A new formula for estimation of low-density lipoprotein cholesterol in an ethnic Chinese population
-
Ching-Yun Hu
, Chia-Lin Lee , Wayne H.-H. Sheu , Jun-Sing Wang , I-Te Lee , Yuh-Min Song , Chia-Po Fu , Jiin-Tsae Ling , Yu-Fen Li and Shih-Yi Lin
Abstract
Background: Low-density lipoprotein cholesterol (LDL-C) is an established risk factor for cardiovascular disease and is usually estimated by the Friedewald formula (FF) calculated from three parameters, namely, total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C). We aimed to develop a new and simple formula (NF) for LDL-C estimation.
Methods: This cross-sectional study enrolled two study populations (a testing group, n=16,749, and a validation group, n=4940). Linear regression analysis was used in the testing group to investigate the association between measured LDL-C (mLDL-C) and TC concentration, and was verified in the validation group.
Results: The NF yielded an estimated LDL-C (eLDL-C) equal to 0.75×total cholesterol–0.6465 (mmol/L). For the subjects with TC between 2.58 and 7.74 mmol/L, the difference between mLDL-C and eLDL-C using the NF was less than that from the FF (testing group: –0.04 to –0.20 vs. –0.28 to –0.38 mmol/L; validation group: 0.01 to –0.12 vs. –0.23 to –0.30 mmol/L; p<0.001, respectively). The predictability of the NF was not inferior to that of the FF in subjects with different triglyceride and HDL-C concentrations, and was not affected by diabetes diagnosis and statin use. However, the NF performed similar to or worse than the FF at TC concentrations <2.58 mmol/L and >7.74 mmol/L, respectively.
Conclusions: In the Chinese population, the accuracy of eLDL-C measurement with the NF was better than that with the FF, especially in subjects with TC levels between 2.58 and 7.74 mmol/L. The NF is simple and may be used for screening as well as for follow-up of patients on lipid lowering agents.
Acknowledgments
The authors would like to thank the Clinical Informatics Research & Development Center of Taichung Veterans General Hospital, Taichung, Taiwan, for data collection (F14043, F14051). Writing support was provided by Jim Ascencio, a native English speaker.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Financial support: This study was funded by grants from the National Science Council (NSC 101-2314-B-075A-006-MY3) and Taichung Veterans General Hospital, Taichung, Taiwan, ROC (TCVGH-1030101C; TCVGH-1020101C; TCVGH-1013001C; TCVGH-1003001C).
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organisation(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Kannel WB, Castelli WP, Gordon T, McNamara PM. Serum cholesterol, lipoproteins, and the risk of coronary heart disease. The Framingham study. Ann Intern Med 1971;74:1–12.10.7326/0003-4819-74-1-1Search in Google Scholar PubMed
2. Gordon T, Kannel WB, Castelli WP, Dawber TR. Lipoproteins, cardiovascular disease, and death. The Framingham study. Arch Intern Med 1981;141:1128–31.10.1001/archinte.1981.00340090024008Search in Google Scholar
3. Cohen JC, Boerwinkle E, Mosley TH, Jr., Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 2006;354:1264–72.10.1056/NEJMoa054013Search in Google Scholar PubMed
4. Kizer JR, Madias C, Wilner B, Vaughan CJ, Mushlin AI, Trushin P, et al. Relation of different measures of low-density lipoprotein cholesterol to risk of coronary artery disease and death in a meta-regression analysis of large-scale trials of statin therapy. Am J Cardiol 2010;105:1289–96.10.1016/j.amjcard.2009.12.051Search in Google Scholar PubMed PubMed Central
5. Angelakopoulou A, Shah T, Sofat R, Shah S, Berry DJ, Cooper J, et al. Comparative analysis of genome-wide association studies signals for lipids, diabetes, and coronary heart disease: Cardiovascular Biomarker Genetics Collaboration. Eur Heart J 2012;33:393–407.10.1093/eurheartj/ehr225Search in Google Scholar PubMed PubMed Central
6. Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143–421.10.1161/circ.106.25.3143Search in Google Scholar
7. Keevil JG, Cullen MW, Gangnon R, McBride PE, Stein JH. Implications of cardiac risk and low-density lipoprotein cholesterol distributions in the US for the diagnosis and treatment of dyslipidemia: data from National Health and Nutrition Examination Survey 1999–2002. Circulation 2007;115:1363–70.10.1161/CIRCULATIONAHA.106.645473Search in Google Scholar PubMed
8. Reiner Z, Catapano AL, De Backer G, Graham I, Taskinen MR, Wiklund O, et al. [ESC/EAS Guidelines for the management of dyslipidaemias]. Rev Esp Cardiol 2011;64:1168.e1–60.10.1016/j.recesp.2011.09.014Search in Google Scholar PubMed
9. Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM, Blum CB, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol 2014;63:3024–5.10.1016/j.jacc.2013.11.002Search in Google Scholar PubMed
10. Bachorik PS. Measurement of low density lipoprotein cholesterol. In: Rifai WG, Dominiczak MH, editors. Handbook of lipoprotein testing.Washington, DC: AACC Press, 1997:145–60.Search in Google Scholar
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;41:1414–20.10.1093/clinchem/41.10.1414Search in Google Scholar
12. 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;48:236–54.10.1093/clinchem/48.2.236Search in Google Scholar
13. Bairaktari ET, Seferiadis KI, Elisaf MS. Evaluation of methods for the measurement of low-density lipoprotein cholesterol. J Cardiovasc Pharmacol Ther 2005;10:45–54.10.1177/107424840501000106Search in Google Scholar PubMed
14. 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;18:499–502.10.1093/clinchem/18.6.499Search in Google Scholar
15. 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):13–9.10.1258/acb.2012.011259Search in Google Scholar PubMed
16. Onyenekwu CP, Hoffmann M, Smit F, Matsha TE, Erasmus RT. Comparison of LDL-cholesterol estimate using the Friedewald formula and the newly proposed de Cordova formula with a directly measured LDL-cholesterol in a healthy South African population. Ann Clin Biochem 2014;51:672–9.10.1177/0004563214520750Search in Google Scholar PubMed
17. Cordova CM, Schneider CR, Juttel ID, Cordova MM. Comparison of LDL-cholesterol direct measurement with the estimate using the Friedewald formula in a sample of 10,664 patients. Arq Bras Cardiol 2004;83:482–7; 76–81.10.1590/S0066-782X2004001800006Search in Google Scholar PubMed
18. McNamara JR, Cohn JS, Wilson PW, Schaefer EJ. Calculated values for low-density lipoprotein cholesterol in the assessment of lipid abnormalities and coronary disease risk. Clin Chem 1990;36:36–42.10.1093/clinchem/36.1.36Search in Google Scholar
19. Rubies-Prat J, Reverter JL, Senti M, Pedro-Botet J, Salinas I, Lucas A, et al. Calculated low-density lipoprotein cholesterol should not be used for management of lipoprotein abnormalities in patients with diabetes mellitus. Diabetes Care 1993;16:1081–6.10.2337/diacare.16.8.1081Search in Google Scholar PubMed
20. Matas C, Cabre M, La Ville A, Prats E, Joven J, Turner PR, et al. Limitations of the Friedewald formula for estimating low-density lipoprotein cholesterol in alcoholics with liver disease. Clin Chem 1994;40:404–6.10.1093/clinchem/40.3.404Search in Google Scholar
21. Nauck M, Kramer-Guth A, Bartens W, Marz W, Wieland H, Wanner C. Is the determination of LDL cholesterol according to Friedewald accurate in CAPD and HD patients? Clin Nephrol 1996;46:319–25.Search in Google Scholar
22. Gazi I, Tsimihodimos V, Filippatos TD, Saougos VG, Bairaktari ET, Tselepis AD, et al. LDL cholesterol estimation in patients with the metabolic syndrome. Lipids Health Dis 2006;5:8.10.1186/1476-511X-5-8Search in Google Scholar PubMed PubMed Central
23. Gazi IF, Elisaf M. LDL-cholesterol calculation formulas in patients with or without the metabolic syndrome. Int J Cardiol 2007;119:414–5.10.1016/j.ijcard.2006.07.139Search in Google Scholar
24. Vohnout B, Vachulova A, Blazicek P, Dukat A, Fodor G, Lietava J. Evaluation of alternative calculation methods for determining LDL cholesterol. Vnitr Lek 2008;54:961–4.Search in Google Scholar
25. 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;310:2061–8.10.1001/jama.2013.280532Search in Google Scholar
26. 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;9:52.10.1186/1476-511X-9-52Search in Google Scholar
27. 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;423:135–40.10.1016/j.cca.2013.04.009Search in Google Scholar
28. Sugiuchi H, Uji Y, Okabe H, Irie T, Uekama K, Kayahara N, et al. Direct measurement of high-density lipoprotein cholesterol in serum with polyethylene glycol-modified enzymes and sulfated alpha-cyclodextrin. Clin Chem 1995;41:717–23.10.1093/clinchem/41.5.717Search in Google Scholar
29. Arranz-Pena ML, Tasende-Mata J, Martin-Gil FJ. Comparison of two homogeneous assays with a precipitation method and an ultracentrifugation method for the measurement of HDL-cholesterol. Clin Chem 1998;44:2499–505.10.1093/clinchem/44.12.2499Search in Google Scholar
30. Sugiuchi H, Irie T, Uji Y, Ueno T, Chaen T, Uekama K, et al. Homogeneous assay for measuring low-density lipoprotein cholesterol in serum with triblock copolymer and alpha-cyclodextrin sulfate. Clin Chem 1998;44:522–31.10.1093/clinchem/44.3.522Search in Google Scholar
31. Esteban-Salan M, Guimon-Bardesi A, de La Viuda-Unzueta JM, Azcarate-Ania MN, Pascual-Usandizaga P, Amoroto-Del-Rio E. Analytical and clinical evaluation of two homogeneous assays for LDL-cholesterol in hyperlipidemic patients. Clin Chem 2000;46:1121–31.10.1093/clinchem/46.8.1121Search in Google Scholar
32. Nauck M, Graziani MS, Bruton D, Cobbaert C, Cole TG, Lefevre F, et al. Analytical and clinical performance of a detergent-based homogeneous LDL-cholesterol assay: a multicenter evaluation. Clin Chem 2000;46:506–14.10.1093/clinchem/46.4.506Search in Google Scholar
33. Nauck M, Rifai N. Analytical performance and clinical efficacy of three routine procedures for LDL cholesterol measurement compared with the ultracentrifugation-dextran sulfate-Mg(2+) method. Clin Chim Acta 2000;294:77–92.10.1016/S0009-8981(99)00250-8Search in Google Scholar
34. 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;62:732–9.10.1016/j.jacc.2013.01.079Search in Google Scholar PubMed
35. Choi SY, Park HE, Kim MK, Shin CS, Cho SH, Oh BH. Difference between calculated and direct-measured low-density lipoprotein cholesterol in subjects with diabetes mellitus or taking lipid-lowering medications. J Clin Lipidol 2012;6: 114–20.10.1016/j.jacl.2011.12.007Search in Google Scholar PubMed
36. 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;9:27.10.1186/1476-511X-9-27Search in Google Scholar PubMed PubMed Central
37. 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;102:117–20.10.1016/j.ijcard.2004.05.009Search in Google Scholar PubMed
38. Association AD. Standards of medical care in diabetes – 2014. Diabetes Care 2014;37(Suppl 1):S14–80.10.2337/dc14-S014Search in Google Scholar PubMed
39. Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A, et al. Major lipids, apolipoproteins, and risk of vascular disease. J Am Med Assoc 2009;302:1993–2000.10.1001/jama.2009.1619Search in Google Scholar PubMed PubMed Central
40. Mora S, Rifai N, Buring JE, Ridker PM. Comparison of LDL cholesterol concentrations by Friedewald calculation and direct measurement in relation to cardiovascular events in 27,331 women. Clin Chem 2009;55:888–94.10.1373/clinchem.2008.117929Search in Google Scholar PubMed PubMed Central
41. Myers GL, Kimberly MM, Waymack PP, Smith SJ, Cooper GR, Sampson EJ. A reference method laboratory network for cholesterol: a model for standardization and improvement of clinical laboratory measurements. Clin Chem 2000;46:1762–72.10.1093/clinchem/46.11.1762Search in Google Scholar
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Articles in the same Issue
- Frontmatter
- Editorials
- Laboratory medicine does matter in science (and medicine)… yet many seem to ignore it
- The standardization of the urine albumin assays: no longer deferrable
- Reviews
- The role of telomeres and vitamin D in cellular aging and age-related diseases
- Atypical hemolytic uremic syndrome: from diagnosis to treatment
- Clinical relevance and contemporary methods for counting blood cells in body fluids suspected of inflammatory disease
- EFLM Opinion Paper
- How to assess the quality of your analytical method?
- Genetics and Molecular Diagnostics
- Validation of CFTR intronic variants identified during cystic fibrosis population screening by a minigene splicing assay
- General Clinical Chemistry and Laboratory Medicine
- Uncertainty in measurement for 43 biochemistry, immunoassay, and hemostasis routine analytes evaluated by a method using only external quality assessment data
- A study examining the bias of albumin and albumin/creatinine ratio measurements in urine
- National survey on appropriateness of clinical biochemistry reporting in China
- Potentiometric measurement of urinary iodine concentration in patients with thyroid diseases with and without previous exposure to non-radioactive iodine
- Determination of 21-hydroxylase autoantibodies: inter-laboratory concordance in the Euradrenal International Serum Exchange Program
- Value of a commercial kit for detecting anti-C1q autoantibodies and correlation with immunological and clinical activity of lupus nephritis
- Comparison of the bead-based simultaneous analysis of specific platelet antibodies assay (SASPA) and Pak Lx Luminex technology with the monoclonal antibody immobilization of platelet antigens assay (MAIPA) to detect platelet alloantibodies
- Measurement of the inflammatory response in the early postoperative period after hip and knee arthroplasty
- Whole blood thromboelastometry profiles in women with preeclampsia
- Increased plasma soluble urokinase plasminogen activator receptor levels in systemic sclerosis: possible association with microvascular abnormalities and extent of fibrosis
- Reference Values and Biological Variations
- Reference ranges of serum bile acids in children and adolescents
- Infectious Diseases
- Elevated circulating ghrelin, but not peptide YY(3-36) levels, in term neonates with infection
- Cardiovascular Diseases
- Head-to-head comparison of 10 natriuretic peptide assays
- Prognostic role of BNP in children undergoing surgery for congenital heart disease: analysis of prediction models incorporating standard risk factors
- Elevations of inflammatory markers PTX3 and sST2 after resuscitation from cardiac arrest are associated with multiple organ dysfunction syndrome and early death
- Identification of molecular species of oxidized triglyceride in plasma and its distribution in lipoproteins
- A new formula for estimation of low-density lipoprotein cholesterol in an ethnic Chinese population
- Letter to the Editors
- Laboratory medicine: let’s say it is the mirror of science (and medicine)
- The economic burden of hemolysis
- Acute effects of conventional and extended hemodialysis and hemodiafiltration on high-sensitivity cardiac troponins
- Cuvette carryover with the gentamicin assay on the Beckman AU480 analyser
- Comparison study of two commercially available methods for the determination of golimumab and anti-golimumab antibody levels in patients with rheumatic diseases
- Automated alkaline-pH electrophoresis followed by densitometry does not correlate with cation-exchange (CE)-HPLC in quantification of HbA2 and variant hemoglobins
- Progression from light chain myeloma to secondary plasma cell leukemia accompanied by peripheral blood eosinophilia
- Harmonization of results has not been fully achieved for serum immunoglobulin measurements
- The risk of macrovascular complications in subjects genotyped for common IL-6 gene and TNF-α gene variants
- Comparison of nucleated red blood cell count with four commercial hematological analyzers
- Reply to: The risk of macrovascular complications in subjects genotyped for common IL-6 gene and TNF-α gene variants
- Congress Abstracts
- Congress of Clinical Chemistry and Laboratory Medicine
- 47th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC – Laboratory Medicine)
- 15th EFLM Continuous Postgraduate Course in Clinical Chemistry and Laboratory Medicine