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      Clinical review on triglycerides

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Hypertriglyceridaemia is a common clinical problem. Epidemiologic and genetic studies have established that triglyceride-rich lipoproteins (TRL) and their remnants as important contributors to ASCVD while severe hypertriglyceridaemia raises risk of pancreatitis. While low-density lipoprotein is the primary treatment target for lipid lowering therapy, secondary targets that reflect the contribution of TRL such as apoB and non-HDL-C are recommended in the current guidelines. Reduction of severely elevated triglycerides is important to avert or reduce the risk of pancreatitis. Here we discuss interventions for hypertriglyceridaemia, including diet and lifestyle, established treatments such as fibrates and omega-3 fatty acid preparations and emerging therapies, including various biological agents.

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          Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia

          Deepak Bhatt, P Gabriel Steg, Michael Miller … (2018)
          Patients with elevated triglyceride levels are at increased risk for ischemic events. Icosapent ethyl, a highly purified eicosapentaenoic acid ethyl ester, lowers triglyceride levels, but data are needed to determine its effects on ischemic events.
          Article 0 comments Cited 727 times – based on 0 reviews     Review now
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            2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol

            Scott M. Grundy, Neil J Stone, Alison L Bailey … (2018)
            Article 0 comments Cited 683 times – based on 0 reviews     Review now
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              Cardiovascular and Metabolic Effects of ANGPTL3 Antisense Oligonucleotides.

              Mark J. Graham, Richard Lee, Teresa A Brandt … (2017)
              Background Epidemiologic and genomewide association studies have linked loss-of-function variants in ANGPTL3, encoding angiopoietin-like 3, with low levels of plasma lipoproteins. Methods We evaluated antisense oligonucleotides (ASOs) targeting Angptl3 messenger RNA (mRNA) for effects on plasma lipid levels, triglyceride clearance, liver triglyceride content, insulin sensitivity, and atherosclerosis in mice. Subsequently, 44 human participants (with triglyceride levels of either 90 to 150 mg per deciliter [1.0 to 1.7 mmol per liter] or >150 mg per deciliter, depending on the dose group) were randomly assigned to receive subcutaneous injections of placebo or an antisense oligonucleotide targeting ANGPTL3 mRNA in a single dose (20, 40, or 80 mg) or multiple doses (10, 20, 40, or 60 mg per week for 6 weeks). The main end points were safety, side-effect profile, pharmacokinetic and pharmacodynamic measures, and changes in levels of lipids and lipoproteins. Results The treated mice had dose-dependent reductions in levels of hepatic Angptl3 mRNA, Angptl3 protein, triglycerides, and low-density lipoprotein (LDL) cholesterol, as well as reductions in liver triglyceride content and atherosclerosis progression and increases in insulin sensitivity. After 6 weeks of treatment, persons in the multiple-dose groups had reductions in levels of ANGPTL3 protein (reductions of 46.6 to 84.5% from baseline, P<0.01 for all doses vs. placebo) and in levels of triglycerides (reductions of 33.2 to 63.1%), LDL cholesterol (1.3 to 32.9%), very-low-density lipoprotein cholesterol (27.9 to 60.0%), non-high-density lipoprotein cholesterol (10.0 to 36.6%), apolipoprotein B (3.4 to 25.7%), and apolipoprotein C-III (18.9 to 58.8%). Three participants who received the antisense oligonucleotide and three who received placebo reported dizziness or headache. There were no serious adverse events. Conclusions Oligonucleotides targeting mouse Angptl3 retarded the progression of atherosclerosis and reduced levels of atherogenic lipoproteins in mice. Use of the same strategy to target human ANGPTL3 reduced levels of atherogenic lipoproteins in humans. (Funded by Ionis Pharmaceuticals; ClinicalTrials.gov number, NCT02709850 .).
              Article 0 comments Cited 226 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Eur Heart J
                Journal ID (iso-abbrev): Eur. Heart J
                Journal ID (publisher-id): eurheartj
                Title: European Heart Journal
                Publisher: Oxford University Press
                ISSN (Print): 0195-668X
                ISSN (Electronic): 1522-9645
                Publication date (Print): 01 January 2020
                Publication date (Electronic): 25 November 2019
                Publication date PMC-release: 25 November 2019
                Volume: 41
                Issue: 1 , Focus Issue on Lipids
                Pages: 99-109c
                Affiliations
                [1 ] Klinik und Poliklinik für Kardiologie, Universitätsklinikum Leipzig , Liebigstr. 20, Leipzig, Germany
                [2 ] University Munich, Medical Department 4 - Grosshadern , Marchioninistr. 15, Munich, Germany
                [3 ] Irving Institute for Clinical and Translational Medicine, Vagelos College of Physicians and Surgeons, Columbia University , 630 West 168th Street, New York, NY, USA
                [4 ] Department of Medicine, Robarts Research Institute, Western University , London, Ontario, Canada
                Author notes
                Corresponding author. Tel: +49 341 97 12650, Email: Ulrich.Laufs@ 123456medizin.uni-leipzig.de
                Author information
                http://orcid.org/0000-0003-2620-9323
                http://orcid.org/0000-0001-9873-0412
                http://orcid.org/0000-0003-2861-5325
                Article
                Publisher ID: ehz785
                DOI: 10.1093/eurheartj/ehz785
                PMC ID: 6938588
                PubMed ID: 31764986
                SO-VID: b17e2bc8-8db2-4e7d-807e-400931af2b7f
                Copyright © © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                Date received : 30 June 2019
                Date revision received : 20 August 2019
                Date accepted : 23 October 2019
                Page count
                Pages: 14
                Categories
                Subject: Clinical Review
                Subject: Clinical Update

                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords:  triglycerides,review,lipoproteins,treatment,hypertriglyceridaemia
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords:  triglycerides, review, lipoproteins, treatment, hypertriglyceridaemia

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