Long-term experience with lomitapide treatment in patients with homozygous familial hypercholesterolemia: Over 10 years of efficacy and safety data.

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by loss of low-density lipoprotein receptor (LDLR) function, an extreme elevation of circulating low-density lipoprotein cholesterol (LDL-C) from birth and substantially reduced life expectancy, if untreated. Patients with HoFH are frequently diagnosed late and have a markedly elevated risk of premature atherosclerotic cardiovascular disease (ASCVD).

Sources Of Material: The current European Atherosclerosis Society consensus statement on the treatment of HoFH recommends an LDL-C goal of <55 mg/dL for adults with ASCVD or major ASCVD risk factors, <70 mg/dL for adults without ASCVD risk factors, and <115 mg/dL for pediatric patients without ASCVD.

Global disparities in access to lipid-lowering therapies for patients with homozygous familial hypercholesterolemia - A physician survey.

Background: Lipid levels and atherosclerotic cardiovascular disease (ASCVD) outcomes have been shown to differ globally in patients with homozygous familial hypercholesterolemia (HoFH), which may be related to availability and accessibility of lipid-lowering therapy (LLT).

Objective: In the current study, we investigated global disparities in availability and accessibility of LLTs for patients with HoFH.

Methods: Physicians participating in the HoFH International Clinical Collaborators (HICC, NCT04815005) were invited to complete an online survey on registration status, reimbursement, and access to various LLTs.

Impact of statins as immune-modulatory agents on inflammatory markers in adults with chronic diseases: A systematic review and meta-analysis.

While numerous studies have extensively documented the pleiotropic effects of statins, including their capacity to reduce inflammation, there is a lack of research estimating the anti-inflammatory effectiveness of statins among individuals with chronic diseases. This meta-analysis evaluates the effect of statin therapy on inflammatory markers and the lipid profile in patients with chronic diseases by analysing evidence from randomized controlled trials (RCTs). We conducted a systematic review and searched articles published between 1st January 1999 and 31st December 2023 in databases including PubMed, Web of Science, Scopus, and Cochrane.

Implementation strategies for improving the care of familial hypercholesterolaemia from the International Atherosclerosis Society: next steps in implementation science and practice.

Familial hypercholesterolaemia (FH) is the most common monogenic condition associated with premature atherosclerotic cardiovascular disease. Early detection and initiation of cholesterol lowering therapy combined with lifestyle changes improves the prognosis of patients with FH significantly. The International Atherosclerosis Society (IAS) published a new guidance for implementing best practice in the care of FH.

Real-world family planning and pregnancy practices in women with homozygous familial hypercholesterolemia.

Background And Aims: Homozygous familial hypercholesterolemia (HoFH) is characterized by extremely high plasma low-density lipoprotein cholesterol (LDL-C) levels and high premature atherosclerotic cardiovascular disease risk. During pregnancy LDL-C levels increase, while limited therapeutic options are available. This international study documented current approaches of healthcare professionals (HCPs) to family planning, pregnancy, and breastfeeding in HoFH.

Life Course Approach for Managing Familial Hypercholesterolemia.

Treatment of familial hypercholesterolemia is directed toward the moment of the medical encounter. However, risk for heart disease as a consequence of having familial hypercholesterolemia is related to lifelong exposure to elevated low-density lipoprotein cholesterol, rather than low-density lipoprotein cholesterol level at a specific time point. The purpose of this review is to reassess contemporary research on treatment of familial hypercholesterolemia and current evidence-based guidelines, to present an approach that emphasizes treatment across the life course, and to recognize the importance of family experiences to care.

Homozygous Familial Hypercholesterolemia Treatment: New Developments.

Purpose Of Review: Homozygous familial hypercholesterolaemia (HoFH) is characterized by marked elevation of low-density lipoprotein cholesterol (LDLC) and premature atherosclerotic cardiovascular disease. This is a review of novel pharmacological therapies to lower LDLC in patients with HoFH.

Recent Findings: Novel therapies can be broadly divided by whether their efficacy is dependent or independent of residual low-density lipoprotein receptor (LDLR) function.

Cardiovascular outcomes in patients with homozygous familial hypercholesterolaemia on lipoprotein apheresis initiated during childhood: long-term follow-up of an international cohort from two registries.

Background: Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disease characterised by extremely high plasma LDL cholesterol from birth, causing atherosclerotic cardiovascular disease at a young age. Lipoprotein apheresis in combination with lipid-lowering drugs effectively reduce LDL cholesterol, but long-term health outcomes of such treatment are unknown. We aimed to investigate the long-term cardiovascular outcomes associated with lipoprotein apheresis initiated in childhood or adolescence.

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.

Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk.

Background: High triglyceride levels are associated with increased cardiovascular risk, but whether reductions in these levels would lower the incidence of cardiovascular events is uncertain. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, reduces triglyceride levels and improves other lipid levels.

Methods: In a multinational, double-blind, randomized, controlled trial, we assigned patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia (triglyceride level, 200 to 499 mg per deciliter), and high-density lipoprotein (HDL) cholesterol levels of 40 mg per deciliter or lower to receive pemafibrate (0.

Familial Hypercholesterolemia Identification by Machine Learning Using Lipid Profile Data Performs as Well as Clinical Diagnostic Criteria.

Background: Familial hypercholesterolemia (FH) is a common genetic disorder and, if not diagnosed and treated early, results in premature cardiovascular disease. Most individuals with FH are undiagnosed and machine learning offers a new prospect to improve FH identification. Our objective was to create a machine learning model from basic lipid profile data with better screening performance than LDL-C (low-density lipoprotein cholesterol) cutoff levels and diagnostic performance comparable to the Dutch Lipid Clinic Network criteria.

RNA-based therapy in the management of lipid disorders: a review.

This review focuses on antisense oligonucleotides and small interfering ribonucleic acid therapies approved or under development for the management of lipid disorders. Recent advances in RNA-based therapeutics allow tissue-specific targeting improving safety. Multiple potential target proteins have been identified and RNA-based therapeutics have the potential to significantly improve outcomes for patients with or at risk for atherosclerotic cardiovascular disease.

A Case Series Assessing the Effects of Lomitapide on Carotid Intima-Media Thickness in Adult Patients with Homozygous Familial Hypercholesterolaemia in a Real-World Setting.

Introduction: Homozygous familial hypercholesterolaemia (HoFH) is characterised by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) and results from multiple mutations in genes affecting the LDL receptor pathway. Patients are at risk of premature atherosclerotic cardiovascular disease (ASCVD) and premature death. Lomitapide is a microsomal triglyceride transfer protein inhibitor developed to treat HoFH, but cardiovascular outcome data are lacking.

Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study.

Background: Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulting in extremely elevated low-density lipoprotein cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Current guidance about its management and prognosis stems from small studies, mostly from high-income countries. The objective of this study was to assess the clinical and genetic characteristics, as well as the impact, of current practice on health outcomes of HoFH patients globally.

The therapeutic management of South African dyslipidaemic patients at very high cardiovascular risk (CARDIO TRACK): a cross-sectional study.

Background: Dyslipidaemia is a major modifiable risk factor for atherosclerotic cardiovascular disease. At the time the study was conducted, guidelines recommended a low-density lipoprotein cholesterol (LDL-C) target of less than 1.8 mmol/l and a reduction of at least 50% if the baseline LDL-C was between 1.

Novel PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) Variants in Patients With Familial Hypercholesterolemia From Cape Town.

Objective: Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein-cholesterol and markedly increased cardiovascular risk. In patients with a genetic diagnosis, low-density lipoprotein receptor () mutations account for >90% of cases, apolipoprotein B () mutations for ≈5% of cases, while proprotein convertase subtilisin kexin type 9 () gain of function mutations are rare (<1% of cases). We aimed to evaluate the functional impact of several novel variants in a cohort of patients with FH by genetic cascade screening and in vitro functionality assays.

Efficacy and Safety of Alirocumab in Adults With Homozygous Familial Hypercholesterolemia: The ODYSSEY HoFH Trial.

Background: Homozygous familial hypercholesterolemia (HoFH) is characterized by extremely elevated low-density lipoprotein-cholesterol (LDL-C) levels and early onset atherosclerotic cardiovascular disease despite treatment with conventional lipid-lowering treatment.

Objectives: This study was designed to assess LDL-C reduction with the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab in adult patients with HoFH.

Methods: This randomized, double-blind, placebo-controlled, parallel-group, phase 3 study evaluated efficacy and safety of alirocumab 150 mg every 2 weeks.

Effects of evolocumab therapy and low LDL-C levels on vitamin E and steroid hormones in Chinese and global patients with type 2 diabetes.

Aims: We assessed the change from baseline in vitamin E, steroid hormones, adrenocorticotropic hormone (ACTH), and gonadotropins, overall and by lowest achieved low-density lipoprotein-cholesterol (LDL-C) level, in patients with type 2 diabetes and dyslipidaemia after 12 weeks of treatment with evolocumab.

Materials And Methods: This was a prespecified analysis of vitamin E, cortisol, ACTH, gonadal hormones and gonadotropins in the 12-week, placebo-controlled BERSON trial of evolocumab in patients with type 2 diabetes and dyslipidaemia. In BERSON, 981 (451 in China) patients on daily atorvastatin 20 mg were randomized to placebo or one of two doses of evolocumab.

Long-Term Evolocumab in Patients With Familial Hypercholesterolemia.

Background: Proprotein convertase subtilisin/kexin type 9 inhibitor therapy is a treatment option for patients with familial hypercholesterolemia (FH) who are unable to reach low-density lipoprotein cholesterol (LDL-C) goals.

Objectives: The aim of this study was to provide long-term safety and efficacy data for evolocumab in patients with homozygous FH (HoFH) and severe heterozygous FH (HeFH).

Methods: In this open-label, single-arm study, patients with HoFH or severe HeFH ≥12 years of age and on stable lipid-lowering therapy began subcutaneous evolocumab 420 mg monthly or 420 mg every 2 weeks if on lipoprotein apheresis.