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

Alicia N Lyle; Elias N Flores; Clark C Coffman; Alex H Doty; Otoe Sugahara; Florian Kronenberg; L Renee Ruhaak; Christa M Cobbaert; Hubert W Vesper

doi:10.1016/j.jacl.2025.02.010

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

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

Authors

Alicia N Lyle¹, Elias N Flores², Clark C Coffman³, Alex H Doty³, Otoe Sugahara², Florian Kronenberg⁴, L Renee Ruhaak⁵, Christa M Cobbaert⁵, Hubert W Vesper²

Affiliations

¹ Division of Laboratory Sciences, Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA (Drs Lyle, Flores, Coffman, Doty, Sugahara, Vesper). Electronic address: ALyle@cdc.gov.
² Division of Laboratory Sciences, Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA (Drs Lyle, Flores, Coffman, Doty, Sugahara, Vesper).
³ Division of Laboratory Sciences, Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA (Drs Lyle, Flores, Coffman, Doty, Sugahara, Vesper); Battelle, Columbus, OH, USA (Drs Coffman, Doty).
⁴ Department of Genetics, Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria (Dr Kronenberg).
⁵ Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands (Drs Ruhaak, Cobbaert).

PMID: 40102115
DOI: 10.1016/j.jacl.2025.02.010

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.

Publication types

Comparative Study

MeSH terms

Cardiovascular Diseases / blood
Chromatography, Liquid
Humans
Lipoprotein(a)* / blood
Reference Standards
Reproducibility of Results

Substances

Lipoprotein(a)