Balance of non-Lp(a) apoB and Lp(a) with Coronary Plaque Phenotypes and MACE: Insights from PROSPECT II and CASABLANCA.

AIMS: Apolipoprotein B (apoB)-containing lipoproteins contribute heterogeneously to atherosclerosis. While apoB particles are major determinants of plaque burden, Lp(a) has been linked to plaque inflammation and instability. We investigated the associations of non-Lp(a) apoB, Lp(a), and their relative balance with coronary plaque burden and vulnerability. METHODS AND RESULTS: Among 854 patients with recent myocardial infarction enrolled in the PROSPECT II near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) study, total apoB was converted to nmol/L and non-Lp(a) apoB calculated by subtracting Lp(a) in nmol/L. The non-Lp(a) apoB/Lp(a) ratio was used to characterize the relative predominance of these lipoprotein classes. Higher non-Lp(a) apoB was independently associated with greater plaque burden (plaque percentage volume; β = 0.19, 95% confidence interval [CI] 0.05-0.33; P = 0.009), but not with lipid core burden index. In contrast, lower non-Lp(a) apoB/Lp(a) ratio tertile were associated with higher odds of plaque burden ≥70% (odds ratio [OR] 1.47, 95% CI 1.04-2.07; P = 0.029) and the composite vulnerability endpoint of plaque burden ≥70% and maxLCBI4mm ≥324.7 (OR 1.62, 95% CI 1.12-2.33; P = 0.011). In an exploratory external cohort from the CASABLANCA study, lower ratios identified an Lp(a)- and oxidized phospholipid-enriched phenotype and were associated with higher unadjusted cardiovascular risk. CONCLUSIONS: Non-Lp(a) apoB and Lp(a) demonstrate distinct associations with coronary plaque burden and vulnerability. Differentiating Lp(a)-associated from non-Lp(a)-associated apoB particle pools provides complementary information on coronary plaque phenotype, and the non-Lp(a) apoB/Lp(a) ratio summarizes their relative predominance.