Comparison of Martin/Hopkins, Sampson/NIH, and Friedewald Equations for the Estimation of Low-Density Lipoprotein Cholesterol and its Effect on Treatment Thresholds for Patients at a Large Academic Medical Center
Authors: Bayes Matthew , Manthei David , Gherasim Carmen 
Published: October 2024

Abstract

Background
Low-density lipoprotein cholesterol (LDL-C) is routinely used in the clinical management of patients at risk for cardiovascular disease (CVD). Currently, LDL-C is frequently calculated with results from the standard lipid panel (total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and triglycerides (TG)); the Friedewald equation is one commonly utilized calculation for LDL-C (FLDL-C). Despite its well-documented limitations, including incorrect estimation of LDL-C with high TGs, the Friedewald equation is still used by many clinical laboratories where patients having TG levels &gt;400 mg/dL are reflexed to direct LDL (DLDL-C) measurement. Recent guidelines recommend the use of “modern” equations such as Martin/Hopkins (MLDL-C) and Sampson/NIH (SLDL-C) equations which account for variations in TG and non-HDL-C. In this study, we assessed the accuracy of the Martin/Hopkins and Sampson/NIH equations for estimating LDL-C levels up to 800 mg/dL in our patient populations and the impact of the equations to patients’ reclassification. As a comparison with previous studies, the misclassification of patients with dyslipidemia into incorrect LDL-C based treatment groups (&lt;70, 70-99, 100-189, and &gt;= 190 mg/dL) is calculated.

Methods
Lipid panel and DLDL-C results are obtained using Siemens Advia and Atellica chemistry analyzers. Data analysis including calculation of mean absolute difference (MAD) between DLDL-C and calculated LDL-C and analysis of treatment group misclassification for TG &lt; 400 and 400 – 800 mg/dL is performed using Python 3.11.5, Pandas 2.1.4, and Scipy 1.11.1.

Results
9,306 out of 296,362 lipid panels from 2021 to 2023 have either corresponding provider ordered (DLDL-C) testing or reflex DLDL-C testing performed. For all TG values, MAD (mg/dL)/total treatment group misclassification (%) is: FLDL-C 42.14/50.66, MLDL-C 21.09/30.03, and SLDL-C 25.51/40.22. For TG values &lt; 400 mg/dL: FLDL-C 19.33/32.21, MDLD-C 16.67/27.84, and SLDL-C 16.73/28.20 with a sample size of 3,614. For TG values 400 - 800 mg/dL: FLDL-C 47.66/65.25, MLDL-C 20.75/30.48, and SLDL-C 31.36/48.8 with a sample size of 4,855. In particular, the Martin/Hopkins vs. Sampson/NIH vs. Friedewald treatment group misclassifications (%) for TG 400 – 800 mg/dL are: DLDL &lt; 70 mg/dL 6.34/1.67/0.60, DLDL 70 – 99 mg/dL 9.31/14.91 /20.62, DLDL 100 – 189 mg/dL 10.53/26.26/38.19, DLDL &gt;= 190 mg/dL 4.30/5.95/5.58.

Conclusion
In terms of misclassification rates across LDL-C based treatment groups used in prior studies, the Martin/Hopkins equation performs better overall than the current Friedewald equation and gives similar overall rates of misclassification (27.84 vs. 30.48%) between the TG &lt; 400 mg/dL and the TG 400 – 800 mg/dL groups, allowing the possibility to reflex to direct LDL-C testing only at the higher threshold of TG 800 mg/dL, reducing reflexed DLDL tests by over 100 per month at our institution. A potential source of error is chemistry analyzer DLDL testing rather than the gold standard LDL-C β-quantification used in previous studies.