The vicious circle of chronic kidney disease and hypertriglyceridemia: What is first, the hen or the egg?

Chronic kidney disease (CKD) is documented to cause alterations in lipid metabolism, and this was considered a potent driver of increased cardiovascular risk. Among the diverse alteration of lipid traits in CKD, research endeavours have predominantly concentrated on low-density lipoproteins (LDL) in view of the potent pro-atherogenic role of these lipoprotein particles and the demonstration of protective cardiovascular effect of reducing LDL. However, few studies have focused on the metabolism of triglyceride-rich lipoproteins and even fewer on their role in causing kidney damage.

Protocol for oil red O staining of low-density lipoproteins for in vivo cell treatment.

Low-density lipoproteins (LDLs) are the most abundant circulating lipoproteins and the most critical factor in the development of atherosclerosis. This protocol allows the staining of LDLs with oil red O to monitor particle uptake in bright-field microscopy. Here, we describe how to stain isolated LDLs using oil red O and how to use them to monitor LDL uptake in time-lapse experiments or fixed cells.

Consensus document on diagnosis and management of familial hypercholesterolemia from the Italian Society for the Study of Atherosclerosis (SISA).

Aims: Familial Hypercholesterolemia (FH) is a genetic disorder of lipoprotein metabolism that causes an increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Although early diagnosis and treatment of FH can significantly improve the cardiovascular prognosis, this disorder is underdiagnosed and undertreated. For these reasons the Italian Society for the Study of Atherosclerosis (SISA) assembled a Consensus Panel with the task to provide guidelines for FH diagnosis and treatment.

Contemporary lipid-lowering management and risk of cardiovascular events in homozygous familial hypercholesterolaemia: insights from the Italian LIPIGEN Registry.

Aims: The availability of novel lipid-lowering therapies (LLTs) has remarkably changed the clinical management of homozygous familial hypercholesterolaemia (HoFH). The impact of these advances was evaluated in a cohort of 139 HoFH patients followed in a real-world clinical setting.

Methods And Results: The clinical characteristics of 139 HoFH patients, along with information about LLTs and low-density lipoprotein cholesterol (LDL-C) levels at baseline and after a median follow-up of 5 years, were retrospectively retrieved from the records of patients enrolled in the LIPid transport disorders Italian GEnetic Network-Familial Hypercholesterolaemia (LIPIGEN-FH) Registry.

Sex Differences in Diagnosis, Treatment, and Cardiovascular Outcomes in Homozygous Familial Hypercholesterolemia.

Importance: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic condition characterized by extremely increased low-density lipoprotein (LDL) cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Heterozygous familial hypercholesterolemia (HeFH) is more common than HoFH, and women with HeFH are diagnosed later and undertreated compared to men; it is unknown whether these sex differences also apply to HoFH.

Objective: To investigate sex differences in age at diagnosis, risk factors, lipid-lowering treatment, and ASCVD morbidity and mortality in patients with HoFH.

Genetic heterogeneity of familial hypercholesterolaemia in two populations from two different countries.

Background: Familial hypercholesterolemia (FH) is a genetically determined monogenic disorder of predominantly autosomal dominant inheritance. A number of studies on differences in the genetic profile of patients with FH have demonstrated the importance of a more substantive evaluation of genetic features. The aim of this study was to evaluate the genetic profile of patients with clinical FH among Italian and Russian patients.

Real-World Effectiveness of PCSK9 Inhibitors in Reducing LDL-C in Patients With Familial Hypercholesterolemia in Italy: A Retrospective Cohort Study Based on the AIFA Monitoring Registries.

Background Information on the real-world use of proprotein convertase subtilisin kexin 9 inhibitors (PCKS9is) in familial hypercholesterolemia are limited. We evaluated the pattern of prescription and the long-term efficacy of alirocumab and evolocumab in Italian patients with familial hypercholesterolemia in clinical practice. Methods and Results The data set for analysis was extracted from the PCKS9i Italian Medicines Agency (AIFA) registry and included 2484 patients with heterozygous familial hypercholesterolemia (HeFH) and 62 patients with homozygous familial hypercholesterolemia (HoFH) who were prescribed PCKS9is from February 2017 to December 2021.

ANGPTL3 Deficiency and Risk of Hepatic Steatosis.

Background: ANGPTL3 (angiopoietin-like 3) is a therapeutic target for reducing plasma levels of triglycerides and low-density lipoprotein cholesterol. A recent trial with vupanorsen, an antisense oligonucleotide targeting hepatic production of ANGPTL3, reported a dose-dependent increase in hepatic fat. It is unclear whether this adverse effect is due to an on-target effect of inhibiting hepatic ANGPTL3.

Effectiveness of clinical scores in predicting coronary artery disease in familial hypercholesterolemia: a coronary computed tomography angiography study.

Purpose: One of the major challenges in the management of familial hypercholesterolemia (FH) is the stratification of cardiovascular risk in asymptomatic subjects. Our purpose is to investigate the performance of clinical scoring systems, Montreal-FH-score (MFHS), SAFEHEART risk (SAFEHEART-RE) and FH risk score (FHRS) equations and Dutch Lipid Clinic Network (DLCN) diagnostic score, in predicting extent and severity of CAD at coronary computed tomography angiography (CCTA) in asymptomatic FH.

Material And Methods: One-hundred and thirty-nine asymptomatic FH subjects were prospectively enrolled to perform CCTA.

How ANGPTL3 Inhibition Will Help Our Clinical Practice?

Purpose Of Review: This review aims to summarize the most recently published literature highlighting the potential of pharmacological inhibition of ANGPTL3 in treating patients suffering from dyslipidemias. The rational for this strategy will be discussed considering evidence describing the role of ANGPTL3 in lipid metabolism and the consequences of its deficiency in humans.

Recent Findings: Recent trials have demonstrated the efficacy and safety of ANGPTL3 inhibition in treating homozygous familial hypercholesterolemia even in those patients carrying biallelic null/null variants, thus supporting the notion that the LDL-lowering effect of ANGPLT3 inhibition is LDLR-independent.

Recent Apolipoprotein CIII trials.

Purpose Of Review: This review will briefly revise the evidence concerning the pharmacological inhibition of Apolipoprotein CIII (ApoCIII) in patients with hypertriglyceridemia.

Recent Findings: ApoCIII is a plasma apolipoprotein playing a major role in the metabolism of triglyceride-rich lipoproteins, namely chylomicrons and very-low-density lipoproteins as well as in the pathological processes involved in atherosclerosis. Therefore, ApoCIII is a potential new target for reducing plasma levels of TRLs and, thereby, cardiovascular risk.

Efficacy of Long-Term Treatment of Autosomal Recessive Hypercholesterolemia With Lomitapide: A Subanalysis of the Pan-European Lomitapide Study.

Autosomal recessive hypercholesterolemia (ARH) is a rare autosomal recessive disorder of low-density lipoprotein (LDL) metabolism caused by pathogenic variants in the gene. Like homozygous familial hypercholesterolemia, ARH is resistant to conventional LDL-lowering medications and causes a high risk of atherosclerotic cardiovascular diseases (ASCVDs) and aortic valve stenosis. Lomitapide is emerging as an efficacious therapy in classical HoFH, but few data are available for ARH.

New and Emerging Therapies for Dyslipidemia.

Atherosclerotic cardiovascular disease (ASCVD) continues to represent a growing global health challenge. Despite guideline-recommended treatment of ASCVD risk, including antihypertensive, high-intensity statin therapy, and antiaggregant agents, high-risk patients, especially those with established ASCVD and patients with type 2 diabetes, continue to experience cardiovascular events. Recent years have brought significant developments in lipid and atherosclerosis research.

The Fibrinogen-like Domain of ANGPTL3 Facilitates Lipolysis in 3T3-L1 Cells by Activating the Intracellular Erk Pathway.

Background: ANGPTL3 stimulates lipolysis in adipocytes, but the underlying molecular mechanism is yet unknown. The C-terminal fibrinogen-like domain of ANGPTL3 (ANGPTL3-Fld) activates the AKT pathway in endothelial cells. Hence, we evaluated whether ANGPTL3-Fld stimulates lipolysis in adipocytes through the MAPK kinase pathway.

Metabolic Syndrome but Not Fatty Liver-Associated Genetic Variants Correlates with Glomerular Renal Function Decline in Patients with Non-Alcoholic Fatty Liver Disease.

The association between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) has been extensively demonstrated. Recent studies have focused attention on the role of patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism in the association between NAFLD and CKD in non-metabolic adults and children, but the genetic impact on NAFLD-CKD association is still a matter of debate. The aim of the study was to investigate the impact of PNPLA3, transmembrane 6 superfamily member 2 (TM6SF2), membrane-bound O-acyltransferase domain containing 7 (MBOAT7) and glucokinase regulatory protein (GCKR) gene variants rather than metabolic syndrome features on renal function in a large population of NAFLD patients.

Efficacy and safety of lomitapide in homozygous familial hypercholesterolaemia: the pan-European retrospective observational study.

Aims: Lomitapide is a lipid-lowering agent indicated as an adjunct therapy for adult homozygous familial hypercholesterolaemia (HoFH). This study evaluated the medium-term effectiveness and safety of lomitapide in a large cohort of HoFH patients in Europe.

Methods And Results: In a multicentre retrospective, observational study including 75 HoFH patients treated with lomitapide in a real-world clinical setting from 9 European countries, low-density lipoprotein cholesterol (LDL-C) changes, adverse events (AEs), and major adverse cardiovascular events (MACE) were assessed.