Can genetic testing help in the management of dyslipidaemias?
Purpose of review
The aim of this study was to evaluate the potential role of genetic testing, particularly next-generation DNA sequencing, in diagnosing and managing dyslipidaemias, particularly monogenic dyslipidaemias.
Recent findings
Targeted DNA sequencing of the genes causing monogenic dyslipidaemias is becoming more accessible. Some societies’ position statements advise selective utilization of DNA testing in combination with clinical and biochemical assessment. However, high-quality peer-reviewed evidence showing that a DNA-based diagnosis impacts upon long-term patient outcomes is currently lacking. Nonethe...
Source: Current Opinion in Lipidology - July 30, 2020 Category: Lipidology Tags: HYPERLIPIDEMIA AND CARDIOVASCULAR DISEASE: Edited by Paul N. Durrington Source Type: research
Small interfering RNA to proprotein convertase subtilisin/kexin type 9: transforming LDL-cholesterol-lowering strategies
Purpose of review
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is a new strategy to reduce LDL cholesterol (LDL-C), that is currently pursued by mAbs. A promising novel approach to target PCSK9 is using small interfering RNAs to inhibit hepatic PCSK9 synthesis. The first small interfering RNA developed for this purpose is inclisiran. Here, we review its clinical trial data and potential impact on patient management.
Recent findings
Inclisiran achieves sustained, additional 50% LDL-C reduction in patients receiving background statin therapy. Resulting LDL-C changes can be maintained by an infrequent...
Source: Current Opinion in Lipidology - July 30, 2020 Category: Lipidology Tags: HYPERLIPIDEMIA AND CARDIOVASCULAR DISEASE: Edited by Paul N. Durrington Source Type: research
Evidence for improved survival with treatment of homozygous familial hypercholesterolemia
Purpose of review
Homozygous familial hypercholesterolemia (HoFH) is an orphan disease caused by biallelic mutations at the LDL receptor (LDLR) gene, with a prevalence estimated at 1 : 250 000 to 1 : 630 000. HoFH is characterized by extremely elevated plasma levels of LDL-C greater than 10 mmol/l (>387 mg/dl), tendinous and cutaneous xanthomas in youth and premature atherosclerotic cardiovascular disease (ASCVD). The expected prevalence varies from country to country depending on the presence of founder effects, genetic probability and life expectancy. Untreated, HoFH is a fatal condition before age 30. ...
Source: Current Opinion in Lipidology - July 30, 2020 Category: Lipidology Tags: HYPERLIPIDEMIA AND CARDIOVASCULAR DISEASE: Edited by Paul N. Durrington Source Type: research
Non-HDL or LDL cholesterol in heterozygous familial hypercholesterolaemia: findings of the Simon Broome Register
We examined the implications of the use of non-HDL-C as opposed to LDL-C in 253 people with hypercholesterolaemia before treatment and 573 after treatment in whom fasting total serum cholesterol, HDL-C and LDL-C had been recorded and the diagnosis of heterozygous familial hypercholesterolemia (heFH) was investigated by genetic testing. The difference and the limits of agreement between non-HDL-C and LDL-C calculated using the Friedewald formula were assessed in those with and without heFH-causing mutations.
Summary
There were 147 mutation-positive and 106 mutation-negative pretreatment participants and 395 mutation-posi...
Source: Current Opinion in Lipidology - July 30, 2020 Category: Lipidology Tags: HYPERLIPIDEMIA AND CARDIOVASCULAR DISEASE: Edited by Paul N. Durrington Source Type: research
Editorial introduction
No abstract available (Source: Current Opinion in Lipidology)
Source: Current Opinion in Lipidology - July 30, 2020 Category: Lipidology Tags: EDITORIAL INTRODUCTION Source Type: research
Metabolism of lipoprotein(a): new findings, implications and outstanding issues
No abstract available (Source: Current Opinion in Lipidology)
Source: Current Opinion in Lipidology - May 1, 2020 Category: Lipidology Tags: BIMONTHLY UPDATE: Edited by Alan Rees Source Type: research
The LDL cholesterol in stroke limbo: how low can we go?
No abstract available (Source: Current Opinion in Lipidology)
Source: Current Opinion in Lipidology - May 1, 2020 Category: Lipidology Tags: BIMONTHLY UPDATE: Edited by Alan Rees Source Type: research
Regulation of lipoprotein lipase-mediated lipolysis of triglycerides
Purpose of review
To discuss the recent developments in structure, function and physiology of lipoprotein lipase (LpL) and the regulators of LpL, which are being targeted for therapy.
Recent findings
Recent studies have revealed the long elusive crystal structure of LpL and its interaction with glycosylphosphatidylinositol anchored high-density lipoprotein binding protein 1 (GPIHBP1). New light has been shed on LpL being active as a monomer, which brings into questions previous thinking that LpL inhibitors like angiopoietin-like 4 (ANGPTL4) and stabilizers like LMF1 work on disrupting or maintaining LpL in dimer form....
Source: Current Opinion in Lipidology - May 1, 2020 Category: Lipidology Tags: LIPID METABOLISM: Edited by Henry Ginsberg Source Type: research
Apolipoprotein C-II: the re-emergence of a forgotten factor
Purpose of review
Apolipoprotein C-II (apoC-II) is a critical cofactor for the activation of lipoprotein lipase (LPL), a plasma enzyme that hydrolyzes triglycerides (TG) on TG-rich lipoproteins (TRL). Although apoC-II was first discovered nearly 50 years ago, there is renewed interest in it because of the recent efforts to develop new drugs for the treatment of hypertriglyceridemia (HTG). The main topic of this review will be the development of apoC-II mimetic peptides as a possible new therapy for cardiovascular disease.
Recent findings
We first describe the biochemistry of apoC-II and its role in TRL metabolism. We ...
Source: Current Opinion in Lipidology - May 1, 2020 Category: Lipidology Tags: LIPID METABOLISM: Edited by Henry Ginsberg Source Type: research
The next generation of triglyceride-lowering drugs: will reducing apolipoprotein C-III or angiopoietin like protein 3 reduce cardiovascular disease?
This article aims to review the role of apoC-III and angptl3 in triglyceride metabolism and combine early clinical evidence of CVD reducing potential of these new therapeutic targets.
Recent findings
Angptl3 inhibition by mAb or antisense therapy has recently completed phase I and II studies, respectively and demonstrate robust apolipoprotein B (apoB) lowering up to 46%. Volanesorsen is an antisense therapy approved for patients with extremely elevated plasma triglyceride levels in which it showed no consistent apoB reduction. However, the GalNAc-conjugated oligonucleotide showed moderate (up to ∼30%) apoB reduction i...
Source: Current Opinion in Lipidology - May 1, 2020 Category: Lipidology Tags: LIPID METABOLISM: Edited by Henry Ginsberg Source Type: research
Remnant lipoproteins: are they equal to or more atherogenic than LDL?
Purpose of review
To critically appraise new insights into the biology of remnant lipoproteins and their putative role in the pathophysiology of atherosclerotic cardiovascular disease, and to compare the atherogenicity of remnant particles with that of low-density lipoproteins (LDL).
Recent findings
New in-vivo stable isotope tracer studies of the kinetics of apoB48 and apoB100-containing lipoproteins in postprandial conditions have revealed that apoB48-containing very low-density lipoproteins (VLDL) accumulated markedly in hypertriglyceridemic patients. These intestinally-derived particles were cleared slowly, and re...
Source: Current Opinion in Lipidology - May 1, 2020 Category: Lipidology Tags: LIPID METABOLISM: Edited by Henry Ginsberg Source Type: research
Lipoprotein(a): is it more, less or equal to LDL as a causal factor for cardiovascular disease and mortality?
Purpose of review
To summarize the recent studies directly comparing LDL and lipoprotein(a) as causal factors for cardiovascular disease and mortality.
Recent findings
In approximately 100,000 individuals from the Copenhagen General Population Study for risk of myocardial infarction, in observational analyses per 39 mg/dl (1 mmol/l) cholesterol increase, the hazard ratio was 1.3 (95% confidence interval: 1.2–1.3) for LDL cholesterol and 1.6 (1.4–1.9) for lipoprotein(a) cholesterol. In corresponding genetic analyses, the causal risk ratio was 2.1 (1.3–3.4) for LDL and 2.0 (1.6–2.6) for lipoprotein(a). Also, a...
Source: Current Opinion in Lipidology - May 1, 2020 Category: Lipidology Tags: LIPID METABOLISM: Edited by Henry Ginsberg Source Type: research
Homozygous familial hypercholesterolemia: what treatments are on the horizon?
Purpose of review
Homozygous familial hypercholesterolemia (HoFH) is a rare disorder associated with early atherosclerotic disease due to impairment of the LDL receptor (LDLR) pathway. Because of their molecular defect, current treatment options have limited success in bringing HoFH patient to LDL-C target and morbidity and mortality remain high. We review current and upcoming therapies directed at HoFH, including gene therapy.
Recent findings
Recent real-world studies have confirmed the strength in lomitapide as a treatment adjunct to statins and other lipid-lowering therapies in HoFH patients. The approval of propro...
Source: Current Opinion in Lipidology - May 1, 2020 Category: Lipidology Tags: LIPID METABOLISM: Edited by Henry Ginsberg Source Type: research
Familial hypercholesterolemia: is it time to separate monogenic from polygenic familial hypercholesterolemia?
Purpose of review
This review explores the concepts of monogenic and the so-called polygenic familial hypercholesterolemia and how the identification of familial hypercholesterolemia as a monogenic condition and its separation from polygenic primary hypercholesterolemia may have implications for clinical practice.
Recent findings
Through genetic testing, a mutation in any of the three known autosomal dominant familial hypercholesterolemia-causing genes is found in 60–80% of cases with a clinical diagnosis of definite familial hypercholesterolemia. As individuals with a polygenic basis for their hypercholesterolemia ...
Source: Current Opinion in Lipidology - May 1, 2020 Category: Lipidology Tags: LIPID METABOLISM: Edited by Henry Ginsberg Source Type: research
Editorial introduction
No abstract available (Source: Current Opinion in Lipidology)
Source: Current Opinion in Lipidology - May 1, 2020 Category: Lipidology Tags: EDITORIAL INTRODUCTION Source Type: research
