Familial chylomicronaemia syndrome in pregnancy - report of two cases managed with plasma exchange.

Familial chylomicronaemia syndrome (FCS) is a rare genetic disorder characterised by significantly elevated triglyceride levels which increases the risk of acute pancreatitis. Due to the changes in lipid metabolism during pregnancy, triglyceride levels may rise further, particularly in the third trimester, and cause challenges in the management of these patients. Apart from strict dietary restriction of all fats, there is limited evidence on the efficacy of pharmacological treatment with omega-3 fatty acids and fibrates in maintaining triglyceride levels below the desired threshold of 10 mmol/L.

Effect of evolocumab on carotid plaque composition in asymptomatic carotid artery stenosis (EVOCAR-1) using magnetic resonance imaging.

Background And Aims: To determine the effect of evolocumab treatment in patients with asymptomatic carotid artery stenosis ≥50% on carotid plaque morphology and composition, as determined by magnetic resonance imaging.

Methods: We conducted a double-blind randomized controlled trial in patients with asymptomatic carotid artery plaque with ≥50% stenosis and low-density lipoprotein-associated cholesterol (LDL-C) ≥1.8 mmol/L, despite standard lipid-lowering therapy, with 12 months of evolocumab or placebo injection every two weeks.

Lipoprotein(a) testing in lipid clinics across the UK: Results of a national survey.

Lipoprotein(a) is an independent risk factor for cardiovascular disease and its use is recommended in national and international guidelines for cardiovascular disease risk stratification. We undertook a survey to understand the availability and application of lipoprotein(a) measurement across UK lipid clinics. Fifty-three out of an estimated 200 lipid clinics (27%) provided responses.

The current status of lipoprotein (a) measurement in clinical biochemistry laboratories in the UK: Results of a 2021 national survey.

Background: Lipoprotein(a) (Lp(a)) is now established as a causal risk factor for cardiovascular disease (CVD) and accurate laboratory measurement is of pivotal importance in reducing Lp(a) associated risk. The consensus statement by HEART UK in 2019 included recommendations to improve standardisation of clinical laboratory measurement and reporting of Lp(a).

Methods: A 16 question, electronic audit survey was circulated to 190 accredited clinical biochemistry laboratories to assess the adoption of these recommendations in the UK.

Derivation and comparison of formulae for the adjustment of total calcium.

Background: Free ionized calcium (Ca) is the biologically active component of total calcium (TCa) and hence responsible for its biological action. TCa is routinely adjusted for albumin using several formulae (e.g.

Severe Hypertriglyceridaemia and Chylomicronaemia Syndrome-Causes, Clinical Presentation, and Therapeutic Options.

We have reviewed the genetic basis of chylomicronaemia, the difference between monogenic and polygenic hypertriglyceridaemia, its effects on pancreatic, cardiovascular, and microvascular complications, and current and potential future pharmacotherapies. Severe hypertriglyceridaemia (TG > 10 mmol/L or 1000 mg/dL) is rare with a prevalence of <1%. It has a complex genetic basis.

The effect of adjusting LDL-cholesterol for Lp(a)-cholesterol on the diagnosis of familial hypercholesterolaemia.

Background: Familial hypercholesterolaemia (FH) diagnostic tools help prioritise patients for genetic testing and include LDL-C estimates commonly calculated using the Friedewald equation. However, cholesterol contributions from lipoprotein(a) (Lp(a)) can overestimate 'true' LDL-C, leading to potentially inappropriate clinical FH diagnosis.

Objective: To assess how adjusting LDL-C for Lp(a)-cholesterol affects FH diagnoses using Simon Broome (SB) and Dutch Lipid Clinic Network (DLCN) criteria.

Lipid lowering with inclisiran: a real-world single-centre experience.

Objective: The reduction in circulating low-density lipoprotein cholesterol (LDL-c) is the primary aim of lipid-lowering therapies as a method of atherosclerotic cardiovascular disease risk reduction. Inclisiran is a new and potent lipid-lowering drug that is shown to be effective in reducing LDL-c in randomised controlled trials, however, real-world data of its use are not yet known. We sought to analyse the early effects of this drug in a tertiary centre lipid and cardiovascular risk clinic.

National Institute for Health and Care Excellence guidelines for lipid management.

This article provides a summary of the available lipid-lowering therapies in the UK and how they fit into national guidelines. In addition, comparison is made between the current National Institute for Health and Care Excellence lipid modification guidelines and international guidance such as those published by the European Society of Cardiology/European Atherosclerosis Society and American Heart Association/American College of Cardiology.

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.

Side Effect Patterns in a Crossover Trial of Statin, Placebo, and No Treatment.

Background: Most people who begin statins abandon them, most commonly because of side effects.

Objectives: The purpose of this study was to assess daily symptom scores on statin, placebo, and no treatment in participants who had abandoned statins.

Methods: Participants received 12 1-month medication bottles, 4 containing atorvastatin 20 mg, 4 placebo, and 4 empty.

The use of whole blood capillary samples to measure 15 analytes for a home-collect biochemistry service during the SARS-CoV-2 pandemic: A proposed model from North West London Pathology.

Background: The COVID-19 pandemic has drastically changed the delivery of secondary care services. Self-collection of capillary blood at home can facilitate the monitoring of patients with chronic disease to support virtual clinics while mitigating the risk of SARS-CoV-2 infection and transmission.

Objective: To investigate the comparability of whole blood capillary and plasma venous samples for 15 routinely used biochemical analytes and to develop and pilot a user-friendly home-collection kit to support virtual outpatient clinical services.

Managing hyperlipidaemia in patients with COVID-19 and during its pandemic: An expert panel position statement from HEART UK.

The emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes Coronavirus Disease 2019 (COVID-19) has resulted in a pandemic. SARS-CoV-2 is highly contagious and its severity highly variable. The fatality rate is unpredictable but is amplified by several factors including advancing age, atherosclerotic cardiovascular disease, diabetes mellitus, hypertension and obesity.

Lp(a): When and how to measure it.

Lipoprotein(a) has long been regarded as a risk factor for cardiovascular disease; however, its routine use in clinical practice has been hampered by difficulties inherent in the measurement of this complex lipoprotein. The major challenges relate to its size heterogeneity and related issues including (1) use of appropriate calibrators (2) standardization of calibration protocols (3) traceability and (4) reporting units. In the UK, results from the current EQA schemes for lipoprotein(a) suggest that there is considerable work required to standardize lipoprotein(a) measurement.

The effects of dyslipidaemia and cholesterol modulation on erythrocyte susceptibility to malaria parasite infection.

Background: Malaria disease commences when blood-stage parasites, called merozoites, invade human erythrocytes. Whilst the process of invasion is traditionally seen as being entirely merozoite-driven, emerging data suggests erythrocyte biophysical properties markedly influence invasion. Cholesterol is a major determinant of cell membrane biophysical properties demanding its interrogation as a potential mediator of resistance to merozoite invasion of the erythrocyte.

HEART UK consensus statement on Lipoprotein(a): A call to action.

Lipoprotein(a), Lp(a), is a modified atherogenic low-density lipoprotein particle that contains apolipoprotein(a). Its levels are highly heritable and variable in the population. This consensus statement by HEART UK is based on the evidence that Lp(a) is an independent cardiovascular disease (CVD) risk factor, provides recommendations for its measurement in clinical practice and reviews current and emerging therapeutic strategies to reduce CVD risk.

Lipoprotein apheresis efficacy, challenges and outcomes: A descriptive analysis from the UK Lipoprotein Apheresis Registry, 1989-2017.

Background And Aims: In 2008, the National Institute of Health and Care Excellence in the UK recommended that patients undergoing lipoprotein apheresis (LA) should be included in an anonymised registry. The UK Lipoprotein Apheresis Registry was subsequently established in 2011.

Methods: Between 2011 and 2017, data was entered retrospectively and prospectively by seven LA centres in the UK for 151 patients.

Management of hypertriglyceridaemic pancreatitis in the acute setting and review of literature.

Acute pancreatitis (AP) is a potentially life-threatening complication of severe hypertriglyceridaemia, which is the third most common cause of AP after gallstone disease and alcohol excess. Standard therapy involves the use of lipid-lowering agents, low-molecular-weight heparin and insulin infusion. In some cases, when standard medical therapies fail, non-pharmacological methods based on the removal of triglycerides with therapeutic plasma exchange can provide positive results in the acute phase.

RAMP2 Influences Glucagon Receptor Pharmacology via Trafficking and Signaling.

Endogenous satiety hormones provide an attractive target for obesity drugs. Glucagon causes weight loss by reducing food intake and increasing energy expenditure. To further understand the cellular mechanisms by which glucagon and related ligands activate the glucagon receptor (GCGR), we investigated the interaction of the GCGR with receptor activity modifying protein (RAMP)2, a member of the family of receptor activity modifying proteins.

Development of a UHPLC-MS/MS (SRM) method for the quantitation of endogenous glucagon and dosed GLP-1 from human plasma.

Aim: The performance of glucagon and GLP-1 immunoassays is often poor, but few sensitive LC-MS/MS methods exist as alternatives.

Experimental: A multiplexed LC-MS/MS method using a 2D extraction technique was developed.

Results: The method was established for the quantitation of endogenous glucagon (LLOQ: 15 pg/ml) and dosed GLP-1 (LLOQ: 25 pg/ml) in human plasma, and is the first such method avoiding immunoenrichment.