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COMPARISON OF DIRECTLY MEASURED LDL-CHOLESTEROL WITH CALCULATED LDL-CHOLESTEROL USING FRIEDEWALD, DE CORDOVA, AHMADI AND VUJOVIC FORMULAS
Corresponding Author(s) : Noor Alicezah Mohd Kasim
Malaysian Journal of Clinical Biochemistry,
Vol. 1 No. 1 (2024): Young Scientists Award (33rd MACB Conference 2023)
Abstract
This study aimed to compare the measured LDL-C (LDLD) with the Friedewald (LDLF), de Cordova (LDLDC), Ahmadi (LDLA), and Vujovic (LDLV) formulas, and establish the formula that provides the most reliable LDL-C results. Seventy-two subjects were enrolled in this study. Fasting blood samples were collected, and the serum was utilized for the analysis of lipid profiles. The percentage difference between the calculated LDL-C and LDLD was established. The strength between LDLD and calculated LDL-C was measured through Pearson correlation analysis. The level of agreement was evaluated through Bland-Altman analysis. The study encompassed LDLD measurements ranging from 0.05 mmol/L to 36.91 mmol/L. The lowest percentage difference of mean LDL-C between calculated and LDLD is observed in LDLV (7.14%). The LDLD measurement showed a positive and strongest correlation to LDLDC in evaluating LDL-C (r = 0.958, p<0.001). However, only LDLV showed a certain level of agreement with LDLD, with no significant bias observed (mean difference ± SD = 0.54±2.69). Vujovic formula could be used to estimate LDL-C values in hypo/hypercholesterolemic and normolipidemic individuals. LDLV formula was the most accurate and reliable calculated LDL-C when compared to LDLD measurements ranging from 0.05 mmol/L to 36.91 mmol/L.
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- Ahmadi, S. A., Boroumand, M.-A., GOUHARI, M. K., Tajik, P., & Dibaj, S.-M. (2008). The impact of low serum triglyceride on LDL-cholesterol estimation.
- Chen, Y., Zhang, X., Pan, B., Jin, X., Yao, H., Chen, B., . . . Chen, H. (2010). A modified formula for calculating low-density lipoprotein cholesterol values. Lipids in health and disease, 9, 1-5.
- Choi, H., Shim, J.-S., Lee, M. H., Yoon, Y. M., Choi, D. P., & Kim, H. C. (2016). Comparison of formulas for calculating low-density lipoprotein cholesterol in general population and high-risk patients with cardiovascular disease. Korean circulation journal, 46(5), 688-698.
- Contois, J. H., Warnick, G. R., & Sniderman, A. D. (2011). Reliability of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B measurement. Journal of clinical lipidology, 5(4), 264-272.
- de Cordova, C. M. M., & de Cordova, M. M. (2013). A new accurate, simple formula for LDL-cholesterol estimation based on directly measured blood lipids from a large cohort. Annals of Clinical Biochemistry, 50(1), 13-19. https://doi.org/10.1258/acb.2012.011259
- Detection, N. C. E. P. E. P. o., & Adults, T. o. H. B. C. i. (2002). 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). The Program.
- Expert Panel on Detection, E. (2001). Executive summary of the 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). Jama, 285(19), 2486-2497.
- Feingold, K. R. (2000). Introduction to Lipids and Lipoproteins. In K. R. Feingold, B. Anawalt, M. R. Blackman, A. Boyce, G. Chrousos, E. Corpas, W. W. de Herder, K. Dhatariya, K. Dungan, J. Hofland, S. Kalra, G. Kaltsas, N. Kapoor, C. Koch, P. Kopp, M. Korbonits, C. S. Kovacs, W. Kuohung, B. Laferrère, M. Levy, E. A. McGee, R. McLachlan, M. New, J. Purnell, R. Sahay, A. S. Shah, F. Singer, M. A. Sperling, C. A. Stratakis, D. L. Trence, & D. P. Wilson (Eds.), Endotext. MDText.com, Inc. Copyright © 2000-2023, MDText.com, Inc.
- Friedewald, W. T., Levy, R. I., & Fredrickson, D. S. (1972). Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical chemistry, 18(6), 499-502.
- Ginsberg, H. N., Rosenson, R. S., Hovingh, G. K., Letierce, A., Samuel, R., Poulouin, Y., & Cannon, C. P. (2022). LDL-C calculated by Friedewald, Martin-Hopkins, or NIH equation 2 versus beta-quantification: pooled alirocumab trials. Journal of Lipid Research, 63(1).
- Grundy, S. M., Cleeman, J. I., Merz, C. N. B., Brewer Jr, H. B., Clark, L. T., Hunninghake, D. B., . . . Stone, N. J. (2004). Implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines. Circulation, 110(2), 227-239.
- Hattori, Y., Suzuki, M., Tsushima, M., Yoshida, M., Tokunaga, Y., Wang, Y., . . . Ryomoto, K. I. (1998). 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, 138(2), 289-299.
- Jung, E., Kong, S. Y., Ro, Y. S., Ryu, H. H., & Shin, S. D. (2022). Serum Cholesterol Levels and Risk of Cardiovascular Death: A Systematic Review and a Dose-Response Meta-Analysis of Prospective Cohort Studies. Int J Environ Res Public Health, 19(14). https://doi.org/10.3390/ijerph19148272
- Karkhaneh, A., Bagherieh, M., Sadeghi, S., & Kheirollahi, A. (2019). Evaluation of eight formulas for LDL-C estimation in Iranian subjects with different metabolic health statuses. Lipids in health and disease, 18(1), 1-11.
- Lee, J., Jang, S., Jeong, H., & Ryu, O.-H. (2020). Validation of the Friedewald formula for estimating low density lipoprotein cholesterol: the Korea National Health and Nutrition Examination Survey, 2009 to 2011. The Korean Journal of Internal Medicine, 35(1), 150.
- Lindsey, C. C., Graham, M. R., Johnston, T. P., Kiroff, C. G., & Freshley, A. (2004). A Clinical Comparison of Calculated versus Direct Measurement of Low‐Density Lipoprotein Cholesterol Level. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 24(2), 167-172.
- Martin, S. S., Giugliano, R. P., Murphy, S. A., Wasserman, S. M., Stein, E. A., Češka, R., . . . Tikkanen, M. J. (2018). Comparison of low-density lipoprotein cholesterol assessment by Martin/Hopkins estimation, Friedewald estimation, and preparative ultracentrifugation: insights from the FOURIER trial. JAMA cardiology, 3(8), 749-753.
- Martins, J., Steyn, N., Rossouw, H. M., & Pillay, T. S. (2023). Best practice for LDL-cholesterol: when and how to calculate. Journal of Clinical Pathology, 76(3), 145-152.
- Miller, W. G., Myers, G. L., Sakurabayashi, I., Bachmann, L. M., Caudill, S. P., Dziekonski, A., . . . Leary, E. T. (2010). Seven direct methods for measuring HDL and LDL cholesterol compared with ultracentrifugation reference measurement procedures. Clinical chemistry, 56(6), 977-986.
- Nasrin, N. (2017). Newly-developed De Cordova’ s Formula for Calculation of LDL Cholesterol in Bangladeshi Population. Borneo Journal of Medical Sciences (BJMS), 11(3), 25-34.
- Nauck, M., Warnick, G. R., & Rifai, N. (2002). Methods for measurement of LDL-cholesterol: a critical assessment of direct measurement by homogeneous assays versus calculation. Clinical chemistry, 48(2), 236-254.
- Piani, F., Cicero, A. F., Ventura, F., Dormi, A., Fogacci, F., Patrono, D., . . . D'Addato, S. (2021). Evaluation of twelve formulas for LDL-C estimation in a large, blinded, random Italian population. International Journal of Cardiology, 330, 221-227.
- Rim, J. H., Lee, Y.-h., Lee, M. H., Kim, H. Y., Choi, J., Lee, B.-W., . . . Lee, S.-G. (2016). Comparison and validation of 10 equations including a novel method for estimation of LDL-cholesterol in a 168,212 Asian population. Medicine, 95(14).
- Tomo, S., Sankanagoudar, S., & Sharma, P. (2022). Cordova Formula for Low-Density Lipoprotein-Cholesterol Estimation: Not Only the Simplest of All But Also Superior to Other Formulae at a Higher Range of Triglyceride. Anatolian Journal of Cardiology, 26(7), 520.
- Vujovic, A., Kotur-Stevuljevic, J., Spasic, S., Bujisic, N., Martinovic, J., Vujovic, M., . . . Pajic, D. (2010). Evaluation of different formulas for LDL-C calculation. Lipids in health and disease, 9(1), 27. https://doi.org/10.1186/1476-511X-9-27
- Wadhwa, N., & Krishnaswamy, R. (2016). Comparison of LDL-Cholesterol Estimate using Various Formulae with Directly Measured LDL-Cholesterol in Indian Population. J Clin Diagn Res, 10(12), Bc11-bc13. https://doi.org/10.7860/jcdr/2016/22272.9018
- WHO. (2021). Cardiovascular diseases (CVDs) [Fact sheets]. https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)
- Wolska, A., & Remaley, A. T. (2020). Measuring LDL-cholesterol: what is the best way to do it? Current opinion in cardiology, 35(4), 405.
References
Ahmadi, S. A., Boroumand, M.-A., GOUHARI, M. K., Tajik, P., & Dibaj, S.-M. (2008). The impact of low serum triglyceride on LDL-cholesterol estimation.
Chen, Y., Zhang, X., Pan, B., Jin, X., Yao, H., Chen, B., . . . Chen, H. (2010). A modified formula for calculating low-density lipoprotein cholesterol values. Lipids in health and disease, 9, 1-5.
Choi, H., Shim, J.-S., Lee, M. H., Yoon, Y. M., Choi, D. P., & Kim, H. C. (2016). Comparison of formulas for calculating low-density lipoprotein cholesterol in general population and high-risk patients with cardiovascular disease. Korean circulation journal, 46(5), 688-698.
Contois, J. H., Warnick, G. R., & Sniderman, A. D. (2011). Reliability of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B measurement. Journal of clinical lipidology, 5(4), 264-272.
de Cordova, C. M. M., & de Cordova, M. M. (2013). A new accurate, simple formula for LDL-cholesterol estimation based on directly measured blood lipids from a large cohort. Annals of Clinical Biochemistry, 50(1), 13-19. https://doi.org/10.1258/acb.2012.011259
Detection, N. C. E. P. E. P. o., & Adults, T. o. H. B. C. i. (2002). 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). The Program.
Expert Panel on Detection, E. (2001). Executive summary of the 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). Jama, 285(19), 2486-2497.
Feingold, K. R. (2000). Introduction to Lipids and Lipoproteins. In K. R. Feingold, B. Anawalt, M. R. Blackman, A. Boyce, G. Chrousos, E. Corpas, W. W. de Herder, K. Dhatariya, K. Dungan, J. Hofland, S. Kalra, G. Kaltsas, N. Kapoor, C. Koch, P. Kopp, M. Korbonits, C. S. Kovacs, W. Kuohung, B. Laferrère, M. Levy, E. A. McGee, R. McLachlan, M. New, J. Purnell, R. Sahay, A. S. Shah, F. Singer, M. A. Sperling, C. A. Stratakis, D. L. Trence, & D. P. Wilson (Eds.), Endotext. MDText.com, Inc. Copyright © 2000-2023, MDText.com, Inc.
Friedewald, W. T., Levy, R. I., & Fredrickson, D. S. (1972). Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical chemistry, 18(6), 499-502.
Ginsberg, H. N., Rosenson, R. S., Hovingh, G. K., Letierce, A., Samuel, R., Poulouin, Y., & Cannon, C. P. (2022). LDL-C calculated by Friedewald, Martin-Hopkins, or NIH equation 2 versus beta-quantification: pooled alirocumab trials. Journal of Lipid Research, 63(1).
Grundy, S. M., Cleeman, J. I., Merz, C. N. B., Brewer Jr, H. B., Clark, L. T., Hunninghake, D. B., . . . Stone, N. J. (2004). Implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines. Circulation, 110(2), 227-239.
Hattori, Y., Suzuki, M., Tsushima, M., Yoshida, M., Tokunaga, Y., Wang, Y., . . . Ryomoto, K. I. (1998). 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, 138(2), 289-299.
Jung, E., Kong, S. Y., Ro, Y. S., Ryu, H. H., & Shin, S. D. (2022). Serum Cholesterol Levels and Risk of Cardiovascular Death: A Systematic Review and a Dose-Response Meta-Analysis of Prospective Cohort Studies. Int J Environ Res Public Health, 19(14). https://doi.org/10.3390/ijerph19148272
Karkhaneh, A., Bagherieh, M., Sadeghi, S., & Kheirollahi, A. (2019). Evaluation of eight formulas for LDL-C estimation in Iranian subjects with different metabolic health statuses. Lipids in health and disease, 18(1), 1-11.
Lee, J., Jang, S., Jeong, H., & Ryu, O.-H. (2020). Validation of the Friedewald formula for estimating low density lipoprotein cholesterol: the Korea National Health and Nutrition Examination Survey, 2009 to 2011. The Korean Journal of Internal Medicine, 35(1), 150.
Lindsey, C. C., Graham, M. R., Johnston, T. P., Kiroff, C. G., & Freshley, A. (2004). A Clinical Comparison of Calculated versus Direct Measurement of Low‐Density Lipoprotein Cholesterol Level. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 24(2), 167-172.
Martin, S. S., Giugliano, R. P., Murphy, S. A., Wasserman, S. M., Stein, E. A., Češka, R., . . . Tikkanen, M. J. (2018). Comparison of low-density lipoprotein cholesterol assessment by Martin/Hopkins estimation, Friedewald estimation, and preparative ultracentrifugation: insights from the FOURIER trial. JAMA cardiology, 3(8), 749-753.
Martins, J., Steyn, N., Rossouw, H. M., & Pillay, T. S. (2023). Best practice for LDL-cholesterol: when and how to calculate. Journal of Clinical Pathology, 76(3), 145-152.
Miller, W. G., Myers, G. L., Sakurabayashi, I., Bachmann, L. M., Caudill, S. P., Dziekonski, A., . . . Leary, E. T. (2010). Seven direct methods for measuring HDL and LDL cholesterol compared with ultracentrifugation reference measurement procedures. Clinical chemistry, 56(6), 977-986.
Nasrin, N. (2017). Newly-developed De Cordova’ s Formula for Calculation of LDL Cholesterol in Bangladeshi Population. Borneo Journal of Medical Sciences (BJMS), 11(3), 25-34.
Nauck, M., Warnick, G. R., & Rifai, N. (2002). Methods for measurement of LDL-cholesterol: a critical assessment of direct measurement by homogeneous assays versus calculation. Clinical chemistry, 48(2), 236-254.
Piani, F., Cicero, A. F., Ventura, F., Dormi, A., Fogacci, F., Patrono, D., . . . D'Addato, S. (2021). Evaluation of twelve formulas for LDL-C estimation in a large, blinded, random Italian population. International Journal of Cardiology, 330, 221-227.
Rim, J. H., Lee, Y.-h., Lee, M. H., Kim, H. Y., Choi, J., Lee, B.-W., . . . Lee, S.-G. (2016). Comparison and validation of 10 equations including a novel method for estimation of LDL-cholesterol in a 168,212 Asian population. Medicine, 95(14).
Tomo, S., Sankanagoudar, S., & Sharma, P. (2022). Cordova Formula for Low-Density Lipoprotein-Cholesterol Estimation: Not Only the Simplest of All But Also Superior to Other Formulae at a Higher Range of Triglyceride. Anatolian Journal of Cardiology, 26(7), 520.
Vujovic, A., Kotur-Stevuljevic, J., Spasic, S., Bujisic, N., Martinovic, J., Vujovic, M., . . . Pajic, D. (2010). Evaluation of different formulas for LDL-C calculation. Lipids in health and disease, 9(1), 27. https://doi.org/10.1186/1476-511X-9-27
Wadhwa, N., & Krishnaswamy, R. (2016). Comparison of LDL-Cholesterol Estimate using Various Formulae with Directly Measured LDL-Cholesterol in Indian Population. J Clin Diagn Res, 10(12), Bc11-bc13. https://doi.org/10.7860/jcdr/2016/22272.9018
WHO. (2021). Cardiovascular diseases (CVDs) [Fact sheets]. https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)
Wolska, A., & Remaley, A. T. (2020). Measuring LDL-cholesterol: what is the best way to do it? Current opinion in cardiology, 35(4), 405.