Skip to main content
SpringerLink
Log in
Book cover

Cardiovascular Risk Assessment in Primary Prevention pp 377–390Cite as

Apolipoprotein B in Primary Prevention: Ready for Time Prime?

  • Chapter
  • First Online:

  • 813 Accesses

Part of the book series: Contemporary Cardiology ((CONCARD))

Abstract

The causal role of atherogenic lipoprotein cholesterol deposition in the initiation of atherosclerosis is well established. Cholesterol-based markers, in particular low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C), are routinely targeted in clinical practice for cardiovascular disease prevention. Given the significant variability in cholesterol content within apolipoprotein B (apoB)-containing lipoproteins, it has been postulated that levels of apoB particles are a complementary measure of risk and target of treatment. Individual-level analyses have shown that discordance between apoB and LDL-C or non-HDL-C is not uncommon, particularly in the presence of hypertriglyceridemia; in this setting, discordantly high apoB is associated with increased risk of future events. In this book chapter, we review the metabolism of apoB-containing lipoproteins, supporting evidence for their role in cardiovascular risk prediction, and the current guidelines recommendations for use and implementation of apoB in clinical care.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Avogaro P, Bon GB, Cazzolato G, Quinci GB. Are apolipoproteins better discriminators than lipids for atherosclerosis? Lancet. 1979;1(8122):901–3.

    Article  CAS  PubMed  Google Scholar 

  • Barter PJ, Ballantyne CM, Carmena R, Castro Cabezas M, Chapman MJ, Couture P, et al. Apo B versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirty-person/ten-country panel. J Intern Med. 2006;259(3):247–58.

    Article  CAS  PubMed  Google Scholar 

  • Benn M, Nordestgaard BG, Jensen GB, Tybjaerg-Hansen A. Improving prediction of ischemic cardiovascular disease in the general population using apolipoprotein B: the Copenhagen City Heart Study. Arterioscler Thromb Vasc Biol. 2007;27(3):661–70.

    Article  CAS  PubMed  Google Scholar 

  • Berneis KK, Krauss RM. Metabolic origins and clinical significance of LDL heterogeneity. J Lipid Res. 2002;43(9):1363–79.

    Article  CAS  PubMed  Google Scholar 

  • Boekholdt SM, Arsenault BJ, Mora S, Pedersen TR, LaRosa JC, Nestel PJ, et al. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis. JAMA. 2012;307(12):1302–9.

    Article  CAS  PubMed  Google Scholar 

  • Brownstein AJ, Martin SS. More accurate LDL-C calculation: externally validated, guideline endorsed. Clin Chim Acta. 2020;506:149–53.

    Article  CAS  PubMed  Google Scholar 

  • Cao J, Steffen BT, Guan W, Remaley AT, McConnell JP, Palamalai V, et al. A comparison of three apolipoprotein B methods and their associations with incident coronary heart disease risk over a 12-year follow-up period: the Multi-Ethnic Study of Atherosclerosis. J Clin Lipidol. 2018;12(2):300–4.

    Article  PubMed  Google Scholar 

  • Collins R, Reith C, Emberson J, Armitage J, Baigent C, Blackwell L, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016;388(10059):2532–61.

    Article  CAS  PubMed  Google Scholar 

  • Contois JH, Delatour V. Apolipoprotein B measurement: need for standardization. J Clin Lipidol. 2018;12(2):264–5.

    Article  PubMed  Google Scholar 

  • de Graaf J, Couture P, Sniderman A. A diagnostic algorithm for the atherogenic apolipoprotein B dyslipoproteinemias. Nat Clin Pract Endocrinol Metab. 2008;4(11):608–18.

    Article  PubMed  CAS  Google Scholar 

  • Delatour V, Clouet-Foraison N, Gaie-Levrel F, Marcovina SM, Hoofnagle AN, Kuklenyik Z, et al. Comparability of lipoprotein particle number concentrations across ES-DMA, NMR, LC-MS/MS, immunonephelometry, and VAP: in search of a candidate reference measurement procedure for apoB and non-HDL-P standardization. Clin Chem. 2018;64(10):1485–95.

    Article  PubMed  Google Scholar 

  • Elovson J, Chatterton JE, Bell GT, Schumaker VN, Reuben MA, Puppione DL, et al. Plasma very low density lipoproteins contain a single molecule of apolipoprotein B. J Lipid Res. 1988;29(11):1461–73.

    Article  CAS  PubMed  Google Scholar 

  • Emerging Risk Factors C, Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009;302(18):1993–2000.

    Article  Google Scholar 

  • Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38(32):2459–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ference BA, Kastelein JJP, Ray KK, Ginsberg HN, Chapman MJ, Packard CJ, et al. Association of triglyceride-lowering LPL variants and LDL-C-lowering LDLR variants with risk of coronary heart disease. JAMA. 2019;321(4):364–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fredrickson DS, Levy RI, Lees RS. Fat transport in lipoproteins–an integrated approach to mechanisms and disorders. N Engl J Med. 1967;276(5):273–81. concl.

    Article  CAS  PubMed  Google Scholar 

  • Garvey WT, Kwon S, Zheng D, Shaughnessy S, Wallace P, Hutto A, et al. Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance. Diabetes. 2003;52(2):453–62.

    Article  CAS  PubMed  Google Scholar 

  • Griffin BA, Caslake MJ, Yip B, Tait GW, Packard CJ, Shepherd J. Rapid isolation of low density lipoprotein (LDL) subfractions from plasma by density gradient ultracentrifugation. Atherosclerosis. 1990;83(1):59–67.

    Article  CAS  PubMed  Google Scholar 

  • Grundy SM, Vega GL, Tomassini JE, Tershakovec AM. Correlation of non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol with apolipoprotein B during simvastatin + fenofibrate therapy in patients with combined hyperlipidemia (a subanalysis of the SAFARI trial). Am J Cardiol. 2009;104(4):548–53.

    Article  CAS  PubMed  Google Scholar 

  • Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Circulation. 2019;139(25):e1082–e143.

    PubMed  Google Scholar 

  • International Federation for Clinical Chemistry (IFCC). IFCC working group on apolipoprotein standardization by mass spectrometry (WG-APO MS). 2017. http://www.ifcc.org/ifcc-scientific-division/sd-working-groups/wg-apo-ms/.

  • Jacobson TA, Ito MK, Maki KC, Orringer CE, Bays HE, Jones PH, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1 - executive summary. J Clin Lipidol. 2014;8(5):473–88.

    Article  PubMed  Google Scholar 

  • Jellinger PS, Handelsman Y, Rosenblit PD, Bloomgarden ZT, Fonseca VA, Garber AJ, et al. American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr Pract. 2017;23(Suppl 2):1–87.

    Article  PubMed  Google Scholar 

  • Kohli-Lynch CN, Thanassoulis G, Moran AE, Sniderman AD. The clinical utility of apoB versus LDL-C/non-HDL-C. Clin Chim Acta. 2020;508:103–8.

    Article  CAS  PubMed  Google Scholar 

  • Lamarche B, Moorjani S, Lupien PJ, Cantin B, Bernard PM, Dagenais GR, et al. Apolipoprotein A-I and B levels and the risk of ischemic heart disease during a five-year follow-up of men in the Quebec cardiovascular study. Circulation. 1996;94(3):273–8.

    Article  CAS  PubMed  Google Scholar 

  • Langlois MR, Sniderman AD. Non-HDL cholesterol or apoB: which to prefer as a target for the prevention of atherosclerotic cardiovascular disease? Curr Cardiol Rep. 2020;22(8):67.

    Article  PubMed  Google Scholar 

  • Langlois MR, Chapman MJ, Cobbaert C, Mora S, Remaley AT, Ros E, et al. 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. Clin Chem. 2018;64(7):1006–33.

    Article  CAS  PubMed  Google Scholar 

  • Langlois MR, Nordestgaard BG, Langsted A, Chapman MJ, Aakre KM, Baum H, et al. Quantifying atherogenic lipoproteins for lipid-lowering strategies: consensus-based recommendations from EAS and EFLM. Clin Chem Lab Med. 2020;58(4):496–517.

    Article  CAS  PubMed  Google Scholar 

  • Lawler PR, Akinkuolie AO, Ridker PM, Sniderman AD, Buring JE, Glynn RJ, et al. Discordance between circulating atherogenic cholesterol mass and lipoprotein particle concentration in relation to future coronary events in women. Clin Chem. 2017a;63(4):870–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lawler PR, Akinkuolie AO, Chu AY, Shah SH, Kraus WE, Craig D, et al. Atherogenic lipoprotein determinants of cardiovascular disease and residual risk among individuals with low low-density lipoprotein cholesterol. J Am Heart Assoc. 2017b;6(7):e005549.

    Article  PubMed  PubMed Central  Google Scholar 

  • Linsel-Nitschke P, Gotz A, Erdmann J, Braenne I, Braund P, Hengstenberg C, et al. Lifelong reduction of LDL-cholesterol related to a common variant in the LDL-receptor gene decreases the risk of coronary artery disease – a Mendelian Randomisation study. PLoS One. 2008;3(8):e2986.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–88.

    Article  PubMed  Google Scholar 

  • Mora S, Otvos JD, Rifai N, Rosenson RS, Buring JE, Ridker PM. Lipoprotein particle profiles by nuclear magnetic resonance compared with standard lipids and apolipoproteins in predicting incident cardiovascular disease in women. Circulation. 2009;119(7):931–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mora S, Buring JE, Ridker PM. Discordance of low-density lipoprotein (LDL) cholesterol with alternative LDL-related measures and future coronary events. Circulation. 2014;129(5):553–61.

    Article  CAS  PubMed  Google Scholar 

  • Mora S, Caulfield MP, Wohlgemuth J, Chen Z, Superko HR, Rowland CM, et al. Atherogenic lipoprotein subfractions determined by ion mobility and first cardiovascular events after random allocation to high-intensity statin or placebo: the justification for the use of statins in prevention: an intervention trial evaluating rosuvastatin (JUPITER) trial. Circulation. 2015;132(23):2220–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nordestgaard BG. A test in context: lipid profile, fasting versus nonfasting. J Am Coll Cardiol. 2017;70(13):1637–46.

    Article  PubMed  Google Scholar 

  • Otvos JD, Mora S, Shalaurova I, Greenland P, Mackey RH, Goff DC Jr. Clinical implications of discordance between low-density lipoprotein cholesterol and particle number. J Clin Lipidol. 2011;5(2):105–13.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pencina MJ, D’Agostino RB, Zdrojewski T, Williams K, Thanassoulis G, Furberg CD, et al. Apolipoprotein B improves risk assessment of future coronary heart disease in the Framingham Heart Study beyond LDL-C and non-HDL-C. Eur J Prev Cardiol. 2015;22(10):1321–7.

    Article  PubMed  Google Scholar 

  • Richardson TG, Sanderson E, Palmer TM, Ala-Korpela M, Ference BA, Davey Smith G, et al. Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: a multivariable Mendelian randomisation analysis. PLoS Med. 2020;17(3):e1003062.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ridker PM, Mora S, Rose L, Group JTS. Percent reduction in LDL cholesterol following high-intensity statin therapy: potential implications for guidelines and for the prescription of emerging lipid-lowering agents. Eur Heart J. 2016;37(17):1373–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Robinson JG, Wang S, Jacobson TA. Meta-analysis of comparison of effectiveness of lowering apolipoprotein B versus low-density lipoprotein cholesterol and nonhigh-density lipoprotein cholesterol for cardiovascular risk reduction in randomized trials. Am J Cardiol. 2012;110(10):1468–76.

    Article  CAS  PubMed  Google Scholar 

  • Rosenson RS, Jacobson TA, Preiss D, Djedjos CS, Dent R, Bridges I, et al. Efficacy and safety of the PCSK9 inhibitor evolocumab in patients with mixed hyperlipidemia. Cardiovasc Drugs Ther. 2016;30(3):305–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sathiyakumar V, Park J, Quispe R, Elshazly MB, Michos ED, Banach M, et al. Impact of novel low-density lipoprotein-cholesterol assessment on the utility of secondary non-high-density lipoprotein-C and apolipoprotein B targets in selected worldwide dyslipidemia guidelines. Circulation. 2018;138(3):244–54.

    Article  CAS  PubMed  Google Scholar 

  • Sniderman AD. Differential response of cholesterol and particle measures of atherogenic lipoproteins to LDL-lowering therapy: implications for clinical practice. J Clin Lipidol. 2008;2(1):36–42.

    Article  PubMed  Google Scholar 

  • Sniderman AD, Robinson JG. ApoB in clinical care: pro and con. Atherosclerosis. 2019;282:169–75.

    Article  CAS  PubMed  Google Scholar 

  • Sniderman A, Shapiro S, Marpole D, Skinner B, Teng B, Kwiterovich PO Jr. Association of coronary atherosclerosis with hyperapobetalipoproteinemia [increased protein but normal cholesterol levels in human plasma low density (beta) lipoproteins]. Proc Natl Acad Sci U S A. 1980;77(1):604–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sniderman A, Tremblay A, Bergeron J, Gagne C, Couture P. Diagnosis of type III hyperlipoproteinemia from plasma total cholesterol, triglyceride, and apolipoprotein B. J Clin Lipidol. 2007;1(4):256–63.

    Article  PubMed  Google Scholar 

  • Sniderman AD, Williams K, Contois JH, Monroe HM, McQueen MJ, de Graaf J, et al. A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes. 2011;4(3):337–45.

    Article  PubMed  Google Scholar 

  • Sniderman AD, Couture P, Martin SS, DeGraaf J, Lawler PR, Cromwell WC, et al. Hypertriglyceridemia and cardiovascular risk: a cautionary note about metabolic confounding. J Lipid Res. 2018;59(7):1266–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sniderman AD, Thanassoulis G, Glavinovic T, Navar AM, Pencina M, Catapano A, et al. Apolipoprotein B particles and cardiovascular disease: a narrative review. JAMA Cardiol. 2019;4(12):1287–95.

    Article  PubMed  PubMed Central  Google Scholar 

  • Thanassoulis G, O’Donnell CJ. Mendelian randomization: nature’s randomized trial in the post-genome era. JAMA. 2009;301(22):2386–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thanassoulis G, Williams K, Ye K, Brook R, Couture P, Lawler PR, et al. Relations of change in plasma levels of LDL-C, non-HDL-C and apoB with risk reduction from statin therapy: a meta-analysis of randomized trials. J Am Heart Assoc. 2014;3(2):e000759.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Varghese B, Park J, Chew E, Sajja A, Brownstein A, Pallazola VA, et al. Importance of the triglyceride level in identifying patients with a Type III Hyperlipoproteinemia phenotype using the ApoB algorithm. J Clin Lipidol. 2021;15(1):104–115.e9.

    Article  PubMed  Google Scholar 

  • Walldius G, Jungner I, Holme I, Aastveit AH, Kolar W, Steiner E. High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet. 2001;358(9298):2026–33.

    Article  CAS  PubMed  Google Scholar 

  • Welsh C, Celis-Morales CA, Brown R, Mackay DF, Lewsey J, Mark PB, et al. Comparison of conventional lipoprotein tests and apolipoproteins in the prediction of cardiovascular disease. Circulation. 2019;140(7):542–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Whelton SP, Meeusen JW, Donato LJ, Jaffe AS, Saenger A, Sokoll LJ, et al. Evaluating the atherogenic burden of individuals with a Friedewald-estimated low-density lipoprotein cholesterol <70 mg/dL compared with a novel low-density lipoprotein estimation method. J Clin Lipidol. 2017;11(4):1065–72.

    Article  PubMed  Google Scholar 

  • Wilkins JT, Li RC, Sniderman A, Chan C, Lloyd-Jones DM. Discordance between apolipoprotein B and LDL-cholesterol in young adults predicts coronary artery calcification: the CARDIA study. J Am Coll Cardiol. 2016;67(2):193–201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zuber V, Gill D, Ala-Korpela M, Langenberg C, Butterworth A, Bottolo L, et al. High-throughput multivariable Mendelian randomization analysis prioritizes apolipoprotein B as key lipid risk factor for coronary artery disease. Int J Epidemiol. 2021;50(3):893–901.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Baltimore, MD, USA

    Renato Quispe & Bibin Varghese

  2. Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Seth S. Martin

  3. Welch Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Seth S. Martin

Authors
  1. Renato Quispe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bibin Varghese
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seth S. Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Seth S. Martin .

Editor information

Editors and Affiliations

  1. Section on Cardiovascular Disease, Wake Forest University School of Medicine, Winston Salem, NC, USA

    Michael D. Shapiro

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Quispe, R., Varghese, B., Martin, S.S. (2022). Apolipoprotein B in Primary Prevention: Ready for Time Prime?. In: Shapiro, M.D. (eds) Cardiovascular Risk Assessment in Primary Prevention. Contemporary Cardiology. Humana, Cham. https://doi.org/10.1007/978-3-030-98824-1_18

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-98824-1_18

  • Published:

  • Publisher Name: Humana, Cham

  • Print ISBN: 978-3-030-98823-4

  • Online ISBN: 978-3-030-98824-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation