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Research ArticleSpecial Report

Quantifying Atherogenic Lipoproteins: Current and Future Challenges in the Era of Personalized Medicine and Very Low Concentrations of LDL Cholesterol. A Consensus Statement from EAS and EFLM

Michel R. Langlois, M. John Chapman, Christa Cobbaert, Samia Mora, Alan T. Remaley, Emilio Ros, Gerald F. Watts, Jan Borén, Hannsjörg Baum, Eric Bruckert, Alberico Catapano, Olivier S. Descamps, Arnold von Eckardstein, Pia R. Kamstrup, Genovefa Kolovou, Florian Kronenberg, Anne Langsted, Kari Pulkki, Nader Rifai, Grazyna Sypniewska, Olov Wiklund, B∅rge G. Nordestgaard, for the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Joint Consensus Initiative
DOI: 10.1373/clinchem.2018.287037 Published May 2018
Michel R. Langlois
Department of Laboratory Medicine, AZ St-Jan, Brugge, and University of Ghent, Belgium;
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  • For correspondence: michel.langlois@azsintjan.be
M. John Chapman
National Institute for Health and Medical Research (INSERM), and Endocrinology-Metabolism Service, Pitié-Salpetriere University Hospital, Paris, France;
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Christa Cobbaert
Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands;
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Samia Mora
Divisions of Preventive and Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA;
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Alan T. Remaley
Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
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Emilio Ros
Lipid Clinic, Department of Endocrinology and Nutrition, Institut d'Investigacions Biomèdiques August Pi Sunyer, Hospital Clínic, Barcelona and Ciber Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Spain;
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Gerald F. Watts
Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, University of Western Australia, Perth, Australia;
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Jan Borén
Sahlgrenska University Hospital, Gothenburg, Sweden;
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Hannsjörg Baum
Institute for Laboratory Medicine, Blutdepot und Krankenhaushygiene, Regionale Kliniken Holding RKH GmbH, Ludwigsburg, Germany;
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Eric Bruckert
Pitié-Salpetriere University Hospital, Paris, France;
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Alberico Catapano
Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy;
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Olivier S. Descamps
Hopital de Jolimont, Haine-Saint-Paul, Belgium;
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Arnold von Eckardstein
Institute for Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland;
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Pia R. Kamstrup
Herlev and Gentofte Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark;
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Genovefa Kolovou
Cardiology Department, Onassis Cardiac Surgery Center, Athens, Greece;
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Florian Kronenberg
Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria;
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Anne Langsted
Herlev and Gentofte Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark;
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Kari Pulkki
Department of Clinical Chemistry, University of Turku and Turku University Hospital, Turku, Finland;
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Nader Rifai
Boston Children's Hospital, Harvard Medical School, Boston, MA;
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Grazyna Sypniewska
Department of Laboratory Medicine, Collegium Medicum, NC University, Bydgoszcz, Poland.
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Olov Wiklund
Sahlgrenska University Hospital, Gothenburg, Sweden;
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B∅rge G. Nordestgaard
Herlev and Gentofte Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark;
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Abstract

Background: The European Atherosclerosis Society–European Federation of Clinical Chemistry and Laboratory Medicine Consensus Panel aims to provide recommendations to optimize atherogenic lipoprotein quantification for cardiovascular risk management.

Content: We critically examined LDL cholesterol, non-HDL cholesterol, apolipoprotein B (apoB), and LDL particle number assays based on key criteria for medical application of biomarkers. (a) Analytical performance: Discordant LDL cholesterol quantification occurs when LDL cholesterol is measured or calculated with different assays, especially in patients with hypertriglyceridemia >175 mg/dL (2 mmol/L) and low LDL cholesterol concentrations <70 mg/dL (1.8 mmol/L). Increased lipoprotein(a) should be excluded in patients not achieving LDL cholesterol goals with treatment. Non-HDL cholesterol includes the atherogenic risk component of remnant cholesterol and can be calculated in a standard nonfasting lipid panel without additional expense. ApoB more accurately reflects LDL particle number. (b) Clinical performance: LDL cholesterol, non-HDL cholesterol, and apoB are comparable predictors of cardiovascular events in prospective population studies and clinical trials; however, discordance analysis of the markers improves risk prediction by adding remnant cholesterol (included in non-HDL cholesterol) and LDL particle number (with apoB) risk components to LDL cholesterol testing. (c) Clinical and cost-effectiveness: There is no consistent evidence yet that non-HDL cholesterol-, apoB-, or LDL particle-targeted treatment reduces the number of cardiovascular events and healthcare-related costs than treatment targeted to LDL cholesterol.

Summary: Follow-up of pre- and on-treatment (measured or calculated) LDL cholesterol concentration in a patient should ideally be performed with the same documented test method. Non-HDL cholesterol (or apoB) should be the secondary treatment target in patients with mild to moderate hypertriglyceridemia, in whom LDL cholesterol measurement or calculation is less accurate and often less predictive of cardiovascular risk. Laboratories should report non-HDL cholesterol in all standard lipid panels.

  • Received for publication January 22, 2018.
  • Accepted for publication April 9, 2018.
  • © 2018 American Association for Clinical Chemistry
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Clinical Chemistry: 65 (2)
Vol. 65, Issue 2
February 2019
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Quantifying Atherogenic Lipoproteins: Current and Future Challenges in the Era of Personalized Medicine and Very Low Concentrations of LDL Cholesterol. A Consensus Statement from EAS and EFLM
Michel R. Langlois, M. John Chapman, Christa Cobbaert, Samia Mora, Alan T. Remaley, Emilio Ros, Gerald F. Watts, Jan Borén, Hannsjörg Baum, Eric Bruckert, Alberico Catapano, Olivier S. Descamps, Arnold von Eckardstein, Pia R. Kamstrup, Genovefa Kolovou, Florian Kronenberg, Anne Langsted, Kari Pulkki, Nader Rifai, Grazyna Sypniewska, Olov Wiklund, B∅rge G. Nordestgaard, for the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Joint Consensus Initiative
Clinical Chemistry Jan 2018, clinchem.2018.287037; DOI: 10.1373/clinchem.2018.287037
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Quantifying Atherogenic Lipoproteins: Current and Future Challenges in the Era of Personalized Medicine and Very Low Concentrations of LDL Cholesterol. A Consensus Statement from EAS and EFLM
Michel R. Langlois, M. John Chapman, Christa Cobbaert, Samia Mora, Alan T. Remaley, Emilio Ros, Gerald F. Watts, Jan Borén, Hannsjörg Baum, Eric Bruckert, Alberico Catapano, Olivier S. Descamps, Arnold von Eckardstein, Pia R. Kamstrup, Genovefa Kolovou, Florian Kronenberg, Anne Langsted, Kari Pulkki, Nader Rifai, Grazyna Sypniewska, Olov Wiklund, B∅rge G. Nordestgaard, for the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Joint Consensus Initiative
Clinical Chemistry Jan 2018, clinchem.2018.287037; DOI: 10.1373/clinchem.2018.287037

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