Evaluation of four different equations for calculating LDL-C with eight different direct HDL-C assays

Abstract

Background: Low-density lipoprotein cholesterol (LDL-C) is often calculated (cLDL-C) by the Friedewald equation, which requires high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). Because there have been considerable changes in the measurement of HDL-C with the introduction of direct assays, several alternative equations have recently been proposed.

Methods: We compared 4 equations (Friedewald, Vujovic, Chen, and Anandaraja) for cLDL-C, using 8 different direct HDL-C (dHDL-C) methods. LDL-C values were calculated by the 4 equations and determined by the β quantification reference method procedure in 164 subjects.

Results: For normotriglyceridemic samples (TG<200mg/dl), between 6.2% and 24.8% of all results exceeded the total error goal of 12% for LDL-C, depending on the dHDL-C assay and cLDL-C equation used. Friedewald equation was found to be the optimum equation for most but not all dHDL-C assays, typically leading to less than 10% misclassification of cardiovascular risk based on LDL-C. Hypertriglyceridemic samples (>200mg/dl) showed a large cardiovascular risk misclassification rate (30%-50%) for all combinations of dHDL-C assays and cLDL-C equations.

Conclusion: The Friedewald equation showed the best performance for estimating LDL-C, but its accuracy varied considerably depending on the specific dHDL-C assay used. None of the cLDL-C equations performed adequately for hypertriglyceridemic samples.

Figure 1. Cardiovascular disease risk misclassification by various equations for cLDL-C in samples with TG< 200 mg/dL

Subjects (n=145) with normal serum triglycerides (< 200 mg/dL) were classified into cardiovascular risk categories based on LDL-C performed by the reference method and by the indicated equation and dHDL-C assay. Results are shown as % of participants who were misclassified by cLDL-C into either a lower risk category (hatched bars) or higher risk category (open bars). dHDL-C assays are displayed in ascending order according to increasing total misclassifications. Asterisks (*) indicate the equation that produced the lowest total % misclassification for the indicated dHDL-C assay when compared to other equations, using the same dHDL-C assay. dHDL-C assays: Da, Daiichi; De, Denka; Ky; Kyowa; Ro; Roche; Se; Serotec; Sy, Sysmex; Um, UMA; Wa, Wako.

Figure 2. Cardiovascular disease risk misclassification by various equations for cLDL-C in samples with TG between

200 mg/dL and 400 mg/dL. Subjects (n=19) with serum triglycerides between 200 and 400 mg/dL were classified into cardiovascular risk categories based on LDL-C performed by the reference method and by the indicated equation and dHDL-C assay. Results are shown as % of participants who were misclassified by cLDL-C into either a lower risk category (hatched bars) or a higher risk category (open bars). dHDL-C assays are displayed in ascending order, according to increasing total misclassification. dHDL-C assays: Da, Daiichi; De, Denka; Ky; Kyowa; Ro; Roche; Se; Serotec; Sy, Sysmex; Um, UMA; Wa, Wako.