Key points are not available for this paper at this time.
Lipoprotein(a) Lp(a) carries cholesterol Lp(a)-C, yet the cholesterol composition of Lp(a) particles and its relationship to apolipoprotein(a) apo(a) isoform size remains incompletely defined. Prior estimates of Lp(a)-C have relied on fixed-percentage assumptions rather than direct biochemical measurement, limiting insight into particle-level heterogeneity. We developed a direct immunocapture assay using the monoclonal antibody LPA4 to quantify Lp(a)-C in plasma and applied it to 94 individuals spanning a wide range of Lp(a) concentrations and apo(a) isoform sizes. Lp(a)-C was strongly correlated with Lp(a) molar concentration (R = 0.925, P 24 KIV) showed lower Lp(a)-C (3.0 ± 1.5 mg/dL) (P < 0.001). In contrast, particle-normalized metrics demonstrated the opposite pattern: both the Lp(a)-C/Lp(a) molar ratio and Lp(a)-C/Lp(a)-apoB mass ratio increased progressively with apo(a) isoform size (P < 0.001), indicating greater cholesterol content per Lp(a) particle among larger isoforms. These findings demonstrate a dissociation between circulating Lp(a)-C concentration, which primarily reflects particle number, and cholesterol content per particle, which varies systematically with apo(a) isoform size. Direct measurement of Lp(a)-C identifies compositional heterogeneity not captured by conventional estimation methods and may provide a framework for future studies of isoform-dependent variation in Lp(a) structure and function.
Tsimikas et al. (2026) studied this question.