Association between cytokines and functional, hemodynamic parameters, and clinical outcomes in pulmonary arterial hypertension
Bibliographic record
Abstract
To assess the relationship of cytokines with functional and clinical outcomes in pulmonary arterial hypertension (PAH). Endothelial dysfunction and vascular inflammation are characteristic of PAH. We investigated whether markers of angiogenesis and inflammation associated with functional, hemodynamic parameters, and clinical outcomes in PAH. PAH patients (n = 206) were pooled from two clinical trials: TRUST-1 and FREEDOM-C2. Baseline and post-treatment cytokine levels were correlated to baseline clinical and hemodynamic parameters, were assessed in clinical subgroups, and were associated with clinical outcomes. In 206 patients (mean age = 48 years; 74% women) with WHO group-1 PAH, most cytokine levels were higher in those with 6-min walking distance (6MWD) < median (335 m) vs. those above median, including Ang-1 (11.9 ± 10.1 vs. 5.9 ± 6.0 ng/mL), Ang-2 (14.3 ± 11.8 vs. 12.2 ± 11.2 ng/mL), and MMP-9 (221 ± 262.3 vs. 119 ± 171 ng/mL). Baseline 6MWD inversely correlated with Ang-1 (r = -0.27, P < 0.0001), Ang-2 (r = -0.20, P = 0.004), and MMP-9 (r = -0.27, P < 0.0001). MMP-9 levels differed significantly by NYHA functional class ( P = 0.001) suggesting an association between MMP-9 and subjective PAH severity. Mean Ang-2 levels were higher in those with baseline right atrial pressure (RAP) > 15 mmHg compared to those with RAP < 15 mmHg (23,841 vs. 11,020 pg/mL). Baseline RAP was associated with change in MMP-9 levels (r = -0.53, P = 0.03). Finally, baseline Ang-1, VEGF and MMP-9 levels were associated with risk of death and hospitalization at 16-week follow-up. Inflammatory cytokines and vascular angiogenesis markers are associated with baseline functional, hemodynamic parameters in PAH, and predict death and hospitalization. Larger prospective studies are needed to confirm the utility of cytokines in PAH.
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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 | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".