On the cusp of global lipoprotein(a) standardization

Abstract Lipoprotein(a) (Lp(a)) has the reputation of being the most misunderstood metric in laboratory medicine. The unique apolipoprotein(a) (apo(a)) in Lp(a) is very heterogenous, the kringle IV domain of apo(a) being formed by 12–50 kringles due to 3 to ∼40 KIV 2 repeats. The variable number of repeated identical KIV 2 domains causes KIV 2 -dependent antibodies to form different amounts of immunocomplexes with apo(a), leading to higher recovery for larger and lower recovery for smaller apo(a) particles than the calibrator. Consequently, the required identity between the analyte in samples and in assay calibrator(s), which is at the basis of any immunoassay, cannot be accomplished in the case of Lp(a). Global Lp(a) standardization was first attempted in the nineties by an IFCC Working Group on Lp(a) Standardization using an ELISA-based reference measurement procedure (RMP) with monoclonal anti-apo(a) antibodies against unique epitopes. WHO-IFCC reference material (RM), named SRM2B, was established with apo(a) expressed in molar units. Currently, a 2nd generation, ISO 15193 compliant, IFCC-endorsed multiplex RMP based on quantitative Mass Spectrometry (MS) has been developed. Traceability to SRM2B is maintained using a value transfer protocol that assigned values to commutable serum-based secondary RMs. ISO 15194 compliant serum-based RMs are currently available. A network of three calibration laboratories runs the harmonized apo(a) RMP. Equipped with a state-of-the-art calibration hierarchy for Lp(a) and using a 2-step approach, it is prime time for global Lp(a) standardization to ensure effective implementation of Lp(a) clinical guidelines and refined cardiovascular precision diagnostics.