2016 ESC EAS Guidelines for the Management of DLP | Cardiovascular Diseases | Cholesterol

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  ESC/EAS GUIDELINES 2016 ESC/EAS Guidelines for the Managementof Dyslipidaemias The Task Force for the Management of Dyslipidaemias of theEuropean Society of Cardiology (ESC) and European AtherosclerosisSociety (EAS)DevelopedwiththespecialcontributionoftheEuropeanAssocciationfor Cardiovascular Prevention & Rehabilitation (EACPR) Authors/Task Force Members: Alberico L. Catapano *  (Chairperson) (Italy),Ian Graham *  (Chairperson) (Ireland), Guy De Backer (Belgium), Olov Wiklund(Sweden), M. John Chapman (France), Heinz Drexel (Austria), Arno W. Hoes(The Netherlands), Catriona S. Jennings (UK), Ulf Landmesser (Germany),Terje R. Pedersen (Norway), Z ˇ eljko Reiner (Croatia), Gabriele Riccardi (Italy),Marja-Riita Taskinen (Finland), Lale Tokgozoglu (Turkey), W. M. MoniqueVerschuren(TheNetherlands),CharalambosVlachopoulos(Greece),DavidA.Wood(UK), Jose Luis Zamorano (Spain) Additional Contributor: Marie-Therese Cooney (Ireland)Document Reviewers: Lina Badimon (CPG Review Coordinator) (Spain), Christian Funck-Brentano (CPG Review Coordinator) (France), Stefan Agewall (Norway), Gonzalo Baro´n-Esquivias (Spain), Jan Bore´n (Sweden),Eric Bruckert (France), Alberto Cordero (Spain), Alberto Corsini (Italy), Pantaleo Giannuzzi (Italy), * Corresponding authors: Alberico L. Catapano, Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, and Multimedica IRCCS(MI) Italy.Tel: + 39025031 8401,Fax: + 3902 50318386,E-mail: alberico.catapano@unimi.it;Ian Graham, Cardiology Department, HermitageMedical Clinic, OldLucan Road,Dublin 20, Dublin, Ireland. Tel:  + 353 1 6459715, Fax:  + 353 1 6459714, E-mail: ian@grahams.net ESC Committee for Practice Guidelines (CPG) and National Cardiac Society Reviewers  can be found in the Appendix. ESC entities having participated in the development of this document:Associations : Acute Cardiovascular Care Association (ACCA), European Association for Cardiovascular Prevention & Rehabilitation (EACPR), European Association of Cardiovas-cular Imaging (EACVI), European Association of Percutaneous Cardiovascular Interventions (EAPCI), Heart Failure Association (HFA) Councils : Council on Cardiovascular Nursing and Allied Professions, Council for Cardiology Practice, Council on Cardiovascular Primary Care, Council on Hypertension  Working Groups : Atherosclerosis & Vascular Biology, Cardiovascular Pharmacotherapy, Coronary Pathophysiology & Microcirculation, E-cardiology, Myocardial and PericardialDiseases, Peripheral Circulation, Thrombosis.ThecontentoftheseEuropeanSocietyofCardiology(ESC)andEuropeanAtherosclerosisSocietyGuidelineshasbeenpublishedforpersonalandeducationaluseonly.Nocommercialuseisauthorized.NopartoftheESCGuidelinesmaybetranslatedorreproducedinanyformwithoutwrittenpermissionfromtheESC.Permissioncanbeobtaineduponsubmissionof a written request to Oxford University Press, the publisher of the European Heart Journal and the party authorized to handle such permissions on behalf of the ESC(journals.permissions@oup.com). Disclaimer  . The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their publication. The ESC is not responsible in the event of any contradiction, discrepancy and/or ambiguity between the ESC Guidelines and any other official recom-mendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encour-aged to take the ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or  therapeutic medical strategies; however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate andaccurate decisions in consideration of each patient’s health condition and in consultation with that patient and, where appropriate and/or necessary, the patient’s caregiver. Nor do the ESC Guidelines exempthealth professionalsfromtaking into full andcarefulconsideration the relevant official updated recommendationsor guidelines issued by the competentpublic health authorities in order to manage each patient’s case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also thehealth professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription. & 2016 European Society of Cardiology and European Atherosclerosis Association. All rights reserved. For permissions please email: journals.permissions@oup.com. European Heart Journaldoi:10.1093/eurheartj/ehw272   European Heart Journal Advance Access published August 27, 2016   b  y g u e  s  t   on N o v e m b  e r 2 1  ,2  0 1  6 h  t   t   p :  /   /   e  ur h  e  a r  t   j   . oxf   or  d  j   o ur n a l   s  . or  g /  D o wnl   o a  d  e  d f  r  om   Franc¸ois Gueyffier (France), Goran Krstac ˇ ic´ (Croatia), Maddalena Lettino (Italy), Christos Lionis (Greece),Gregory Y. H. Lip (UK), Pedro Marques-Vidal (Switzerland), Davor Milicic (Croatia), Juan Pedro-Botet (Spain),Massimo F. Piepoli (Italy), Angelos G. Rigopoulos (Germany), Frank Ruschitzka (Switzerland), Jose´ Tun ˜ o´n (Spain),ArnoldvonEckardstein(Switzerland),MichalVrablik(CzechRepublic),ThomasW.Weiss(Austria),BryanWilliams(UK), Stephan Windecker (Switzerland), and Reuven Zimlichman (Israel) The disclosure forms of the authors and reviewers are available on the ESC website www.escardio.org/guidelines. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Keywords  dyslipidaemias  †  cholesterol  †  triglycerides  †  low-density lipoproteins  †  high-density lipoproteins  † apolipoprotein B  †  lipoprotein remnants  †  total cardiovascular risk   †  treatment, lifestyle  †  treatment,drugs  †  treatment, adherence Table of Contents List of abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51. What is cardiovascular disease prevention? . . . . . . . . . . . . . 61.1 Definition and rationale . . . . . . . . . . . . . . . . . . . . . . 61.2 Development of the Joint Task Force guidelines . . . . . . 61.3 Cost-effectiveness of prevention . . . . . . . . . . . . . . . . 72. Total cardiovascular risk . . . . . . . . . . . . . . . . . . . . . . . . . 82.1 Total cardiovascular risk estimation . . . . . . . . . . . . . . 82.1.1 Rationale for assessing total cardiovascular diseaserisk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82.1.2 How to use the risk estimation charts . . . . . . . . . . 122.2 Risk levels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132.2.1 Risk- based intervention strategies . . . . . . . . . . . . 133. Evaluation of laboratory lipid and apolipoprotein parameters . 143.1 Fasting or non-fasting? . . . . . . . . . . . . . . . . . . . . . . . 163.2 Intra-individual variation . . . . . . . . . . . . . . . . . . . . . . 163.3 Lipid and lipoprotein analyses . . . . . . . . . . . . . . . . . . 163.3.1 Total cholesterol . . . . . . . . . . . . . . . . . . . . . . . 163.3.2 Low-density lipoprotein cholesterol . . . . . . . . . . . 163.3.3 Non-high-density lipoprotein cholesterol . . . . . . . . 173.3.4 High-density lipoprotein cholesterol . . . . . . . . . . . 183.3.5 Triglycerides . . . . . . . . . . . . . . . . . . . . . . . . . . 183.3.6 Apolipoproteins . . . . . . . . . . . . . . . . . . . . . . . . 183.3.7 Lipoprotein(a) . . . . . . . . . . . . . . . . . . . . . . . . . 193.3.8 Lipoprotein particle size . . . . . . . . . . . . . . . . . . . 193.3.9 Genotyping . . . . . . . . . . . . . . . . . . . . . . . . . . . 194. Treatment targets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205. Lifestyle modifications to improve the plasma lipid profile . . . 215.1 The influence of lifestyle on total cholesterol and low-density lipoprotein cholesterol levels . . . . . . . . . . . . . . . . 235.2 The influence of lifestyle on triglyceride levels . . . . . . . 245.3 The influence of lifestyle on high-density lipoproteincholesterol levels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245.4 Lifestyle recommendations to improve the plasma lipidprofile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245.4.1 Body weight and physical activity . . . . . . . . . . . . . 245.4.2 Dietary fat. . . . . . . . . . . . . . . . . . . . . . . . . . . . 255.4.3 Dietary carbohydrate and fibre . . . . . . . . . . . . . . 255.4.4 Alcohol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255.4.5 Smoking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255.5 Dietary supplements and functional foods for the treatment of dyslipidaemias . . . . . . . . . . . . . . . . . . . . . . 255.5.1 Phytosterols . . . . . . . . . . . . . . . . . . . . . . . . . . 265.5.2 Monacolin and red yeast rice. . . . . . . . . . . . . . . . 265.5.3 Dietary fibre . . . . . . . . . . . . . . . . . . . . . . . . . . 265.5.4 Soy protein . . . . . . . . . . . . . . . . . . . . . . . . . . . 265.5.5 Policosanol and berberine . . . . . . . . . . . . . . . . . 265.5.6 n-3 unsaturated fatty acids . . . . . . . . . . . . . . . . . 265.6 Other features of a healthy diet contributing tocardiovascular disease prevention . . . . . . . . . . . . . . . . . . 266. Drugs for treatment of hypercholesterolaemia . . . . . . . . . . 276.1 Statins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276.1.1 Mechanism of action . . . . . . . . . . . . . . . . . . . . . 276.1.2 Efficacyofcardiovasculardiseasepreventioninclinicalstudies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276.1.3 Adverse effects of statins . . . . . . . . . . . . . . . . . . 296.1.4 Interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . 306.2 Bile acid sequestrants . . . . . . . . . . . . . . . . . . . . . . . 306.2.1 Mechanism of action . . . . . . . . . . . . . . . . . . . . . 306.2.2 Efficacy in clinical studies . . . . . . . . . . . . . . . . . . 306.2.3 Adverse effects and interactions . . . . . . . . . . . . . 306.3 Cholesterol absorption inhibitors . . . . . . . . . . . . . . . 306.3.1 Mechanism of action . . . . . . . . . . . . . . . . . . . . . 306.3.2 Efficacy in clinical studies . . . . . . . . . . . . . . . . . . 316.3.3 Adverse effects and interactions . . . . . . . . . . . . . 316.4 PCSK9 inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . 316.4.1 Mechanism of action . . . . . . . . . . . . . . . . . . . . . 316.4.2 Efficacy in clinical studies . . . . . . . . . . . . . . . . . . 316.4.3 Adverse effects and interactions . . . . . . . . . . . . . 316.5 Nicotinic acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316.6 Drug combinations . . . . . . . . . . . . . . . . . . . . . . . . . 326.6.1 Statins and cholesterol absorption inhibitors . . . . . 326.6.2 Statins and bile acid sequestrants . . . . . . . . . . . . . 326.6.3 Other combinations . . . . . . . . . . . . . . . . . . . . . 327. Drugs for treatment of hypertriglyceridaemia . . . . . . . . . . . 327.1 Triglycerides and cardiovascular disease risk. . . . . . . . . 327.2 Definition of hypertriglyceridaemia . . . . . . . . . . . . . . 337.3 Strategies to control plasma triglycerides . . . . . . . . . . . 33ESC/EAS Guidelines Page 2 of 72   b  y g u e  s  t   on N o v e m b  e r 2 1  ,2  0 1  6 h  t   t   p :  /   /   e  ur h  e  a r  t   j   . oxf   or  d  j   o ur n a l   s  . or  g /  D o wnl   o a  d  e  d f  r  om   7.4 Statins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337.5 Fibrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337.5.1 Mechanism of action . . . . . . . . . . . . . . . . . . . . . 337.5.2 Efficacy in clinical trials . . . . . . . . . . . . . . . . . . . . 337.5.3 Adverse effects and interactions . . . . . . . . . . . . . 347.6 Nicotinic acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347.6.1 Mechanism of action . . . . . . . . . . . . . . . . . . . . . 347.6.2 Efficacy in clinical trials . . . . . . . . . . . . . . . . . . . . 347.7 n-3 fatty acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347.7.1 Mechanism of action . . . . . . . . . . . . . . . . . . . . . 347.7.2 Efficacy in clinical trials . . . . . . . . . . . . . . . . . . . . 347.7.3 Safety and interactions . . . . . . . . . . . . . . . . . . . . 358. Drugs affecting high-density lipoprotein cholesterol ( Table 20 ) 358.1 Statins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 358.2 Fibrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 358.3 Nicotinic acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . 358.4 Cholesteryl ester transfer protein inhibitors . . . . . . . . . 368.5 Future perspectives. . . . . . . . . . . . . . . . . . . . . . . . . 369. Management of dyslipidaemia in different clinical settings . . . . 369.1 Familial dyslipidaemias . . . . . . . . . . . . . . . . . . . . . . . 369.1.1 Familial combined hyperlipidaemia . . . . . . . . . . . . 369.1.2 Familial hypercholesterolaemia . . . . . . . . . . . . . . 369.1.2.1 Heterozygous familial hypercholesterolaemia . . 369.1.2.2 Homozygous familial hypercholesterolaemia . . . 389.1.2.3 Familial hypercholesterolaemia in children . . . . 389.1.3 Familial dysbetalipoproteinaemia . . . . . . . . . . . . . 389.1.4 Genetic causes of hypertriglyceridaemia . . . . . . . . 389.1.4.1 Action to prevent acute pancreatitis in severehypertriglyceridaemia . . . . . . . . . . . . . . . . . . . . . . . 399.1.5 Other genetic disorders of lipoprotein metabolism( Table 23 ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399.2 Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 409.3 Women . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 409.3.1 Primary prevention . . . . . . . . . . . . . . . . . . . . . . 409.3.2 Secondary prevention . . . . . . . . . . . . . . . . . . . . 409.3.3 Non-statin lipid-lowering drugs . . . . . . . . . . . . . . 409.3.4 Hormone therapy . . . . . . . . . . . . . . . . . . . . . . . 409.4 Older persons . . . . . . . . . . . . . . . . . . . . . . . . . . . . 409.4.1 Primary prevention . . . . . . . . . . . . . . . . . . . . . . 419.4.2 Secondary prevention . . . . . . . . . . . . . . . . . . . . 419.4.3 Adverse effects, interactions and adherence . . . . . . 419.5 Diabetes and metabolic syndrome . . . . . . . . . . . . . . . 429.5.1 Specific features of dyslipidaemia in insulin resistanceand type 2 diabetes ( Table 25 ) . . . . . . . . . . . . . . . . . . . 429.5.2 Evidence for lipid-lowering therapy. . . . . . . . . . . . 429.5.2.1 Low-density lipoprotein cholesterol . . . . . . . . 429.5.2.2 Triglycerides and high-density lipoproteincholesterol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 429.5.3 Treatment strategies for subjects with type 2 diabetesand metabolic syndrome . . . . . . . . . . . . . . . . . . . . . . 439.5.4 Type 1 diabetes . . . . . . . . . . . . . . . . . . . . . . . . 439.6 Patients with acute coronary syndrome and patientsundergoing percutaneous coronary intervention . . . . . . . . . 439.6.1 Specific lipid management issues in acute coronarysyndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 439.6.2 Lipid management issues in patients undergoingpercutaneous coronary intervention . . . . . . . . . . . . . . . 449.7 Heart failure and valvular diseases . . . . . . . . . . . . . . . 449.7.1 Prevention of incident heart failure in coronary arterydisease patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . 449.7.2 Chronic heart failure . . . . . . . . . . . . . . . . . . . . . 449.7.3 Valvular disease . . . . . . . . . . . . . . . . . . . . . . . . 459.8 Autoimmune diseases . . . . . . . . . . . . . . . . . . . . . . . 459.9 Chronic kidney disease . . . . . . . . . . . . . . . . . . . . . . 459.9.1 Lipoprotein profile in chronic kidney disease . . . . . 459.9.2 Evidence for lipid management in patients withchronic kidney disease . . . . . . . . . . . . . . . . . . . . . . . . 469.9.3 Safety of lipid management in patients with chronickidney disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 469.9.4 Recommendations of lipid management for patientswith chronic kidney disease . . . . . . . . . . . . . . . . . . . . 469.10 Transplantation ( Table 31 ) . . . . . . . . . . . . . . . . . . . 469.11 Peripheral arterial disease . . . . . . . . . . . . . . . . . . . . 479.11.1 Lower extremities arterial disease . . . . . . . . . . . 479.11.2 Carotid artery disease . . . . . . . . . . . . . . . . . . . 479.11.3 Retinal vascular disease . . . . . . . . . . . . . . . . . . 489.11.4 Secondary prevention in patients with aorticabdominal aneurysm . . . . . . . . . . . . . . . . . . . . . . . . . 489.11.5 Renovascular atherosclerosis . . . . . . . . . . . . . . . 489.12 Stroke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 489.12.1 Primary prevention of stroke . . . . . . . . . . . . . . . 489.12.2 Secondary prevention of stroke . . . . . . . . . . . . . 499.13 Human immunodeficiency virus patients . . . . . . . . . . 499.14 Mental disorders. . . . . . . . . . . . . . . . . . . . . . . . . . 4910. Monitoring of lipids and enzymes in patients on lipid-lowering therapy ( Table 36 ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5111. Strategies to encourage adoption of healthy lifestyle changesand adherence to lipid-modifying therapies . . . . . . . . . . . . . . . 5111.1 Achieving and adhering to healthy lifestyle changes . . . 5111.2 Adhering to medications . . . . . . . . . . . . . . . . . . . . 5412. To do and not to do messages from the Guidelines . . . . . . 5713. Appendix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5814. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 List of abbreviations ABI ankle-brachial indexACC American College of CardiologyACCELERATE Assessment of Clinical Effects of Cholesteryl Es- ter Transfer Protein Inhibition with EvacetrapibinPatientsataHigh-RiskforVascularOutcomesACCORD Action to Control Cardiovascular Risk inDiabetesACS acute coronary syndromeAFCAPS/TEXCAPSAir Force/Texas Coronary Atherosclerosis Pre-vention StudyAHA American Heart AssociationAIM-HIGH Atherothrombosis Intervention in MetabolicSyndrome with Low HDL/High Triglycerides:Impact on Global Health OutcomesALT alanine aminotransferaseApo apolipoprotein ESC/EAS Guidelines  Page 3 of 72   b  y g u e  s  t   on N o v e m b  e r 2 1  ,2  0 1  6 h  t   t   p :  /   /   e  ur h  e  a r  t   j   . oxf   or  d  j   o ur n a l   s  . or  g /  D o wnl   o a  d  e  d f  r  om   ART antiretroviral treatmentASSIGN CV risk estimation model from the ScottishIntercollegiate Guidelines Network ASTRONOMER AorticStenosisProgressionObservation:Meas-uring Effects of RosuvastatinAURORA A study to evaluate the Use of Rosuvastatin insubjects On Regular haemodialysis: an Assess-ment of survival and cardiovascular eventsBIP Bezafibrate Infarction Prevention studyBMI body mass indexCABG coronary artery bypass graft surgeryCAC coronary artery calciumCAD coronary artery diseaseCARE Cholesterol and Recurrent EventsCETP cholesteryl ester transfer proteinCHD coronary heart diseaseCIMT carotid intima-media thicknessCK creatine kinaseCKD chronic kidney diseaseCTT Cholesterol Treatment TrialistsCV cardiovascular CVD cardiovascular diseaseCYP cytochrome P4504D Die Deutsche Diabetes DialyseDASH Dietary Approaches to Stop HypertensionDGAT-2 diacylglycerol acyltransferase-2DHA docosahexaenoic acidDLCN Dutch Lipid Clinic Network EAS European Atherosclerosis SocietyEMA European Medicines AgencyEPA eicosapentaenoic acidER extended releaseESC European Society of CardiologyESRD end-stage renal diseaseEU European UnionFACE-BD Fondamental Academic Centers of Expertise inBipolar DisordersFATS Familial Atherosclerosis Treatment StudyFCH familial combined hyperlipidaemiaFDA US Food and Drug AdministrationFDC fixed-dose combinationFH familial hypercholesterolaemiaFIELD Fenofibrate Intervention and Event Lowering inDiabetesFOCUS Fixed-Dose Combination Drug for SecondaryCardiovascular PreventionGFR glomerular filtration rateGISSI GruppoItalianoperlo Studiodella Sopravviven-za nell’Infarto MiocardicoGP general practitioner GWAS genome-wide association studiesHAART highly active antiretroviral treatmentHATS HDL-Atherosclerosis Treatment StudyHbA1C glycated haemoglobinHeFH heterozygous familial hypercholesterolaemiaHDL-C high-density lipoprotein cholesterolHF heart failureHHS Helsinki Heart StudyHIV human immunodeficiency virusHMG-CoA hydroxymethylglutaryl-coenzyme AHPS Heart Protection StudyHPS2-THRIVE Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular EventsHoFH homozygous familial hypercholesterolaemiaHTG hypertriglyceridaemiaHR hazard ratiohs-CRP high-sensitivity C-reactive proteinICD International Classification of DiseasesIDEAL Incremental Decrease In End-points ThroughAggressive Lipid-lowering TrialIDL intermediate-density lipoproteinsILLUMINATE Investigation of Lipid Level Management toUnderstand its Impact in Atherosclerotic EventsIMPROVE-IT Improved Reduction of Outcomes: Vytorin Effi-cacy International Trial JUPITER Justification for the Use of Statins in Prevention:an Intervention Trial Evaluating RosuvastatinKDIGO Kidney Disease: Improving Global OutcomesLAL lysosomal acid lipaseLCAT lecithin cholesterol acyltransferaseLDL-C low-density lipoprotein cholesterolLDLR low-density lipoprotein receptor LEAD lower extremities arterial diseaseLIPID Long-Term Intervention with Pravastatin in Is-chemic DiseaseLPL lipoprotein lipaseLp lipoproteinMetS metabolic syndromeMI myocardial infarctionMTP microsomal triglyceride transfer proteinMUFA monounsaturated fatty acidNICE National Institute for Health and CareExcellenceNNRTI non-nucleoside reverse transcriptase inhibitor NNT number needed to treatNPC1L1 Niemann-Pick C1-like protein 1NSTE-ACS non-ST elevation acute coronary syndromeNYHA New York Heart AssociationPAD peripheral arterial diseasePCI percutaneous coronary interventionPCSK9 proprotein convertase subtilisin/kexin type 9PPAR- a  peroxisome proliferator-activated receptor- a PROCAM Prospective Cardiovascular Munster StudyPROSPER Prospective Studyof Pravastatin in the ElderlyatRisk PUFA polyunsaturated fatty acidRAAS renin–angiotensin–aldosterone systemRCT randomized controlled trialREACH Reduction of Atherothrombosis for ContinuedHealthREDUCE-IT Reduction of Cardiovascular Events withEPA-Intervention Trial ESC/EAS Guidelines Page 4 of 72   b  y g u e  s  t   on N o v e m b  e r 2 1  ,2  0 1  6 h  t   t   p :  /   /   e  ur h  e  a r  t   j   . oxf   or  d  j   o ur n a l   s  . or  g /  D o wnl   o a  d  e  d f  r  om 
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