Evinacumab and Cardiovascular Outcome in Patients With Homozygous Familial Hypercholesterolemia.

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.

Treatment of pediatric heterozygous familial hypercholesterolemia 7 years after the EAS recommendations: Real-world results from a large French cohort.

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.

Low Density Lipoprotein Cholesterol Decreases the Expression of Adenosine A Receptor and Lipid Rafts-Protein Flotillin-1: Insights on Cardiovascular Risk of Hypercholesterolemia.

High blood levels of low-density lipoprotein (LDL)-cholesterol (LDL-C) are associated with atherosclerosis, mainly by promoting foam cell accumulation in vessels. As cholesterol is an essential component of cell plasma membranes and a regulator of several signaling pathways, LDL-C excess may have wider cardiovascular toxicity. We examined, in untreated hypercholesterolemia (HC) patients, selected regardless of the cause of LDL-C accumulation, and in healthy participants (HP), the expression of the adenosine A receptor (AR), an anti-inflammatory and vasodilatory protein with cholesterol-dependent modulation, and Flotillin-1, protein marker of cholesterol-enriched plasma membrane domains.

Hyperlipidaemia in diabetes: are there particular considerations for next-generation therapies?

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.

Increased FH-Risk-Score and Diabetes Are Cardiovascular Risk Equivalents in Heterozygous Familial Hypercholesterolemia.

Background: Familial hypercholesterolemia (FH) is a genetic condition causing premature atherosclerotic cardiovascular disease (ASCVD). It is well established that patients with FH should be treated with statin therapy. However, there exists discordance concerning low-density lipoprotein cholesterol-lowering goals in the management of these patients between different guidelines worldwide.

High Physical Activity Volume Is Associated With an Increase in the Calibre of the Lower Limb Veins Without Impact on Functional Discomfort: the VARISPORT Study.

Objective: The relationship between physical activity and lower limb veins is complex. If a sedentary lifestyle is considered to be negative on lower limb veins, specific information on physical activity varicose vein volume is sparse, especially the effect of high physical activity volume. The main objective of the VARISPORT study was to evaluate lower limb veins (clinically, morphologically, and haemodynamically) and chronic venous disease symptoms in subjects exposed to high physical activity volume compared with a group of non-exposed subjects.

Prognostic models for short-term annual risk of severe complications and mortality in patients living with type 2 diabetes using a national medical claim database.

Objective: Prognostic models in patients living with diabetes allow physicians to estimate individual risk based on medical records and biological results. Clinical risk factors are not always all available to evaluate these models so that they may be complemented with models from claims databases. The objective of this study was to develop, validate and compare models predicting the annual risk of severe complications and mortality in patients living with type 2 diabetes (T2D) from a national claims data.

Metabolic syndrome predicts cardiovascular risk and mortality in familial hypercholesterolemia.

Background: The association between familial hypercholesterolemia (FH) and premature atherosclerotic cardiovascular disease (ASCVD) is well established. Several risk factors other than the cumulative low-density lipoprotein cholesterol (LDL-C) have been shown to modulate the severity of the phenotype in these patients. However, the effect of the metabolic syndrome (MetS) on ASCVD risk in FH remains to be determined.

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

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.

Factors Predicting Statin Initiation During Childhood in Familial Hypercholesterolemia: Importance of Genetic Diagnosis.

Objective: To identify childhood and parental factors associated with initiation of statin therapy in children with heterozygous familial hypercholesterolemia (HeFH), including underlying genetic diagnosis or parental premature atherosclerotic cardiovascular disease (ASCVD).

Study Design: This multicenter cohort study included 245 HeFH child-parent pairs from the REFERCHOL national register (2014-2020). Demographic and clinical characteristics at the last visit were collected.

Systematic review of adapted physical activity and therapeutic education of patients with chronic venous disease.

Background: Chronic venous disease (CVD), comprising impaired lower limb venous return, will lead to chronic distal venous pressure overload manifested by various clinical signs and symptoms and resulting in diminished quality of life. The CEAP (Clinical, Etiology, Anatomy, and Pathophysiology) classification of CVD distinguishes six stages (C0-C6) using clinical, etiologic, anatomic, and pathophysiologic parameters. In the present study, we analyzed the effects of adapted physical activity (APA) and patient-oriented therapeutic education (PTE) programs on the clinical signs, symptoms, and quality of life of patients with CVD.

Effectiveness of Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy on Lipid Levels in Type 2 Diabetes: a Meta-analysis.

Introduction: Obesity and its co-morbidities, including type 2 diabetes (T2DM) and dyslipidemia, are accompanied by excess cardiovascular morbi-mortality. Aside from excess low density lipoprotein-cholesterol (LDL-C), atherogenic dyslipidemia (AD), mainly characterized by elevated triglycerides and decreased high density lipoprotein-cholesterol (HDL-C) levels, is often present in T2DM obese patients. Bariatric surgery, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), has become a reference treatment in that population.

Dunnigan lipodystrophy syndrome: French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins).

Dunnigan syndrome, or Familial Partial Lipodystrophy type 2 (FPLD2; ORPHA 2348), is a rare autosomal dominant disorder due to pathogenic variants of the LMNA gene. The objective of the French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins), is to provide health professionals with a guide to optimal management and care of patients with FPLD2, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), is available on the French Health Authority website (in French).

A Rare Mutation in Associated with Lipodystrophy Drives Premature Cell Senescence.

Many proteins are causative for inherited partial lipodystrophies, including lamins, the essential constituents of the nuclear envelope scaffold called the lamina. By performing high throughput sequencing on a panel of genes involved in lipodystrophies, we identified a heterozygous mutation in gene (c.700C > T p.

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

Background: Familial Hypercholesterolemia (FH) is an underdiagnosed condition with an increased cardiovascular risk. It is unknown whether lipid accumulation plays a role in structural myocardial changes. Cardiovascular Magnetic Resonance (CMR) is the reference technique for the morpho-functional evaluation of heart chambers through cine sequences and for myocardial tissue characterization through late gadolinium enhancement (LGE) and T1 mapping images.

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

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare life-threatening condition that represents a therapeutic challenge. The vast majority of HoFH patients fail to achieve LDL-C targets when treated with the standard protocol, which associates maximally tolerated dose of lipid-lowering medications with lipoprotein apheresis (LA). Lomitapide is an emerging therapy in HoFH, but its place in the treatment algorithm is disputed because a comparison of its long-term efficacy versus LA in reducing LDL-C burden is not available.

Role of growth hormone in hepatic and intestinal triglyceride-rich lipoprotein metabolism.

Background: Elevated plasma concentrations of hepatic- and intestinally-derived triglyceride-rich lipoproteins (TRL) are implicated in the pathogenesis of atherosclerotic cardiovascular disease and all-cause mortality. Excess of TRL is the driving cause of atherogenic dyslipidemia commonly occurring in insulin-resistant individuals such as patients with obesity, type 2 diabetes and metabolic syndrome. Interestingly, growth hormone (GH)-deficient individuals display similar atherogenic dyslipidemia, suggesting an important role of GH and GH deficiency in the regulation of TRL metabolism.

Familial Hypercholesterolemia-Risk-Score: A New Score Predicting Cardiovascular Events and Cardiovascular Mortality in Familial Hypercholesterolemia.

Objective: Familial hypercholesterolemia (FH) is associated with a high risk of premature atherosclerotic cardiovascular disease (ASCVD). However, this risk is highly heterogeneous and current risk prediction algorithms for FH suffer from limitations. The primary objective of this study was to develop a score predicting incident ASCVD events over 10 years in a large multinational FH cohort.

SGLT2 inhibitors as potentially helpful drugs in PI3K inhibitor-induced diabetes: a case report.

Background: Hyperglycemia is the most common side-effect of phosphatidylinositol 3-kinase (PI3K) inhibitors that are approved for the treatment of some advanced or metastatic breast cancers. This side-effect is likely due to the central role of PI3K in insulin signalling. Here we report the use of a sodium-glucose cotransporter 2 (SGLT2) inhibitor to manage severe hyperglycemia.

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

Objectives: This 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).

Background: Common 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).

Excess body weight is an independent risk factor for severe forms of COVID-19.

Background And Aims: Few studies distinguished the independent role of overweight/obesity or their associated-comorbidities in the evolution towards severe forms of COVID-19. Obesity as a unifying risk factor for severe COVID-19 is an emerging hypothesis. The aim of this study was to evaluate whether excessive body weight per se, was a risk factor for developing a severe form of COVID-19.

Familial Chylomicronemia Syndrome (FCS): Recent Data on Diagnosis and Treatment.

Purpose Of Review: Familial chylomicronemia syndrome (FCS) is a rare recessive genetic disorder often underdiagnosed with potentially severe clinical consequences. In this review, we describe the clinical and biological characteristics of the disease together with its main complication, i.e.