Triglyceride to High-Density Lipoprotein Cholesterol (TG/HDL-C) ratio as a Marker of Subclinical Coronary Atherosclerosis and Hepatic Steatosis in Familial Hypercholesterolaemia.

Objective: Features of the cardiometabolic syndrome are prevalent in patients with familial hypercholesterolaemia (FH). Triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, a surrogate marker of insulin resistance, may be a robust predictor of cardiac events in the general population. We explored the association between TG/HDL-C ratio and high-risk coronary artery plaque (HRP) and hepatic steatosis (HS) in asymptomatic patients with FH.

Olezarsen, a liver-directed ASO therapy for hypertriglyceridemia.

Introduction: Apolipoprotein (apo)C-III, a key regulator of plasma triglyceride (TG) levels, is a prime candidate for the treatment of hypertriglyceridemia (HTG), prevention of acute pancreatitis, and reduction of future atherosclerotic cardiovascular disease (ASCVD) events.

Areas Covered: We discuss the role of apoC-III as a therapeutic target for HTG, describe the pharmacodynamics, pharmacokinetics, and metabolism of olezarsen, as well as report on the findings of recent clinical trials with this liver-directed antisense oligonucleotide (ASO).

Expert Opinion: Olezarsen, a GalNac-conjugated ASO targeting apoC-III, can reduce TG levels by ~ 50% in patients with extreme HTG due to familial chylomicronemia syndrome, as well as in patients with moderate HTG.

Hyperammonaemia: review of the pathophysiology, aetiology and investigation.

Acute hyperammonaemia is a medical emergency as it can progress to cerebral oedema, seizures, coma and death. Hepatic encephalopathy secondary to cirrhotic disease or portosystemic shunting are relatively well-known causes, but non-cirrhotic aetiologies of acute hyperammonaemia are less well-known, especially in the emergency department. However, an elevated ammonia is not required to make the diagnosis of hepatic encephalopathy.

Opportunistic Detection of Phytosterolaemia during Genetic Testing for FH: Case Series and Contextual Review.

Background: Homozygous phytosterolaemia, is a rare autosomal recessive disorder which lead to severely elevated plasma levels of plant phytosterols causing an increased risk of coronary artery disease (CAD) and mimics the clinical presentation of familial hypercholesterolaemia(FH). Integration of the genetic variants for homozygous phytosterolaemia into the genetic panel for FH in clinical practice likely increases the detection of milder genetic forms of phytosterolaemia, of which the implications to clinical practice including cascade testing remain unclear.

Results: We report three families with pathogenic loss-of-function variants in ABCG5 and/or ABCG8, in which probands were identified incidentally when genetically testing them for FH.

Cascade testing of children and adolescents for elevated Lp(a) in pedigrees with familial hypercholesterolaemia.

Elevated plasma lipoprotein(a) [Lp(a)] is a common, inherited condition independently causing cardiovascular disease. Recent expert recommendations suggest opportunistically testing for elevated Lp(a) during cascade testing for familial hypercholesterolaemia (FH). We investigated the effectiveness of detecting elevated Lp(a) in 103 children and adolescents who were first-degree relatives of 66 adult index FH cases as part of an established FH cascade screening program.

The Adrenal Vein Sampling Outcomes Study (AVOS): success rates following adrenalectomy for unilateral primary aldosteronism.

The objective was to determine the clinical and biochemical success rates and assess the nature of follow-up after adrenalectomy in patients with unilateral primary aldosteronism (PA), subtyped by adrenal vein sampling (AVS) in West Australia (WA) using the Primary Aldosteronism Surgical Outcome (PASO) criteria. Clinical and biochemical outcomes were retrospectively evaluated in patients with unilateral PA who underwent adrenalectomy according to AVS between September 2017 and September 2020. Pre- and post-surgical data were collected using a standardised questionnaire, review of clinic letters and examination of private and public pathology results and radiological reports.

Lipid-lowering therapies and cardiovascular risk-stratification strategies in adults with type 1 diabetes.

Purpose Of Review: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of mortality in adults with type 1 diabetes (T1D). Although dyslipidaemia is a modifiable and prevalent risk factor in individuals with T1D, determining when to initiate lipid-lowering therapy for primary prevention of ASCVD can be challenging. In this article, recommendations for lipid-lowering therapy from updated clinical guidelines over the last 5 years, additional risk-stratification methods, hypertriglyceridaemia management and potential barriers to optimal care in adults with T1D are discussed.

A variant in the fibronectin (FN1) gene, rs1250229-T, is associated with decreased risk of coronary artery disease in familial hypercholesterolaemia.

Background: Increased risk of coronary artery disease (CAD) in familial hypercholesterolaemia (FH) is modified by factors beyond defects in the low-density lipoprotein receptor pathway. The rs1250229-T single nucleotide polymorphism (SNP) in the FN1 gene is associated with CAD in genome-wide association studies and is in linkage disequilibrium with another SNP (rs1250259-T) in FN1 that is associated with decrease fibronectin secretion.

Objective: We investigated whether rs1250229-T was also associated with prevalent CAD in patients with genetically confirmed FH.

Attainment of Lipid Targets Following Coronary Artery Bypass Graft Surgery: Can We Do Better?

Objective: Patients undergoing coronary artery bypass graft (CABG) surgery remain at high cardiovascular risk; however, few studies have evaluated lipid management and attainment of lipid targets in these patients. We investigated the proportion of CABG surgery patients who attained low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (HDL-C) targets.

Methods: Data were retrospectively obtained from patients undergoing CABG surgery at an Australian tertiary hospital between February 2015 and August 2020.

Monogenic diabetes due to an INSR mutation in a child with severe insulin resistance.

Summary: We report a case of an 11-year-old girl presenting with a new diagnosis of diabetes associated with a heterozygous missense mutation in the insulin receptor (INSR) gene. This case highlights that INSR gene variants can be a cause for monogenic diabetes in children and adolescents and the need for genetic evaluation in atypical presentations of diabetes. We also describe the possible role of metformin in treating individuals with type A insulin resistance syndrome due to INSR gene variants.

An Opportunity to Improve Secondary Prevention With Icosapent Ethyl in Patients Who Have Undergone Coronary Artery Bypass Graft Surgery.

Introduction: Icosapent ethyl reduces cardiovascular events in high-risk patients with hypertriglyceridaemia on statin therapy. However, it is not widely available and the potential application following coronary artery bypass graft (CABG) surgery is not well-established. We aimed to determine the real-world percentage of CABG surgery patients who may be eligible for the therapy.

Cascade testing for elevated lipoprotein(a) in relatives of probands with familial hypercholesterolaemia and elevated lipoprotein(a).

Background And Aims: Familial hypercholesterolaemia (FH) and elevated plasma lipoprotein(a) [Lp(a)] are inherited conditions independently associated with atherosclerotic cardiovascular disease. This study investigated the detection of new cases of elevated Lp(a) during cascade testing of relatives of probands with a definite diagnosis of FH and elevated Lp(a) (≥50 mg/dL).

Methods: Relatives from 62 adult probands were tested for FH genetically and for elevated Lp(a) using an immunoassay.

Pilot study of universal screening of children and child-parent cascade testing for familial hypercholesterolaemia in Australia.

Aim: Familial hypercholesterolaemia (FH) is a common and treatable cause of premature coronary artery disease. However, the majority of individuals with FH remain undiagnosed. This study investigated the feasibility, acceptability and cost-effectiveness of screening children aged 1-2 years for FH at the time of an immunisation.

Synopsis of an integrated guidance for enhancing the care of familial hypercholesterolaemia: an Australian perspective.

Introduction: Familial hypercholesterolaemia (FH) is a common, heritable and preventable cause of premature coronary artery disease, with significant potential for positive impact on public health and healthcare savings. New clinical practice recommendations are presented in an abridged guidance to assist practitioners in enhancing the care of all patients with FH.

Main Recommendations: Core recommendations are made on the detection, diagnosis, assessment and management of adults, children and adolescents with FH.

Essentials of a new clinical practice guidance on familial hypercholesterolaemia for physicians.

Familial hypercholesterolaemia (FH) is a common, heritable and preventable cause of premature coronary artery disease. New clinical practice recommendations are presented to assist practitioners in enhancing the care of all patients with FH. Core recommendations are made on the detection, diagnosis, assessment and management of adults, children and adolescents with FH.

Integrated Guidance for Enhancing the Care of Familial Hypercholesterolaemia in Australia.

Familial hypercholesterolaemia (FH) is a dominant and highly penetrant monogenic disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL)-cholesterol concentration and, if untreated, leads to premature atherosclerosis and coronary artery disease (CAD). There are approximately 100,000 people with FH in Australia. However, an overwhelming majority of those affected remain undetected and inadequately treated, consistent with FH being a leading challenge for public health genomics.

Lipoprotein(a) in Patients With Type 2 Diabetes and Premature Coronary Artery Disease in the Coronary Care Unit.

Introduction: Lipoprotein(a) [Lp(a)] and diabetes are independently associated with premature coronary artery disease (pCAD). However, there is an inverse relationship between Lp(a) concentration and type 2 diabetes (T2D) risk. We examine whether Lp(a) distribution in patients with pCAD differs between those with or without T2D, and whether elevated Lp(a) is associated with pCAD in patients with T2D.