Abstract 17551: Association between Circulating Matrix Gla Protein and Progression of Aortic Stenosis: A Substudy of the ASTRONOMER Trial
Bibliographic record
Abstract
Background: In a previous substudy of the ASTRONOMER trial, we reported that metabolic syndrome (MetS) is associated with faster progression of aortic stenosis (AS). Recent studies suggested that dysregulation of mineral metabolism could play a role in the pathogenesis of AS. The carboxylated form of the Matrix Gla Protein (MGP) is an inhibitor of ectopic calcification. The aim of this study was to determine the association between levels of the total (i.e. carboxylated and non carboxylated) MGP and AS progression rate. Methods: Among the 269 patients randomized in ASTRONOMER, mean follow-up time 3.4 ±1.3yrs, 217 had measurement of circulating level of total MGP. None of them had hypercholesterolemia, diabetes or CAD. However, 29% had hypertension and 28% MetS. AS progression rate was measured with the annualized increase in peak aortic jet velocity (V peak ). Results: In the whole cohort, MGP level was associated with AS progression rate in univariate analysis (r=0.15; p=0.03) but not in multivariate analysis. There was an interaction (p=0.03) between MGP level and age with respect to its relationship with AS progression rate. In patients with age peak , and status of randomization, higher MGP level (p=0.008) and MetS (p=0.001) were independent predictors of faster AS progression in younger patients. MGP level was positively related to age (p=0.03), LDL-chol (p=0.02), oxidized-LDL (p=0.005), glycaemia (p=0.001), and HOMA index (p=0.05). In multivariate analysis, oxidized-LDL (p=0.03) and glycaemia (p=0.01) were the only two factors independently associated with MGP level. Conclusion: This study reports an association between total circulating MGP levels and faster AS progression in younger patients. These findings suggest that valvular calcification may lead to increased MGP expression, perhaps in a feedback attempt to physiologically reduce bone-like formation of calcium deposits in the valve. Further studies with measures of both forms of MGP are needed to clarify the exact role of the MGP system in AS.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".