Lp(a) makes up 15% of all atherogenic particles at the highest Lp(a) levels, a particle-based analysis of 158,260 patients (J Clin Lipidol 2022)

Background: Elevated lipoprotein (a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). As clinical LDL cholesterol [LDL-C] incorporates cholesterol from Lp(a) [Lp(a)-C], there is interest in quantifying the contribution of Lp(a)-C to LDL-C given implications for risk assessment, diagnosis, and treatment. Estimating Lp(a)-C is subject to inaccuracies; measuring Lp(a) particle number [Lp(a)-P] is more accurate.

Objective: To capture how Lp(a) contributes to the concentration of atherogenic particles, we demonstrate a particle-based approach using readily available measures of Lp(a)-P and apolipoprotein B (apoB).

Methods: Using the Very Large Database of Lipids (VLDbL), we compared Lp(a)-P (nmol/L) with all apoB containing particles ("apoB-P"). apoB-P was calculated by converting apoB mass to molar concentration using the preserved molecular weight of apoB100 (512 kg/mol). We calculated the percentage of Lp(a)-P relative to apoB-P by Lp(a)-P deciles and stratified by triglycerides, LDL-C, and non-HDL-C.

Results: 158,260 patients from the VLDbL were included. The fraction Lp(a)-P/apoB-P increased with rising Lp(a)-P. Lp(a)-P comprised on average 3% of apoB containing particles among the study population and 15% at the highest Lp(a)-P decile. Lp(a)-P/apoB-P decreased at higher levels of triglycerides and LDL-C owing to larger contributions from VLDL and LDL.

Conclusions: We demonstrate a particle-based approach to quantify the contribution of Lp(a) to all apoB-containing particles using validated and widely available clinical assays. This approach keeps in line with recommendations to move away from mass-based measurements of Lp(a) and prioritize more accurate particle-based measurements. Future research applying this method could define clinically meaningful thresholds and inform use in risk assessment and management.