Circulation, 1 1 2025 Oxidized Phospholipids, Lipoprotein(a), and Cardiovascular Outcomes after Acute Coronary Syndrome. Tsimikas S, Szarek M, Cobbaert CM, Romijn F, Jukema JW, Bhatt DL, Bittner VA, Diaz R, Fazio S, Garon G, Yuan C, Gong XM, Goodman SG, White HD, Witztum JL, Steg PG, Schwartz GG, ODYSSEY OUTCOMES investigators
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 (Pinteraction=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.
