Quantifying contribution of Lipoprotein (a) to atherogenic lipoprotein burden: a novel particle-based approach

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 atherogenic lipoprotein burden, 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 atherogenic particles (non-HDL-P). Non-HDL-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 non-HDL-P by Lp(a)-P deciles and stratified across sex, age, triglycerides, LDL-C, and non-HDL-C. Results: 158,260 patients from the VLDbL were included. The fraction Lp(a)-P/non-HDL-P increased with rising Lp(a)-P. Lp(a)-P comprised on average 3% of atherogenic particles among the study population and 15% at the highest Lp(a)-P decile. Findings were similar when stratified by sex. When stratified by age, Lp(a)-P/non-HDL-P was highest among the youngest and oldest patients. Lp(a)-P/non-HDL-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 total atherogenic particle burden using validated and widely available laboratory assays. Future research applying this method could define clinically meaningful thresholds and inform use in risk assessment and management.