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Received on November 19, 2007
Accepted on April 16, 2008
Lipids, Lipoproteins, and Cardiovascular Risk Factors |
1 Quest Diagnostics Nichols Institute, San Juan Capistrano, CA
2 Children's Hospital of Oakland Research Institute (CHORI), Oakland, CA
3 Lawrence Livermore National Laboratory, Livermore, CA
* To whom correspondence should be addressed. E-mail: michael.p.caulfield{at}questdiagnostics.com.
BACKGROUND: Current methods for measuring the concentrations of lipoprotein particles and their distributions in particle subpopulations are not standardized. We describe here and validate a new gas-phase differential electrophoretic macromolecular mobility-based method (ion mobility, or IM) for direct quantification of lipoprotein particles, from small, dense HDL to large, buoyant, very-low-density lipoprotein (VLDL).
METHODS: After an ultracentrifugation step to remove albumin, we determined the size and concentrations of lipoprotein particles in serum samples using IM. Scan time is 2 min and covers a particle range of 17.2–540.0 Å. After scanning, data are pooled by totaling the particle number across a predetermined size range that corresponds to particular lipoprotein subclasses. IM results were correlated with those of standard methods for cholesterol and apolipoprotein analysis.
RESULTS: Intra- and interassay coefficients of variation for LDL particle size were <1.0%. The intra- and interassay variation for LDL and HDL particle subfraction measurements was <20%. IM-measured non-HDL correlated well with apolipoprotein B (r = 0.92).
CONCLUSIONS: The IM method provides accurate, reproducible, direct determination of size and concentration for a broad range of lipoprotein particles. Use of this methodology in studies of patients with cardiovascular disease and other pathologic states will permit testing of its clinical utility for risk assessment and management of these conditions.
The following articles in journals at HighWire Press have cited this article:
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  K. Musunuru, M. Orho-Melander, M. P. Caulfield, S. Li, W. A. Salameh, R. E. Reitz, G. Berglund, B. Hedblad, G. Engstrom, P. T. Williams, et al. Ion Mobility Analysis of Lipoprotein Subfractions Identifies Three Independent Axes of Cardiovascular Risk Arterioscler Thromb Vasc Biol, November 1, 2009; 29(11): 1975 - 1980. [Abstract] [Full Text] [PDF]
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 H. R. Superko Advanced Lipoprotein Testing and Subfractionation Are Clinically Useful Circulation, May 5, 2009; 119(17): 2383 - 2395. [Full Text] [PDF]
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S. Mora Advanced Lipoprotein Testing and Subfractionation Are Not (Yet) Ready for Routine Clinical Use Circulation, May 5, 2009; 119(17): 2396 - 2404. [Full Text] [PDF]
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 J. H. Contois, J. P. McConnell, A. A. Sethi, G. Csako, S. Devaraj, D. M. Hoefner, and G. R. Warnick Apolipoprotein B and Cardiovascular Disease Risk: Position Statement from the AACC Lipoproteins and Vascular Diseases Division Working Group on Best Practices Clin. Chem., March 1, 2009; 55(3): 407 - 419. [Abstract] [Full Text] [PDF]
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J. D. Otvos, L. L. Rudel, and J. P. McConnell Concerns Regarding Lipoprotein Particle Measurement by Ion Mobility Analysis Clin. Chem., December 1, 2008; 54(12): 2086 - 2087. [Full Text] [PDF]
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M. P. Caulfield, S. Li, G. Lee, P. A. Blanche, W. A. Salameh, W. H. Benner, R. E. Reitz, and R. M. Krauss In Reply Clin. Chem., December 1, 2008; 54(12): 2088 - 2089. [Full Text] [PDF]
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 M. A. Ruby, D. K. Nomura, C. S. S. Hudak, L. M. Mangravite, S. Chiu, J. E. Casida, and R. M. Krauss Overactive endocannabinoid signaling impairs apolipoprotein E-mediated clearance of triglyceride-rich lipoproteins PNAS, September 23, 2008; 105(38): 14561 - 14566. [Abstract] [Full Text] [PDF]
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