Association of apolipoprotein B and lipoprotein(a) with severe atherosclerotic cardiovascular disease in patients with acute coronary syndrome: the modifying effect of prior lipid-lowering therapy.
A Meseguer Hernandez, F Buendia Santiago, J M Andreu Cayuelas, L Risco Eres, M B Villamarin Heredia, J Merino Romero, M I Banos Maturano, I Gonzalez Fernandez, C A Azcondo San Segundo, M Gimenez Pinana, F Selles Lopez, A Fernandez Reina, L Martinez Gascon, R Rubio Paton, J A Castillo MorenoAbstract
Introduction
The interplay between apolipoprotein B (apoB) and Lipoprotein(a) [Lp(a)] in determining atherosclerotic cardiovascular disease (ASCVD) severity remains complex, particularly under the influence of lipid-lowering therapy (LLT).
Purpose
To evaluate the association of apoB and Lp(a) with severe ASCVD in patients hospitalized for acute coronary syndrome (ACS).
Methods
An observational study was conducted in ACS patients, in whom fasting lipid profiles, including apoB and Lp(a) levels, were obtained. Severe ASCVD was defined as a prior multiterritory ASCVD and/or three-vessel coronary disease on index angiography. Multivariable logistic regression was used to identify independent predictors of severe ASCVD, including the interaction between apoB and prior LLT, and log-transformed Lp(a) levels to account for skewed distribution. Stratified analyses were performed according to LLT status.
Results
815 ACS patients were included. Severe ASCVD was present in 47.5% of the cohort, and 50.9% were on prior LLT. In the overall multivariable model (table), female sex was independently associated with a lower likelihood of severe ASCVD. Conversely, diabetes, hypertension, Lp(a) levels, and prior LLT emerged as independent factors associated with severe ASCVD. A significant apoB × LLT interaction was also identified.
Stratified analyses revealed divergent patterns (figure): in LLT-naive patients, apoB was a significant determinant of severe disease, while Lp(a) showed no significant association. Conversely, in patients on prior LLT, Lp(a) emerged as a strong independent predictor of severe ASCVD, whereas lower apoB levels were paradoxically associated with higher disease burden, likely reflecting more intensive therapy in high-risk individuals.
Conclusions
In ACS patients, the predictive value of lipid biomarkers for disease severity is fundamentally modified by prior LLT. Lp(a) is a key driver of residual risk and disease burden in patients already on therapy, while apoB remains the primary marker in untreated individuals. Recognition of these patterns is essential to identify very high-risk individuals who may benefit from emerging Lp(a)-targeted therapies.TableFigure