Abstract
Objectives
Low-density lipoprotein cholesterol (LDL-C) is the main laboratory parameter used for the management of cardiovascular disease. The aim of this study was to compare measured LDL-C with LDL-C as calculated by the Friedewald, Martin/Hopkins, Vujovic, and Sampson formulas with regard to triglyceride (TG), LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C)/TG ratio.
Methods
The 1,209 calculated LDL-C results were compared with LDL-C measured using ultracentrifugation-precipitation (first study) and direct (second study) methods. The Passing-Bablok regression was applied to compare the methods. The percentage difference between calculated and measured LDL-C (total error) and the number of results exceeding the total error goal of 12% were established.
Results
There was good correlation between the measurement and calculation methods (r 0.962–0.985). The median total error ranged from −2.7%/+1.4% (first/second study) for Vujovic formula to −6.7%/−4.3% for Friedewald formula. The numbers of underestimated results exceeding the total error goal of 12% were 67 (Vujovic), 134 (Martin/Hopkins), 157 (Samspon), and 239 (Friedewald). Less than 7% of those results were obtained for samples with TG >4.5 mmol/L. From 57% (Martin/Hopkins) to 81% (Vujovic) of underestimated results were obtained for samples with a non-HDL-C/TG ratio of <2.4.
Conclusions
The Martin/Hopkins, Vujovic and Sampson formulas appear to be more accurate than the Friedewald formula. To minimize the number of significantly underestimated LDL-C results, we propose the implementation of risk categories according to non-HDL-C/TG ratio and suggest that for samples with a non-HDL-C/TG ratio of <1.2, the LDL-C level should not be calculated but measured independently from TG level.
Funding source: Medical University of Gdańsk
Award Identifier / Grant number: ST 02-0125/07/524
-
Research funding: Medical University of Gdańsk grant no. ST 02–0125/07/524.
-
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Competing interests: Authors state no conflict of interest.
-
Informed consent: Informed consent was obtained from all individuals included in the first study. In the second study, retrospective data was collected anonymously from laboratory database.
-
Ethical approval: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013), and has been approved by the Independent Bioethics Commission for Research of the Medical University of Gdańsk (Poland) (NKBBN 541/2014-2015 and 612/2017-2018).
References
1. Roth, GA, Johnson, C, Abajobir, A, Abd-Allah, F, Abera, SF, Abyu, G, et al.. Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J Am Coll Cardiol 2017;70:1–25.10.1016/j.jacc.2017.04.052Search in Google Scholar PubMed PubMed Central
2. Mach, F, Baigent, C, Catapano, AL, Koskinas, KC, Casula, M, Badimon, L, et al.. ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2019;41:111–88.10.1093/eurheartj/ehz455Search in Google Scholar PubMed
3. Nauck, M, Warnick, GR, Rifai, N. Methods for measurement of LDL-cholesterol: a critical assessment of direct measurement by homogeneous assays versus calculation. Clin Chem 2002;48:236–54. https://doi.org/10.1093/clinchem/48.2.236.Search in Google Scholar
4. 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/10.1093/clinchem/18.6.499.Search in Google Scholar
5. Wolska, A, Remaley, AT. Measuring LDL-cholesterol: what is the best way to do it? Curr Opin Cardiol 2020;35:405–11.10.1097/HCO.0000000000000740Search in Google Scholar PubMed PubMed Central
6. Martin, SS, Blaha, MJ, Elshazly, MB, Toth, PP, Kwiterovich, PO, Blumenthal, RS, et al.. Comparison of a novel method vs the Friedewald equation for estimating low-density lipoprotein cholesterol levels from the standard lipid profile. J Am Med Assoc 2013;310:2061–8. https://doi.org/10.1001/jama.2013.280532.Search in Google Scholar PubMed PubMed Central
7. Vujovic, A, Kotur-Stevuljevic, J, Spasic, S, Bujisic, N, Martinovic, J, Vujovic, M, et al.. Evaluation of different formulas for LDL-C calculation. Lipids Health Dis 2010;9:27. https://doi.org/10.1186/1476-511x-9-27.Search in Google Scholar PubMed PubMed Central
8. Sampson, M, Ling, C, Sun, Q, Harb, R, Ashmaig, M, Warnick, R, et al.. A new equation for calculation of low-density lipoprotein cholesterol in patients with normolipidemia and/or hypertriglyceridemia. JAMA Cardiol 2020;5:1–9. https://doi.org/10.1001/jamacardio.2020.0013.Search in Google Scholar PubMed PubMed Central
9. Cwiklinska, A, Gliwinska, A, Senderowska, Z, Kortas-Stempak, B, Kuchta, A, Dabkowski, K, et al.. Impact of phosphatidylcholine liposomes on the compositional changes of VLDL during lipoprotein lipase (LPL)-mediated lipolysis. Chem Phys Lipids 2016;195:63–70.10.1016/j.chemphyslip.2015.12.007Search in Google Scholar PubMed
10. Kuchta, A, Strzelecki, A, Cwiklinska, A, Gruchala, M, Zdrojewski, Z, Kortas-Stempak, B, et al.. HDL subpopulations containing apoA-I without apoA-II (LpA-I) in patients with angiographically proven coronary artery disease. J Cardiol 2017;69:523–8. https://doi.org/10.1016/j.jjcc.2016.04.007.Search in Google Scholar PubMed
11. Bachorik, PS, Ross, JW. National cholesterol education Program recommendations for measurement of low-density lipoprotein cholesterol: executive summary. The national cholesterol education Program working group on lipoprotein measurement. Clin Chem 1995;41:1414–20. https://doi.org/10.1093/clinchem/41.10.1414.Search in Google Scholar
12. 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:BC11–3. https://doi.org/10.7860/JCDR/2016/22272.9018.Search in Google Scholar PubMed PubMed Central
13. Srisurin, W. The reliability of calculated low-density lipoprotein cholesterol from four different formulas in Thai diabetic patients. J Med Assoc Thai 2014;97:589–97.Search in Google Scholar
14. Oliveira, MJ, van Deventer, HE, Bachmann, LM, Warnick, GR, Nakajima, K, Nakamura, M, et al.. Evaluation of four different equations for calculating LDL-C with eight different direct HDL-C assays. Clin Chim Acta 2013;423:135–40. https://doi.org/10.1016/j.cca.2013.04.009.Search in Google Scholar PubMed PubMed Central
15. Martin, SS, Giugliano, RP, Murphy, SA, Wasserman, SM, Stein, EA, Ceška, R, et al.. Comparison of low-density lipoprotein cholesterol assessment by martin/hopkins estimation, Friedewald estimation, and preparative ultracentrifugation: insights from the FOURIER trial. JAMA Cardiol 2018;3:749–53. https://doi.org/10.1001/jamacardio.2018.1533.Search in Google Scholar PubMed PubMed Central
16. 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.Search in Google Scholar PubMed
17. 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 Atherosclerosis Thromb 2016;23:1355–64. https://doi.org/10.5551/jat.35972.Search in Google Scholar PubMed PubMed Central
18. Palmer, MK, Barter, PJ, Lundman, P, Nicholls, SJ, Toth, PP, Karlson, BW. Comparing a novel equation for calculating low-density lipoprotein cholesterol with the Friedewald equation: a VOYAGER analysis. Clin Biochem 2019;64:24–9. https://doi.org/10.1016/j.clinbiochem.2018.10.011.Search in Google Scholar PubMed
19. Zafrir, B, Saliba, W, Flugelman, MY. Comparison of novel equations for estimating low-density lipoprotein cholesterol in patients undergoing coronary angiography. J Atheroscler Thromb 2020;27:1359–73. doi:https://doi.org/10.5551/jat.57133.Search in Google Scholar PubMed PubMed Central
20. Lin, QZ, Chen, YQ, Guo, LL, Xiang, QY, Tian, F, Wen, T, et al.. Comparison of non-fasting LDL-C levels calculated by Friedewald formula with those directly measured in Chinese patients with coronary heart disease after a daily breakfast. Clin Chim Acta 2019;495:399–405. https://doi.org/10.1016/j.cca.2019.05.010.Search in Google Scholar PubMed
21. Meeusen, JW, Snozek, CL, Baumann, NA, Jaffe, AS, Saenger, AK. Reliability of calculated low-density lipoprotein cholesterol. Am J Cardiol 2015;116:538–40. https://doi.org/10.1016/j.amjcard.2015.05.013.Search in Google Scholar PubMed
22. 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.Search in Google Scholar PubMed PubMed Central
23. Ćwiklińska, A, Mickiewicz, A, Kowalski, R, Kortas-Stempak, B, Kuchta, A, Mucha, K, et al.. Detection of lipoprotein X (LpX) - a challenge in patients with severe hypercholesterolaemia. J Med Biochem 2020;39:283–9. https://doi.org/10.2478/jomb-2019-0038.Search in Google Scholar PubMed PubMed Central
24. Langlois, MR, Descamps, OS, van der Laarse, A, Weykamp, C, Baum, H, Pulkki, K, et al.. Clinical impact of direct HDLc and LDLc method bias in hypertriglyceridemia. A simulation study of the EAS-EFLM Collaborative Project Group. Atherosclerosis 2014;233:83–90. https://doi.org/10.1016/j.atherosclerosis.2013.12.016.Search in Google Scholar PubMed
Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2020-1366).
© 2020 Walter de Gruyter GmbH, Berlin/Boston