Abstract 18221: Interleukin-6 in Patients With HFrEF and the Effect of Dapagliflozin: Insights From DAPA-HF
Bibliographic record
Abstract
Introduction: Inflammation plays an important pathophysiological role in the development and progression of heart failure (HF). Interleukin-6 (IL-6) is a circulating cytokine which is the main regulator of the release of C-reactive protein (CRP) along with pro-inflammatory cytokines. It has been suggested that one of the potential mechanisms of action of sodium glucose co-transporter 2 (SGLT2) inhibitors may be to reduce inflammation. We examined the association between IL-6 and outcomes in patients with HF with reduced ejection fraction (HFrEF) in the DAPA-HF trial and its relationship with the effect of dapagliflozin. Methods: Key inclusion criteria were: 1) NYHA class II-IV, 2) LVEF ≤40%, 3) elevated NT-proBNP and 4) eGFR ≥30 ml/min/1.73m 2 . The primary outcome was a composite of a first episode of worsening HF or cardiovascular death. IL-6 (Roche Diagnostics, e411) was measured at baseline and 52 weeks. Results: Median (IQR) baseline IL-6 was 6.01 pg/mL (interquartile range 4.18-9.29) in the 2980/4774 with available data. Baseline IL-6 quartiles were: Q1 ≤4.18 pg/mL, Q2 4.19-6.01 pg/mL, Q3 16.02-9.29 pg/mL, Q4 ≥9.3 pg/mL. Median high-sensitivity CRP at baseline was 1.13 mg/L and 3.78 mg/L in those with an IL-6 level < or ≥ the median, respectively. The adjusted risk of the primary outcome relative to Q1 was: Q2 = HR 1.39 (95%CI 1.02, 1.89), Q3 = HR 1.55 (1.15, 2.08), Q4 = 2.07 (1.55, 2.76) ( Fig A ). The beneficial effect of dapagliflozin compared with placebo was consistent whether IL-6 was analysed in quartiles (P int = 0.77) or as a continuous variable (P int = 0.69 [ Fig B ]). The placebo-corrected relative change in IL-6 at 52 weeks was -4.1% (95%CI -9.1, +1.2), p=0.13. Conclusions: In DAPA-HF, elevated IL-6 levels were an independent predictor of the risk of cardiovascular death or worsening HF. Dapagliflozin reduced the risk of cardiovascular death or worsening HF regardless of baseline IL-6.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".