group or Placebo group. Each half was split into 3 bouts of 12 minutes. Following each bout, maximal strike speed (MSS), sprint test (ST), maximal sprint accelerations (MA) and metabolic power (MP) were determined in both groups. Arterial (AF) and venous flows (VF) were measured at rest and at the end of half-time. LEFS group exhibited beneficial effects on performance compared to the Placebo group with a likely effect for MSS, ST, MA, and a possible effect for MP. AF and VF increased statistically more in LEFS group compared to Placebo group. The use of specific calf-pump LFES during half-time of a youth simulated soccer match attenuated the decrease in performance during the second half compared to Placebo group. This effect is most marked at the beginning of the second half with regards to explosive parameters. [ABSTRACT FROM AUTHOR]

Abstract Background Low plasma high-density lipoprotein-cholesterol (HDL-c) level is commonly present in obesity and represents an independent cardiovascular risk factor. However, obese patients are a very heterogeneous population and the factors and mechanisms that contribute to low HDL-c remain unclear. The aim of this study was to investigate the association between plasma HDL-c levels and plasma hormonal profiles (insulin, adiponectin, resistin, leptin and ghrelin) in subsets of class II and III obese patients. Methods Fasting plasma levels of glucose, total cholesterol, LDL-c, HDL-c, triglycerides, free fatty acids, apoproteins A-I, B-100, B-48, C-II, C-III, insulin, hs-CRP, adipocytokines (adiponectin, resistin, leptin), unacylated ghrelin, body composition (DXA) and resting energy expenditure were measured in three subsets of obese patients: 17 metabolically abnormal obese (MAO) with metabolic syndrome and the typical metabolic dyslipidaemia, 21 metabolically healthy obese (MHO) without metabolic syndrome and with a normal lipid profile, and 21 isolated low HDL-c obese patients (LHO) without metabolic syndrome, compared to 21 healthy lean control subjects. Results Insulin resistance (HOMA-IR) increased gradually from MHO to LHO and from LHO to MAO patients (p < 0.05 between MHO and MAO and between LHO and MAO). In multiple regression analysis, serum unacylated ghrelin levels were only positively and independently associated with HDL-c levels in the LHO group (p = 0.032). Conclusions These results suggest that, in class II and III obese patients with an isolated low HDL-c phenotype, unacylated ghrelin is positively associated with HDL-c level independently of insulin resistance and CRP levels, and may contribute to the highly prevalent low HDL-c level seen in obesity.

Background and Aims: PCSK9 is a key regulator of LDL-cholesterol levels. PCSK9 gain of function variants (GOFVs) cause autosomal dominant hypercholesterolemia (ADH). The first described PCSK9-GOFV, p.Ser127Arg, almost exclusively reported in France, represents 67 % of the PCSK9 French GOFVs due to a founder effect. Few other carriers are reported in South Africa and Norway. This study aims to estimate when the common ancestor lived and to describe a cohort of p.Ser127Arg carriers., Methods: Eight families and 14 p.Ser127Arg carriers were genotyped and phenotyped. Haplotypes were constructed using 11 microsatellites around PCSK9 and 6 intragenic single nucleotide polymorphisms (SNPs). To add to the biological analysis, eight additional p.Ser127Arg carriers, 12 carriers of other PCSK9-GOFVs, 93 LDLR loss of function variant (LOFV) carriers and 49 non-carriers subjects were phenotyped., Results: The most common ancestor of p.Ser127Arg was estimated to have lived 775 years ago [95 % CI: 575-1075]. French Protestants exiled after the revocation of the Edict of Nantes in 1685 AD likely brought the variant to South Africa and Norway. As expected for ADH subjects, carriers of LDLR-LOFV, the p.Ser127Arg, or other PCSK9-GOFVs showed significantly higher LDL-C levels than that of the non-carriers. Interestingly, LDL-C levels are higher for LDLR-LOFVs and for the reduced secreted p.Ser127Arg than for secreted PCSK9-GOFVs, suggesting a greater effect of the p.Ser127Arg. Conversely, HDL-C was significantly lower for LDLR-LOFV and p.Ser127Arg carriers., Conclusions: This first report from a large cohort of PCSK9-p.Ser127Arg carriers provides observations suggesting a stronger hypercholesterolemic potential of the mutated pro-PCSK9 compared with the secreted mature protein. This work also provides additional data to support the association between PCSK9 and HDL metabolism, and molecular evidence that this variant appeared in France around 1248 AD (Graphical Abstract = Fig. 1)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Patients with homozygous familial hypercholesterolemia (HoFH) remain at very high cardiovascular risk despite the best standard of care lipid-lowering treatment. The addition of evinacumab, an angiopoietin-like protein 3 monoclonal antibody, more than halves low-density lipoprotein cholesterol in short-term studies. This study evaluated whether the evinacumab response was durable in the long term and improved cardiovascular outcome., Methods: The OLE ELIPSE HoFH (Open-Label Extension to Evinacumab Lipid Studies in Patients With HoFH) study included newly diagnosed patients and those completing the ELIPSE HoFH trial, on stable lipid-lowering therapy including lipoprotein apheresis but not lomitapide. All patients received evinacumab (15 mg/kg intravenously) every 4 weeks, with no change in concomitant lipid-lowering treatment during the first 6 months. The primary efficacy end points were the mean absolute and percentage changes in low-density lipoprotein cholesterol from baseline to 6 months. A key secondary end point was cardiovascular event-free survival, which was compared with a control HoFH cohort not treated with evinacumab or lomitapide and matched for age, sex, and lipoprotein apheresis, derived from French Registry of Familial hypercholesterolemia., Results: Twelve patients, 5 women and 7 men (12-57 years), were enrolled in 3 centers in France. At 6 months, the mean low-density lipoprotein cholesterol reduction with evinacumab was 3.7 mmol/L or 56% (from 6.5 mmol/L at baseline to 2.8 mmol/L; P <0.0001) and was sustained over the median 3.5-year follow-up. No patients on evinacumab experienced cardiovascular events versus 13 events for 5/21 (24%) over 4 years in the control cohort (likelihood P =0.0267)., Conclusions: Real-life, long-term evinacumab adjunctive to lipid-lowering therapy including lipoprotein apheresis led to sustained low-density lipoprotein cholesterol lowering and improved cardiovascular event-free survival of patients with HoFH., Competing Interests: Disclosures S. Béliard reports grants/honoraria from Ultragenyx for clinical trials and consultancy and from Amarin, Amgen, Amryt Novartis, Sanofi for clinical trials, conferences and consultancy. R. Valero reports personal or institutional honoraria for speakers’ bureaux, consultancy, clinical trials and travel/accommodation for professional purposes from Adelia Médical, Akcea, Amarin, Amgen, AstraZeneca, Boehringer-Ingelheim, Dinno Santé, Ionis, Janssen, Lilly, Merck and Co., Nestlé, Novartis, Novo Nordisk, Orkyn, Pfizer, Sanofi-Regeneron, Servier. E. Bruckert reports grants/honoraria for clinical trials/consultancy from MSD, Astra Zeneca, Genfit, Amgen, Sanofi-Aventis, Aegerion/Amryt, Lilly, Mylan/Viatris, Novartis, Pfizer, Servier, Organon, Akcea Therapeutics, and Ultragenyx. M. Farnier reports consultancy honoraria from Abbott, Amarin, Amgen, AstraZeneca, Austell, Kowa, Merck and Co., Organon, Pfizer, Recordati, Sanofi/Regeneron, Servier, SMB, Ultragenyx, and Viatris. A. Gallo reports research grants and honoraria from Amgen, Sanofi and Regeneron, Mylan Viatris, Merck and Co., Akcea Therapeutics, Amryt, Novartis, Servier, Ultragenyx, Amarin, and Eli Lilly. The other authors report no conflicts.

Dyslipidaemias are major cardiovascular risk factors, especially in people with diabetes. In this area, next-generation therapies targeting circulating lipoparticle metabolism (LDL, VLDL, chylomicrons, HDL) have recently been approved by the European and US medical agencies, including anti- proprotein convertase subtilisin/kexin 9 (PCSK9) antibodies; an siRNA targeting PCSK9; bempedoic acid, which targets ATP citrate lyase; an antisense oligonucleotide targeting apolipoprotein C-III; an anti-angiopoietin-like 3 antibody; and a purified omega-3 fatty acid, icosapent ethyl. Other therapies are in different phases of development. There are several important considerations concerning the link between these new lipid-lowering therapies and diabetes. First, since concerns were first raised in 2008 about an increased risk of new-onset diabetes mellitus (NODM) with intensive statin treatment, each new lipid-lowering therapy is being evaluated for its associated risk of NODM, particularly in individuals with prediabetes (impaired fasting glucose and/or impaired glucose tolerance). Second, people with diabetes represent a large proportion of those at high or very high cardiovascular risk in whom these lipid-lowering drugs are currently, or will be, prescribed. Thus, the efficacy of these drugs in subgroups with diabetes should also be closely considered, as well as any potential effects on glycaemic control. In this review, we describe the efficacy of next-generation therapies targeting lipoprotein metabolism in subgroups of people with diabetes and their effects on glycaemic control in individuals with diabetes and prediabetes and in normoglycaemic individuals., (© 2024. The Author(s).)

Background: Heterozygous familial hypercholesterolemia (HeFH) predisposes to premature cardiovascular diseases. Since 2015, the European Atherosclerosis Society has advocated initiation of statins at 8-10 years of age and a low-density lipoprotein cholesterol (LDL-C) target of <135 mg/dL. Longitudinal data from large databases on pharmacological management of pediatric HeFH are lacking., Objective: Here, we describe treatment patterns and LDL-C goal attainment in pediatric HeFH using longitudinal real-world data., Methods: This was a retrospective and prospective multicenter cohort study (2015-2021) of children with HeFH, diagnosed genetically or clinically, aged <18 years, and followed up in the National French Registry of FH (REFERCHOL). Data on the study population as well as treatment patterns and outcomes are summarized as mean±SD., Results: We analyzed the data of 674 HeFH children (age at last visit: 13.1 ± 3.6 years; 82.0 % ≥10 years; 52.5 % females) who were followed up for a mean of 2.8 ± 3.5 years. Initiation of lipid-lowering therapy was on average at 11.8 ± 3.0 years of age for a duration of 2.5 ± 2.8 years. At the last visit, among patients eligible for treatment (573), 36 % were not treated, 57.1 % received statins alone, 6.4 % statins with ezetimibe, and 0.2 % ezetimibe alone. LDL-C was 266±51 mg/dL before treatment and 147±54 mg/dL at the last visit (-44.7 %) in treated patients. Regarding statins, 3.3 %, 65.1 %, and 31.6 % of patients received high-, moderate-, and low-intensity statins, respectively. Overall, 59 % of children on statin therapy alone and 35.1 % on bitherapy did not achieve the LDL-C goal; fewer patients in the older age group did not reach the treatment goal., Conclusion: Pediatric patients with FH followed up in specialist lipid clinics in France receive late treatment, undertreatment, or suboptimal treatment and half of them do not reach the therapeutic LDL-C goal. Finding a more efficient framework for linking scientific evidence to clinical practice is needed., Competing Interests: Declaration of competing interest • NP has received honoraria from ADEN-ALLP, Alexion AMGEN, Amryt, Biocodex, Elsevier, Kowa, Lactalis, Nestlé NHS, NHC, Nutricia-Danone, Orphan Europ, Sanofi, Shire, Ultragenyx • PT has participated in one scientific committee at Ultragenyx laboratories • YP has received honoraria from Servier, Viatris, AMGEN, Sanofi, Bouchara-Recordati • JPR has received remuneration from Sanofi, Ultragenyx • EB has received honoraria from AstraZeneca, AMGEN, MSD, Sanofi and Regeneron, Aegerion/Amryt, Lilly, Ionis-pharmaceuticals, Akcea, Alexion pharma, Servier, Novartis, Mylan/Viatris, Organon and Genfit • AG reports grants and personal fees from AMGEN, Sanofi, Regeneron, Mylan Viatris, MSD, Akcea Therapeutics, Amryt and Ultragenyx. • SB has received honoraria for board, conferences, clinical trial or congress from Aegerion, Akcea, Elivie, Novartis, Sanofi or AMGEN • PP, LR, AV, RR have no conflict of interest related to this article., (Copyright © 2024 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)