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

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.