Testing
CDC standardization program finds Lp(a) interassay variability up to 69.1% across eight clinical laboratories (J Clin Lipidol 2025)
Original title: Interlaboratory comparison of serum lipoprotein(a) analytical results across clinical assays-Steps toward standardization
As part of the CDC Clinical Standardization Programs' new Lp(a) standardization initiative, built on the International Federation of Clinical Chemistry-endorsed liquid-chromatography mass spectrometry reference measurement procedure (RMP), eight clinical laboratories measured Lp(a) in 40 individual donor serum samples and 3 serum pools, with samples also immunophenotyped by Western blot to determine apo(a) isoform sizes. Assay-specific measurements correlated well overall with the RMP, but interassay measurement variation across individual samples ranged from 3.3% to 69.1%, and this variability was not concentration-dependent nor correlated with apo(a) isoform size. The findings quantify a substantial and still poorly explained source of measurement inconsistency across commercial Lp(a) assays, providing a baseline for the CDC's ongoing efforts to standardize Lp(a) testing for clinical decision-making and for evaluating Lp(a)-lowering therapies.
Original 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.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.