Unlike most biomarkers, Lp(a) is far less forgiving on selectivity and metrological shortcomings

Despite being an established causal risk factor for ASCVD, lipoprotein(a) (Lp(a)) remains one of the most misunderstood metrics in cardiovascular risk assessment and clinical practice. Standardization of Lp(a) measurement remains challenging due to the marked heterogeneity in apolipoprotein(a) isoform size and co-existence of genetic variants, which affect immunoassay calibration and inter-method comparability, potentially leading to misclassification of cardiovascular risk and impacting clinical decision-making. Stakeholders concerned about accuracy of Lp(a) testing have spent decades trying to solve what was considered a calibration problem for Lp(a). We currently know there is also a measurand heterogeneity problem as revealed by Lp(a) assays with different selectivity's. Consequently, Lp(a) harmonization ultimately requires a clearly defined measurand and supports the transition from mass-based to molar standardization.