Utility of Advanced Lipoprotein Testing in Clinical Practice

Kenneth R. Feingold

Utility of Advanced Lipoprotein Testing in Clinical Practice

Review

In: Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000.

2026 Apr 27.

Author

Kenneth R. Feingold¹

Book Editors

Kenneth R Feingold¹, Robert A. Adler², S. Faisal Ahmed³, Bradley Anawalt⁴, Marc R Blackman⁵, George Chrousos⁶, Emiliano Corpas⁷, Wouter W de Herder⁸, Ketan Dhatariya⁹, Kathleen Dungan¹⁰, Emma Hamilton¹¹, Johannes Hofland¹², Suzanne Jan de Beur¹³, Sanjay Kalra¹⁴, Gregory Kaltsas¹⁵, Nitin Kapoor¹⁶, Matthew Kim¹⁷, Christian Koch¹⁸, Peter Kopp¹⁹, Márta Korbonits²⁰, Christopher S Kovacs²¹, Wendy Kuohung²², Blandine Laferrère²³, Miles Levy²⁴, Elizabeth A McGee²⁵, Robert McLachlan²⁶, Radhika Muzumdar²⁷, Jonathan Purnell²⁸, Rodolfo Rey²⁹, Rakesh Sahay³⁰, Amy S Shah³¹, Mark A Sperling³², Constantine A Stratakis³³, Dace L Trence³⁴, Don P Wilson³⁵

Affiliation

¹ Emeritus Professor of Medicine, University of California- San Francisco

Book Affiliations

¹ Professor of Medicine Emeritus, University of California, San Francisco, CA
² Chief of Endocrinology and Metabolism at the Richmond Veterans Affairs Medical Center and Professor of Internal Medicine at Virginia Commonwealth University.
³ Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK
⁴ Chief of Medicine at the University of Washington Medical Center and Professor and Vice Chair of the Department of Medicine, University of Washington
⁵ Sr. Physician Scientist, Washington DC VA Medical Center; Professor of Medicine & Rehabilitation Medicine, Georgetown University; Clinical Professor of Medicine, Biochemistry and Molecular Medicine, George Washington University; and Professor of Medicine (Part-time), Johns Hopkins University
⁶ Professor of Pediatrics and Endocrinology, Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, "Aghia Sophia" Children's Hospital, Athens, Greece
⁷ M.D. Ph.D in Gerontology. Honorary Professor of Medicine, Universidad de Alcalá, Madrid. Consultant in Endocrinology, Hospital HLA Guadalajara (Spain).
⁸ Professor of Endocrine Oncology, Erasmus MC and Erasmus MC Cancer Center, Rotterdam, the Netherlands
⁹ Consultant in Diabetes, Endocrinology and General Medicine, Norfolk and Norwich University Hospitals NHS Foundation Trust and University of East Anglia, Norwich, UK.
¹⁰ Professor of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Ohio State University
¹¹ Consultant Endocrinologist at Fiona Stanley (FSH) and Fremantle Hospitals (FH) in Perth, Western Australia
¹² Consultant Endocrinologist, Erasmus MC and Erasmus MC Cancer Center, Rotterdam, the Netherlands
¹³ Professor of Endocrinology and Chief of the Division of Endocrinology and Metabolism at the University of Virginia School of Medicine.
¹⁴ Consultant Endocrinologist, Department of Endocrinology, Bharti Hospital, Karnal, India
¹⁵ Professor of General Medicine-Endocrinology, 1st Department of Propaedeutic Medicine, National and Kapodistrian University of Athens, Athens, Greece
¹⁶ Professor of Endocrinology, Department of Endocrinology, Diabetes and Metabolism, Christian Medical College & Hospital, Vellore, Tamil Nadu, India, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Science, The University of Melbourne, Australia.
¹⁷ Clinical Director of the Division of Endocrinology, Diabetes and Hypertension at Brigham and Women’s Hospital and an Assistant Professor of Medicine at Harvard Medical School. 18. Professor, Division of Endocrinology, Diabetes, Metabolism, Department of Medicine, The University of Tennessee Health Science Center, Memphis, TN, and University of Florida, Jacksonville, FL.
¹⁸ Professor, The University of Tennessee Health Science Center, Memphis, Tennessee
¹⁹ Professor of Medicine and Chief of the Division of Endocrinology, Diabetology and Metabolism, University of Lausanne, Switzerland
²⁰ Professor of Endocrinology and Metabolism, Centre Lead for Endocrinology and Deputy Institute Director, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, England
²¹ University Research Professor and Professor of Medicine (Endocrinology and Metabolism), Obstetrics & Gynecology, and BioMedical Sciences, at Memorial University of Newfoundland in St. John’s, Newfoundland, Canada.
²² Director of the Division of Reproductive Endocrinology at Boston Medical Center and an Associate Professor of Obstetrics and Gynecology at the Boston University School of Medicine
²³ Professor of Medicine, New York Nutrition Obesity Research Center, Division of Endocrinology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
²⁴ Consultant endocrinologist at University Hospitals of Leicester and Honorary Associate Professor at Leicester University
²⁵ Professor of Obstetrics and Gynecology at the University of Vermont and Director of the Division of Reproductive Endocrinology and Infertility. Burlington, Vermont
²⁶ Director of Clinical Research, Hudson Institute of Medical Research; Consultant Endocrinologist, Monash Medical Centre, Melbourne, Australia
²⁷ Allan L. Drash Endowed Chair, Chief, Division of Endocrinology and Diabetes, UPMC Children’s Hospital of Pittsburgh, Professor of Pediatrics and Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA
²⁸ Professor of Medicine, Knight Cardiovascular Institute and the Division of Endocrinology, and Associate Director, Bob and Charlee Moore Institute for Nutrition and Wellness, Oregon Health and Science University, Portland, OR
²⁹ Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET-FEI-División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Gallo 1330, C1425EFD Buenos Aires; and Departamento de Histología, Biología Celular, Embriología y Genética, Facultad de Medicina, Universidad de Buenos Aires, C1121ABG Buenos Aires, Argentina
³⁰ Professor and Head of Department of Endocrinology, Osmania Medical College and Osmania General Hospital, Hyderabad, India.
³¹ Professor of Pediatrics, The University of Cincinnati, Department of Pediatrics and Cincinnati Children’s Hospital Medical Center, Division of Endocrinology, Cincinnati, OH, USA
³² Professorial Lecturer, Division of Pediatric Endocrinology and Diabetes, Icahn School of Medicine at Mount Sinai, New York, NY. Emeritus Professor and Chair, Department of Pediatrics, University of Pittsburgh.
³³ CSO, ELPEN, Inc. & Director, Research Institute, Athens, Greece & Senior Investigator, Human Genetics & Precision Medicine, FORTH (ITE), Heraklion, Greece. Emeritus Scientific Director & Senior Investigator, NICHD, NIH, Bethesda, MD, USA
³⁴ Professor of Medicine, Emeritus, University of Washington, Seattle, WA
³⁵ Endowed Chair, Cardiovascular Health and Risk Prevention, Pediatric Endocrinology and Diabetes, Cook Children's Medical Center, Fort Worth, TX

PMID: 27099901
Bookshelf ID: NBK355893

Excerpt

A standard lipid panel includes total cholesterol, TGs, and HDL-C. LDL-C can then be calculated. While the Friedewald equation is the classical method to calculate LDL-C levels recently developed methods such as Martin Hopkins or Sampson-NIH methods are more accurate when TGs are elevated and/or LCL-C levels are low. Non-HDL-C and “remnant cholesterol” levels can be calculated (non-HDL-C = total cholesterol – HDL-C) (“remnant cholesterol” = total cholesterol – LDL-C -HDL-C). Increasing levels of LDL-C and non-HDL-C are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). However, numerous studies have demonstrated that the association of non-HDL-C with ASCVD is more robust. Approximately 20% of individuals have Lp(a) levels greater than 50mg/dL (125nmol/L) and 30% have Lp(a) levels greater than 30mg/dL (75nmol/L) and elevations in Lp(a) are associated with an increased risk of ASCVD. Both the 2026 ACC/AHA and ESC/EAS guidelines recommend measuring Lp(a) levels once in all patients. If possible, Lp(a) levels should be measured by an isoform-independent method that equally identifies each Lp(a) particle and reports results as concentration in nmol/L. All of the pro-atherogenic lipoproteins (chylomicron remnants, VLDL remnants, IDL, LDL, and Lp(a)) carry one Apo B on their surface such that Apo B levels reflect the total number of atherogenic particles. Most of the circulating Apo B is associated with LDL particles but in individuals with high TG levels, TG rich lipoproteins can make a substantial contribution to Apo B levels. The levels of Apo B, LDL-C, and non-HDL-C are strongly correlated. Almost all studies have shown that Apo B levels are more closely associated with ASCVD than LDL-C levels and the general consensus is that Apo B levels are a more accurate predictor of ASCVD events than LDL-C. Apo B levels are equivalent to non-HDL-C levels in predicting ASCVD but when these measurements are discordant Apo B levels are a more accurate predictor of ASCVD. Many of the patients with elevated Apo B levels relative to non-HDL-C levels are obese, diabetic, have the metabolic syndrome and high TG and low HDL-C levels. The 2026 ACC/AHA guidelines state that “ApoB testing can be useful to improve risk assessment and guide therapy once LDL-C and non–HDL-C goals are met, particularly in those with elevated triglycerides (TG) (>200 mg/dL), diabetes, or low achieved LDL-C (<70 mg/dL)”. The ESC/EAS guidelines states “Apo B analysis is recommended for risk assessment, particularly in people with high TG levels, diabetes, obesity, metabolic syndrome, or very low LDL-C levels and may be preferred over non-HDL-C in people with high TG levels, DM, obesity, or very low LDL-C levels”. It is possible for the clinician to measure a number of other parameters including LDL and HDL size and LDL and HDL particle number. Lipoprotein analysis by Nuclear Magnetic Resonance Spectroscopy (NMR) is offered by LabCorp and Ion-Mobility Analysis is offered by Quest Diagnostics. It should be recognized that the standardization of these assays is not as rigorous as the standardization of routine lipid panel assays. The Centers for Disease Control and Prevention (CDC) maintains a Lipid Standardization Program (LSP) that provides standards for measuring total cholesterol, TGs, HDL-C, Apo A-I, and Apo B. Measurements of LDL and HDL size and particle number are not as standardized, and studies have shown differences in results between different methods. Routine use of advanced lipoprotein testing, such as gradient gel electrophoresis, density gradient ultracentrifugation, NMR spectroscopy, and ion mobility analysis, is not recommended by the 2026 ACC/AHA guidelines. Advanced lipoprotein testing should be limited to scenarios where the availability of such information is likely to change the treatment plan. As additional drugs to treat lipids are developed and our understanding of lipid and lipoprotein metabolism expands in the future the use of advanced lipoprotein analysis may assume a more important role. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

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