Correlation of extended Martin/Hopkins equation with a direct homogeneous assay in assessing low-density lipoprotein cholesterol in patients with hypertriglyceridemia

Abstract

Background: The Friedewald or Martin/Hopkins equation is widely used to estimate low-density lipoprotein cholesterol (LDL-C) at triglyceride (TG) levels <400 mg/dL. In this study, we aimed to validate the recently developed Sampson and extended Martin/Hopkins equations intended for use in patients with TG levels up to 800 mg/dL by comparing them to a direct homogenous assay.

Methods: In total, 8676 participants with serum TG levels <800 mg/dL were enrolled in this study. LDL-C was directly measured using Abbott homogeneous assay (DLDL) and estimated using the Friedewald (FLDL), Martin/Hopkins (MLDL), extended Martin/Hopkins (EMLDL), and Sampson equations (SLDL). The overall concordance between the DLDL and LDL-C estimates was calculated. The performance of the four equations was also compared using Bland-Altman plots and mean absolute difference (MAD).

Results: The EMLDL was more accurate than other LDL-C equations particularly for patients with TG≥400 mg/dL (MAD = 10.43; vs. FLDL: MAD = 21.1; vs. SLDL: MAD 11.62). The overall concordance of FLDL, MLDL, EMLDL, and SLDL with DLDL in TG values ranging from 200 to 799 mg/dL were 52.2, 70.5, 71.6, and 65.7%, respectively (p < 0.001), demonstrating the EMLDL as the most optimal estimation method, particularly for high TG levels (≥200 mg/dL).

Conclusion: Both the original and extended Martin/Hopkins method are optimal in estimating LDL-C levels in clinical laboratories using the Abbott analyzer in patients with TG levels of 200-399 and 400-799 mg/dL, respectively. Meanwhile, caution is need that considerable underestimation of Friedewald and Sampson equation could lead to undertreatment in hypertriglyceridemia.

Keywords: Friedewald equation; Sampson equation; extended Martin/Hopkins equation; hypertriglyceridemia; low-density lipoprotein cholesterol.

FIGURE 1

Bland–Altman plot for the comparison of directly measured LDL‐C (DLDL) and Friedewald equation (A) or Martin/Hopkins equation (B) or extended Martin/Hopkins equation (C) or Sampson equation (D) with TG levels 200–799 mg/dL.

FIGURE 2

Residual error plots for low‐density lipoprotein cholesterol estimated by Friedewald equation (A), Martin/Hopkins equation (B), extended Martin/Hopkins equation (C), and Sampson equation (D) against TG level.

FIGURE 3

Distribution of low‐density lipoprotein cholesterol (LDL‐C) values with TG 400–799 mg/dL by direct measurement (DLDL), Friedewald equation (FLDL), Martin/Hopkins equation (MLDL), extended Martin/Hopkins equation (EMLDL), and Sampson equation (SLDL). The data are presented as percent.