Quantifying the contribution of lipoprotein(a) to all apoB containing particles
Michael Chilazi1, Weili Zheng1, Jihwan Park2
1Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Insights
A new particle-based method accurately quantifies lipoprotein (a) [Lp(a)] contribution to atherogenic particles. This approach improves risk assessment for cardiovascular disease by focusing on particle number over mass measurements.
Area of Science:
- Cardiovascular Science
- Lipid Metabolism
- Biochemistry
Background:
- Elevated lipoprotein (a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD).
- Clinical LDL cholesterol [LDL-C] measurements incorporate cholesterol from Lp(a) [Lp(a)-C], complicating accurate risk assessment.
- Measuring Lp(a) particle number [Lp(a)-P] is more accurate than estimating Lp(a)-C.
Purpose of the Study:
- To develop a particle-based approach for quantifying Lp(a)'s contribution to atherogenic particles.
- To utilize readily available measures of Lp(a)-P and apolipoprotein B (apoB).
Main Methods:
- Compared Lp(a)-P with all apoB-containing particles (apoB-P) using the Very Large Database of Lipids (VLDbL).
- Calculated apoB-P by converting apoB mass to molar concentration.
- Determined the percentage of Lp(a)-P relative to apoB-P, stratified by Lp(a)-P deciles, triglycerides, LDL-C, and non-HDL-C.
Main Results:
- Analyzed data from 158,260 patients.
- The fraction of Lp(a)-P/apoB-P increased with rising Lp(a)-P.
- Lp(a)-P constituted 3% of apoB-P on average, reaching 15% in the highest Lp(a)-P decile; this fraction decreased with higher triglycerides and LDL-C.
Conclusions:
- Demonstrated a validated, particle-based method to quantify Lp(a) contribution to apoB-containing particles.
- This method aligns with recommendations for prioritizing particle-based over mass-based Lp(a) measurements.
- Future research can define clinical thresholds and inform risk assessment and management strategies.
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.
