Learnings from Implementation Strategies to Improve Lipid Management.

Purpose Of Review: Lowering low-density lipoprotein (LDL)-cholesterol reduces cardiovascular risk. International lipid management guidelines recommend LDL-cholesterol goals or thresholds for initiating lipid-lowering therapy. However, contemporary real-world studies have shown that many high- and very high-risk patients are not attaining LDL-cholesterol goals and are not receiving intensive lipid-lowering therapies.

Immediate Versus 5-Year Risk-Guided Initiation of Treatment for Primary Prevention of Cardiovascular Disease for Australians Aged 40 Years: A Health Economic Analysis.

Background And Objective: Current Australian cardiovascular disease (CVD) prevention guidelines calculate 5-year CVD risk and recommend treatment when risk crosses specific thresholds. This may leave risk factors untreated for people with a low short-term (i.e.

Familial Hypercholesterolemia and Cardiovascular Outcomes Amongst Younger Patients Undergoing Coronary Bypass Surgery.

Background: Familial hypercholesterolemia (FH) is an under-recognised but common genetic condition resulting in elevated levels of low-density lipoprotein cholesterol (LDL-C) and a high risk of premature coronary disease. The prevalence of FH among younger patients undergoing coronary bypass surgery is unknown, as is their post-surgical prognosis.

Method: This was a retrospective analysis of younger patients (aged <60 years) undergoing coronary bypass surgery at an Australian tertiary hospital between 2008 and 2022.

Implementation science and genetic testing for familial hypercholesterolemia.

Purpose Of Review: Familial hypercholesterolemia is a treatable genetic disorder of cholesterol metabolism. Genetic testing is the most specific method for diagnosing familial hypercholesterolemia, but it remains underutilized. Implementation science aims to bridge the gap between evidence and practice and, thereby, support improved familial hypercholesterolemia care.

Drugs for dyslipidaemia: the legacy effect of the Scandinavian Simvastatin Survival Study (4S).

Since the discovery of statins and the Scandinavian Simvastatin Survival Study (4S) results three decades ago, remarkable advances have been made in the treatment of dyslipidaemia, a major risk factor for atherosclerotic cardiovascular disease. Safe and effective statins remain the cornerstone of therapeutic approach for this indication, including for children with genetic dyslipidaemia, and are one of the most widely prescribed drugs in the world. However, despite the affordability of generic statins, they remain underutilised worldwide.

Inhibition of the ANGPTL3/8 Complex for the Prevention and Treatment of Atherosclerotic Cardiovascular Disease.

Purpose Of Review: Dyslipidemia is a casual risk factor for atherosclerotic cardiovascular disease (ASCVD). There is an unmet need for more effective treatments for patients with dyslipidemias. Angiopoietin-like protein 3 (ANGPTL3) and ANGPTL8 play key roles in triglyceride trafficking and energy balance in humans.

Adipocyte associated glucocorticoid signaling regulates normal fibroblast function which is lost in inflammatory arthritis.

Fibroblasts play critical roles in tissue homeostasis, but in pathologic states they can drive fibrosis, inflammation, and tissue destruction. Little is known about what regulates the homeostatic functions of fibroblasts. Here, we perform RNA sequencing and identify a gene expression program in healthy synovial fibroblasts characterized by enhanced fatty acid metabolism and lipid transport.

Plasma Protein Biomarkers and Long-Term Cardiovascular Mortality Risk in Patients With Chronic Coronary Heart Disease.

Background: Protein biomarkers that reflect different pathophysiological pathways have been associated with the risk of adverse cardiovascular events. However, it is uncertain whether these associations are sustained with increasing years after the biomarkers are measured.

Methods And Results: In this cohort study, 7745 patients with coronary heart disease who participated in the LIPID (Long-Term Intervention With Pravastatin in Ischemic Disease) trial, BNP (B-type natriuretic peptide), troponin I, cystatin-C, C-reactive protein, d-dimer and midregional proadrenomedullin were measured at baseline and after 1 year.

Early health technology assessment of gene silencing therapies for lowering lipoprotein(a) in the secondary prevention of coronary heart disease.

Background: Olpasiran and pelacarsen are gene-silencing therapies that lower lipoprotein(a). Cardiovascular outcome trials are ongoing. Mendelian randomisation studies estimated clinical benefits from lipoprotein(a) lowering.

Plozasiran for Managing Persistent Chylomicronemia and Pancreatitis Risk.

Background: Persistent chylomicronemia is a genetic recessive disorder that is classically caused by familial chylomicronemia syndrome (FCS), but it also has multifactorial causes. The disorder is associated with the risk of recurrent acute pancreatitis. Plozasiran is a small interfering RNA that reduces hepatic production of apolipoprotein C-III and circulating triglycerides.

Cardiometabolic risk factors in women: what's sauce for the goose is not sauce for the gander.

Purpose Of Review: The aim of this review was to discuss cardiometabolic risk factors that affect women.

Recent Findings: Recent calls to action to address cardiometabolic risk factors specific to women relate to increasing evidence of sex-specific differences in patient-related, drug-related, and socio-demographic factors leading to sub-optimal care of women.

Summary: Certain aspects of common modifiable cardiovascular risk factors (e.

New perspectives on the high-density lipoprotein system and its role in the prevention and treatment of atherosclerotic cardiovascular disease.

Purpose Of Review: The causal role of high-density lipoprotein (HDL) in atherosclerotic cardiovascular disease (CVD) remains debated. Considering recent evidence, the purpose of this review is to a provide a focused update and new perspectives on HDL and CVD.

Recent Findings: A Mendelian randomization study demonstrated an increased risk of CVD when HDL-cholesterol was predominantly transported in larger HDL particles and a decreased risk of CVD when HDL-cholesterol was predominantly transported in smaller HDL particles.

Lipidomic Risk Score to Enhance Cardiovascular Risk Stratification for Primary Prevention.

Background: Accurate risk stratification is vital for primary prevention of cardiovascular disease (CVD). However, traditional tools such as the Framingham Risk Score (FRS) may underperform within the diverse intermediate-risk group, which includes individuals requiring distinct management strategies.

Objectives: This study aimed to develop a lipidomic-enhanced risk score (LRS), specifically targeting risk prediction and reclassification within the intermediate group, benchmarked against the FRS.

Coronary artery event-free or resilient familial hypercholesterolemia: what's in a name?

Purpose Of Review: Familial hypercholesterolemia (FH) is an autosomal semi-dominant condition, characterized by excessive circulating low-density lipoprotein cholesterol (LDL-C) from birth that substantially accelerates the onset and progression of atherosclerotic cardiovascular disease (ASCVD), classically coronary artery disease (CAD). Elevated plasma LDL-C integrated over time is unequivocally the major determinant of ASCVD in heterozygous FH (HeFH); however, the wide variation in incidence and progression of ASCVD suggests a role for a wide spectrum of risk modifiers. We reviewed recent evidence describing the features of an ASCVD-free entity referred to as resilient FH among patients with HeFH.

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.

Application of implementation science for improving the utilization of an international clinical practice guidance on familial hypercholesterolemia.

Background: The International Atherosclerosis Society (IAS) published an evidence-informed guidance for familial hypercholesterolemia (FH) that provides both clinical and implementation recommendations. We reference examples of strategies from the literature to explore how these implementation recommendations can be tailored into implementation strategies at the local-level for stakeholders guided by a framework proposed by Sarkies and Jones.

Methods: Four authors of the IAS guidance selected two published exemplar implementation recommendations for detection, management, and general implementation.

A lipidomic based metabolic age score captures cardiometabolic risk independent of chronological age.

Background: Metabolic ageing biomarkers may capture the age-related shifts in metabolism, offering a precise representation of an individual's overall metabolic health.

Methods: Utilising comprehensive lipidomic datasets from two large independent population cohorts in Australia (n = 14,833, including 6630 males, 8203 females), we employed different machine learning models, to predict age, and calculated metabolic age scores (mAge). Furthermore, we defined the difference between mAge and age, termed mAgeΔ, which allow us to identify individuals sharing similar age but differing in their metabolic health status.