Plasma levels of human growth differentiation factor 15 (GDF-15) and their effect of alirocumab on major adverse cardiovascular events and all-cause death after acute coronary syndrome
Bibliographic record
Abstract
Abstract Background Human growth differentiation factor 15 (GDF-15) is a stress response cytokine of the transforming growth factor-β superfamily with roles in health and disease, cell survival and inflammation, and whose elevated plasma levels impair muscle metabolism and cause cachexia. GDF-15 also may play multiple roles in the pathophysiology of cardiovascular disease. Methods The ODYSSEY OUTCOMES trial compared the PCSK9 inhibitor alirocumab to placebo added to high-intensity or maximum-tolerated statin in patients post-acute coronary syndrome (ACS). We assessed in >11,000 patients for whom biobank samples were available, the relation between GDF-15 levels (Roche Diagnostics) at baseline and at 4 months with risk of major adverse cardiovascular events (MACE; primary endpoint, comprising coronary heart disease death, non-fatal myocardial infarction, fatal/non-fatal ischaemic stroke, unstable angina requiring hospitalization) and all-cause death, with adjustment for age and sex. Results Median GDF-15 (quartile [Q]1, Q3) at baseline was 1022 (755, 1465) pg/mL and was reduced by a placebo-adjusted median of 22 pg/mL with alirocumab (p=0.0009) at month 4. This lowering of GDF-15 by alirocumab may represent the first such report via pharmacotherapy. In the placebo group, baseline GDF-15 was significantly associated with risks of MACE (Figure Panel A) and death (Panel B). Relative risk reduction with alirocumab did not vary according to baseline GDF-15 levels for MACE (Panel C) and death (Panel D). Four-year MACE absolute risk reduction [ARR (95% CI)] with alirocumab at Q1 and Q3 of baseline GDF-15 was 2.0% (0.1%, 3.9%) and 2.6% (0.2%, 5.0%), respectively. Reduction of GDF-15 with alirocumab at month 4 was not associated with subsequent MACE (p=0.46) but was associated with death (p=0.0009), with greater reductions translating to lower risk. Conclusion In patients with recent ACS, GDF-15 is a strong predictor of both MACE and death. Reduction of GDF-15 with alirocumab at month 4 was not associated with subsequent MACE but was associated with death (p=0.0009), with greater ARR reductions translating to lower risk. Figure. Splines for baseline GDF-15 vs risk of MACE (Panel A; spline p<0.0001) or all-cause death (Panel B; spline p<00001) through 4 years in the placebo group; treatment hazard ratio for MACE (Panel C; spline p=0.52) and all-cause death (Panel D; spline p=0.78). All splines reflect adjustment for age and sexFigure
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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 | 0.000 |
| 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".