Circulation. 2025 Dec 1. doi: 10.1161/CIRCULATIONAHA.125.073855. Online ahead of print.

BACKGROUND: Oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) reflect pro-inflammatory properties of Lp(a) (lipoprotein(a)). The effect of OxPL-apoB on major adverse cardiovascular events (MACE) in patients with acute coronary syndrome in recent the era is not known.

METHODS: OxPL-apoB levels and Lp(a) were measured in 11 630 participants before and 5185 participants 4 months after randomization to alirocumab or placebo in the ODYSSEY OUTCOMES trial. Proportional hazards models adjusted for baseline covariates evaluated associations between log₂-transformed OxPL-apoB and Lp(a) with MACEs. Interactions between the 2 biomarkers and treatment were also evaluated.

RESULTS: Participants were followed for a median 2.9 years; the median age was 58 years, and 23.9% were female. Alirocumab reduced median placebo-adjusted OxPL-apoB by 13.0% and Lp(a) by 26.2% (both P<0.0001). In the placebo group, a doubling of baseline OxPL-apoB was associated with a hazard ratio (HR) of 1.081 (95% CI, 1.026-1.139; P=0.0034) for MACEs. Addition of Lp(a) to the model relegated the relationship of OxPL-apoB insignificant. In the alirocumab group, neither OxPL-apoB nor Lp(a) remained significantly associated with MACEs. A significant 3-way interaction was present among continuous log₂ OxPL-apoB, Lp(a) stratified at the median, and treatment group on MACEs (P_interaction=0.0023) so that, in the placebo group, increasing OxPL-apoB was associated with higher risk of MACEs when Lp(a) was below the median concentration but not above. In the alirocumab group, OxPL-apoB was not related to MACE risk irrespective of Lp(a) concentration.

CONCLUSIONS: In patients with recent acute coronary syndrome receiving optimized statin treatment, elevated OxPL-apoB levels predicted MACEs, a relationship abrogated by alirocumab. The interaction of OxPL-apoB and Lp(a) in the placebo group indicates that OxPL-apoB independently predicts MACEs when Lp(a) levels are relatively low.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT001747 and NCT01663402.

PubMed:41321238 | DOI:10.1161/CIRCULATIONAHA.125.073855