Inflammatory Biomarkers Interleukin‐6 and C‐Reactive Protein and Outcomes in Stable Coronary Heart Disease: Experiences From the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial
Bibliographic record
Abstract
Background Evaluation of cardiovascular prognosis in patients with stable coronary heart disease is based on clinical characteristics and biomarkers indicating dysglycemia, dyslipidemia, renal dysfunction, and possibly cardiac dysfunction. Inflammation plays a key role in atherosclerosis, but the association between inflammatory biomarkers and clinical outcomes is less studied in this population. Methods and Results Overall, 15 828 patients with coronary heart disease in the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial were randomized to treatment with darapladib or placebo and observed for a median of 3.7 years. In 14 611 patients, levels of interleukin‐6 ( IL ‐6) and high‐sensitivity C‐reactive protein were measured in plasma samples: median levels were 2.1 (interquartile range, 1.4–3.2) ng/L and 1.3 (interquartile range, 0.6–3.1) mg/L, respectively. Associations between continuous levels or quartile groups and adjudicated outcomes were evaluated by spline graphs and Cox regression adjusted for clinical factors and cardiovascular biomarkers. IL ‐6 was associated with increased risk of major adverse cardiovascular events (quartile 4 versus quartile 1 hazard ratio [ HR ], 1.60; 95% confidence interval [CI], 1.30–1.97; P <0.0001); cardiovascular death ( HR , 2.15; 95% CI, 1.53–3.04; P <0.0001); myocardial infarction ( HR , 1.53; 95% CI, 1.14–2.04; P <0.05); all‐cause mortality ( HR , 2.11; 95% CI, 1.62–2.76; P <0.0001); and risk of hospitalization for heart failure ( HR , 2.28; 95% CI, 1.34–3.89; P <0.001). Cancer death was doubled in the highest IL ‐6 quartile group ( HR , 2.34; 95% CI, 1.20–4.53; P <0.05). High‐sensitivity C‐reactive protein was associated with both cardiovascular and non‐cardiovascular events in the unadjusted model, but these did not remain after multivariable adjustments. Conclusions IL ‐6, an upstream inflammatory marker, was independently associated with the risk of major adverse cardiovascular events, cardiovascular and all‐cause mortality, myocardial infarction, heart failure, and cancer mortality in patients with stable coronary heart disease. IL‐6 might reflect a pathophysiological process involved in the development of these events. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00799903.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".