Are Measurements of LDL Particles Ready for Prime Time?

In this issue of Clinical Chemistry , Ensign et al.(1) report on the differences in 4 methods commonly used to assess LDL subfractions or particles. The results are both interesting and deeply disturbing. In a careful, well-planned study, Ensign and colleagues prospectively and simultaneously collected blood samples as required for each method. Sample analyses by 3 of the methods in question, nuclear magnetic resonance (NMR), density gradient ultracentrifugation (VAP), and gradient gel electrophoresis (GGE), were performed by the laboratories that developed and commercially offer these technologies. The fourth technique, tube gel electrophoresis (TGE), is sold as a commercial reagent set and was performed in the investigators’ own laboratory according to the manufacturer’s specifications.The primary result investigated was LDL pattern, as interpreted by the reporting laboratories. Other results reported by some of the laboratories included particle number/concentration and LDL cholesterol (LDL-C), the current focus of national and international treatment guidelines and therapeutic goals(2)(3).Comparison of the LDL pattern results, as interpreted by the reporting laboratories, revealed substantial disparity between the methods, with only 8% (3 of 40) of samples showing complete agreement among the 4 methods for the most basic and qualitative of the interpretations, that of whether the samples analyzed had what is known as pattern A or pattern B. The 2 assays that agreed most often, NMR and GGE, did so for 28 of 37 samples for which results were available for both methods. This comparability was no better than that obtained with the National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP) III cut-point of 1.70 mmol/L (150 mg/dL) for optimal triglycerides(2), above which pattern B and below which pattern A can be predicted. In the study by Ensign et al, there was observed agreement of NMR with triglyceride results in 28 …