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

Abstract: 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. Keywords: lipoprotein(a), Lp(a), apoprotein(a), apo(a), cardiovascular diseases, heart disease risk factors, analysis