Clinically relevant differences in LDL-c levels estimated by three different equations
A study found clinically meaningful differences in LDL-c values estimated by the Friedewald, Sampson, and Martin/Hopkins equations, especially in patients with TG levels ≥150 mg/dL and at lower LDL-c values.
Discordance Between Standard Equations for Determination of LDL Cholesterol in Patients With AtherosclerosisLiterature - 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.
Methods
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.
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Outcomes
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
- 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.
Conclusion
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.”
References
1. Friedewald W, Levy R, Fredrickson D. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18(6):499–502.
2. Sampson M, Ling C, Sun Q, et al. A new equation for calculation of low-density lipoprotein cholesterol in patients with normolipidemia and/or hypertriglyceridemia. JAMA Cardiol. 2020;5:540–548.
3. Martin SS, Blaha MJ, Elshazly MB, et al. Comparison of a novel method vs the Friedewald equation for estimating low-density lipoprotein cholesterol levels from the standard lipid profile. JAMA. 2013;310:2061–2068.