Lipoprotein(a): Particle vs. Mass and Prevalent Cardiovascular Disease in the Cardiovascular Risk in Young Finns Study population

Background and aims Lipoprotein(a) [Lp(a)] can be reported as mass (mg/dL) or particle concentration (nmol/L). Because Lp(a) acts at the particle level, molar concentration may better reflect biologically relevant exposure. We compared molar- and mass-based Lp(a) in relation to cardiovascular outcomes, risk classification, LPA genetic variation, and apo(a) isoform phenotype in the Young Finns Study. Methods Molar Lp(a) was measured using a traceable Roche Tina-quant Gen.2 assay and mass using a non-traceable Thermo Fisher assay. Associations with cardiovascular outcomes and aortic valve stenosis were assessed by logistic regression in adults aged ≥40 years (N=3,898). Agreement was assessed using Bland-Altman analysis and guideline-based risk reclassification. Associations with LPA genetic risk score and apo(a) isoform phenotype were assessed using Spearman correlation. Results Both metrics showed similar associations across cardiovascular outcomes, with significant associations for coronary artery disease (CAD) and aortic valve stenosis. In fully adjusted CAD models, the odds ratio for the highest versus lowest quintile was 1.55 for molar and 1.67 for mass. Agreement between guideline-based risk categories was 95.6%. Molar assigned 2.9% of individuals to a higher risk category than mass, versus 1.5% in the opposite direction. The molar-to-mass ratio was associated with LPA score and apo(a) isoform size, with greater attenuation after adjustment for molar than mass. Conclusion Molar and mass showed comparable associations with cardiovascular outcomes. However, molar reporting aligned more closely with the genetic and structural determinants of Lp(a) and more often assigned individuals to higher guideline-based risk categories, supporting continued standardization toward particle-based reporting.