Hypercholesterolaemia

OBJECTIVES: Patients with familial hypercholesterolaemia (FH) are genetically burdened by a lifelong elevation of the low-density lipoprotein cholesterol (LDL-C) level, putting them at a very high risk of premature ischaemic heart disease (IHD). This study aims to assess the prevalence of FH among patients admitted for IHD and the preventive treatment status before admission. DESIGN: Observational, retrospective, register-based study. SETTING: Individuals discharged with a diagnosis of IHD were enrolled consecutively throughout 2012-2016 from the cardiac care units of two hospitals in Copenhagen...

INTRODUCTION: Triglyceride-rich remnant lipoproteins (TRLs) are considered atherogenic due to the presence of remnant cholesterol, which is transported by apolipoprotein B. In clinical practice, the concentration of TRLs can be estimated by calculating remnant cholesterol or non-HDL cholesterol levels. AIM: This study aims to investigate the proportion of patients who have low LDL cholesterol (LDL-C) concentration but elevated remnant cholesterol concentration, stratified by the presence of hypertriglyceridaemia and ethnicity, using real-world hospital data...

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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...

Statins are inhibitors of the mevalonic acid pathway that mediates cellular metabolism by producing cholesterol and isoprenoids and are widely used in treating hypercholesterolaemia in humans. Lipophilic statins, including simvastatin, induce death in various tumour cells. However, the cytotoxic mechanisms of statins in tumour cells remain largely unexplored. This study aimed to elucidate the cytotoxic mechanisms of simvastatin in canine lymphoma cells. Simvastatin induced cell death via c-Jun N-terminal kinase (JNK) activation and autophagy in canine T-cell lymphoma cell lines Ema and UL-1, but not in B-cell lines...

No abstract text is available yet for this article.

The amount of the low-density lipoprotein receptor (LDLR) on the surface of hepatocytes is the primary determinant of plasma low-density lipoprotein (LDL)-cholesterol level. Although the synthesis and cellular trafficking of the LDLR have been well-documented, there is growing evidence of additional post-translational mechanisms that regulate or fine tune the surface availability of the LDLR, thus modulating its ability to bind and internalise LDL-cholesterol. Proprotein convertase subtilisin/kexin type 9 and the asialoglycoprotein receptor 1 both independently interact with the LDLR and direct it towards the lysosome for degradation...

BACKGROUND: Studies utilising genotyping methods report the prevalence of familial hypercholesterolaemia to be as high as one in 137 of the adult population. AIM: To estimate the prevalence of familial hypercholesterolaemia measured by clinically coded diagnosis, associated treatments, and lipid measurements observed in UK primary care. DESIGN AND SETTING: This was a retrospective analysis using the Clinical Practice Research Datalink (CPRD) GOLD database...

Cardiologists are encountering a growing number of cancer patients with ischaemic heart disease (IHD). Several factors account for the interrelationship between these two conditions, in addition to improving survival rates in the cancer population. Established cardiovascular (CV) risk factors, such as hypercholesterolaemia and obesity, predispose to both IHD and cancer, through specific mechanisms and via low-grade, systemic inflammation. This latter is also fuelled by clonal haematopoiesis of indeterminate potential...

BACKGROUND: Currently available injectable drugs that target proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce serum LDL cholesterol and improve cardiovascular outcomes. This phase 2 study assessed NNC0385-0434, an oral PCSK9 inhibitor, in individuals receiving oral lipid-lowering therapy. METHODS: In this randomised, double-blind, placebo-controlled and active-controlled trial, 42 research sites across seven countries (Belgium, Germany, Greece, Japan, the Netherlands, Poland, and the USA) recruited individuals with established atherosclerotic cardiovascular disease (aged ≥40 years) or at high risk of atherosclerotic cardiovascular disease (aged >50 years), who had LDL cholesterol concentration of at least 1·8 mmol/L and were receiving maximum tolerated statins and stable lipid-lowering therapy...

Revolutionary advances in the treatment of haemophilia has led to a significant improvement in life expectancy. Associated with this has been an increase in age-related diseases especially atherosclerotic cardiovascular disease (CVD). While people with haemophilia (PWH) develop atherosclerosis at rates similar to the general population, rates of atherothrombosis and mortality related to CVD have been much lower, due to their hypocoagulable state. Changing treatment paradigms, aimed at reducing the risk of bleeding by improving haemostasis to levels approaching normality, has meant the protection they are thought to have had may be lost...

OBJECTIVE: Familial hypercholesterolaemia (FH) variant positive subjects have over double the cardiovascular risk of low-density-lipoprotein-cholesterol (LDL-C) matched controls. It is desirable to optimise FH variant detection. METHODS: We identified 213 subjects with FH gene panel reports ( LDLR , APOB , PCSK9 , and APOE ) based on total cholesterol >310 mg/dL; excluding triglycerides >400 mg/dL, cascade screening, and patients without pre-treatment LDL-C recorded...

Apolipoprotein C3 (apoC3) and angiopoietin-like protein 3 (ANGPTL3) inhibit lipolysis by lipoprotein lipase and may influence the secretion and uptake of various lipoproteins. Genetic studies show that depletion of these proteins is associated with improved lipid profiles and reduced cardiovascular events so it was anticipated that drugs which mimic the effects of loss-of-function mutations would be useful lipid treatments. ANGPTL3 inhibitors were initially developed as a treatment for severe hypertriglyceridaemia including familial chylomicronaemia syndrome (FCS), which is usually not adequately controlled with currently available drugs...

Familial hypercholesterolaemia (FH), a common monogenic disorder, is a preventable cause of premature coronary artery disease and death. Up to 35 million people worldwide have FH, but most remain undetected and undertreated. Several clinical guidelines have addressed the gaps in care of FH, but little focus has been given to implementation science and practice. The International Atherosclerosis Society (IAS) has developed an evidence-informed guidance for the detection and management of patients with FH, supplemented with implementation strategies to optimize contextual models of care...

A man in his mid-40s who had been recently started on alirocumab (a human monoclonal antibody which inhibits proprotein convertase subtilisin/kexin type 9) due to his strong familial cardiovascular risk and refractory hypercholesterolaemia presented with a few-hour history of acute-onset left-sided blurred vision. The best-corrected visual acuities were 6/6 bilaterally and slit-lamp examination was normal. However, optical coherence tomography revealed serous subretinal fluid in the left macula. Optos ultra-widefield retinal imaging and fundus autofluorescence, along with a set of blood tests, did not reveal any alternative causes...

BACKGROUND: OBJECTIVE: This study aimed to systematically synthesise the cost-effectiveness of screening strategies to detect heterozygous familial hypercholesterolemia (FH). METHODS: We searched seven databases from inception to 2 February , 2023, for eligible cost-effective analysis (CEA) that evaluated screening strategies for FH versus the standard care for FH detection. Independent reviewers performed the screening, data extraction and quality evaluation. Cost results were adapted to 2022 US dollars (US$) to facilitate comparisons between studies using the same screening strategies...

BACKGROUND: The NHS Health Check is a preventive programme in the UK designed to screen for cardiovascular risk and to aid in primary disease prevention. Despite its widespread implementation, the effectiveness of the NHS Health Check for longer-term disease prevention is unclear. In this study, we measured the rate of new diagnoses in UK Biobank participants who underwent the NHS Health Check compared with those who did not. METHODS: Within the UK Biobank prospective study, 48,602 NHS Health Check recipients were identified from linked primary care records...

OBJECTIVE: To determine the association of D-dimer to albumin ratio (DAR) with major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) in ischaemic heart failure patients with diabetes mellitus. DESIGN: A retrospective observational cohort study. SETTING: Single centre in Beijing, China, conducted at one of the largest cardiology centres in China. PARTICIPANTS: From June 2017 to June 2019, 3707 patients with heart failure and concomitant multiple vessel disease undergoing elective PCI were screened...

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. METHODS: We included 144 Italian and 79 Russian FH patients; clinical diagnosis was based on the same criteria...

The evidence of anaplastic lymphoma kinase (ALK) inhibitor for non-small cell lung cancer (NSCLC) harbouring sperm antigen with calponin homology and coiled-coil domains 1-like ( SPECC1L )- ALK fusion was limited. In a previous case report, a Chinese, 44-year-old, female non-smoker with stage IV NSCLC harbouring SPECC1L-ALK fusion was treated with crizotinib ± bevacizumab for 23 months (from October 2017 to September 2019) and second-generation ALK inhibitor iruplinalkib for 2.5 months (from October 2019 to January 2020)...