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Comparative Study
. 2025 May-Jun;19(3):531-543.
doi: 10.1016/j.jacl.2025.02.010. Epub 2025 Feb 17.

Interlaboratory comparison of serum lipoprotein(a) analytical results across clinical assays-Steps toward standardization

Alicia N Lyle  1 , Elias N Flores  2 , Clark C Coffman  3 , Alex H Doty  3 , Otoe Sugahara  2 , Florian Kronenberg  4 , L Renee Ruhaak  5 , Christa M Cobbaert  5 , Hubert W Vesper  2
Affiliations
Comparative Study

Interlaboratory comparison of serum lipoprotein(a) analytical results across clinical assays-Steps toward standardization

Alicia N Lyle et al. J Clin Lipidol. 2025 May-Jun.

Abstract

Background: Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular diseases (CVD). Recent clinical guidelines recommend measuring Lp(a); however, the lack of Lp(a) assay standardization presents challenges to using common clinical decision points. Assay standardization may minimize interassay variability. This improves consistency in CVD risk assessment and evaluations of Lp(a) therapeutic efficacy. Genetically determined size variations in the defining apolipoprotein(a) [apo(a)] protein contribute to interindividual Lp(a) heterogeneity. Individuals who express 2 apo(a) isoforms have 2 sizes of apo(a) in circulation, further contributing to Lp(a) heterogeneity.

Objective: The Centers for Disease Control and Prevention's Clinical Standardization Programs (CDC CSP) recently launched an Lp(a) standardization program based on the International Federation of Clinical Chemistry endorsed liquid-chromatography mass spectrometry-based reference measurement procedure (RMP). As part of this program, CDC CSP conducted an interlaboratory comparison study to evaluate current Lp(a) interassay variability and to investigate potential factors contributing to measurement variability.

Methods: Eight clinical laboratories measured Lp(a) in 40 individual donor serum samples and 3 serum pools. Serum samples were immunophenotyped by Western blot analysis to determine Lp(a) isoform sizes. Sample concentrations were measured in duplicate over 2 independent runs.

Results: Assay-specific Lp(a) measurements demonstrated good linear correlation with the RMP. Lp(a) interassay measurement variations ranged from 3.3% to 69.1% across individual samples; however, Lp(a) interassay coefficients of variation did not increase in a concentration-dependent manner and were not correlated with Lp(a) isoform sizes.

Conclusion: This study provides new insights into Lp(a) interassay variability and assay performance in clinical laboratories that will guide future standardization efforts.

Keywords: Apo(a); Apolipoproteins; Assay comparison; Interlaboratory comparison; Lipoprotein(a); Lp(a); Standardization.

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Conflict of interest statement

Declaration of competing interest Authors have disclosed any financial and/or personal relationships where applicable. Florian Kronenberg: honoraria received for lectures, honoraria received from Novartis, Amgen, Silence Therapeutics, and Roche for work on advisory boards; L. Renee Ruhaak: Chair of the IFCC WG APO-MS, otherwise none; Christa M. Cobbaert: Dr. Cobbaert has received research grants from Roche Diagnostics, which were not used to support this study. All the remaining authors report no conflict of interest.

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