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Classification of LDL Phenotypes by 4 Methods of Determining Lipoprotein Particle Size
  1. John J. Sninsky, PhD*,
  2. Charles M. Rowland, MS*,
  3. Arthur M. Baca, MD,
  4. Michael P. Caulfield, PhD,
  5. Harold Robert Superko, MD*
  1. From the *Celera Corporation; †Berkeley HeartLab, Alameda; and ‡Quest Diagnostics Nichols Institute, San Juan Capistrano, CA.
  1. Received April 16, 2013, and in revised form May 23, 2013.
  2. Accepted for publication May 24, 2013.
  3. Reprints: John J. Sninsky, PhD, Celera Corporation, 1401 Harbor Bay Parkway, Alameda, CA 94502. E-mail: John.Sninsky{at}
  4. This symposium was supported in part by a grant from the National Center for Research Resources (R13 RR023236). This was also supported by Quest Diagnostics.
  5. Sninsky and Rowland contributed equally to the study.


Background Low-density lipoprotein cholesterol (LDL-C) lowering is the primary objective of patient management for cardiovascular disease. However, large numbers of patients who have achieved their LDL-C goal remain at risk for cardiovascular events. Low-density lipoprotein subfractions may provide insight into this residual risk. Thus, LDL subfraction standardization and consistency are critical to these efforts.

Aim This study aimed to determine the agreement of the analytical results among 4 methods commonly used for LDL subfractionation, namely, segmented gradient gel electrophoresis (sGGE), ultracentrifugation-vertical auto profile (VAP), nuclear magnetic resonance (NMR), and ion mobility (IM).

Methods Blood samples were collected from 228 apparently healthy adults and sent to 4 clinical reference laboratories for analysis. The LDL phenotype was reported as pattern A (larger, less dense particles) or pattern B (smaller, more dense particles), respectively, and was the primary measure of comparison. An intermediate pattern (A/B) was also reported for sGGE and VAP.

Results We observed complete agreement in the LDL phenotype among the 4 methods in 64% of subjects and agreement among at least 3 of the 4 methods in 87% of subjects. Agreement among pairs of methods ranged from 73% to 98% depending on how differences in reporting of subjects with intermediate results were considered. When subjects having intermediate A/B pattern were excluded, sGGE and IM had the highest agreement (98%) of any pair of methods.

Conclusions We found substantial agreement in the reported LDL phenotype among 4 LDL subfraction measurement technologies as performed by different clinical reference laboratories.

Key Words
  • LDL phenotype
  • triglyceride
  • HDL-C
  • triglyceride/HDL-C ratio
  • LDL subfraction methods

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