Advances in the pharmacological management of hyperlipidemia through the use of combination therapies.

Introduction: Lipid-lowering therapies are well established for the treatment of cardiovascular disease (CVD). Historically monotherapy studies have been performed, but the introduction of statins has led to these drugs being recognized as baseline therapies and to the investigation of combination therapy of both older and newer medications with them.

Areas Covered: Surrogate marker studies have shown additive effects on LDL-C, triglycerides and HDL-C of combination therapies with statins and these have extended to lipoprotein (a).

Novel agents for treating severe hypertriglyceridemia.

The PALISADE trial extended the data available for inhibition of apolipoprotein (apo) C3 inhibition for treating severe hypertriglyceridemia. 75 patients with persistent chylomicronemia were allocated to 2 doses of plozasiran or placebo. Triglycerides were reduced by a net 53%-58%, and a borderline significant 17% reduction was seen in pancreatitis events.

Baseline Characteristics of Participants in STAREE: A Randomized Trial for Primary Prevention of Cardiovascular Disease Events and Prolongation of Disability-Free Survival in Older People.

Background: The risk-benefit balance of statin use in healthy older people is uncertain. We describe the baseline characteristics of the STAREE (Statins in Reducing Events in the Elderly) trial, which is a randomized, double-blind, placebo-controlled trial among community-dwelling older people; the trial evaluated the effect of atorvastatin 40 mg for the prevention of major cardiovascular events (cardiovascular death, nonfatal myocardial infarction or stroke), and on disability-free survival (survival free of both dementia and persistent physical disability).

Methods And Results: STAREE enrolled people aged ≥70 years from 1583 general practices across Australia with no history of clinical cardiovascular disease, diabetes, or dementia.

Ethnic Diversity and Distinctive Features of Familial Versus Multifactorial Chylomicronemia Syndrome: Insights From the UK FCS National Registry.

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 (FCS, 74; MCS, 80) from the UK FCS national registry and the UK arm of the FCS International Quality Improvement and Service Evaluation Project.

Two successful pregnancies -in patients taking Volanesorsen for familial chylomicronemia syndrome.

Familial chylomicronemia syndrome (FCS) is a rare inherited disorder characterized by severe hypertriglyceridemia, posing a heightened risk of acute pancreatitis. Recently, Volanesorsen, an APOC3 antisense oligonucleotide, gained approval for FCS treatment in the UK. Caution is advised during pregnancy due to limited safety data, although animal studies show no toxicity/teratogenicity.

Lipid clinic experience with bempedoic acid in three UK centres.

Objective: Novel lipid-lowering therapies are being introduced. Few studies exist of the real-world effectiveness of adenosine-tri-phosphate citrate lyase inhibition with bempedoic acid.

Methods: This study audited bempedoic acid therapy in 216 consecutive patients from three hospital centres - a university hospital ( = 77) and two district general hospitals ( = 106 and 33).

Validation of the familial chylomicronaemia syndrome (FCS) score in an ethnically diverse cohort from UK FCS registry: Implications for diagnosis and differentiation from multifactorial chylomicronaemia syndrome (MCS).

Background And Aims: Prognosis and management differ between familial chylomicronaemia syndrome (FCS), a rare autosomal recessive disorder, and multifactorial chylomicronaemia syndrome (MCS) or severe mixed hyperlipidaemia. A clinical scoring tool to differentiate these conditions has been devised but not been validated in other populations. The objective of this study was to validate this score in the UK population and identify any additional factors that might improve it.

Preventive cardiology for the aging population: how can we better design clinical trials of statins?

Introduction: Older adults form a fast-increasing proportion of the world population. However, gains in increasing quantity of life have not been accompanied by similar gains in quality of life. Older people frequently experience frailty, memory problems, and chronic diseases including cardiovascular disease (CVD) and neurodegenerative diseases.

Assessment of ethnic inequalities in diagnostic coding of familial hypercholesterolaemia (FH): A cross-sectional database study in Lambeth, South London.

Background And Aims: Differences in the perceived prevalence of familial hypercholesterolemia (FH) by ethnicity are unclear. In this study, we aimed to assess the prevalence, determinants and management of diagnostically-coded FH in an ethnically diverse population in South London.

Methods: A cross-sectional analysis of 40 practices in 332,357 adult patients in Lambeth was undertaken.

Determinants of lipid clinic referral and attendance in a multi-ethnic adult population in south London: a cross-sectional study.

Background: Primary dyslipidaemias, including familial hypercholesterolaemia, are underdiagnosed genetic disorders that substantially increase risk for premature coronary artery disease in adults. Early identification of primary dyslipidaemias via lipid clinic referral optimises patient management and enables cascade screening of relatives. Improving the identification of primary dyslipidaemias, and understanding disparities in ascertainment and management, is an NHS priority.

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.

Statins for extension of disability-free survival and primary prevention of cardiovascular events among older people: protocol for a randomised controlled trial in primary care (STAREE trial).

Introduction: The world is undergoing a demographic transition to an older population. Preventive healthcare has reduced the burden of chronic illness at younger ages but there is limited evidence that these advances can improve health at older ages. Statins are one class of drug with the potential to prevent or delay the onset of several causes of incapacity in older age, particularly major cardiovascular disease (CVD).

Colesevelam - a bile acid sequestrant for treating hypercholesterolemia and improving hyperglycemia.

Introduction: Low density Lipoprotein cholesterol)LDL-C) levels show a clear relationship with cardiovascular disease (CVD). Statins are first line agents to reduce LDL-C and CVD risk. However, combination lipid-lowering therapy is often required to achieve large reductions in LDL-C.

Hypertriglyceridaemia: an update.

Triglycerides (TGs) form part of the standard lipid profile. Elevations in TGs are associated with increased cardiovascular disease risk through triglyceride-rich lipoprotein particles found as part of non-HDL cholesterol. Many elevations of TGs are secondary to other causes, but primary hypertriglyceridaemia syndromes need to be identified.

Lipidomics in diabetes.

Purpose Of Review: Multiple studies have shown a strong association between lipids and diabetes. These are usually described through the effects of cholesterol content of lipid particles and in particular low-density lipoprotein. However, lipoprotein particles contain other components, such as phospholipids and more complex lipid species, such as ceramides and sphingolipids.

Elevated Lipoprotein(a): Background, Current Insights and Future Potential Therapies.

Lipoprotein(a) forms a subfraction of the lipid profile and is characterized by the addition of apolipprotein(a) (apo(a)) to apoB100 derived particles. Its levels are mostly genetically determined inversely related to the number of protein domain (kringle) repeats in apo(a). In epidemiological studies, it shows consistent association with cardiovascular disease (CVD) and most recently with extent of aortic stenosis.

Screening for patients with Gaucher's disease using routine pathology results: PATHFINDER (ferritin, alkaline phosphatase, platelets) study.

Aims: Lysosomal β-glucocerebrosidase A (GBA) deficiency causes Gaucher disease (GD), a recessive disorder caused by bi-allelic mutations in GBA. The prevalence of GD is associated with ethnicity but largely unknown and potentially underestimated in many countries. GD may manifest with organomegaly, bone involvement, and neurological symptoms as well as abnormal laboratory biomarkers.

Triglycerides and cardiovascular disease.

Purpose Of Review: Triglycerides (TGs) are measured as part of routine lipid profiles but their relationship to cardiovascular disease (CVD) risk has been controversial and overshadowed by high-density lipoprotein cholesterol (HDL-C).

Recent Findings: Epidemiological studies show a clear relationship of TG-containing lipoproteins including remnant particles with CVD risk with the effect being most clearly demonstrated through the excess risk captured by non-HDL-C compared with low-density lipoprotein-cholesterol (LDL-C). Mendelian randomisation studies show a consistent relationship of gene variants linked to TG metabolism with rates of CVD.

Impact of Therapeutic Inertia on Long-Term Blood Pressure Control: A Monte Carlo Simulation Study.

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Cost-Effectiveness of Initiating Pharmacological Treatment in Stage One Hypertension Based on 10-Year Cardiovascular Disease Risk: A Markov Modeling Study.

Antihypertensive drug treatment is cost-effective for adults at high risk of developing cardiovascular disease (CVD). However, the cost-effectiveness in people with stage 1 hypertension (140-159 mm Hg systolic blood pressure) at lower CVD risk remains unclear. The objective was to establish the 10-year CVD risk threshold where initiating antihypertensive drug treatment for primary prevention in adults, with stage 1 hypertension, becomes cost-effective.