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Classification of LDL phenotypes by 4 methods of determining lipoprotein particle size
John J Sninsky1, Charles M Rowland, Arthur M Baca
1Celera Corporation, Alameda, CA 94502, USA. John.Sninsky@celera.com
Insights
Four common methods show substantial agreement in classifying low-density lipoprotein (LDL) subfractions, crucial for assessing cardiovascular risk beyond LDL-C levels.
Area of Science:
- Cardiovascular Disease Research
- Biomarker Analysis
- Clinical Chemistry
Background:
- Low-density lipoprotein cholesterol (LDL-C) reduction is key in cardiovascular disease management.
- Residual cardiovascular risk persists in many patients despite achieving LDL-C goals.
- Low-density lipoprotein (LDL) subfractions may offer insights into this residual risk, necessitating standardized measurement.
Purpose of the Study:
- To evaluate the analytical agreement among four common LDL subfractionation methods: segmented gradient gel electrophoresis (sGGE), ultracentrifugation-vertical auto profile (VAP), nuclear magnetic resonance (NMR), and ion mobility (IM).
Main Methods:
- Blood samples from 228 healthy adults were analyzed across four clinical reference laboratories using sGGE, VAP, NMR, and IM.
- The primary comparison was the LDL phenotype classification: Pattern A (large, less dense LDL) or Pattern B (small, dense LDL).
- An intermediate Pattern A/B was also considered for sGGE and VAP.
Main Results:
- Complete agreement in LDL phenotype was observed among the four methods in 64% of subjects.
- Agreement among at least three methods occurred in 87% of subjects.
- Excluding intermediate results, segmented gradient gel electrophoresis (sGGE) and ion mobility (IM) showed the highest pairwise agreement (98%).
Conclusions:
- Substantial agreement exists in LDL phenotype reporting across four different LDL subfraction measurement technologies.
- These findings support the consistency of LDL subfraction analysis when performed by various clinical reference laboratories.
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.
