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Time to Make a Change: Assessing LDL-C Accurately in the Era of Modern Pharmacotherapeutics and Precision Medicine

  • Vincent A. Pallazola
  • Renato Quispe
  • Mohamed B. Elshazly
  • Rachit Vakil
  • Vasanth Sathiyakumar
  • Steven R. Jones
  • Seth S. Martin
Lipids (E. Michos, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Lipids

Abstract

Purpose of Review

The Friedewald equation for estimation of low-density lipoprotein cholesterol (LDL-C) was published in 1972 as an alternative to direct assessment by preparative ultracentrifugation. In this equation, very low-density lipoprotein is estimated by dividing triglycerides by a fixed factor (5 in mg/dL or 2.2 in mmol/L) and subtracting this term from non-high-density lipoprotein cholesterol (non-HDL-C). This method was derived in fasting samples from a small cohort of patients with primarily genetic dyslipidemias followed at the NIH. The method served well as the global standard for LDL-C estimation for decades, but is not well suited to modern clinical practice because it tends to underestimate LDL-C at low LDL-C and high triglyceride levels. The concern is that underestimation could lead to undertreatment in high-risk patients.

Recent Findings

Derived from big data and now validated around the world, a novel LDL-C equation created at Johns Hopkins replaces the fixed factor seen in the classic equation with a patient-specific variable based on triglyceride and non-HDL-C levels.

Summary

Given its superior accuracy in fasting and non-fasting populations alike, the novel equation is now the preferred method for LDL-C estimation and is being incorporated by leading clinical laboratories.

Keywords

Cardiovascular prevention Dyslipidemia Lipid metabolism Friedewald equation Novel low-density lipoprotein equation Precision medicine 

Abbreviations

LDL-C

Low-density lipoprotein cholesterol

VLDL-C

Very low-density lipoprotein cholesterol

IDL-C

Intermediate-density lipoprotein cholesterol

HDL-C

High-density lipoprotein cholesterol

Non-HDL-C

Non-high-density lipoprotein cholesterol

PCSK9

Proprotein convertase subtilisin/kexin type 9

TG

Triglycerides

TC

Total cholesterol

NCEP

National Cholesterol Education Program

ASCVD

10-year atherosclerotic cardiovascular disease

ACC

American College of Cardiology

CTT

Cholesterol Treatment Trialists

IMPROVE-IT

Improved Reduction of Outcomes: Vytorin Efficacy International Trial

FOURIER

Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk

Notes

Compliance with Ethical Standards

Conflict of Interest

SSM and SRJ have patent applications pending on the novel equation for LDL-C estimation. In addition, SSM reports personal fees for serving on scientific advisory boards for Amgen, Sanofi/Regeneron, Quest Diagnostics, and Akcea Therapeutics, as well as grants/research support from the PJ Schafer Cardiovascular Research Fund, the David and June Trone Family Foundation, American Heart Association, Aetna Foundation, Maryland Innovation Initiative, Nokia, Google, Apple, and iHealth.

Authors VP, RQ, ME, RV, and VS have no conflicts of interest to disclose.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502.  https://doi.org/10.1016/0002-9149(88)90248-2.CrossRefGoogle Scholar
  2. 2.
    Martin SS, Blaha MJ, Elshazly MB, Brinton EA, Toth PP, McEvoy JW, et al. Friedewald-estimated versus directly measured low-density lipoprotein cholesterol and treatment implications. J Am Coll Cardiol. 2013;62(8):732–9.  https://doi.org/10.1016/j.jacc.2013.01.079.CrossRefPubMedGoogle Scholar
  3. 3.
    Berry PH, Macdonald JS, Alberts AW, et al. Brain and optic system pathology in hypocholesterolemic dogs treated with a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Am J Pathol. 1988;132(3):427–43.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Neaton JD, Blackburn H, Jacobs D, Kuller L, Lee DJ, Sherwin R, et al. Serum cholesterol level and mortality findings for men screened in the multiple risk factor intervention trial. Multiple Risk Factor Intervention Trial Research Group. Arch Intern Med. 1992;152(7):1490–500.  https://doi.org/10.1001/archinte.152.7.1490.CrossRefPubMedGoogle Scholar
  5. 5.
    Wiviott SD, Cannon CP, Morrow DA, Ray KK, Pfeffer MA, Braunwald E, et al. Can low-density lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy: a PROVE IT-TIMI 22 substudy. J Am Coll Cardiol. 2005;46(8):1411–6.  https://doi.org/10.1016/j.jacc.2005.04.064.CrossRefPubMedGoogle Scholar
  6. 6.
    Scharnagl H, Nauck M, Wieland H, Marz W. The Friedewald formula underestimates LDL cholesterol at low concentrations. Clin Chem Lab Med. 2001;39:426–31.  https://doi.org/10.1515/cclm.2001.068.CrossRefPubMedGoogle Scholar
  7. 7.
    Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017 May 4;376(18):1713–22.  https://doi.org/10.1056/nejmoa1615664.CrossRefGoogle Scholar
  8. 8.
    Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults. J Am Coll Cardiol. 2014;63(25):2889–934.  https://doi.org/10.1016/j.jacc.2013.11.002.CrossRefPubMedGoogle Scholar
  9. 9.
    Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1489–99.  https://doi.org/10.1056/nejmoa1501031.CrossRefPubMedGoogle Scholar
  10. 10.
    Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366(9493):1267–78.  https://doi.org/10.1016/s0140-6736(05)67394-1.CrossRefPubMedGoogle Scholar
  11. 11.
    Martin SS, Blumenthal RS, Miller M. LDL cholesterol: the lower the better. Med Clin North Am. 2012;96(1):13–26.  https://doi.org/10.1016/j.mcna.2012.01.009.CrossRefPubMedGoogle Scholar
  12. 12.
    Sabatine MS, Wiviott SD, Im K, Murphy SA, Giugliano RP. Efficacy and safety of further lowering of low-density lipoprotein cholesterol in patients starting with very low levels: a meta-analysis. JAMA Cardiol. 2018;  https://doi.org/10.1001/jamacardio.2018.2258.CrossRefGoogle Scholar
  13. 13.
    Zulewski H, Ninnis R, Miserez AR, Baumstark MW, Keller U. VLDL and IDL apolipoprotein B-100 kinetics in familial hypercholesterolemia due to impaired LDL receptor function or to defective apolipoprotein B-100. J Lipid Res. 1998;39(2):380–7.  https://doi.org/10.1016/0021-9150(95)96509-q.CrossRefPubMedGoogle Scholar
  14. 14.
    Brown WV, Levy RI, Fredrickson DS. Studies of the proteins in human plasma very low density lipoproteins. J Biol Chem. 1969;244(20):5687–94.PubMedGoogle Scholar
  15. 15.
    Gibbons GF, Islam K, Pease RJ. Mobilisation of triacylglycerol stores. Biochim Biophys Acta. 2000;1483(1):37–57.  https://doi.org/10.1016/s1388-1981(99)00182-1.CrossRefPubMedGoogle Scholar
  16. 16.
    Olefsky J, Reaven GM, Farquhar JW. Effects of weight reduction on obesity. Studies of lipid and carbohydrate metabolism in normal and hyperlipoproteinemic subjects. J Clin Invest. 1974;53(1):64–76.  https://doi.org/10.1172/jci107560.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Kissebah AH, Alfarsi S, Adams PW. Integrated regulation of very low density lipoprotein triglyceride and apolipoprotein-B kinetics in man: normolipemic subjects, familial hypertriglyceridemia and familial combined hyperlipidemia. Metab Clin Exp. 1981;30(9):856–68.  https://doi.org/10.1016/0026-0495(81)90064-0.CrossRefPubMedGoogle Scholar
  18. 18.
    Vergès BL. Dyslipidaemia in diabetes mellitus. Review of the main lipoprotein abnormalities and their consequences on the development of atherogenesis. Diabetes Metab. 1999;25(Suppl 3):32–40.PubMedGoogle Scholar
  19. 19.
    Quispe R, Hendrani A, Elshazly MB, Michos ED, McEvoy JW, Blaha MJ, et al. Accuracy of low-density lipoprotein cholesterol estimation at very low levels. BMC Med. 2017;15(1):83.  https://doi.org/10.1186/s12916-017-0852-2.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J. 2016;37:2999–3058.  https://doi.org/10.1093/eurheartj/ehw272.CrossRefPubMedGoogle Scholar
  21. 21.
    Anderson TJ, Gregoire J, Pearson GJ, et al. 2016 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2016;32:1263–82.  https://doi.org/10.1016/j.cjca.2016.07.510.CrossRefPubMedGoogle Scholar
  22. 22.
    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--full report. J Clin Lipidol. 2015;9:129–69.  https://doi.org/10.1016/j.jacl.2015.02.003.CrossRefPubMedGoogle Scholar
  23. 23.
    Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387–97.  https://doi.org/10.1056/NEJMoa1410489.CrossRefPubMedGoogle Scholar
  24. 24.
    Murphy SA, Cannon CP, Blazing MA, Giugliano RP, White JA, Lokhnygina Y, et al. Reduction in total cardiovascular events with ezetimibe/simvastatin post-acute coronary syndrome the IMPROVE-IT trial. J Am Coll Cardiol. 2016;67(4):353–61.  https://doi.org/10.1016/j.jacc.2015.10.077.CrossRefPubMedGoogle Scholar
  25. 25.
    Nordestgaard BG, Langsted A, Mora S, Kolovou G, Baum H, Bruckert E, et al. Fasting is not routinely required for determination of a lipid profile: clinical and laboratory implications including flagging at desirable concentration cut-points-a joint consensus statement from the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine. Eur Heart J. 2016;37(25):1944–58.  https://doi.org/10.1373/clinchem.2016.258897.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Langsted A, Freiberg JJ, Nordestgaard BG. Fasting and nonfasting lipid levels: influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction. Circulation. 2008;118:2047–56.  https://doi.org/10.1161/circulationaha.108.804146.CrossRefPubMedGoogle Scholar
  27. 27.
    Ruge T, Svensson M, Eriksson JW, Olivecrona G. Tissue-specific regulation of lipoprotein lipase in humans: effects of fasting. Eur J Clin Investig. 2005;35:194–200.  https://doi.org/10.1111/j.1365-2362.2005.01470.x.CrossRefGoogle Scholar
  28. 28.
    Ladu MJ, Kapsas H, Palmer WK. Regulation of lipoprotein lipase in adipose and muscle tissues during fasting. Am J Phys. 1991;260:R953–9.  https://doi.org/10.1152/ajpregu.1991.260.5.r953.CrossRefGoogle Scholar
  29. 29.
    Mora S. Nonfasting for routine lipid testing: from evidence to action. JAMA Intern Med. 2016;176(7):1005–6.  https://doi.org/10.1001/jamainternmed.2016.1979.CrossRefPubMedGoogle Scholar
  30. 30.
    Mora S, Rifai N, Buring JE, Ridker PM. Fasting compared with nonfasting lipids and apolipoproteins for predicting incident cardiovascular events. Circulation. 2008;118:993–1001.  https://doi.org/10.1161/circulationaha.108.777334.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Ridker PM, Rifai N, Cook NR, Bradwin G, Buring JE. Non-HDL cholesterol, apolipoproteins A-I and B100, standard lipid measures, lipid ratios, and CRP as risk factors for cardiovascular disease in women. JAMA. 2005;294:326–33.  https://doi.org/10.1001/jama.294.3.326.CrossRefPubMedGoogle Scholar
  32. 32.
    Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007;298:299–308.  https://doi.org/10.1001/jama.298.3.299.CrossRefPubMedGoogle Scholar
  33. 33.
    Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA. 2007;298:309–16.  https://doi.org/10.1001/jama.298.3.309.CrossRefPubMedGoogle Scholar
  34. 34.
    van Deventer HE, Miller WG, Myers GL, Sakurabayashi I, Bachmann LM, Caudill SP, et al. Non-HDL cholesterol shows improved accuracy for cardiovascular risk score classification compared to direct or calculated LDL cholesterol in a dyslipidemic population. Clin Chem. 2011;57:490–501.  https://doi.org/10.1373/clinchem.2010.154773.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Nordestgaard BG. A test in context: lipid profile, fasting versus nonfasting. J Am Coll Cardiol. 2017;70:1637–46.  https://doi.org/10.1016/j.jacc.2017.08.006.CrossRefPubMedGoogle Scholar
  36. 36.
    Driver SL, Martin SS, Gluckman TJ, Clary JM, Blumenthal RS, Stone NJ. Fasting or nonfasting lipid measurements: it depends on the question. J Am Coll Cardiol. 2016;67:1227–34.  https://doi.org/10.1016/j.jacc.2015.12.047.CrossRefPubMedGoogle Scholar
  37. 37.
    Sathiyakumar V, Park J, Golozar A, Lazo M, Quispe R, Guallar E, et al. Fasting versus nonfasting and low-density lipoprotein cholesterol accuracy. Circulation. 2018;137:10–9.  https://doi.org/10.1161/circulationaha.117.030677.CrossRefPubMedGoogle Scholar
  38. 38.
    Winocour PH, Ishola M, Durrington PN. Validation of the Friedewald formula for the measurement of low density lipoprotein cholesterol in insulin-dependent diabetes mellitus. Clin Chim Acta. 1989;179(1):79–83.  https://doi.org/10.1016/0009-8981(89)90025-9.CrossRefPubMedGoogle Scholar
  39. 39.
    Warnick GR, Knopp RH, Fitzpatrick V, Branson L. Estimating low-density lipoprotein cholesterol by the Friedewald equation is adequate for classifying patients on the basis of nationally recommended cutpoints. Clin Chem. 1990;36(1):15–9.PubMedGoogle Scholar
  40. 40.
    Tremblay AJ, Morrissette H, Gagné JM, Bergeron J, Gagné C, Couture P. Validation of the Friedewald formula for the determination of low-density lipoprotein cholesterol compared with beta-quantification in a large population. Clin Biochem. 2004;37(9):785–90.  https://doi.org/10.1016/j.clinbiochem.2004.03.008.CrossRefPubMedGoogle Scholar
  41. 41.
    Knopfholz J, Disserol CC, Pierin AJ, et al. Validation of the Friedewald formula in patients with metabolic syndrome. Cholesterol. 2014;2014:261878.  https://doi.org/10.1155/2014/261878.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    DeLong DM, DeLong ER, Wood PD, Lippel K, Rifkind BM. A comparison of methods for the estimation of plasma low- and very low-density lipoprotein cholesterol: the lipid research clinics prevalence study. JAMA. 1986;256(17):2372–7.  https://doi.org/10.1001/jama.1986.03380170088024.CrossRefPubMedGoogle Scholar
  43. 43.
    Rim JH, Lee YH, Lee MH, Kim HY, Choi J, Lee BW, et al. Comparison and validation of 10 equations including a novel method for estimation of LDL-cholesterol in a 168,212 Asian population. Medicine (Baltimore). 2016;95(14):e3230.  https://doi.org/10.1097/md.0000000000003230.CrossRefGoogle Scholar
  44. 44.
    Rao A, Parker AH, El-sheroni NA, Babelly MM. Calculation of low-density lipoprotein cholesterol with use of triglyceride/cholesterol ratios in lipoproteins compared with other calculation methods. Clin Chem. 1988;34(12):2532–4.PubMedGoogle Scholar
  45. 45.
    McNamara JR, Cohn JS, Wilson PWF, Schaefer E. Calculated values for low-density lipoprotein cholesterol in the assessment of lipid abnormalities and coronary disease risk. Clin Chem. 1990;36:36–42.PubMedGoogle Scholar
  46. 46.
    Hattori Y, Suzuki M, Tsushima M, Yoshida M, Tokunaga Y, Wang Y, et al. Development of approximate formula for LDL-chol, LDL-apo B and LDL-chol/LDL-apo B as indices of hyperapobetalipoproteinemia and small dense LDL. Atherosclerosis. 1998;138(2):289–99.  https://doi.org/10.1016/s0021-9150(98)00034-3.CrossRefPubMedGoogle Scholar
  47. 47.
    Martins J, Olorunju SA, Murray LM, Pillay TS. Comparison of equations for the calculation of LDL-cholesterol in hospitalized patients. Clin Chim Acta. 2015;444:137–42.  https://doi.org/10.1016/j.cca.2015.01.037.CrossRefPubMedGoogle Scholar
  48. 48.
    Anandaraja S, Narang R, Godeswar R, Laksmy R, Talwar KK. Low-density lipoprotein cholesterol estimation by a new formula in Indian population. Int J Cardiol. 2005;102(1):117–20.  https://doi.org/10.1016/j.ijcard.2004.05.009.CrossRefPubMedGoogle Scholar
  49. 49.
    Krishnaveni P, Gowda VM. Assessing the validity of Friedewald’s formula and Anandraja’s formula for serum LDL-cholesterol calculation. J Clin Diagn Res. 2015;9(12):BC01–4.  https://doi.org/10.7860/jcdr/2015/16850.6870.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Teerakanchana T, Puavilai W, Suriyaprom K, Tungtrongchitr R. Comparative study of LDL-cholesterol levels in Thai patients by the direct method and using the Friedewald formula. Southeast Asian J Trop Med Public Health. 2007;38(3):519–27.PubMedGoogle Scholar
  51. 51.
    Osegbe I, Ugonabo M, Chukwuka C, Meka I, Nwosu N. Comparison of calculated versus directly-measured low-density lipoprotein-cholesterol: an evaluation of ten formulas for an HIV-positive population in sub-Saharan Africa. J Lab Physicians. 2017;9(2):111–5.  https://doi.org/10.4103/0974-2727.199632.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Ahmadi SA, Boroumand MA, Gohari-moghaddam K, Tajik P, Dibaj SM. The impact of low serum triglyceride on LDL-cholesterol estimation. Arch Iran Med. 2008;11(3):318–21.PubMedGoogle Scholar
  53. 53.
    Chen Y, Zhang X, Pan B, Jin X, Yao H, Chen B, et al. A modified formula for calculating low-density lipoprotein cholesterol values. Lipids Health Dis. 2010;9:52.  https://doi.org/10.1186/1476-511x-9-52.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Vujovic A, Kotur-stevuljevic J, Spasic S, et al. Evaluation of different formulas for LDL-C calculation. Lipids Health Dis. 2010;9:27.CrossRefGoogle Scholar
  55. 55.
    Choi H, Shim JS, Lee MH, Yoon YM, Choi DP, Kim HC. Comparison of formulas for calculating low-density lipoprotein cholesterol in general population and high-risk patients with cardiovascular disease. Korean Circ J. 2016;46(5):688–98.  https://doi.org/10.4070/kcj.2016.46.5.688.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Wadhwa N, Krishnaswamy R. Comparison of LDL-cholesterol estimate using various formulae with directly measured LDL-cholesterol in Indian population. J Clin Diagn Res. 2016;10(12):BC11–3.  https://doi.org/10.7860/jcdr/2016/22272.9018.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    De cordova CM, De cordova MM. A new accurate, simple formula for LDL-cholesterol estimation based on directly measured blood lipids from a large cohort. Ann Clin Biochem. 2013;50(Pt 1):13–9.  https://doi.org/10.1258/acb.2012.011259.CrossRefPubMedGoogle Scholar
  58. 58.
    •• Martin SS, Blaha MJ, Elshazly MB, et al. Comparison of a novel method vs the Friedewald equation for estimating low-density lipoprotein cholesterol levels from the standard lipid profile. JAMA. 2013;310:2061–8.  https://doi.org/10.1001/jama.2013.280532. Initial study to propose the Martin LDL-C equation, which is currently being incorporated globally as the new standard of LDL-C estimation. CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Chaen H, Kinchiku S, Miyata M, Kajiya S, Uenomachi H, Yuasa T, et al. Validity of a novel method for estimation of low-density lipoprotein cholesterol levels in diabetic patients. J Atheroscler Thromb. 2016;23(12):1355–64.  https://doi.org/10.5551/jat.35972.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Lee J, Jang S, Son H. Validation of the Martin method for estimating low-density lipoprotein cholesterol levels in Korean adults: findings from the Korea National Health and Nutrition Examination Survey, 2009-2011. PLoS One. 2016;11(1):e0148147.  https://doi.org/10.1371/journal.pone.0148147.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Mehta R, Reyes-rodríguez E, Yaxmehen Bello-chavolla O, et al. Performance of LDL-C calculated with Martin's formula compared to the Friedewald equation in familial combined hyperlipidemia. Atherosclerosis. 2018;  https://doi.org/10.1016/j.atherosclerosis.2018.06.868.CrossRefGoogle Scholar
  62. 62.
    Kang M, Kim J, Lee SY, Kim K, Yoon J, Ki H. Martin’s equation as the most suitable method for estimation of low-density lipoprotein cholesterol levels in Korean adults. Korean J Fam Med. 2017;38(5):263–9.  https://doi.org/10.4082/kjfm.2017.38.5.263.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Bachorik P. Measurement of low-density-lipoprotein cholesterol. In: Rifai N, Warnick G, Dominiczak M, editors. Handbook of lipoprotein testing, 2nd ed. Washington D.C: AACC Press; 2000. p. 245.Google Scholar
  64. 64.
    Miller WG, Myers GL, Sakurabayashi I, Bachmann LM, Caudill SP, Dziekonski A, et al. Seven direct methods for measuring HDL and LDL cholesterol compared with ultracentrifugation reference measurement procedures. Clin Chem. 2010;56:977–86.  https://doi.org/10.1373/clinchem.2009.142810.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Whelton SP, Meeusen JW, Donatp 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.  https://doi.org/10.1016/j.jacl.2017.05.005.CrossRefPubMedGoogle Scholar
  66. 66.
    Martin S, Giugliano R, Murphy S, et al. Martin/Hopkins estimation, Friedewald and beta-quantification of LDL-C in patients in FOURIER. J Clin Lipidol. 2018;12(2):565–6.  https://doi.org/10.1016/j.jacl.2018.03.071.CrossRefGoogle Scholar
  67. 67.
    Sathiyakumar V, Park J, Quispe R, Elshazly MB, Michos ED, Banach M, et al. Impact of novel LDL-C assessment on the utility of secondary non-HDL-C and ApoB targets in selected worldwide dyslipidemia guidelines. Circulation. 2018;138:244–54.  https://doi.org/10.1161/circulationaha.117.032463.CrossRefPubMedGoogle Scholar
  68. 68.
    Meeusen JW, Lueke AJ, Jaffe AS, Saenger AK. Validation of a proposed novel equation for estimating LDL cholesterol. Clin Chem. 2014;60(12):1519–23.  https://doi.org/10.1373/clinchem.2014.227710.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Vincent A. Pallazola
    • 1
  • Renato Quispe
    • 1
  • Mohamed B. Elshazly
    • 2
  • Rachit Vakil
    • 1
  • Vasanth Sathiyakumar
    • 1
  • Steven R. Jones
    • 1
  • Seth S. Martin
    • 1
  1. 1.Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular DiseaseJohns Hopkins HospitalBaltimoreUSA
  2. 2.Division of Cardiology, Department of MedicineWeill Cornell Medical College-QatarDohaQatar

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