DOCSLIB.ORG

Lipid Modification to Reduce Cardiovascular Risk

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Lipid Modification to Reduce Cardiovascular Risk Atherosclerosis 290 (2019) 140–205 Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis 2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid ☆ T modification to reduce cardiovascular risk ∗ ∗∗ Authors/Task Force Members (François Macha, ,2, Colin Baigentb, ,2, ∗∗∗ Alberico L. Catapanoc, ,1,2, Konstantinos C. Koskinasd, Manuela Casulae,f,1, Lina Badimong, M. John Chapmanh,i,cm,1, Guy G. De Backerj, Victoria Delgadok, Brian A. Ferencel, Ian M. Grahamm, Alison Hallidayn, Ulf Landmessero,p,q, Borislava Mihaylovar,s, Terje R. Pedersent, Gabriele Riccardiu,1, Dimitrios J. Richterv, Marc S. Sabatinew, Marja-Riitta Taskinenx,1, Lale Tokgozogluy,1, Olov Wiklundz), ESC National Cardiac Societies (Djamaleddine Nibouchean, Parounak H. Zelveianao, Peter Siostrzonekap, Ruslan Najafovaq, Philippe van de Bornear, Belma Pojskicas, Arman Postadzhiyanat, Lambros Kyprisau, Jindřich Špinarav, Mogens Lytken Larsenaw, Hesham Salah Eldinax, Margus Viigimaaay, Timo E. Strandbergaz, Jean Ferrièresba, Rusudan Agladzebb, Ulrich Laufsbc, Loukianos Rallidisbd, László Bajnokbe, Thorbjörn Gudjónssonbf, Vincent Maherbg, Yaakov Henkinbh, Michele Massimo Guliziabi, Aisulu Mussagaliyevabj, Gani Bajraktaribk, Alina Kerimkulovabl, Gustavs Latkovskisbm, Omar Hamouibn, Rimvydas Slapikasbo, Laurent Visserbp, Philip Dinglibq, Victoria Ivanovbr, Aneta Boskovicbs, Mbarek Nazzibt, Frank Visserenbu, Irena Mitevskabv, Kjetil Retterstølbw, Piotr Jankowskibx, Ricardo Fontes-Carvalhoby, Dan Gaitabz, Marat Ezhovca, Marina Foscolicb, Vojislav Gigacc, Daniel Pellacd, Zlatko Frasce, Leopoldo Perez de Islacf, Emil Hagströmcg, Roger Lehmannch, Leila Abidci, Oner Ozdogancj, Olena Mitchenkock, Riyaz S. Patelcl), ESC Committee for Practice Guidelines (CPG) (Stephan Windeckeraa, Victor Aboyansab, Colin Baigentac, Jean-Philippe Colletab, Veronica Deanab, Victoria Delgadoad, Donna Fitzsimonsac, Chris P. Galeac, Diederick Grobbeead, Sigrun Halvorsenae, Gerhard Hindricksaf, Bernard Iungab, Peter Jüniag, Hugo A. Katusaf, Ulf Landmesseraf, Christophe Leclercqab, Maddalena Lettinoah, Basil S. Lewisai, Bela Merkelyaj, Christian Muelleraa, Steffen Petersenac, Anna Sonia Petronioah, Dimitrios J. Richterak, Marco Roffiaa, Evgeny Shlyakhtoal, Iain A. Simpsonac, Miguel Sousa-Uvaam, Rhian M. Touyzac) a Cardiology Department, Geneva University Hospital, 4 Gabrielle-Perret-Gentil, 1211, Geneva, Switzerland b Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Roosevelt Drive, Oxford OX3 7LF, UnitedKingdom c Department of Pharmacological and Biomolecular Sciences, University of Milan, Multimedica IRCCS, Via Balzaretti, 9, 20133, Milan, Italy d Cardiology, Bern University Hospital (Inselspital), Bern, Switzerland e Epidemiology and Preventive Pharmacology Service (SEFAP), Department of Pharmacological and Biomolecular Sciences (DiSFeB), University of Milan, Milan, Italy f IRCCS MultiMedica, Sesto S. Giovanni, Milan, Italy g Cardiovascular Program-ICCC and CiberCV, IR-Hospital de la Santa Creu i Sant Pau, Barcelona, Spain h National Institute for Health and Medical Research (INSERM), Paris, France i Division of Endocrinology- Metabolism, Pitie-Salpetriere University Hospital, Paris, France j Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium k Cardiology, Leiden University Medical Center, Leiden, Netherlands l Centre for Naturally Randomized Trials, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom m Cardiology, Trinity College, Dublin, Ireland ☆ The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). The disclosure forms of all experts involved in the development of these Guidelines are available on the ESC website www.escardio.org/guidelines. ∗ Corresponding author. ∗∗ Corresponding author. ∗∗∗ Corresponding author. https://doi.org/10.1016/j.atherosclerosis.2019.08.014 Available online 31 August 2019 0021-9150/ © 2019 European Society of Cardiology and Elsevier B.V. All rights reserved. F. Mach, et al. Atherosclerosis 290 (2019) 140–205 n Nuffield Department of Surgery, University of Oxford, NIHR Oxford Biomedical Research Centre, Oxford, UnitedKingdom o Department of Cardiology, Charite Universitätsmedizin Berlin, Berlin, Germany p Berlin Institute of Health (BIH), Berlin, Germany q German Center of Cardiovascular Research (DZHK), Berlin, Germany r Nuffield Department of Population Health, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UnitedKingdom s Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom t Preventive Cardiology, Oslo University Hospital, Aker, Oslo, Norway u Clinical Medicine and Surgery, Federico II University, Naples, Italy v Cardiac Department, Euroclinic, Athens, Greece w TIMI Study Group, Division of Cardiovascular Medicine, Brigham, Women's Hospital and Harvard Medical School, Boston, MA, United States of America x Research Program for Clinical and Molecular Metabolism, University of Helsinki, Helsinki, Finland y Cardiology, Hacettepe University, Ankara, Turkey z Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden cm Sorbonne University, Paris, France aa Switzerland ab France ac United Kingdom ad Netherlands ae Norway af Germany ag Canada ah Italy ai Israel aj Hungary ak Greece al Russian Federation am Portugal an Algerian Society of Cardiology, Algeria ao Armenian Cardiologists Association, Armenia ap Austrian Society of Cardiology, Austria aq Azerbaijan Society of Cardiology, Azerbaijan ar Belgian Society of Cardiology, Belgium as Association of Cardiologists of Bosnia and Herzegovina, Bosnia and Herzegovina at Bulgarian Society of Cardiology, Bulgaria au Cyprus Society of Cardiology, Cyprus av Czech Society of Cardiology, Czech Republic aw Danish Society of Cardiology, Denmark ax Egyptian Society of Cardiology, Egypt ay Estonian Society of Cardiology, Estonia az Finnish Cardiac Society, Finland ba French Society of Cardiology, France bb Georgian Society of Cardiology, Georgia bc German Cardiac Society, Germany bd Hellenic Society of Cardiology, Greece be Hungarian Society of Cardiology, Hungary bf Icelandic Society of Cardiology, Iceland bg Irish Cardiac Society, Ireland bh Israel Heart Society, Israel bi Italian Federation of Cardiology, Italy bj Association of Cardiologists of Kazakhstan, Kazakhstan bk Kosovo Society of Cardiology, Republic of Kosovo bl Kyrgyz Society of Cardiology, Kyrgyzstan bm Latvian Society of Cardiology, Latvia bn Lebanese Society of Cardiology, Lebanon bo Lithuanian Society of Cardiology, Lithuania bp Luxembourg Society of Cardiology, Luxembourg bq Maltese Cardiac Society, Malta br Moldavian Society of Cardiology, Republic of Moldova bs Montenegro Society of Cardiology, Montenegro bt Moroccan Society of Cardiology, Morocco bu Netherlands Society of Cardiology, Netherlands bv North Macedonian Society of Cardiology, North Macedonia bw Norwegian Society of Cardiology, Norway bx Polish Cardiac Society, Poland by Portuguese Society of Cardiology, Portugal bz Romanian Society of Cardiology, Romania ca Russian Society of Cardiology, Russian Federation cb San Marino Society of Cardiology, San Marino cc Cardiology Society of Serbia, Serbia cd Slovak Society of Cardiology, Slovakia ce Slovenian Society of Cardiology, Slovenia cf Spanish Society of Cardiology, Spain cg Swedish Society of Cardiology, Sweden ch Swiss Society of Cardiology, Switzerland 141 F. Mach, et al. Atherosclerosis 290 (2019) 140–205 ci Tunisian Society of Cardiology and Cardio-Vascular Surgery, Tunisia cj Turkish Society of Cardiology, Turkey ck Ukrainian Association of Cardiology, Ukraine cl British Cardiovascular Society, United Kingdom of Great Britain and Northern Ireland ARTICLE INFO Keywords: Guidelines Dyslipidaemias Cholesterol; Triglycerides Low-density lipoproteins High-density lipoproteins Apolipoprotein B Lipoprotein(a) Lipoprotein remnants Total cardiovascular risk Treatment (lifestyle) Treatment (drugs) Treatment (adherence) Very low-density lipoproteins Familial hypercholesterolaemia 1. Preamble of a given condition according to ESC Committee for Practice Guidelines (CPG) policy. A critical evaluation of diagnostic and therapeutic proce- Guidelines summarize and evaluate available evidence with the aim dures was performed, including assessment of the risk–benefit ratio. The of assisting health professionals in proposing the best management level of evidence and the strength of the recommendation of particular strategies for an individual patient with a given condition. Guidelines management options were weighed and graded according to predefined and their recommendations should facilitate decision making of health ESC scales, as outlined in the tables below. professionals in their daily practice. However, the final decisions con- The experts of the writing and reviewing panels provided declara- cerning an individual patient must be made by the responsible health tion of interest forms for all relationships that might be perceived as professional(s) in consultation with the patient and caregiver as ap- real or potential sources of conflicts of interest. These forms were propriate. (see Table 1) compiled into one file and can be found on the ESC website (http:// A great number of guidelines have been issued in recent years by the www.escardio.org/guidelines).
Load more

Recommended publications
  • (AAV1-LPLS447X) Gene Therapy for Lipoprotein Lipase Deficiency
    Gene Therapy (2013) 20, 361–369 & 2013 Macmillan Publishers Limited All rights reserved 0969-7128/13 www.nature.com/gt ORIGINAL ARTICLE Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPLS447X) gene therapy for lipoprotein lipase deficiency: an open-label trial D Gaudet1,2,JMe´ thot1,2,SDe´ry1, D Brisson1,2, C Essiembre1, G Tremblay1, K Tremblay1,2, J de Wal3, J Twisk3, N van den Bulk3, V Sier-Ferreira3 and S van Deventer3 We describe the 2-year follow-up of an open-label trial (CT-AMT-011–01) of AAV1-LPLS447X gene therapy for lipoprotein lipase (LPL) deficiency (LPLD), an orphan disease associated with chylomicronemia, severe hypertriglyceridemia, metabolic complications and potentially life-threatening pancreatitis. The LPLS447X gene variant, in an adeno-associated viral vector of serotype 1 (alipogene tiparvovec), was administered to 14 adult LPLD patients with a prior history of pancreatitis. Primary objectives were to assess the long-term safety of alipogene tiparvovec and achieve a X40% reduction in fasting median plasma triglyceride (TG) at 3–12 weeks compared with baseline. Cohorts 1 (n ¼ 2) and 2 (n ¼ 4) received 3 Â 1011 gc kg À 1, and cohort 3 (n ¼ 8) received 1 Â 1012 gc kg À 1. Cohorts 2 and 3 also received immunosuppressants from the time of alipogene tiparvovec administration and continued for 12 weeks. Alipogene tiparvovec was well tolerated, without emerging safety concerns for 2 years. Half of the patients demonstrated a X40% reduction in fasting TG between 3 and 12 weeks. TG subsequently returned to baseline, although sustained LPLS447X expression and long-term changes in TG-rich lipoprotein characteristics were noted independently of the effect on fasting plasma TG.
    [Show full text]
  • Nustendi, INN-Bempedoic Acid, Ezetimibe
    Summary of risk management plan for Nustendi (Bempedoic acid/Ezetimibe) This is a summary of the risk management plan (RMP) for Nustendi. The RMP details important risks of Nustendi, how these risks can be minimized, and how more information will be obtained about Nustendi's risks and uncertainties (missing information). Nustendi's summary of product characteristics (SmPC) and its package leaflet give essential information to healthcare professionals and patients on how Nustendi should be used. This summary of the RMP for Nustendi should be read in the context of all this information, including the assessment report of the evaluation and its plain-language summary, all which is part of the European Public Assessment Report (EPAR). Important new concerns or changes to the current ones will be included in updates of Nustendi's RMP. I. The Medicine and What It Is Used For Nustendi is authorized for treatment of primary hypercholesterolemia in adults, as an adjunct to diet (see SmPC for the full indication). It contains bempedoic acid as the active substance and it is given by mouth. Further information about the evaluation of Nustendi’s benefits can be found in Nustendi’s EPAR, including in its plain-language summary, available on the EMA website, under the medicine’s webpage https://www.ema.europa.eu/en/medicines/human/EPAR/nustendi II. Risks Associated With the Medicine and Activities to Minimize or Further Characterize the Risks Important risks of Nustendi, together with measures to minimize such risks and the proposed studies for learning
    [Show full text]
  • Cholesteryl Ester-Transfer Protein Inhibitors Stimulate Aldosterone Biosynthesis in Adipocytes Through Nox-Dependent Processes S
    Supplemental material to this article can be found at: http://jpet.aspetjournals.org/content/suppl/2015/01/23/jpet.114.221002.DC1 1521-0103/353/1/27–34$25.00 http://dx.doi.org/10.1124/jpet.114.221002 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 353:27–34, April 2015 Copyright ª 2015 by The American Society for Pharmacology and Experimental Therapeutics Cholesteryl Ester-Transfer Protein Inhibitors Stimulate Aldosterone Biosynthesis in Adipocytes through Nox-Dependent Processes s Francisco J. Rios, Karla B. Neves, Aurelie Nguyen Dinh Cat, Sarah Even, Roberto Palacios, Augusto C. Montezano, and Rhian M. Touyz Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom (F.J.R., A.N.D.C., S.E., A.C.M., R.M.T.); Faculty of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil (K.B.N.); and Departamento de Bioquímica, Fisiología y Genética Molecular Facultad de CC. de la Salud, Universidad Rey Juan Carlos, Madrid, Spain (R.P.) Downloaded from Received October 29, 2014; accepted January 22, 2015 ABSTRACT Hyperaldosteronism and hypertension were unexpected side whereby CETP inhibitors mediate effects, cells were pretreated effects observed in trials of torcetrapib, a cholesteryl ester-transfer with inhibitors of Nox1/Nox4 [GKT137831; 2-(2-chlorophenyl)-4-[3- jpet.aspetjournals.org protein (CETP) inhibitor that increases high-density lipoprotein. (dimethylamino)phenyl]-5-methyl-1H-pyrazolo[4,3-c]pyridine- Given that CETP inhibitors are lipid soluble, accumulate in adipose 3,6(2H,5H)-dione], Nox1 (ML171 [2-acetylphenothiazine]), mitochondria tissue, and have binding sites for proteins involved in adipogenesis, (rotenone), and STAT3 (S3I-201 [2-hydroxy-4-(((4-methylphenyl) and that adipocytes are a source of aldosterone, we questioned sulfonyloxy)acetyl)amino)-benzoic acid]).
    [Show full text]
  • A Novel Therapeutic Drug for the Treatment of Familial Hypercholesterolemia, Hyperlipidaemia, and Hypercholesterolemia
    International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 8, Issue 3, 2016 Review Article MIPOMERSEN: A NOVEL THERAPEUTIC DRUG FOR THE TREATMENT OF FAMILIAL HYPERCHOLESTEROLEMIA, HYPERLIPIDAEMIA, AND HYPERCHOLESTEROLEMIA AJAY KUMAR1, ARUN ACHARYA2, DINOBANDHU NANDI3, NEHA SHARMA4, EKTA CHITKARA1* 1Department of Paramedical Sciences, Lovely Professional University, Phagwara-144411, Punjab (India) Email: [email protected] Received: 25 Dec 2015 Revised and Accepted: 13 Jan 2016 ABSTRACT Familial Hypercholesterolemia (FH) is one of the most common autosomal dominant disorders which exist in either heterozygous form or a homozygous form. These two forms are prevalent in 1 in 500 and 1 in a million population respectively. FH results in premature atherosclerosis; as early as childhood in case of homozygous (HoFH) form and in adults in case of heterozygous (HeFH) form. In case of HoFH both the alleles for LDL- receptor are defective, whereas the mutation in the single allele is the cause for HeFH. Both the forms of the disease are associated with high levels of LDL-C and lipoprotein (a) in plasma, with high morbidity and mortality rate caused by cardiovascular disease. In several past years, different lipid-lowering drugs like Statins (HMG-coenzyme-A reductase inhibitor), MTTP inhibitor, CETP inhibitors, PCSK9 inhibitor, thyroid mimetics, niacin, bile acid sequestrants and lipid apheresis were administered to patients with FH, to achieve the goal of reducing plasma LDL-C and lipoprotein (a). However, such drugs proved inefficient to achieve the goals because of several reasons. Mipomersen is a 20 nucleotide antisense oligonucleotide; a novel lipid-lowering therapeutic drug currently enrolled in the treatment of patients with HoFH, HeFH and other forms of hypercholesterolemia.
    [Show full text]
  • Next-Generation Sequencing Transforms Today's Biology
    Evolving new therapies for the prevention of atherosclerosis: a glimpse of the near future G.K. Hovingh MD PhD ([email protected]) Department of Vascular Medicine AMC Amsterdam The Netherlands Today BMJ 2013;347:f544 www.chinadaily.com.cn/life/2009- 04/21/content_7698500.htm What we know - CVD major burden - LDL-C causally related with CVD - LDL-C goals: the lower the better - Statins : corner stone in therapy How well do we do? Reduction in MACE statin vs placebo (%) 0 -30 Potential for further risk reduction -100 Where do we go? Reduction in MACE statin vs placebo (%) 0 Potential for further -30 risk reduction -50 = further LDL-C lowering? and or Additional Rx? -100 A glance at the future… Atherosclerosis • LDL • HDL • TG • Lp(a) • Inflammation Lipid Modifying Drugs • Cholesterol absorption inhibitors • Squalene synthase inhibitors (SSI) • Microsomal triglyceride transfer protein (MTP) inhibitors • Acyl coenzyme A acyltransferase (ACAT) inhibitors • Diacylglycerol acyltransferase (DGAT) inhibitors • Thyroxin receptor agonists • ApoB mRNA antisense drugs • PCSK9 antibodies • ApoA1-based strategies (iv) • Cholesterol ester transfer protein (CETP) inhibitors ApoA-1 based therapy ApoA1 Mimetics, such as APL-180 Novartis Full-length ApoA1, such as ApoA1 Cerenis Therapeutics Pre-Beta HDL, as generated by delipidation, HDL Therapeutics Inc. Reconstituted HDL, CSL Ltd. ApoA1 Milano MDCO216, The Medicines Company Trimeric ApoA1, Borean Pharma and now Roche RVX-208, as developed by Resverlogix Fx-5A, as developed by Kinemed Inc. HDL
    [Show full text]
  • Classification of Medicinal Drugs and Driving: Co-Ordination and Synthesis Report
    Project No. TREN-05-FP6TR-S07.61320-518404-DRUID DRUID Driving under the Influence of Drugs, Alcohol and Medicines Integrated Project 1.6. Sustainable Development, Global Change and Ecosystem 1.6.2: Sustainable Surface Transport 6th Framework Programme Deliverable 4.4.1 Classification of medicinal drugs and driving: Co-ordination and synthesis report. Due date of deliverable: 21.07.2011 Actual submission date: 21.07.2011 Revision date: 21.07.2011 Start date of project: 15.10.2006 Duration: 48 months Organisation name of lead contractor for this deliverable: UVA Revision 0.0 Project co-funded by the European Commission within the Sixth Framework Programme (2002-2006) Dissemination Level PU Public PP Restricted to other programme participants (including the Commission x Services) RE Restricted to a group specified by the consortium (including the Commission Services) CO Confidential, only for members of the consortium (including the Commission Services) DRUID 6th Framework Programme Deliverable D.4.4.1 Classification of medicinal drugs and driving: Co-ordination and synthesis report. Page 1 of 243 Classification of medicinal drugs and driving: Co-ordination and synthesis report. Authors Trinidad Gómez-Talegón, Inmaculada Fierro, M. Carmen Del Río, F. Javier Álvarez (UVa, University of Valladolid, Spain) Partners - Silvia Ravera, Susana Monteiro, Han de Gier (RUGPha, University of Groningen, the Netherlands) - Gertrude Van der Linden, Sara-Ann Legrand, Kristof Pil, Alain Verstraete (UGent, Ghent University, Belgium) - Michel Mallaret, Charles Mercier-Guyon, Isabelle Mercier-Guyon (UGren, University of Grenoble, Centre Regional de Pharmacovigilance, France) - Katerina Touliou (CERT-HIT, Centre for Research and Technology Hellas, Greece) - Michael Hei βing (BASt, Bundesanstalt für Straßenwesen, Germany).
    [Show full text]
  • Statins and Lipid Lowering Agents
    CARDIOVASCULAR Z/Ks^h>ZZh'^͗ ^dd/E^E>/W/>KtZ/E''Ed^ /E^d/Ɛ EEZd/Ɛ W/Ɛ x/d'Zs/Z ;ŝŬƚĂƌǀLJͿ x>s/d'Zs/Zͬ x KZs/Z/E ;WŝĨĞůƚƌŽ͕ x &s/ZE ;^ƵƐƚŝǀĂ͕ ŽŽƐƚĞĚǁŝƚŚƌŝƚŽŶĂǀŝƌ xK>hd'Zs/Z ;dŝǀŝĐĂLJ͕ K//^dd ;^ƚƌŝďŝůĚ͕ ĞůƐƚƌŝŐŽͿ ƚƌŝƉůĂͿ ;EŽƌǀŝƌͿŽƌĐŽďŝĐŝƐƚĂƚ dƌŝƵŵĞƋ͕:ƵůƵĐĂ͕ŽǀĂƚŽͿ 'ĞŶǀŽLJĂͿ x Z/>W/s/Z/E ;ĚƵƌĂŶƚ͕ x dZs/Z/E ;/ŶƚĞůĞŶĐĞͿ xdEs/Z ;ZĞLJĂƚĂnj͕ xZ>d'Zs/Z ŽŵƉůĞƌĂ͕KĚĞĨƐĞLJ͕ x Es/ZW/E ǀŽƚĂnjͿ ;/ƐĞŶƚƌĞƐƐͿ :ƵůƵĐĂͿ ;sŝƌĂŵƵŶĞͿ xZhEs/Z ;WƌĞnjŝƐƚĂ͕ WƌĞnjĐŽďŝdž͕^LJŵƚƵnjĂͿ x>KW/Es/Z ;<ĂůĞƚƌĂͿ ^dd/E^ xƚŽƌǀĂƐƚĂƚŝŶ WŽƚĞŶƚŝĂůĨŽƌ nƐƚĂƚŝŶ WŽƚĞŶƚŝĂůĨŽƌ pƐƚĂƚŝŶ WŽƚĞŶƚŝĂůĨŽƌ nƐƚĂƚŝŶ͘hƐĞ ;>ŝƉŝƚŽƌͿ ůŽǁĞƐƚƐƚĂƚŝŶĚŽƐĞƉŽƐƐŝďůĞ ;ŵĂdžŝŵƵŵϮϬŵŐ ĂƚŽƌǀĂƐƚĂƚŝŶĚĂŝůLJͿ͘ xZŽƐƵǀĂƐƚĂƚŝŶ WŽƚĞŶƚŝĂůĨŽƌ nƐƚĂƚŝŶ WŽƚĞŶƚŝĂůĨŽƌ nƐƚĂƚŝŶ͘hƐĞ ;ƌĞƐƚŽƌͿ ůŽǁĞƐƚƐƚĂƚŝŶĚŽƐĞƉŽƐƐŝďůĞ ;ŵĂdžŝŵƵŵϭϬŵŐ ƌŽƐƵǀĂƐƚĂƚŝŶĚĂŝůLJͿ͘ xWŝƚĂǀĂƐƚĂƚŝŶ ;>ŝǀĂůŽͿ xWƌĂǀĂƐƚĂƚŝŶ WŽƚĞŶƚŝĂůĨŽƌ nƐƚĂƚŝŶ WŽƚĞŶƚŝĂůĨŽƌ nƐƚĂƚŝŶ ;WƌĂǀĂĐŚŽůͿ x>ŽǀĂƐƚĂƚŝŶ WŽƚĞŶƚŝĂůĨŽƌ nƐƚĂƚŝŶĂŶĚ WŽƚĞŶƚŝĂůĨŽƌ pƐƚĂƚŝŶ WŽƚĞŶƚŝĂůĨŽƌ nƐƚĂƚŝŶĂŶĚ ;DĞǀĂĐŽƌͿ͕ ƚŽdžŝĐŝƚLJ ƚŽdžŝĐŝƚLJ ƐŝŵǀĂƐƚĂƚŝŶ ;ŽĐŽƌͿ CARDIOVASCULAR INSTIs NNRTIs PIs xBICTEGRAVIR (Biktarvy) xELVITEGRAVIR/ x DORAVIRINE (Pifeltro, x EFAVIRENZ (Sustiva, Boosted with ritonavir xDOLUTEGRAVIR (Tivicay, COBICISTAT (Stribild, Delstrigo) Atripla) (Norvir) or cobicistat Triumeq, Juluca) Genvoya) x RILPIVIRINE (Edurant, x ETRAVIRINE (Intelence) xATAZANAVIR (Reyataz, xRALTEGRAVIR Complera, Odefsey, x NEVIRAPINE Evotaz) (Isentress) Juluca) (Viramune) xDARUNAVIR (Prezista, Prezcobix, Symtuza) xLOPINAVIR (Kaletra) FIBRATES xFenofibrate, bezafibrate, gemfibrozil CHOLESTEROL ABSORPTION INHIBITOR xEzetimibe
    [Show full text]
  • 1 CETP Inhibition Improves HDL Function but Leads to Fatty Liver and Insulin Resistance in CETP-Expressing Transgenic Mice on A
    Page 1 of 55 Diabetes CETP inhibition improves HDL function but leads to fatty liver and insulin resistance in CETP-expressing transgenic mice on a high-fat diet Lin Zhu1,2, Thao Luu2, Christopher H. Emfinger1,2, Bryan A Parks5, Jeanne Shi2,7, Elijah Trefts3, Fenghua Zeng4, Zsuzsanna Kuklenyik5, Raymond C. Harris4, David H. Wasserman3, Sergio Fazio6 and John M. Stafford1,2,3,* 1VA Tennessee Valley Healthcare System, 2Division of Diabetes, Endocrinology, & Metabolism, 3Department of Molecular Physiology and Biophysics, 4Devision of Nephrology and Hypertension, Vanderbilt University School of Medicine. 5Division of Laboratory Sciences, Centers for Disease Control and Prevention. 6The Center for Preventive Cardiology at the Knight Cardiovascular Institute, Oregon Health & Science University. 7Trinity College of Art and Science, Duke University. * Address correspondence and request for reprints to: John. M. Stafford, 7445D Medical Research Building IV, Nashville, TN 37232-0475, phone (615) 936-6113, fax (615) 936- 1667 Email: [email protected] Running Title: CETP inhibition and insulin resistance Word Count: 5439 Figures: 7 Tables: 1 1 Diabetes Publish Ahead of Print, published online September 13, 2018 Diabetes Page 2 of 55 Abstract In clinical trials inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels but doesn’t robustly improve cardiovascular outcomes. About 2/3 of trial participants were obese. Lower plasma CETP activity is associated with increased cardiovascular risk in human studies, and protective aspects of CETP have been observed in mice fed a high-fat diet (HFD) with regard to metabolic outcomes. To define if CETP inhibition has different effects depending on the presence of obesity, we performed short- term anacetrapib treatment in chow- and HFD-fed CETP-transgenic mice.
    [Show full text]
  • Classification Decisions Taken by the Harmonized System Committee from the 47Th to 60Th Sessions (2011
    CLASSIFICATION DECISIONS TAKEN BY THE HARMONIZED SYSTEM COMMITTEE FROM THE 47TH TO 60TH SESSIONS (2011 - 2018) WORLD CUSTOMS ORGANIZATION Rue du Marché 30 B-1210 Brussels Belgium November 2011 Copyright © 2011 World Customs Organization. All rights reserved. Requests and inquiries concerning translation, reproduction and adaptation rights should be addressed to [email protected]. D/2011/0448/25 The following list contains the classification decisions (other than those subject to a reservation) taken by the Harmonized System Committee ( 47th Session – March 2011) on specific products, together with their related Harmonized System code numbers and, in certain cases, the classification rationale. Advice Parties seeking to import or export merchandise covered by a decision are advised to verify the implementation of the decision by the importing or exporting country, as the case may be. HS codes Classification No Product description Classification considered rationale 1. Preparation, in the form of a powder, consisting of 92 % sugar, 6 % 2106.90 GRIs 1 and 6 black currant powder, anticaking agent, citric acid and black currant flavouring, put up for retail sale in 32-gram sachets, intended to be consumed as a beverage after mixing with hot water. 2. Vanutide cridificar (INN List 100). 3002.20 3. Certain INN products. Chapters 28, 29 (See “INN List 101” at the end of this publication.) and 30 4. Certain INN products. Chapters 13, 29 (See “INN List 102” at the end of this publication.) and 30 5. Certain INN products. Chapters 28, 29, (See “INN List 103” at the end of this publication.) 30, 35 and 39 6. Re-classification of INN products.
    [Show full text]
  • Clinofibrate Improved Canine Lipid Metabolism in Some but Not All Breeds
    NOTE Internal Medicine Clinofibrate improved canine lipid metabolism in some but not all breeds Yohtaro SATO1), Nobuaki ARAI2), Hidemi YASUDA3) and Yasushi MIZOGUCHI4)* 1)Graduate School of Agriculture, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa 214-8571, Japan 2)Spectrum Lab Japan, 1-5-22-201 Midorigaoka, Meguro-ku, Tokyo 152-0034, Japan 3)Yasuda Veterinary Clinic, 1-5-22 Midorigaoka, Meguro-ku, Tokyo 152-0034, Japan 4)School of Agriculture, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa 214-8571, Japan ABSTRACT. The objectives of this study were to assess if Clinofibrate (CF) treatment improved J. Vet. Med. Sci. lipid metabolism in dogs, and to clarify whether its efficacy is influenced by canine characteristics. 80(6): 945–949, 2018 We collected medical records of 306 dogs and performed epidemiological analyses. Lipid values of all lipoproteins were significantly decreased by CF medication, especially VLDL triglyceride doi: 10.1292/jvms.17-0703 (TG) concentration (mean reduction rate=54.82%). However, 17.65% of dogs showed drug refractoriness in relation to TG level, and Toy Poodles had a lower CF response than other breeds (OR=5.36, 95% CI=2.07–13.90). Therefore, our study suggests that genetic factors may have an Received: 22 December 2017 effect on CF response, so genetic studies on lipid metabolism-related genes might be conducted Accepted: 9 March 2018 to identify variations in CF efficacy. Published online in J-STAGE: KEY WORDS: clinofibrate, descriptive epidemiology, drug response, dyslipidemia, Toy Poodle 26 March 2018 High serum cholesterol (Cho) and triglyceride (TG) concentrations in dogs are caused by various factors such as lack of exercise, high fat diets, obesity, neutralization, age, diseases and breed [6, 21, 24].
    [Show full text]
  • Statins: Mechanism of Action and Effects
    J.Cell.Mol.Med. Vol 5, No 4, 2001 pp. 378-387 Review Statins: mechanism of action and effects Camelia Stancu, Anca Sima * "Nicolae Simionescu" Institute of Cellular Biology and Pathology, Bucharest, Romania Received: November 12, 2001; Accepted: December 5, 2001 • Introduction • Effects on • Classification of statins - cholesterol esterification and - How they are obtained its accumulation in macrophages - Liver metabolism - endothelial cell function - Physico-chemical properties - inflammatory process - Specific activity - proliferation, migration and • Mechanisms for the action of statins apoptosis of arterial smooth muscle cells - Mechanisms involving lipids - stability of the atherosclerotic plaque - Mechanisms involving intracellular - platelets activation signaling pathways - coagulation process • Beneficial effects of statins • Adverse effects of statins therapy • Conclusions Abstract The beneficial effects of statins are the result of their capacity to reduce cholesterol biosyntesis, mainly in the liver, where they are selectively distributed, as well as to the modulation of lipid metabolism, derived from their effect of inhibition upon HMG-CoA reductase. Statins have antiatherosclerotic effects, that positively correlate with the percent decrease in LDL cholesterol. In addition, they can exert antiatherosclerotic effects independently of their hypolipidemic action. Because the mevalonate metabolism generates a series of isoprenoids vital for different cellular functions, from cholesterol synthesis to the control of cell growth and differentiation, HMG-CoA reductase inhibition has beneficial pleiotropic effects. Consequently, statins reduce significantly the incidence of coronary events, both in primary and secondary prevention, being the most efficient hypolipidemic compounds that have reduced the rate of mortality in coronary patients. Independent of their hypolipidemic properties, statins interfere with events involved in bone formation and impede tumor cell growth.
    [Show full text]
  • Dysfunctional High-Density Lipoproteins in Type 2 Diabetes Mellitus: Molecular Mechanisms and Therapeutic Implications
    Journal of Clinical Medicine Review Dysfunctional High-Density Lipoproteins in Type 2 Diabetes Mellitus: Molecular Mechanisms and Therapeutic Implications Isabella Bonilha 1 , Francesca Zimetti 2,* , Ilaria Zanotti 2 , Bianca Papotti 2 and Andrei C. Sposito 1,* 1 Atherosclerosis and Vascular Biology Laboratory (AtheroLab), Cardiology Department, State University of Campinas (Unicamp), Campinas 13084-971, Brazil; [email protected] 2 Department of Food and Drug, University of Parma, 43124 Parma, Italy; [email protected] (I.Z.); [email protected] (B.P.) * Correspondence: [email protected] (F.Z.); [email protected] (A.C.S.); Tel.: +39-05-2190-6172 (F.Z.); +55-19-3521-7098 (A.C.S.); Fax: +55-1-9328-9410 (A.C.S.) Abstract: High density lipoproteins (HDLs) are commonly known for their anti-atherogenic prop- erties that include functions such as the promotion of cholesterol efflux and reverse cholesterol transport, as well as antioxidant and anti-inflammatory activities. However, because of some chronic inflammatory diseases, such as type 2 diabetes mellitus (T2DM), significant changes occur in HDLs in terms of both structure and composition. These alterations lead to the loss of HDLs’ physiological functions, to transformation into dysfunctional lipoproteins, and to increased risk of cardiovascular disease (CVD). In this review, we describe the main HDL structural/functional alterations observed in T2DM and the molecular mechanisms involved in these T2DM-derived modifications. Finally, the main available therapeutic interventions targeting HDL in diabetes are discussed. Citation: Bonilha, I.; Zimetti, F.; Keywords: high density lipoprotein; type 2 diabetes mellitus; HDL function; glycation; oxidation; Zanotti, I.; Papotti, B.; Sposito, A.C.
    [Show full text]