Physicians' Academy for Cardiovascular Education

Clinically relevant differences in LDL-c levels estimated by three different equations

Discordance Between Standard Equations for Determination of LDL Cholesterol in Patients With Atherosclerosis

Literature - Sajja A, Li HF, Spinelli KJ et al., - J Am Coll Cardiol. 2022 Feb 15;79(6):530-541. doi: 10.1016/j.jacc.2021.11.042.

Introduction and methods

Background and aim of the study

The most common means to estimate LDL-c is the Friedewald equation, which was developed in the 1970s from a relatively small sample of individuals [1]. However, the Friedewald equation has a reduced accuracy in patients with low LDL-c and high TG levels. To address this limitation, the Martin/Hopkins and Sampson equations were developed [2,3]. This study investigated the differences in estimated LDL-c using the Friedewald, Sampson, and Martin/Hopkins equations.


Electronic health record data were retrospectively analyzed. A total of 146,106 patients with clinical ASCVD and ≥1 lipid panel with a TG level <400 mg/dL were included. Mean age was 68 years, 56% were male and 91% were white. LDL-c was estimated in mg/dL using the Friedewald, Sampson, and Martin/Hopkins equations.

Concordance between the equations was assessed in three comparator groups (index equation vs comparator):

- Friedewald vs Sampson

- Friedewald vs Martin/Hopkins

- Sampson vs Martin/Hopkins

Patients were categorized as concordant if LDL-c was <70 mg/dL in both equations and discordant if LDL-c was <70 mg/dL for the index equation and ≥70 mg/dL for the comparator.



Key outcomes included the rates of discordance between LDL-c equations at an LDL-c cutpoint of 70 mg/dL in all patients and in those with TG levels ≥150 mg/dL.

Other outcomes included the percentage of patients having >10-mg/dL LDL-c differences for comparisons between equations, the absolute magnitudes of discordance, and rates of discordance with other LDL-c cutpoints.

Main results


This study found clinically meaningful differences in LDL-c values in patienten with ASCVD estimated by the Friedewald, Sampson, and Martin/Hopkins equations, especially in patients with TG levels ≥150 mg/dL and at lower LDL-c cutpoints.

The authors wrote: “Use of the Friedewald or Sampson equations in this population may lead to underestimation of LDL-c and, consequently, undertreatment of those at highest risk.”


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Find this article online at J Am Coll Cardiol.

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