Mechanisms
New "risk-weighted apoB" metric corrects for apoB underestimating risk when Lp(a) is high, using its roughly sevenfold greater atherogenicity per particle (Lipids Health Dis 2024)
Original title: Lipoprotein(a) and risk-weighted apolipoprotein B: a novel metric for atherogenic risk
Because apolipoprotein B (apoB) directly counts atherogenic particles in plasma, it is the preferred refinement over LDL cholesterol for estimating atherosclerotic cardiovascular disease risk. However, Mendelian randomisation studies show Lp(a) is roughly seven times more atherogenic than LDL per apoB particle, so in patients with elevated Lp(a), apoB can substantially underestimate true risk, and the association between apoB and incident coronary heart disease weakens or disappears even as the LDL cholesterol-CHD association strengthens. The authors propose risk-weighted apoB, calculated in nmol/L as apoB plus Lp(a) times six, which lets clinicians estimate what proportion of a patient's overall atherogenic risk is captured by apoB alone versus carried specifically by Lp(a) particles. The metric's risk estimates align with those from large epidemiological and Mendelian randomisation studies, offering a simple practical tool to reconcile apoB, LDL cholesterol and Lp(a) when assessing a patient's true lipid-driven risk.
Original abstract
Background: Retention of apolipoprotein B (apoB)-containing lipoproteins within the arterial wall plays a major causal role in atherosclerotic cardiovascular disease (ASCVD). There is a single apoB molecule in all apoB-containing lipoproteins. Therefore, quantitation of apoB directly estimates the number of atherogenic particles in plasma. ApoB is the preferred measurement to refine the estimate of ASCVD risk. Low-density lipoprotein (LDL) particles are by far the most abundant apoB-containing particles. In patients with elevated lipoprotein(a) (Lp(a)), apoB may considerably underestimate risk because Mendelian randomization studies have shown that the atherogenicity of Lp(a) is approximately 7-fold greater than that of LDL on a per apoB particle basis. In subjects with increased Lp(a), the association between LDL-cholesterol and incident CHD (coronary heart disease) is increased, but the association between apoB and incident CHD is diminished or even lost. Thus, there is a need to understand the mechanisms of Lp(a), LDL-cholesterol and apoB-related CHD risk and to provide clinicians with a simple practical tool to address these complex and variable relationships. How can we understand a patient's overall lipid-driven atherogenic risk? What proportion of this risk does apoB capture? What proportion of this risk do Lp(a) particles carry? To answer these questions, we created a novel metric of atherogenic risk: risk-weighted apolipoprotein B.
Methods: In nmol/L: Risk-weighted apoB = apoB - Lp(a) + Lp(a) x 7 = apoB + Lp(a) x 6. Proportion of risk captured by apoB = apoB divided by risk-weighted apoB. Proportion of risk carried by Lp(a) = Lp(a) × 7 divided by risk-weighted apoB.
Results: Risk-weighted apoB agrees with risk estimation from large epidemiological studies and from several Mendelian randomization studies.
Conclusions: ApoB considerably underestimates risk in individuals with high Lp(a) levels. The association between apoB and incident CHD is diminished or even lost. These phenomena can be overcome and explained by risk-weighted apoB.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.