Relative value of plasma nitrotyrosine for predicting mortality in patients with coronary artery diseases
Bibliographic record
Abstract
Background: Reactive oxygen species (ROS) mediate the signalling of chief inflammatory pathways throughout all stages of atherosclerosis from endothelial dysfunction to plaque rupture. Activated leukocytes within the atherosclerotic lesion produce ROS, causing local and systemic oxidative injury; however, contributions of ROS production to the clinical features atherosclerosis have not yet been clearly established. Markers of oxidative stress include nitrotyrosine (N-tyr), a post-translational modification generated by reactive nitrogen species. N-tyr is enriched in atherosclerotic lesions, where it activates interstitial metalloproteases, which destabilize the lesion and induce plaque rupture. Recent findings associate circulating N-tyr levels with CAD pathogenesis: N-tyr levels are elevated in patients with established CAD, increased by risk factors associated with atherosclerosis, and reduced by statin therapy. The value circulating N-tyr may have for predicting outcome in CAD patients has not yet been determined. Study Design: We tested the hypothesis that elevated N-tyr predicts mortality in patients with coronary artery disease. Plasma levels of N-tyr were measured using an enzyme-linked immunoassay (Hycult) in a cohort of 619 patients with angiographic evidence of coronary artery disease. After a mean follow-up time of 8.5 years, cases of all-cause mortality (145 cases) and cardiovascular mortality (76 cases) were collected using BC Vital Statistics Agency. The relative value of plasma N-tyr for prediction of mortality was determined using Cox proportional hazards model with adjustment for the following covariates: age, sex, smoking status, hypertension, BMI, LDL-cholesterol, total:HDL-cholesterol, plasma c-reactive protein, personal or known family history of CAD, and reported use of lipid-lowering or antioxidant therapies. Interpretation: Patients whose plasma N-tyr levels were above the cohort median (71.75 nmol/L) had an increased risk of mortality, however this increased risk did not reach conventional statistical significance after covariate adjustment [HR(CI):1.39(0.96-2.01) p=0.07]. No significant association was observed between N-tyr levels and risk of cardiovascular mortality. While this investigation did not reveal a strong association between elevated N-tyr levels and cardiovascular mortality, the trend for increased risk of all-cause mortality indicates that this marker of oxidative stress could be used to identify patients for whom oxidative processes contribute significantly to disease pathogenesis. Further studies are warranted to establish the clinical value of N-tyr and other oxidative stress biomarkers, with the ultimate goal of improving patient risk assessment, and monitoring primary and secondary cardiovascular risk-reduction strategies.
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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 | 0.005 | 0.009 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 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".