PCSK9-directed therapies: an update.

Purpose Of Review: Two large cardiovascular outcomes trials of monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9) demonstrated that therapeutic inhibition of extracellular PCSK9 markedly reduces LDL cholesterol concentration and cardiovascular risk. Several novel strategies to inhibit PCSK9 function are in development. Different mechanisms of action may determine specific properties with potential relevance for patient care.

Clinical and genetic diagnosis of familial hypercholesterolaemia in patients undergoing coronary angiography: the Ludwigshafen Risk and Cardiovascular Health Study.

Aims: To investigate the prevalence of familial hypercholesterolaemia (FH) and compare the performance of clinical criteria and genetic testing in patients undergoing coronary angiography.

Methods And Results: The prevalence of FH was determined with the Dutch Lipid Clinical Network (DLCN), US 'Make Early Diagnosis to Prevent Early Death' (US-MEDPED), Simon Broome (SB) criteria, the 'familial hypercholesterolaemia case ascertainment tool' (FAMCAT), and a clinical algorithm. Genetic screening was conducted with a custom array from Affymetrix (CARRENAL array) harbouring 944 FH mutations.

LDL cholesterol target attainment in cardiovascular high- and very-high-risk patients with statin intolerance: a simulation study.

The inability to tolerate sufficient doses of statins, statin intolerance (SI), contributes to the non-achievement of guideline-recommended low-density lipoprotein cholesterol (LDL-C) treatment targets. Patients with SI require alternative lipid-lowering therapies (LLT). We conducted a simulation study on LDL-C target achievement with oral LLT (ezetimibe, bempedoic acid) in patients with SI, using representative data of 2.

The German CaRe high registry for familial hypercholesterolemia - Sex differences, treatment strategies, and target value attainment.

Background And Aims: Familial hypercholesterolemia (FH) is among the most common genetic disorders in primary care. However, only 15% or less of patients are diagnosed, and few achieve the goals for low-density lipoprotein cholesterol (LDL-C). In this analysis of the German Cascade Screening and Registry for High Cholesterol (CaRe High), we examined the status of lipid management, treatment strategies, and LDL-C goal attainment according to the ESC/EAS dyslipidemia guidelines.

Behavioural and nondirective parent training for children with externalising disorders: First steps towards personalised treatment recommendations.

For children with externalising disorders, parent training programmes with different theoretical foundations are available. Currently, there is little knowledge concerning which programme should be recommended to a family based on their individual needs (e.g.

Simulation study on LDL cholesterol target attainment, treatment costs, and ASCVD events with bempedoic acid in patients at high and very-high cardiovascular risk.

Background And Aims: The LDL cholesterol (LDL-C) treatment goals recommended by the 2019 ESC/EAS guidelines are only achieved in a minority of patients. The study objective was to estimate the impact of bempedoic acid treatment on LDL-C target attainment, drug costs, and atherosclerotic cardiovascular disease (ASCVD) events. The simulation used a Monte Carlo approach in a representative cohort of German outpatients at high or very-high cardiovascular risk.

Process Mechanisms in Behavioral Versus Nondirective Guided Self-help for Parents of Children with Externalizing Behavior.

The study examined potential mediating effects of therapist behaviors in the per-protocol sample (n = 108) of a randomized controlled trial comparing a behavioral and a nondirective guided self-help intervention for parents of children with externalizing disorders (4-11 years). Additionally, from an exploratory perspective, we analyzed a sequential model with parental adherence as second mediator following therapist behavior. Outcomes were child symptom severity of attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder rated by blinded clinicians, and parent-rated child functional impairment.

Trends in Ezetimibe Prescriptions as Monotherapy or Fixed-Dose Combination in Germany 2012-2021.

Aims: Addition of ezetimibe to statin therapy is recommended by current guidelines when low-density lipoprotein cholesterol (LDL-C) targets are not achieved with statin monotherapy. Fixed-dose combinations (FDC) improve medication adherence and facilitate risk factor control. We assessed prescription trends of ezetimibe as monotherapy or FDC with statins.

[Lipoprotein apheresis : State of the art and case report of the longest HELP treatment worldwide].

Lipoprotein apheresis is an extracorporeal procedure for the treatment of patients with homozygous familial hypercholesterolemia, patients with severe treatment-resistant hypercholesterolemia and patients with lipoprotein(a) hypercholesterolemia, who show progressive atherosclerotic cardiovascular disease despite optimal treatment. This article reports on the historical developments of the procedures, the most frequently used methods for apheresis as well as the data situation on efficacy and tolerability. Randomized prospective studies on clinical outcomes are not available.

[Update on PCSK9 inhibition].

Lowering of low-density lipoprotein (LDL) cholesterol represents one of the most effective interventions in cardiovascular prevention. Besides the oral treatment with statins, ezetimibe and bempedoic acid, subcutaneously administered inhibitors of proprotein convertase subtilisin-kexin type 9 (PCSK9) have been established as further cornerstones of lipid-lowering treatment. The antibodies evolocumab and alirocumab are administered subcutaneously every 2-4 weeks and lower LDL cholesterol by around 60%, independent of pre-treatment with very good tolerability.

Effects of Computer-Assisted Social Skills Training in Children With Disruptive Behavior Disorders: A Randomized Controlled Trial.

Objective: Computer-assisted child-focused interventions are expected to improve efficiency and personalization of therapist-led treatments for children and adolescents. However, therapist-led, outpatient interventions using computer assistance are lacking for children with oppositional defiant disorder (ODD) or conduct disorder (CD). The present randomized controlled trial examined the efficacy of individualized computer-assisted social skills training for children with aggressive behavior compared to a resource activation intervention.

[Modern lipid-lowering drugs-A means to counter the problem of undertreatment?].

Background: An elevated low-density lipoproteincholesterol (LDL-C) level is one of the most important modifiable cardiovascular risk factors. Despite potent combination treatment, the LDL‑C target values are not achieved in many high-risk patients.

Objective: Presentation of the rationale for lowering LDL‑C, the current status of lipid-lowering treatment and established and novel approaches to lower LDL‑C.

Investigation of the Influence of Moisture Content on Fatigue Behaviour of HPC by Using DMA and XRCT.

High-performance concrete (HPC) is a topic of current research and construction projects, due to its outstanding compressive strength and durability. In particular, its behaviour under high-cycle fatigue loading is the focus of current investigations, to further pave the way to highly challenging long-lasting constructions; e.g.

Obesity-An Update on the Basic Pathophysiology and Review of Recent Therapeutic Advances.

Obesity represents a major public health problem with a prevalence increasing at an alarming rate worldwide. Continuous intensive efforts to elucidate the complex pathophysiology and improve clinical management have led to a better understanding of biomolecules like gut hormones, antagonists of orexigenic signals, stimulants of fat utilization, and/or inhibitors of fat absorption. In this article, we will review the pathophysiology and pharmacotherapy of obesity including intersection points to the new generation of antidiabetic drugs.

Familial chylomicronemia syndrome due to a heterozygous deletion of the chromosome 8 treated with the apoCIII inhibitor volanesorsen: A case report.

Rationale: Familial chylomicronemia syndrome is a congenital, severe form of hypertriglyceridemia associated with increased risk of acute pancreatitis. Treatment options are limited.

Patient Concerns: A 52-year-old woman was referred with recurrent pancreatitis and severe hypertriglyceridemia to our lipid clinic.

Treatment components in behavioral versus nondirective telephone-assisted self-help interventions for parents of children with externalizing behavior problems.

Background: The aim of this study was to analyze treatment differentiation in a behavioral and a nondirective telephone-assisted self-help intervention for parents of children with externalizing behavior problems, including the development and evaluation of a rating scale.

Methods: In a randomized controlled trial, 149 parents of children aged 4-11 years with externalizing behavior problems were allocated to a behavioral or a nondirective guided self-help intervention. Parents in both conditions received eight self-help booklets and ten telephone consultations.

Cutaneous manifestations in familial hypercholesterolaemia.

Background And Aims: Familial hypercholesterolaemia (FH) is associated with high cardiovascular risk and underdiagnosed. Cutaneous manifestations are traditionally used as a major criterion of FH. They are included in the Dutch Lipid Clinic Network or Simon Broome registry criteria.

Genetic Variation in Sodium-glucose Cotransporter 2 and Heart Failure.

Inhibition of sodium-glucose cotransporter 2 (SGLT2) represents an emerging pharmaceutical approach for the treatment of heart failure. The mechanisms by which SGLT2 inhibitors reduce the risk of heart failure are not well understood. The objective of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in the SLC5A2 gene, encoding SGLT2, and heart failure, and to assess potential mediators of this association.

PCSK9 Inhibition: Insights From Clinical Trials and Future Prospects.

In 2003, clinical observations led to the discovery of the involvement of proprotein convertase subtilisin/kexin type 9 (PCSK9) in lipid metabolism. Functional studies demonstrated that PCSK9 binds to the low-density lipoprotein (LDL) receptor directing it to its lysosomal degradation. Therefore, carriers of gain-of-function mutations in exhibit decreased expression of LDL receptors on the hepatocyte surface and have higher LDL cholesterol (LDL-C) levels.

Non-statin lipid-lowering therapy over time in very-high-risk patients: effectiveness of fixed-dose statin/ezetimibe compared to separate pill combination on LDL-C.

Background: Many patients at very-high atherosclerotic cardiovascular disease risk do not reach guideline-recommended targets for LDL-C. There is a lack of data on real-world use of non-statin lipid-lowering therapies (LLT) and little is known on the effectiveness of fixed-dose combinations (FDC). We therefore studied prescription trends in oral non-statin LLT and their effects on LDL-C.

Targeting RNA With Antisense Oligonucleotides and Small Interfering RNA: JACC State-of-the-Art Review.

There is an unmet clinical need to reduce residual cardiovascular risk attributable to apolipoprotein B-containing lipoproteins, particularly low-density lipoprotein and remnant particles. Pharmacological targeting of messenger RNA represents an emerging, innovative approach. Two major classes of agents have been developed-antisense oligonucleotides and small interfering RNA.