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
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 . 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.
- Estimated LDL-c values were consistently higher with the Martin/Hopkins equation, compared with the Friedewald and Sampson equations.
- Discordance rates were 15% for the Friedewald vs Martin/Hopkins comparison (in other words, in 15% of cases the Friedewald equation estimated a LDL-c value <70 mg/dL, while the Martin/Hopkins equation estimated a LDL-c value ≥70 mg/dL.), 9% for the Friedewald vs Sampson comparison, and 7% for the Sampson vs Martin/Hopkins comparison.
- Discordance rates were higher in patients with TG ≥150 mg/dL (41%, 23%, and 23% for the Friedewald vs Martin/Hopkins, Friedewald vs Sampson and Sampson vs Martin/Hopkins, respectively).
- For the Friedewald and Martin/Hopkins comparison, >10-mg/dL differences in LDL-c were found in 48% of all patients and in 67% of patients with TG levels ≥150 mg/dL.
- The absolute magnitude of discordance in all patients with LDL-c <70 mg/dL by the Friedewald equation and ≥70 mg/dL by the Martin/Hopkins equation was 11.8 ± 7.5 (mean ± SD) mg/dL, and 14.8 ± 6.7 mg/dL in those with TG ≥150 mg/dL. The corresponding values for the Friedewald vs Sampson comparison were 6.3 ± 3.8 mg/dL and 8.2 ± 3.2 mg/dL, respectively.
- Discordance rates increased when a lower LDL-c cutpoint of 55 mg/dL was used: 23% for the Friedewald vs Martin/Hopkins comparison, 15% for the Friedewald vs Sampson comparison and 10% for the Sampson vs Martin/Hopkins comparison. The discordance rates for comparisons with a LDL-c cutpoint of 55 mg/dL in those with TG levels ≥150 mg/dL were 60%, 36% and 37%, respectively.
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.”