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

• Published in: Clinical chemistry (Baltimore, Md.) Vol. 48; no. 2; pp. 236 - 254
• Main Authors: Nauck, Matthias, Warnick, G. Russell, Rifai, Nader
• Format: Journal Article
• Language: English
• Published: Washington, DC Am Assoc Clin Chem 01.02.2002; American Association for Clinical Chemistry
• Subjects: Autoanalysis; Biological and medical sciences; Cholesterol, LDL - blood; Diabetes Mellitus - diagnosis; Electrophoresis; Humans; Investigative techniques, diagnostic techniques (general aspects); Kidney Failure, Chronic - diagnosis; Liver Failure - diagnosis; Medical sciences; Metabolic diseases; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Practice Guidelines as Topic; Ultracentrifugation; Human; Biochemical analysis; Metabolic diseases; Cholesterol LDL; Lipids; Hyperlipoproteinemia; Assay; Direct method; Hypercholesterolemia; Clinical biology; Calculation; Diagnosis; Technique; Dyslipemia; Comparative study
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1093/clinchem/48.2.236

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. 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. 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. 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.