Related Experiment Video
Updated: Apr 4, 2026
Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
Published on: November 10, 2017
A comparative study of four independent methods to measure LDL particle concentration
Paul N Hopkins1, James V Pottala2, M Nazeem Nanjee1
1Cardiovascular Genetics, Cardiovascular Medicine, Department of Internal Medicine, University of Utah, Salt Lake City, UT 84108, USA.
Insights
This study compared four methods for measuring low-density lipoprotein particle concentration (LDL-P), finding ultracentrifugation most precise and one nuclear magnetic resonance spectroscopy method least precise. Results aid future clinical applications of LDL-P testing.
Area of Science:
- Cardiovascular diagnostics
- Lipidomics
- Analytical chemistry
Background:
- Low-density lipoprotein particle concentration (LDL-P) is a superior predictor of cardiovascular events compared to LDL cholesterol (LDL-C).
- Limited studies have directly compared various LDL-P measurement methodologies, especially against ultracentrifugation.
Purpose of the Study:
- To evaluate the comparability and precision of four distinct LDL-P measurement methods.
- To assess the performance of electrophoretic and nuclear magnetic resonance spectroscopy (NMR) methods against ultracentrifugation.
Main Methods:
- Serum samples from 48 individuals were analyzed in triplicate across three laboratories.
- Four LDL-P methods were employed: ultracentrifugation (reference), a novel electrophoretic method, and two NMR spectroscopy techniques (LS-NMR and HD-NMR).
Main Results:
- Ultracentrifugation demonstrated the highest precision, while LS-NMR exhibited the lowest (p < 0.0001), though all methods yielded clinically acceptable coefficients of variation (CVs).
- The electrophoretic method's precision was comparable to ultracentrifugation; HD-NMR showed intermediate precision.
- HD-NMR regression analysis against ultracentrifugation yielded the closest slope to 1 (0.90) and intercept to 0 (-48). The two NMR methods correlated well (r=0.95) but showed a significant vertical shift.
Conclusions:
- The comparative analysis provides valuable data for selecting appropriate LDL-P measurement methods.
- Findings support the utility of these LDL-P methods in future cardiovascular research and clinical practice.
Background:
Low-density lipoprotein particle concentration (LDL-P) is generally more predictive of clinical cardiovascular endpoints than LDL cholesterol (LDL-C). Few studies have directly compared multiple LDL-P methods, particularly with ultracentrifugation.
Objective:
Examine comparability and precision of 4 LDL-P methods.
Methods:
We divided serum from 48 subjects into blinded triplicates and measured LDL-P in 3 separate laboratories by 4 methods: ultracentrifugation (reference method), a novel electrophoretic method, and nuclear magnetic resonance spectroscopy (NMR) by 2 independent methods: a 400 MHz Vantera(®) instrument supplied by Liposcience (LS-NMR) and operated at ARUP Laboratories, and a 600 MHz Bruker instrument (ASCEND 600) operated at Health Diagnostic Laboratory (HD-NMR).
Results:
Of the 4 methods, ultracentrifugation was the most precise and LS-NMR the least; the latter had a significantly greater CV (p < 0.0001) as compared with all 3 of the other methods, although all CVs were clinically acceptable. The electrophoretic method showed similar precision to ultracentrifugation, while HD-NMR was intermediate. The HD-NMR had the slope closest to 1 (0.90, 95% CI 0.71 to 1.09) and the intercept closest to 0 (-48, -353 to 256) compared to the ultracentrifugation method in Deming regression models. While the two NMR methods correlated well (r = 0.95) with each other and had a slope equivalent to 1 (1.08, 0.98 to 1.19), their intercept in Deming regression excluded 0 (194, 53 to 335) indicating a vertical shift between the two methods.
Conclusions:
This LDL-P method comparison may prove useful for future research and clinical applications.
