Lipoprotein(a) in Residual Cardiovascular Risk: Measurement Challenges, Assay Standardisation, and Clinical...

Lipoprotein(a) [Lp(a)] is a largely genetically determined, independent contributor to residual atherosclerotic cardiovascular disease (ASCVD) risk, but its clinical interpretation is constrained by measurement complexity. Variation in apolipoprotein(a) [apo(a)] KIV2 copy number, glycosylation, lipid composition, and isoform co-expression complicates mass-based reporting and may cause isoform-sensitive bias in immunoassays. This review examines how these metrological limitations affect Lp(a) reporting, assay comparability, LDL-C estimation, and clinical risk stratification. Current evidence supports preferential use of validated molar reporting (nmol/L) and discourages fixed conversion between mg/dL and nmol/L. Automated immunoassays remain practical for screening and population studies, whereas ELISA and LC-MS/MS have complementary roles in assay validation, reference-method development, and standardisation. Clinically, high Lp(a) may distort calculated LDL-C, and fixed 30% Lp(a)-cholesterol correction can misclassify risk or treatment response. Harmonised molar measurement, ancestry-inclusive validation, and clearer distinction between intact Lp(a) particles and free apo(a) are essential for improving risk assessment and implementing Lp(a)-targeted therapies.