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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

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Calculated low-density lipoprotein cholesterol remains a viable and important test for screening and targeting therapy

Ntei Abudu1 / Stanley S. Levinson2

1Warde Medical Laboratory, Ann Arbor, MI, USA

2Department of Pathology and Laboratory Medicine, University of Louisville, Louisville, KY, USA and Laboratory Service, VAMC, Louisville, KY, USA

Corresponding author: Stanley S. Levinson, Laboratory Service, VAMC, 800 Zorn Avenue, Louisville, KY 40206-1466, USA Phone: +1-502-287-5565/5572, Fax: +1-502-287-6265,

Citation Information: Clinical Chemical Laboratory Medicine. Volume 45, Issue 10, Pages 1319–1325, ISSN (Online) 14374331, ISSN (Print) 14346621, DOI: 10.1515/CCLM.2007.291, October 2007

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Background: Most clinical laboratories use calculated (C) low-density lipoprotein cholesterol (LDL-C) for measurement. Some studies have questioned the linearity of CLDL-C in the clinically useful low range. Moreover, it is generally believed that calculation leads to poor precision such that variation in CLDL-C is greater than the 4% guideline since the calculation is dependent on three primary variables. Actually, the degree of variability of a calculated value will be small if the variability of each primary value is small as compared to its contribution to the calculated value. When LDL-C is low, high-density lipoprotein cholesterol (HDL-C), that has poorer precision, becomes more important in defining the precision of CLDL-C. New homogeneous (direct) HDL-C (dHDL) methods show better precision than the older heterogeneous methods. We hypothesized that a direct homogeneous HDL-C method would substantially improve the low range precision of LDL-C as compared to older heterogeneous HDL-C methods.

Methods: We compared CLDL-C to a standardized electrophoretic method that shows very high precision. We also compared the precision of CLDL-C calculated using a homogeneous dHDL and a heterogeneous indirect method.

Results: We found good linearity for CLDL-C down to 500 mg/L (×0.002586). The main source of CLDL-C variation was HDL-C. Precision was within guidelines when the dHDL method was used. Using our automated methods for lipoprotein lipids, assuming our reference method is accurate, the formula that calculated CLDL-C (mg/dL) using triglyceride (mg/dL) (×0.001129) ×0.2 suggested by some gave more accurate results than the formula using triglyceride (mg/dL) ×0.16 suggested by others.

Conclusions: Given the potential for CLDL-C to meet the precision guidelines, until direct LDL-C methods can be refined, CLDL-C should continue to be the primary test used for assessing LDL-C clinically. Standardized testing for CLDL-C for manufacturers should be available so that the formula used for each instrument can provide well-defined accuracy.

Clin Chem Lab Med 2007;45:1319–25.

Keywords: calculated low-density lipoprotein cholesterol; heterogeneous high-density lipoprotein cholesterol; linearity; precision

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