Metrological traceability of medical test results is essential to guarantee their comparability in time and space across the globe. Test result comparability is accomplished by establishing, validating and implementing internationally endorsed reference measurement systems, as prerequisites for correct diagnosis and risk classification and for monitoring therapeutic effects.
During this lecture the state-of-the-science regarding the clinical utility of the genetically determined apolipoprotein (a) in Lp(a) will be explained as well as the challenges that current Lp(a) measurement procedures bring along. In the past the principles of metrological traceability were not fully understood; consequently insufficient analytical performance of commercial Lp(a) tests had masked the clinical utility of Lp(a) for cardiovascular disease risk assessment about 15 years. The unique structural characteristics of polymorphic apolipoprotein(a) in Lp(a) led to high variability in Lp(a) mass. In addition, the calibrator isoform composition also affected Lp(a) recovery in clinical specimens, small apo(a) isoform carriers being underestimated and large apo(a) isoform carriers being overestimated. Tests expressing Lp(a) in mass units further used incorrect assumptions regarding the protein : lipid ratio of Lp(a). A new reference measurement system that considers the unique apolipoprotein(a) features and produces test results traceable to the International System of Units (SI) is under development by the IFCC working group on Apolipoproteins by Mass Spectrometry. The rationale for the development of this higher order reference measurement system and for transitioning from the former WHO-IFCC immunoassay-based reference measurement system for Lp(a) into a more robust immunoassay-independent mass spectrometry-based reference measurement system and molar units, will be pointed out. The final goal is to guarantee that all commercial Lp(a) tests produce traceable and comparable results within allowable limits of uncertainty that are fit-for-clinical-purpose per intended use.
Literature: LR Ruhaak et al. Development of an LC-MRM-MS-Based Candidate Reference Measurement Procedure for Standardization of Serum Apolipoprotein (a) Tests. Clin Chem 2023, 69: 251-261.
