Relation of apolipoprotein C3 to risk of major adverse cardiovascular events and death after acute coronary syndrome on a background of optimized statin treatment
Bibliographic record
Abstract
Abstract Background Apolipoprotein C3 (ApoC3), a component of triglyceride-rich lipoproteins and some low-density lipoprotein and high-density lipoprotein particles, has been shown to predict incident coronary heart disease (CHD) and major adverse cardiovascular events (MACE). However, it is unknown whether ApoC3 predicts risk in patients with acute coronary syndrome (ACS) receiving contemporary therapies including optimized statin treatment, and if any such association is independent of apolipoprotein B (ApoB) levels. Purpose We assessed the association of ApoC3 with first MACE (CHD death, nonfatal myocardial infarction, fatal or nonfatal ischaemic stroke, or hospitalization for unstable angina) and all-cause death in patients with recent ACS treated with high-intensity or maximum-tolerated statin and blinded PCSK9 inhibitor (alirocumab, ALI) or placebo (PBO). Methods ApoC3 was measured by mass spectrometry at baseline (n=11,956) and after 4 months (M4; n=11,176) of treatment with ALI or PBO in the ODYSSEY OUTCOMES trial (which had 18,924 total participants). In continuous and spline analyses adjusted for treatment group and ApoB, we assessed the association of baseline ApoC3 with risk of MACE and death. In the ALI group we determined association of change in ApoC3 from baseline to M4 with risk of MACE and death after M4 in a model adjusted for baseline ApoC3 and ApoB, and the change in ApoB from baseline to M4. Results Median (Q1, Q3) baseline ApoC3 concentration was in a normal range [85 (65, 113) mg/L]. Continuous ApoC3 was not related to MACE (p=0.50) or death (p=0.51); spline analysis showed a slight curvilinear association of baseline ApoC3 with risk of MACE and death, but no clinically meaningful relationship (Figure). Findings were similar in the PBO group alone, and without adjustment for ApoB (data not shown). At M4, the median (Q1, Q3) change from baseline in ApoC3 was -10 (-27, -5; p<0.0001) mg/L with ALI and 2 (-14, 18; P = NS) mg/L with PBO. Overall, ALI significantly reduced the incidence of MACE (10.1% vs 12.1%; p=0.0006) and death (3.5% vs 4.2%; p=0.045) compared with PBO among those with available baseline ApoC3. However, the change in ApoC3 on treatment with ALI did not predict the risk of MACE or death after M4. Findings were qualitatively similar without adjustment for ApoB or its change. Conclusion In a cohort with recent ACS receiving optimized statin therapy and with median baseline ApoC3 in a normal range, ApoC3 did not provide clinically meaningful prediction of cardiovascular events or death. A modest reduction of ApoC3 by ALI did not associate with subsequent risk of MACE or death. It remains uncertain whether targeted therapies producing larger reductions in ApoC3 from higher baseline levels will affect cardiovascular risk.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".