Abstract 4140204: Relationship of Oxidized Phospholipids and Lp(a) to Outcomes after Acute Coronary Syndrome: A Post Hoc Analysis of the ODYSSEY OUTCOMES Trial
Bibliographic record
Abstract
Background: Oxidized phospholipids (OxPL) are preferentially carried by and contribute to the pro-inflammatory properties of lipoprotein(a) [Lp(a)]. OxPL can be quantitated on all apolipoprotein B-100 containing lipoproteins (OxPL-apoB), a dominant proportion of which are present on Lp(a) particles. Objectives: To assess the effect of PCSK9 inhibition by alirocumab on plasma levels of OxPL-apoB, and the relationship to Lp(a) and major adverse cardiovascular events (MACE) in patients with a recent acute coronary syndrome (ACS) on optimized statin treatment. Methods: OxPL-apoB (Diazyme, Inc) and Lp(a) (TinaQuant, Roche Diagnostics) were measured at baseline (1-12 months after ACS) in a subset of participants in the ODYSSEY OUTCOMES trial with samples available at baseline (prior to randomization to alirocumab or placebo, n=11,630) and log 2 -transformed. Proportional hazards models adjusted for 12 baseline covariates evaluated the association of predictor variables (OxPL-apoB and Lp(a)) with MACE (coronary heart disease death, non-fatal MI, ischemic stroke, and hospitalized unstable angina) and all-cause death, with HRs for doubling of the predictor variable. Results: Baseline OxPL-apoB correlated with Lp(a) (r=0.68, p<0.001). At 4-months, ALI reduced median (IQR) PBO-corrected OxPL-apoB by 15%, P<0.001. In the placebo group, when analyzed in separate models with multivariable adjustment, pre-randomization OxPL-apoB (HR (95% CI) 1.081 (1.026-1.139), p=0.003) and Lp(a) (HR (95% CI) 1.080 (1.041-1.120), p<0.001) each predicted MACE. However, when OxPL-apoB and Lp(a) were placed in the same model only Lp(a) remained significant (HR (95% CI) 1.069 (1.023, 1.118), p=0.003). In the alirocumab group, neither baseline OxPL-apoB nor Lp(a) predicted MACE in individual or joint models. Baseline high sensitivity C-reactive protein predicted all-cause death, but OxPL-apoB and Lp(a) did not. Conclusions: In statin-treated patients with recent ACS assigned to placebo, the increased risk of MACE due to elevated OxPL-apoB appears to be mainly driven by their presence on Lp(a). In patients assigned to alirocumab, these variables were not predictive of MACE, suggesting mitigation of OxPL-apoB and Lp(a)-mediated risk by alirocumab.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.003 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".