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

J Am Coll Cardiol. 2022 Feb 15;79(6):530-541. doi: 10.1016/j.jacc.2021.11.042.


Background: Accurate estimation of low-density lipoprotein cholesterol (LDL-C) is important for guiding cholesterol-lowering therapy. Different methods currently exist to estimate LDL-C.

Objectives: This study sought to assess discordance of estimated LDL-C using the Friedewald, Sampson, and Martin/Hopkins equations.

Methods: Electronic health record data from patients with atherosclerotic cardiovascular disease and triglyceride (TG) levels of <400 mg/dL between October 1, 2015, and June 30, 2019, were retrospectively analyzed. LDL-C was estimated using the Friedewald, Sampson, and Martin/Hopkins equations. Patients were categorized as concordant if LDL-C was <70 mg/dL with each pairwise comparison of equations and as discordant if LDL-C was <70 mg/dL for the index equation and ≥70 mg/dL for the comparator.

Results: The study included 146,106 patients with atherosclerotic cardiovascular disease (mean age: 68 years; 56% male; 91% White). The Martin/Hopkins equation consistently estimated higher LDL-C values than the Friedewald and Sampson equations. Discordance rates were 15% for the Friedewald vs Martin/Hopkins comparison, 9% for the Friedewald vs Sampson comparison, and 7% for the Sampson vs Martin/Hopkins comparison. Discordance increased at lower LDL-C cutpoints and in those with elevated TG levels. Among patients with TG levels of ≥150 mg/dL, a >10 mg/dL difference in LDL-C was present in 67%, 27%, and 23% of patients when comparing the Friedewald vs Martin/Hopkins, Friedewald vs Sampson, and Sampson vs Martin/Hopkins equations, respectively.

Conclusions: Clinically meaningful differences in estimated LDL-C exist among equations, particularly at TG levels of ≥150 mg/dL and/or lower LDL-C levels. Reliance on the Friedewald and Sampson equations may result in the underestimation and undertreatment of LDL-C in those at increased risk.

Keywords: Friedewald equation; LDL-C; Martin/Hopkins equation; Sampson equation; atherosclerotic cardiovascular disease.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Atherosclerosis / blood*
  • Biomarkers / blood
  • Cholesterol, LDL / blood*
  • Female
  • Humans
  • Male
  • Retrospective Studies
  • Triglycerides / blood


  • Biomarkers
  • Cholesterol, LDL
  • Triglycerides