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Introduction
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Publications
Publications (383)
Low-density lipoprotein (LDL) chemically modified by reactive oxygen species (ROS), for example, leaking from red blood cells in the vascular compartment, more readily crosses the vascular endothelium than does nonoxidatively modified LDL to enter tissue fluid. Oxidatively modified LDL (oxLDL) may also be created in the tissue fluid by ROS leaking...
Introduction
Icosapent ethyl (IPE) is indicated for the treatment of severe hypertriglyceridemia (triglycerides ≥500 mg/dl) and for reducing the risk of cardiovascular (CV) events in statin-treated adults with moderately elevated triglycerides (150–499 mg/dl) and established CV disease [secondary prevention (SP)] or diabetes with CV risk factors [p...
Background and Aims
Overweight and obesity are modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) in the general population, but their prevalence in individuals with heterozygous familial hypercholesterolaemia (HeFH) and whether they confer additional risk of ASCVD independent of LDL cholesterol (LDL-C) remains unclear.
Met...
on behalf of the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC) † Abstract Background and Aims
Disclosure: E.S. Stroes: Advisory Board Member; Self; Amgen Inc, Sanofi, Novartis Pharmaceuticals, AstraZeneca, Novo Nordisk, Ionis Pharmaceuticals Inc., Merck, Daiichi Sankyo. Grant Recipient; Self; Ionis Pharmaceuticals Inc., Novo Nordisk, Novartis Pharmaceuticals, Sanofi. V. Alexander: Employee; Self; Ionis Pharmaceuticals Inc. E. Prokopczuk: Em...
BACKGROUND
Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder. This study aimed to study the genotype distribution of FCS-causing genes in the United Kingdom, genotype-phenotype correlation, and clinical differences between FCS and multifactorial chylomicronemia syndrome (MCS).
METHODS
The study included 154 patients (F...
Aims
Historically, atherosclerotic cardiovascular disease (ASCVD) risk profile mitigation has had a predominant focus on low density lipoprotein cholesterol (LDL-C). In this narrative review we explore the residual ASCVD risk profile beyond LDL-C with a focus on hypertriglyceridaemia, recent clinical trials of therapeutics targeting hypertriglyceri...
Bariatric surgery (BS) has emerged an effective intervention in achieving significant and sustained weight loss in patients with type 2 diabetes (T2D). However, comprehensive data on the long-term impact of BS on hypertension is scarce. We aimed to investigate the long-term impact of BS on blood pressure management in individuals within a T2D cohor...
Background
Bariatric surgery is the most effective treatment for severe obesity. There can be variation in the degree of weight reduction following bariatric surgery. It is unknown whether single nucleotide polymorphisms (SNPs) in the glucocorticoid receptor locus (GRL) affect postoperative weight loss and metabolic outcomes.
Materials/methods
We...
There is increasing evidence that obesity is an independent risk factor for the development of microvascular disease. Addressing modifiable risk factors such as obesity may help prevent and even reverse microvascular complications, including neuropathy, nephropathy and retinopathy. In this review article, we examine the evidence for the impact of o...
Purpose of review
To review the discoveries which led to the concept that serum paraoxonase 1 (PON1) is inversely related to atherosclerotic cardiovascular disease (ASCVD) incidence, how this association came to be regarded as causal and how such a role might have evolved.
Recent findings
Animal models suggest a causal link between PON1 present on...
Purpose of review
This review endeavours to explore the aetiopathogenesis and impact of severe hypertriglyceridemia (SHTG) and chylomicronaemia on cardiovascular, and pancreatic complications and summarizes the novel pharmacological options for management.
Recent findings
SHTG, although rare, presents significant diagnostic and therapeutic challen...
Background:
Familial chylomicronemia syndrome is a genetic disorder associated with severe hypertriglyceridemia and severe acute pancreatitis. Olezarsen reduces the plasma triglyceride level by reducing hepatic synthesis of apolipoprotein C-III.
Methods:
In a phase 3, double-blind, placebo-controlled trial, we randomly assigned patients with gen...
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...
IMPORTANCE Homozygous familial hypercholesterolemia (HoFH) is a rare genetic conditioncharacterized by extremely increased low-density lipoprotein (LDL) cholesterol levels andpremature atherosclerotic cardiovascular disease (ASCVD). Heterozygous familialhypercholesterolemia (HeFH) is more common than HoFH, and women with HeFH arediagnosed later and...
Bariatric surgery improves dyslipidaemia and reduces body weight, but it remains unclear how bariatric surgery modulates gene expression in fat cells to influence the proprotein convertase subtilisin/kexin type 9 (PCSK-9) and low-density lipoprotein receptor (LDLR) gene expression. The expression of the PCSK9/LDLR/tumor necrosis factor-alpha (TNFα)...
Purpose of review:
The aim of this study was to provide an overview of the role of novel biomarkers in metabolic syndrome, their association with cardiovascular risk and the impact of bariatric surgery on these biomarkers.
Recent findings:
Metabolic syndrome encompasses an intricate network of health problems, and its constituents extend beyond...
Background and aims:
The VOL4002 study assessed the efficacy and safety of volanesorsen in 22 adults with genetically confirmed familial chylomicronaemia syndrome (FCS) treated in the UK Early Access to Medicines Scheme (EAMS), with ("prior exposure") or without ("treatment naive") previous treatment in the APPROACH and/or APPROACH-OLE volanesorse...
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...
Background:
Familial chylomicronemia syndrome (FCS) is a rare, autosomal recessive genetic disorder characterized by a marked increase in plasma triglyceride (TG) levels and recurrent episodes of pancreatitis. The response to conventional TG-lowering therapies is suboptimal. Volanesorsen, an antisense oligonucleotide that targets hepatic apoC-III...
Diabetes is a metabolic disorder with an increased risk of developing heart failure. Inflammation and damaged vasculature are the cardinal features of diabetes-induced cardiac damage. Moreover, systemic metabolic stress triggers discordant intercellular communication, thus culminating in cardiac dysfunction. Fibroblast growth factor 21 (FGF21) is a...
The dominant sensory phenotype in patients with diabetic polyneuropathy and neuropathic pain is a loss of function. This raises questions as to which mechanisms underlie pain generation in the face of potentially reduced afferent input. One potential mechanism is spinal disinhibition, whereby a loss of spinal inhibition leads to increased ascending...
Paraoxonase 1 (PON1), residing almost exclusively on HDL, was discovered because of its hydrolytic activity towards organophosphates. Subsequently, it was also found to hydrolyse a wide range of substrates, including lactones and lipid hydroperoxides. PON1 is critical for the capacity of HDL to protect LDL and outer cell membranes against harmful o...
Many individuals with marginally abnormal thyroid function test (TFT) results may be treated and it is unknown if the limits of the TSH and FT4 reference intervals reported alongside the laboratory results are associated with the prevalence of levothyroxine treatment. We obtained information regarding reported TFT reference intervals from UK Nation...
Background and aims:
The European Atherosclerosis Society (EAS) Lipid Clinics Network promoted a survey in order to identify and understand how and when lipoprotein(a) [Lp(a)] is tested and clinically evaluated in lipid clinics throughout Europe, and the challenges that may prevent evaluation from being carried out.
Methods:
This survey was divi...
Purpose of review:
Guidelines for cholesterol-lowering treatment generally include extensive review of epidemiological and clinical trial evidence. However, the next logical step, the translation of evidence into clinical advice, occurs not entirely by reasoning, but by a form of consensus in which the prejudices and established beliefs of the soc...
Purpose of review:
The role of lipoprotein (a) in atherogenesis has been the subject of argument for many years. Evidence that it is raised in familial hypercholesterolaemia has been disputed not least because a mechanism related to low density lipoprotein (LDL) receptor mediated catabolism has been lacking. Whether lipoprotein (a) increases the a...
Statins, or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are the mainstay of treatment for hypercholesterolemia as they effectively reduce LDL-C levels and risk of atherosclerotic cardiovascular disease. Apart from hyperglycemia, dyslipidemia and HDL dysfunction are known risk factors for neuropathy in people with obesity and diabete...
Background
Assessing the spectrum of disease risk associated with hypertriglyceridemia is needed to inform potential benefits from emerging triglyceride lowering treatments. We sought to examine the associations between a full range of plasma triglyceride concentration with five clinical outcomes.
Methods
We used linked data from primary and secon...
Background
Emerging evidence suggests an association between impaired high-density lipoprotein (HDL) functionality and cardiovascular disease (CVD). HDL is essential for reverse cholesterol transport (RCT) and reduces inflammation and oxidative stress principally via paraoxonase-1 (PON1). RCT depends on HDL’s capacity to accept cholesterol (cholest...
Objective
To compare quantitatively different recommended goals for cholesterol-lowering treatment in the primary prevention of atherosclerotic cardiovascular disease (ASCVD).
Design
Outcomes at pretreatment low-density lipoprotein (LDL) cholesterol concentrations from 2 to 5 mmol/L and 10-year ASCVD risk from 5% to 30% were modelled, using the de...
Background
Hypertriglyceridemia has been identified as a risk factor for diabetic neuropathy.
Objective
Patients with hypertriglyceridemia underwent assessment of neuropathy and corneal confocal microscopy.
Methods
24 patients with severe hypertriglyceridemia defined as a triglyceride level more than 5.5 mmol/L (485 mg/dL) with no history of diab...
Purpose
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are novel drugs that have proven efficacy in improving cardiovascular outcomes. Roles for the PCSK9 molecule in metabolic pathways beyond LDL receptor processing and cholesterol homeostasis are well established. PCSK9 genetic variants associated with lower LDL-C levels correla...
Myocardial inflammation contributes to cardiomyopathy in diabetic patients through incompletely-defined underlying mechanisms. In both human and time-course experimental samples, diabetic hearts exhibited abnormal endoplasmic reticulum (ER), with a maladaptive shift over time in rodents. Furthermore, as a cardiac ER dysfunction model, mice with car...
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 objecti...
Background
Lysosomal acid lipase deficiency (LALD) is a rare autosomal recessive metabolic disorder. Mutations in the LIPA gene that encodes LAL result in disrupted triglyceride metabolism. Presentations and severity of the disorder are diverse and are often non-specific. Characterisations of LALD include dyslipidaemia and abnormal liver function w...
Background and aims
The causal relationship between LDL cholesterol (LDL-C) and the pathogenesis of atherosclerosis is well established. Previous studies have shown that modifications, glycation and oxidation of LDL enhance its atherogenic potential. Glycation of LDL occurs in it is main protein component, apolipoprotein 100 (ApoB). Our aim was to...
Purpose
Autoantibodies against apolipoprotein A-1 have been associated with cardiovascular disease, poorer CV outcomes and all-cause mortality in obese individuals. The impact of bariatric surgery (BS) on the presence of circulating anti-apoA-1 IgG antibodies is unknown. This study aimed to determine the effect of bariatric surgery on auto-antibodi...
Background
Enzyme replacement therapy (ERT) with olipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is being developed to treat patients with ASM deficiency (ASMD), commonly known as Niemann–Pick disease (NPD) types A or B. This study assessed the effect of ERT on lipid parameters and inflammatory markers.
Methods
Serum and plasma...
Severe obesity is a disease associated with multiple adverse effects on health. Metabolic bariatric surgery (MBS) can have significant effects on multiple body systems and was shown to improve inflammatory markers in previous short-term follow-up studies. We evaluated associations between changes in inflammatory markers (CRP, IL6 and TNFα) and circ...
https://www.easd.org/virtualmeeting/home.html#!resources/b-heat-shock-70-kda-protein-4-declines-after-bariatric-surgery-in-association-with-markers-of-inflammation-and-glycaemia-b
Background
The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial...
Background and aim
Previously we have shown that patients with painful diabetic neuropathy have greater corneal nerve loss compared to patients with painless diabetic neuropathy. This study investigated if the severity of corneal nerve loss was related to the severity of painful diabetic neuropathy (PDN).
Methods
Participants with diabetic neuropa...
Background: Several risk factors contribute to the development of neuropathy, amongst them; a role was suggested also for hypertriglyceridaemia. Aim of this study was to establish whether patients with severe hypertriglyceridaemia, with no diabetes or pre-diabetes, have evidence of neuropathy and small nerve fibre damage using Corneal Confocal Micr...
Background: We have previously shown that subjects with obesity have elevated vibration and thermal perception thresholds and central corneal nerve loss and patients with diabetic neuropathy have greater corneal nerve loss at the inferior whorl compared to the central cornea. In the current study, we assessed whether there is evidence for a dying-b...
Bariatric surgery (BS) results in metabolic pathway recalibration. We have identified potential biomarkers in plasma of people achieving type 2 diabetes mellitus (T2DM) remission after BS. Longitudinal analysis was performed on plasma from 10 individuals following Roux-en-Y gastric bypass (n = 7) or sleeve gastrectomy (n = 3). Sequential window acq...
A Correction to this paper has been published: https://doi.org/10.1007/s11695-020-04943-0
Neuropathic pain has multiple etiologies, but a major feature is small fiber dysfunction or damage. Corneal confocal microscopy (CCM) is a rapid non-invasive ophthalmic imaging technique that can image small nerve fibers in the cornea and has been utilized to show small nerve fiber loss in patients with diabetic and other neuropathies. CCM has comp...
Obesity and associated dyslipidemia may contribute to increased cardiovascular disease. Obesity has also been associated with neuropathy. We have investigated presence of peripheral nerve damage in patients with severe obesity without type 2 diabetes and the status of metabolic syndrome and lipoprotein abnormalities. 47participants with severe obes...
Purpose of review:
Coronavirus Disease 2019 (COVID19) has caused significant global morbidity and mortality, especially in persons with underlying cardiovascular disease. There have been concerns that lipid-lowering therapy (LLT) increases angiotensin-converting enzyme 2 levels. Conversely, pleiotropic effects of statins can theoretically protect...
Purpose of review:
Hyperlipidaemia is associated with the development of neuropathy. Indeed, a mechanistic link between altered lipid metabolism and peripheral nerve dysfunction has been demonstrated in a number of experimental and clinical studies. Furthermore, post hoc analyses of clinical trials of cholesterol and triglyceride-lowering pharmaco...
To assess the impact of renal transplantation on peripheral nerve damage in patients with chronic kidney disease (CKD). Fifteen patients with CKD (eGFR <15 mL/min/1.73m²) underwent longitudinal assessment after renal transplantation (age-56.88 ± 2.53 years, eGFR-46.82 ± 4.86) and were compared to 15 age-matched controls (age-58.25 ± 2.18 years, eGF...
Diabetes is a major risk factor for atherosclerotic cardiovascular disease (ASCVD) in which dyslipidaemia plays a crucial role. Statins are first line therapy for primary and secondary prevention of ASCVD; however, adverse events include reversible musculoskeletal and liver side effects in addition to a diabetogenic association. In this short revie...
Purpose:
Diagnosing early diabetic peripheral neuropathy remains a challenge due to deficiencies in currently advocated end points. The cornea is densely innervated with small sensory fibers, which are structurally and functionally comparable to intraepidermal nerve fibers. Corneal confocal microscopy is a method for rapid, noninvasive scanning of...
Purpose:
Increased corneal and epidermal Langerhans cells (LCs) have been reported in patients with diabetic neuropathy. The aim of this study was to quantify the density of LCs in relation to corneal nerve morphology and the presence of diabetic neuropathy and to determine if this differed in patients with type 1 diabetes mellitus (T1DM), type 2...
Background and Aims: Polycystic ovarian syndrome (PCOS) is associated with increased risk of cardiovascular disease (CVD). The aim of this study was to assess the association between PCOS and markers of HDL functionality and atherogenic LDL modification. Methods: This is a cross-sectional study of 104 women with PCOS [median (IQR); age 29 (24–36) y...
Introduction
Subjects with obesity have metabolic risk factors for nerve fibre damage. Because bariatric surgery improves these risk factors we have assessed whether this can ameliorate nerve fibre damage.
Methods
Twenty-six obese subjects without diabetes (age: 46.23 ± 8.6, BMI: 48.7 ± 1.5, HbA1c: 38.0 ± 4.5) and 20 controls (age: 48.3 ± 6.2, BMI...
PurposeBariatric surgery is associated with deficiencies of vitamins and minerals, and patients are routinely advised supplements postoperatively. We studied prevalence of vitamin B12, folate and iron deficiencies and anaemia before and after bariatric surgery over 4 years of follow-up.Materials and Methods
We performed a retrospective cohort analy...
Purpose: There are limited data on the impact of bariatric surgery on microvascular complications of type 2 diabetes (T2D), particularly diabetic neuropathy. We assessed microvascular complications (especially neuropathy) in obese patients with T2D before and 12 months after bariatric surgery.
Materials and methods: This was a prospective observat...
Background and aim:
Damage to small nociceptive fibres may contribute to painful diabetic neuropathy. We aimed to compare large and small nerve fibre measurements together with skin biopsy and corneal confocal microscopy (CCM) in patients with type 1 diabetes and painful or painless diabetic neuropathy.
Methods:
We have assessed the McGill pain...
Accurately quantifying the progression of diabetic peripheral neuropathy is key to identify individuals who will progress to foot ulceration and to power clinical intervention trials. We have undertaken detailed neuropathy phenotyping to assess the longitudinal utility of different measures of neuropathy in patients with diabetes. Nineteen patients...
Purpose:
Obesity is associated with peripheral neuropathy, which bariatric surgery may ameliorate. The aim of this study was to assess whether corneal confocal microscopy can show a change in corneal nerve morphology and keratocyte density in subjects with severe obesity after bariatric surgery.
Methods:
Twenty obese patients with diabetes (n =...
