HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit an electronic Letter to the Editor about this paper Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (34) Citing Articles via Google Scholar Google Scholar Articles by Nauck, M. Articles by Rifai, N. Search for Related Content PubMed PubMed Citation Articles by Nauck, M. Articles by Rifai, N. Related Collections Lipids, Lipoproteins, and Cardiovascular Risk Factors

Methods for Measurement of LDL-Cholesterol: A Critical Assessment of Direct Measurement by Homogeneous Assays versus Calculation

¹ Department of Clinical Chemistry, University Hospital, D-79106 Freiburg, Germany.

² Pacific Biometrics Research Foundation, Issaquah, WA 98027.

³ Departments of Laboratory Medicine and Pathology, Children’s Hospital and Harvard Medical School, Boston, MA 02115.

^aAddress correspondence to this author at: University Hospital Freiburg, Department of Clinical Chemistry, Hugstetter Strasse 55, D-79106 Freiburg i.Br., Germany. Fax 49-761-270-3444; e-mail manauck{at}med1.ukl.uni-freiburg.de.

Background: Because LDL-cholesterol (LDL-C) is a modifiable risk for coronary heart disease, its routine measurement is recommended in the evaluation and management of hypercholesterolemia. We critically examine here the new homogeneous assays for direct determination of LDL-C.

Approach: This review relies on published studies and data of the authors using research and routine methods for LDL-C determination. We review experience with methods from their earlier use in lipid research laboratories through the transition to routine clinical testing and the recent development of homogeneous assays. We focus on comparative evaluations and characterizations and the performance of the assays.

Content: Homogeneous assays seem to be able to meet current National Cholesterol Education Program (NCEP) requirements for LDL-C testing for precision (CV <4%) and accuracy (bias <4%), when samples collected from nonfasting individuals are used. In addition, all five currently available assays have been certified by the Cholesterol Reference Methods Laboratory Network. The homogeneous methods also appear to better classify individuals into NCEP cutpoints than the Friedewald calculation. However, the limited evaluations to date raise questions about their reliability and specificity, especially in samples with atypical lipoproteins.

Conclusions: Available evidence supports recommending the homogeneous assays for LDL-C to supplement the Friedewald calculation in those cases where the calculation is known to be unreliable, e.g., triglycerides >4000 mg/L. Before the homogeneous assays can be confidently recommended to replace the calculation in routine practice, more evaluation is needed.

The following articles in journals at HighWire Press have cited this article:

				R. Erbel, J. A.C. Delaney, N. Lehmann, R. L. McClelland, S. Mohlenkamp, R. A. Kronmal, A. Schmermund, S. Moebus, N. Dragano, A. Stang, et al. Signs of subclinical coronary atherosclerosis in relation to risk factor distribution in the Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study (HNR) Eur. Heart J., November 2, 2008; 29(22): 2782 - 2791. [Abstract] [Full Text] [PDF]

				S. de Ferranti, D. Shapiro, R. Markowitz, E. Neufeld, N. Rifai, and H. Bernstein Nonfasting Low-Density Lipoprotein Testing: Utility for Cholesterol Screening in Pediatric Primary Care Clinical Pediatrics, June 1, 2007; 46(5): 441 - 445. [Abstract] [PDF]

				C. Garcia-Hejl, P. Vest, C. Renard, A. Merens-Gonthier, A. Boukhira, and H. Thefenne-Astier Falsely Low LDL Cholesterol Results and Cholestasis. Clin. Chem., November 1, 2006; 52(11): 2125 - 2127. [Full Text] [PDF]

				E. T. Bairaktari, K. I. Seferiadis, and M. S. Elisaf Evaluation of Methods for the Measurement of Low-Density Lipoprotein Cholesterol Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 2005; 10(1): 45 - 54. [Abstract] [PDF]

				R. Rej Clinical Chemistry through Clinical Chemistry: A Journal Timeline Clin. Chem., December 1, 2004; 50(12): 2415 - 2458. [Abstract] [Full Text] [PDF]

				N. Rifai, G. R. Cooper, W. V. Brown, W. Friedewald, R. J. Havel, G. L. Myers, and G. R. Warnick Clinical Chemistry Journal Has Contributed to Progress in Lipid and Lipoprotein Testing for Fifty Years Clin. Chem., October 1, 2004; 50(10): 1861 - 1870. [Full Text] [PDF]

				W. Richmond When and how to measure lipids and their role in CHD risk prediction The British Journal of Diabetes & Vascular Disease, May 1, 2003; 3(3): 191 - 198. [Abstract] [PDF]

				S. Usui, H. Kakuuchi, M. Okamoto, Y. Mizukami, and M. Okazaki Differential Reactivity of Two Homogeneous LDL-Cholesterol Methods to LDL and VLDL Subfractions, as Demonstrated by Ultracentrifugation and HPLC Clin. Chem., November 1, 2002; 48(11): 1946 - 1954. [Abstract] [Full Text] [PDF]

				G. R. Warnick, W. G. Miller, P. P. Waymack, and F. P. Anderson Lack of Agreement of Homogeneous Assays with the Reference Method for LDL-Cholesterol May Not Indicate Unreliable Prediction of Risk for Cardiovascular Disease * Authors of the article cited above respond: Clin. Chem., October 1, 2002; 48(10): 1812 - 1815. [Full Text] [PDF]

				C. Cobbaert, C. Weykamp, H. Baadenhuijsen, A. Kuypers, J. Lindemans, and R. Jansen Selection, Preparation, and Characterization of Commutable Frozen Human Serum Pools as Potential Secondary Reference Materials for Lipid and Apolipoprotein Measurements: Study within the Framework of the Dutch Project "Calibration 2000" Clin. Chem., September 1, 2002; 48(9): 1526 - 1538. [Abstract] [Full Text] [PDF]