A modified equation for calculating low density lipoprotein cholesterol in Pakistani population
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Abstract
OBJECTIVE: To derive an equation for accurate estimation of low-density lipoprotein cholesterol (LDL-C) in the Pakistani population.
METHODS: A modified equation was derived on the dataset (n = 59,148) from the Pakistani population, comprising directly measured LDL-C (dLDL-C) and other lipids using a regression model. The equation was validated on an internal (n = 29,633) and external dataset (n = 385,434), and the results were compared with the standard equations being used in the Pakistani population: Friedewald and Teerakanchana equation. The concordance between the dLDL-C and calculated LDL-C (cLDL-C) was determined by median difference (MD) and the agreement between dLDL-C and cLDL-C was analyzed by Bland Altman graphics.
RESULTS: The modified equation (M.Eq) displayed best correlation (r = 0.974) and MD of -0.07 mmol/L on the derivation dataset. Similarly, the equation provided the best correlation and least MD on the internal (r = 0.970, MD = -0.13) and external validation datasets (r = 0.953, MD = -0.02). The Bland-Altman plot for the modified equation displayed the least bias in the derivation (-0.0012 mmol/L), internal validation (-0.13 mmol/L), and external validation (-0.02 mmol/L).
CONCLUSION: The modified equation can be utilized for clinical settings in Pakistan that do not facilitate direct measurements of LDL-C.
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References
Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 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. https://doi.org/10.1093/eurheartj/ehx144
Borén J, John Chapman M, Krauss RM, Packard CJ, Bentzon JF, Binder CJ, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: Pathophysiological, genetic, and therapeutic insights: A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2020;41:2313-30. https://doi.org/10.1093/eurheartj/ehz962
Wadhera RK, Steen DL, Khan I, Giugliano RP, Foody JM. A review of low-density lipoprotein cholesterol, treatment strategies, and its impact on cardiovascular disease morbidity and mortality. J Clin Lipidol 2016;10:472-89. https://doi.org/10.1016/j.jacl.2015.11.010
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.
Brownstein AJ, Martin SS. More accurate LDL-C calculation: Externally validated, guideline endorsed. Clin Chim Acta 2020;506:149-53. https://doi.org/10.1016/j.cca.2020.03.030
Karkhaneh A, Bagherieh M, Sadeghi S, Kheirollahi A. Evaluation of eight formulas for LDL-C estimation in Iranian subjects with different metabolic health statuses. Lipids Health Dis 2019;18(1):231. https://doi.org/10.1186/s12944-019-1178-1
Wolska A, Remaley AT. Measuring LDL-cholesterol: what is the best way to do it? Curr Opin Cardiol 2020;35(4):405-11. https://doi.org/10.1097/hco.0000000000000740
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.
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(5):540-8. https://doi.org/10.1001/jamacardio.2020.0013
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.
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.
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;138:289-99. https://doi.org/10.1016/s0021-9150(98)00034-3
Puavilai W, Laoragpongse D. Is calculated LDL-C by using the new modified Friedewald equation better than the standard Friedewald equation? J Med Assoc Thai 2004;87(6):589-93.
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
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.
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
de Cordova CMM, 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;50:13-9. https://doi.org/10.1258/acb.2012.011259
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. JAMA 2013;310:2061-8. https://doi.org/10.1001/jama.2013.280532
Bauer F, Seibert FS, Rohn B, Babel N, Westhoff TH. Estimation of LDL cholesterol in chronic kidney disease. Eur J Prev Cardiol 2021;28(12):1402-8. https://doi.org/10.1093/eurjpc/zwaa003
Khan M, Ain QT, Nawaz A, Iqbal Khan M, Sadiq F. Indirect calculation of LDL using thirteen equations in Pakistani population. Clin Chim Acta 2022;536:77-85. https://doi.org/10.1016/j.cca.2022.09.010
Dar GM, Dash M, Mahajan B. Teerakanchana’s equation transcends over 12 other LDL-C quantification formulae in the North Indian population. Clin Chim Acta 2022;531:168-76. https://doi.org/10.1016/j.cca.2022.04.006
Pilia G, Chen WM, Scuteri A, Orrú M, Albai G, Dei M, et al. Heritability of cardiovascular and personality traits in 6,148 Sardinians. PLoS Genet 2006;2(8):e132. https://doi.org/10.1371/journal.pgen.0020132
Khan SH, Niazi NK, Sobia F, Fazal N, Manzoor SM, Nadeem A. Friedewald’s equation for calculating LDL-cholesterol: Is it the time to say “Goodbye” and adopt direct LDL cholesterol methods? Pak J Med Sci 2019;35(2):388-93. https://doi.org/10.12669/pjms.35.2.679
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. JAMA 2013;310(19):2061-8. https://doi.org/10.1001/jama.2013.280532
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. J Am Coll Cardiol 2019;73(24):e285-350. https://doi.org/10.1016/j.jacc.2018.11.003
Cicero AFG, Fogacci F, Patrono D, Mancini R, Ramazzotti E, Borghi C, et al. Application of the Sampson equation to estimate LDL-C in children: Comparison with LDL direct measurement and Friedewald equation in the BLIP study. Nutr Metab Cardiovasc Dis 2021;31(6):1911-5. https://doi.org/10.1016/j.numecd.2021.02.034
Piani F, Cicero AFG, Ventura F, Dormi A, Fogacci F, Patrono D, et al. Evaluation of twelve formulas for LDL-C estimation in a large, blinded, random Italian population. Int J Cardiol 2021;330:221-7. https://doi.org/10.1016/j.ijcard.2021.02.009
Steyn N, Muller Rossouw H, Pillay TS, Martins J. Comparability of calculated LDL-C with directly measured LDL-C in selected paediatric and adult cohorts. Clin Chim Acta 2022;537:158-66. https://doi.org/10.1016/j.cca.2022.10.003
Dudi P, Vishwajeet, Yadav SRM, Sharma P, Kumar P, Mirza AA, et al. Derivation of a Modified Friedewald’s equation for LDL cholesterol estimation in Sub-Himalayan population: A comparative study. J Family Med Prim Care 2022;11(5):1826. https://doi.org/10.4103/jfmpc.jfmpc_1063_21
Chowdhury N, Saiedullah M, Khan MAH, Rahman MR. Comparison of modified Friedewald’s formula with direct measurement of low-density lipoprotein cholesterol in Bangladeshi population. Bangladesh Med Res Counc Bull 2013;39(3):120-3. https://doi.org/10.3329/bmrcb.v39i3.20312
Frank ATH, Zhao B, Jose PO, Azar KMJ, Fortmann SP, Palaniappan LP. Racial/Ethnic Differences in Dyslipidemia Patterns. Circulation 2014;129(5):570-9. https://doi.org/10.1161/circulationaha.113.005757