Oxidized Phospholipids, Lipoprotein(a), and Cardiovascular Outcomes After Acute Coronary Syndrome

作者：Sotirios Tsimikas, Michael Szarek, Christa M. Cobbaert, Fred P.H.T.M. Romijn, J. Wouter Jukema, Deepak L. Bhatt, Vera Bittner, Rafael Díaz, Sergio Fazio, Geneviève Garon, Chong Yuan, Xiaomin Gong, Shaun G. Goodman, Harvey D. White, Joseph L. Witztum, Philippe Gabríel Steg, Gregory G. Schwartz, on behalf of the ODYSSEY OUTCOMES Investigators · 发表于：Circulation · 年份：2025 · DOI：10.1161/circulationaha.125.073855 · 被引用次数：6 · 研究领域：Antioxidant Activity and Oxidative Stress、Paraoxonase enzyme and polymorphisms、Neutrophil, Myeloperoxidase and Oxidative Mechanisms

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 log 2 -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 log 2 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 b...