2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk

Journal of the American College of Cardiology, Journal Year: 2022, Volume and Issue: 80(14), P. 1366 - 1418

Published: Aug. 25, 2022

Language: Английский

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A Modern Approach to Dyslipidemia

Endocrine Reviews, Journal Year: 2021, Volume and Issue: 43(4), P. 611 - 653

Published: Oct. 22, 2021

Lipid disorders involving derangements in serum cholesterol, triglycerides, or both are commonly encountered clinical practice and often have implications for cardiovascular risk overall health. Recent advances knowledge, recommendations, treatment options necessitated an updated approach to these disorders. Older classification schemes outlived their usefulness, yielding based on the primary lipid disturbance identified a routine panel as practical starting point. Although monogenic dyslipidemias exist important identify, most individuals with polygenic predisposition, context of secondary factors such obesity type 2 diabetes. With regard disease, elevated low-density lipoprotein cholesterol is essentially causal, guidelines worldwide recommended thresholds targets this variable. Furthermore, recent studies established triglycerides factor, whereas depressed high-density now appears less contributory than was previously believed. An diagnosis assessment may include measurement variables apolipoprotein B lipoprotein(a), together selective use genetic testing diagnose rare familial hypercholesterolemia chylomicronemia syndrome. The ongoing development new agents-especially antisense RNA monoclonal antibodies-targeting will provide additional management options, which turn motivates discussion how best incorporate them into current algorithms.

Language: Английский

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Effect of Vupanorsen on Non–High-Density Lipoprotein Cholesterol Levels in Statin-Treated Patients With Elevated Cholesterol: TRANSLATE-TIMI 70

Circulation, Journal Year: 2022, Volume and Issue: 145(18), P. 1377 - 1386

Published: April 3, 2022

Genetic loss-of-function variants in ANGPTL3 are associated with lower levels of plasma lipids. Vupanorsen is a hepatically targeted antisense oligonucleotide that inhibits Angiopoietin-like 3 (ANGPTL3) protein synthesis.Adults non-high-density lipoprotein cholesterol (non-HDL-C) ≥100 mg/dL and triglycerides 150 to 500 on statin therapy were randomized double-blind fashion placebo or 1 7 vupanorsen dose regimens (80, 120, 160 mg SC every 4 weeks, 60, 80, 2 weeks). The primary end point was placebo-adjusted percentage change from baseline non-HDL-C at 24 weeks. Secondary points included changes triglycerides, low-density (LDL-C), apolipoprotein B (ApoB), ANGPTL3.Two hundred eighty-six subjects randomized: 44 242 vupanorsen. median age 64 (interquartile range, 58-69) years, 44% female, the 132.4 118.0-154.1) mg/dL, 216.2 181.4-270.4) mg/dL. resulted significant decreases over ranging 22.0% 60 weeks arm 27.7% 80 (all P<0.001 for all doses). There dose-dependent reductions ranged 41.3% 56.8% P<0.001). effects LDL-C ApoB more modest (7.9%-16.0% 6.0%-15.1%, respectively) without clear dose-response relationship' only higher achieved statistical significance. decreased manner by 69.9% 95.2% no confirmed instances decline renal function platelet count Injection site reactions >3× elevations alanine aminotransferase aspartate common total monthly doses (up 33.3% 44.4%, respectively), there increase hepatic fat fraction 76%).Vupanorsen administered equivalent 320 significantly reduced additional lipid parameters. liver enzyme frequent doses, fraction.URL: https://clinicaltrials.gov; Unique identifier: NCT04516291.

Language: Английский

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PoLA/CFPiP/PCS/PSLD/PSD/PSH guidelines on diagnosis and therapy of lipid disorders in Poland 2021

Archives of Medical Science, Journal Year: 2021, Volume and Issue: 17(6), P. 1447 - 1547

Published: Nov. 9, 2021

In Poland there are still nearly 20 million individuals with hypercholesterolaemia, most of them unaware their condition; that is also why only ca. 5% patients familial hypercholesterolaemia have been diagnosed; other rare cholesterol metabolism disorders so rarely diagnosed in Poland. Let us hope these guidelines, being an effect work experts representing 6 main scientific societies, as well the network PoLA lipid centers a part EAS centers, certification lipidologists by PoLA, or growing number for diseases, planned Ministry Health, improvements coordinated care after myocardial infarction (KOS-Zawał), reimbursement innovative agents, introduction effective primary prevention program, will make improvement relation to unmet needs diagnostics and treatment possible.

Language: Английский

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The dawn of a new era of targeted lipid-lowering therapies

European Heart Journal, Journal Year: 2021, Volume and Issue: 43(34), P. 3198 - 3208

Published: Nov. 25, 2021

Lipid risk factors for cardiovascular disease depend in part on lifestyle, but optimum control of lipids often demands additional measures. Low-density lipoprotein (LDL) doubtless contributes causally to atherosclerosis. Recent human genetic findings have substantiated a number novel targets lipid-lowering therapy including apolipoprotein C-III, angiopoietin-like protein 3 and 4, V, ATP citrate lyase. These discoveries coupled with advances biotechnology development afford new avenues management LDL other aspects lipid risk. Beyond LDL, treatments targeting triglyceride-rich lipoproteins lipoprotein(a) become available entered clinical development. Biological RNA-directed agents joined traditional small-molecule approaches, which themselves undergone considerable refinement. Innovative strategies increased efficacy some these interventions markedly improved their tolerability. Gene-editing approaches appeared the horizon management. This article reviews this progress offering insight into biological therapeutic discoveries, places them practical patient care perspective.

Language: Английский

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Role of Omega-3 Fatty Acids in Cardiovascular Disease: the Debate Continues

Current Atherosclerosis Reports, Journal Year: 2022, Volume and Issue: 25(1), P. 1 - 17

Published: Dec. 29, 2022

Abstract Purpose of Review The omega-3 fatty acids (n3-FAs), eicosapentaenoic acid (EPA) and docosahexaenoic (DHA), have recently undergone testing for their ability to reduce residual cardiovascular (CV) risk among statin-treated subjects. outcome trials yielded highly inconsistent results, perhaps attributable variations in dosage, formulation, composition. In particular, CV using icosapent ethyl (IPE), a purified ester EPA, reproducibly reduced events progression atherosclerosis compared with mixed EPA/DHA treatments. This review summarizes the mechanistic evidence differences n3-FAs on development manifestations atherothrombotic disease. Recent Findings Large randomized clinical produced discordant outcomes despite similar patient profiles, doses, triglyceride (TG)-lowering effects. A large, trial IPE, prescription EPA only showed robust reduction statin treated patients manner proportional achieved blood concentrations. Multiple formulations not shown such benefits, TG lowering. These inconsistencies inspired investigations into n3-FAs, as DHA distinct membrane interactions, metabolic products, effects cholesterol efflux, antioxidant properties, tissue distribution. maintains normal distribution, enhances endothelial function, combination statins improves features implicated plaque stability reduces lipid content plaques. Summary Insights reductions emerged from different n3-FAs. Among high-risk contemporary care, n3-FA no events. benefits IPE multiple may arise pleiotropic actions that correlate on-treatment levels beyond TG-lowering. include altered platelet inflammation, dysfunction. Elucidating mechanisms vascular protection lead new interventions atherosclerosis, disease continues expand worldwide.

Language: Английский

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Plozasiran, an RNA Interference Agent Targeting APOC3, for Mixed Hyperlipidemia

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: 391(10), P. 899 - 912

Published: May 28, 2024

Persons with mixed hyperlipidemia are at risk for atherosclerotic cardiovascular disease due to an elevated non-high-density lipoprotein (HDL) cholesterol level, which is driven by remnant in triglyceride-rich lipoproteins. The metabolism and clearance of lipoproteins down-regulated through apolipoprotein C3 (APOC3)-mediated inhibition lipase.

Language: Английский

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GalNAc-Lipid nanoparticles enable non-LDLR dependent hepatic delivery of a CRISPR base editing therapy

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 15, 2023

Lipid nanoparticles have demonstrated utility in hepatic delivery of a range therapeutic modalities and typically deliver their cargo via low-density lipoprotein receptor-mediated endocytosis. For patients lacking sufficient receptor activity, such as those with homozygous familial hypercholesterolemia, an alternate strategy is needed. Here we show the use structure-guided rational design series mouse non-human primate studies to optimize GalNAc-Lipid nanoparticle that allows for independent delivery. In receptor-deficient primates administered CRISPR base editing therapy targeting ANGPTL3 gene, introduction optimized GalNAc-based asialoglycoprotein ligand surface increased liver from 5% 61% minimal nontargeted tissues. Similar was noted wild-type monkeys, durable blood protein reduction up 89% six months post dosing. These results suggest may effectively both intact activity well afflicted by hypercholesterolemia.

Language: Английский

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Novel and future lipid-modulating therapies for the prevention of cardiovascular disease

Nature Reviews Cardiology, Journal Year: 2023, Volume and Issue: 20(9), P. 600 - 616

Published: April 13, 2023

Language: Английский

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Dyslipidemia and Cardiovascular Disease: Current Knowledge, Existing Challenges, and New Opportunities for Management Strategies

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(1), P. 363 - 363

Published: Jan. 3, 2023

Cardiovascular disease is the leading cause of morbidity and mortality worldwide, dyslipidemia one major risk factors [...].

Language: Английский

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