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 Table of Contents  
Year : 2022  |  Volume : 12  |  Issue : 6  |  Page : 287-288

Newer equations for calculation of low-density lipoprotein cholesterol – Their significance and utility

Department of Biochemistry, Sir Ganga Ram Hospital, New Delhi, India

Date of Submission16-Jul-2022
Date of Acceptance26-Sep-2022
Date of Web Publication29-Dec-2022

Correspondence Address:
Dr. Seema Bhargava
Department of Biochemistry, Sir Ganga Ram Hospital, Rajender Nagar, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/cmrp.cmrp_66_22

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How to cite this article:
Manocha A, Bhargava S. Newer equations for calculation of low-density lipoprotein cholesterol – Their significance and utility. Curr Med Res Pract 2022;12:287-8

How to cite this URL:
Manocha A, Bhargava S. Newer equations for calculation of low-density lipoprotein cholesterol – Their significance and utility. Curr Med Res Pract [serial online] 2022 [cited 2023 Feb 5];12:287-8. Available from: http://www.cmrpjournal.org/text.asp?2022/12/6/287/366174

Based on the current National Cholesterol Education Programme Adult Treatment Panel III guidelines, lipid profile testing forms an integral part of the diagnosis and management of Cardiovascular Disease (CVD) patients, with the recommended primary target of therapy being low-density lipoprotein cholesterol (LDL-C).[1] Assays for direct measurement of LDL-C are routinely available, however, due to the extra cost of an additional test as well as the poor analytical quality of the LDL assays, calculated values of LDL-C in the routine lipid panel are still commonly used.

Conventionally, the cholesterol content of LDL has been calculated by Friedewald's equation which involves measurements of total cholesterol, triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C).[2] In this equation, LDL-C = (total cholesterol) – (HDL-C) – (TG/5), where TG/5 serves as the fixed ratio for very-low-density lipoprotein (VLDL) estimation. Although still extensively used to calculate LDL-C in lipid profile reports, due to variations in VLDL, this equation is prone to inaccuracies, especially in cases with high TG or low LDL-C levels.[3] Another major shortcoming was the requirement of fasting samples to exclude the presence of chylomicrons, as these tend to overestimate VLDL and underestimate LDL-C.[4]

To overcome the inadequacies of Friedewald's equation, a number of other equations were described, but their performance was only marginally better.[5] A fixed factor of 6 instead of 5 was proposed by DeLong et al. for dividing TG to calculate VLDL; however, this, too, did not adequately address the intra-individual variations.[6] Martin et al.[7] in 2013 formulated the Martin-Hopkins equation for the estimation of LDL-C based on traditional linear regression analysis. They postulated that instead of the fixed ratio of TG: VLDL of 5:1, an adjustable factor for this ratio would provide a more personalized VLDL value and formulated a 180-cell array of TG and non-HDL factors. The advantage of Martin et al.'s study was that since LDL-C calculation was derived from a fairly large sample size of lipid profiles, it provided a more accurate estimate of LDL-C, especially for levels <70 mg/dL in the presence of high TG levels.[7] This approach, based on the vertical auto profile test, showed greater concordance with the LDL-C measured by ultracentrifugation and had the additional advantage of easy integration with the laboratory information system and smartphones. The American College of Cardiology, the American Heart Association guidelines on CVD risk biomarkers as well as European Federation of Clinical Chemistry and Laboratory Medicine have recommended Martin's equation as the preferred calculation method in non-fasting patients and in patients with low LDL-C and/or high TG levels.[8],[9] However, its major drawback was that it needed further validation in patients with hypertriglyceridaemia and sometimes underestimated VLDL-C in high TG samples.[7],[8],[9],[10]

Recently, Sampson et al.,[11] using β-quantification, developed another novel LDL-C equation, in which VLDL estimation was improved by dividing TG by 8.59 instead of 5:

Equation 1 calculated VLDL more accurately than either Friedewald's or Martin's equations, especially when TG levels were high. This was then used to improve the LDL-C calculation in Equation 2.

Equation 2 provided maximum clinical benefit in estimating LDL-C in patients with TG up to 800 mg/dL and/or low LDL-C levels. The advantages of this equation were that it performed well in normolipidaemic patients and could also be used for CVD risk management. Although a little complicated, it can be incorporated into the laboratory information system.[11]

LDL is a major risk factor for cardiovascular diseases, and consequently, treatment targets depend on its accurate estimation. Moreover, the current guidelines recommend that non-fasting samples be routinely used for lipid profile testing except with non-fasting TG >400 mg/dL.[9] Furthermore, aggressive LDL lowering treatment options are now available, leading to lower LDL levels. These factors, coupled with the analytical instability of the available LDL assays and the extra cost of testing an additional parameter, make serum LDL-C estimation challenging. Although Friedewald's equation is still commonly used, Martin–Hopkins equation is now widely accepted as reliable in non-fasting samples and is recommended for calculating LDL-C in patients with LDL <40 mg/dL and/or TG concentration between 175 and 400 mg/dL.[9],[12] Sampson equation also performed well in patients with hypertriglyceridaemia (TG < 00 mg/dL) and/or low LDL, as well as normolipidaemic patients. Hence, as lipid-lowering strategies and analytical assays evolve, additional studies are required in diverse and larger population groups to fully validate the newer methods for LDL-C calculation.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. 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 2001;285:2486-97.  Back to cited text no. 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.  Back to cited text no. 2
Singh G, Hussain Y, Xu Z, Sholle E, Michalak K, Dolan K, et al. Comparing a novel machine learning method to the Friedewald formula and Martin-Hopkins equation for low-density lipoprotein estimation. PLoS One 2020;15:e0239934.  Back to cited text no. 3
Schectman G, Sasse E. Variability of lipid measurements: Relevance for the clinician. Clin Chem 1993;39:1495-503.  Back to cited text no. 4
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.  Back to cited text no. 5
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;256:2372-7.  Back to cited text no. 6
Martin SS, Blaha MJ, Elshazly MB, Toth PP, Kwiterovich PO, Blumenthal RS, et al. Comparison of a novel method versus the Friedewald equation for estimating low-density lipoprotein cholesterol levels from the standard lipid profile. JAMA 2013;310:2061-8.  Back to cited text no. 7
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: Executive summary: A report of the American college of cardiology/American heart association task force on clinical practice guidelines. Circulation 2019;139:e1046-81.  Back to cited text no. 8
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;37:1944-58.  Back to cited text no. 9
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.  Back to cited text no. 10
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;5:540-8.  Back to cited text no. 11
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.  Back to cited text no. 12


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