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

BackgroundLipoprotein(a) [Lp(a)] can be reported as mass concentration (mg/dL) or particle concentration (nmol/L). Because Lp(a) biology is likely mediated at the particle level, molar concentration may better reflect biologically relevant exposure. We compared molar- and mass-based Lp(a) measurements in relation to cardiovascular outcomes, LPA genetic variation, and apo(a) isoform phenotype in a population-based cohort. MethodsLp(a) was measured in 6,182 participants in the Young Finns Study. Among participants aged [≥]40 years, associations with prevalent coronary artery disease (CAD) and composite cardiovascular disease (CVD) were assessed using logistic regression models. Lp(a) was modeled as quintiles, inverse-normal transformed continuous variables, and clinically relevant cut-points. Discrimination and model fit were evaluated using c-statistics and Akaikes Information Criterion. Associations with an LPA genetic risk score (GRS) and apo(a) isoform phenotype were examined using Spearmans correlation analyses. ResultsThe relation between molar and mass Lp(a) was not constant across the concentration range. The molar-to-mass ratio increased across higher clinically relevant Lp(a) categories, indicating concentration-dependent correspondence between nmol/L and mg/dL. The molar-to-mass ratio was directly associated with the LPA GRS and inversely associated with apo(a) isoform size, and these associations were more strongly attenuated after adjustment for molar than for mass Lp(a). Across CAD and composite CVD, molar- and mass-based Lp(a) showed broadly similar associations. In fully adjusted CAD models, the odds ratio for the highest versus lowest quintile was 1.55 for molar Lp(a) and 1.67 for mass Lp(a); corresponding continuous-model ORs were 1.20 and 1.22 per 1-unit increase in inverse-normal transformed Lp(a). Discrimination and global model fit were essentially identical between the two measurement scales. ConclusionsMolar- and mass-based Lp(a) measurements showed comparable epidemiologic associations with prevalent cardiovascular outcomes. However, molar reporting aligned somewhat more closely with the genetic and structural determinants of Lp(a), supporting continued standardization toward particle-based reporting. Clinical PerspectivesO_ST_ABSWhat Is New?C_ST_ABSO_LIIn the Young Finns Study, Lp(a) reported in molar and mass units showed highly similar associations with prevalent coronary artery disease and composite cardiovascular disease. C_LIO_LIThe relation between molar and mass Lp(a) was not fixed: the molar-to-mass ratio varied across clinically relevant Lp(a) concentration ranges and according to apo(a) isoform size. C_LIO_LIMolar Lp(a) showed slightly stronger alignment with the LPA genetic risk score, and ratio-based analyses suggested that genetically and structurally determined assay discordance was more closely captured by molar than by mass measurement. C_LI What Are the Clinical Implications?O_LIMass- and molar-based Lp(a) remain broadly comparable for cardiovascular risk association analyses, but they should not be treated as directly interchangeable using a single universal conversion factor. C_LIO_LIParticle-based reporting in nmol/L may better reflect the biologic dimension of Lp(a), even when disease discrimination is similar to that of mass-based reporting. C_LI