Abstract 17341: Novel Lipid Markers of Calcific Aortic Valve Stenosis
Bibliographic record
Abstract
Introduction: Calcific aortic valve stenosis (CAVS) is the most prevalent cardiac valvular pathology, leading to a high incidence of morbidity and mortality if left untreated. The exact pathophysiology of CAVS is largely undefined. Genetic studies have shown a strong correlation of the Lp(a) gene to developing CAVS. Lp(a) is known to be the carrier of plasma Oxidized Phosphatidylcholine and results in Lysophosphatidic acid (LPA) accumulation. The focus of the present study was to determine if OxPC and LPA in calcific human aortic valves relate with echocardiographic markers of CAVS. Methods: Aortic valves (n=98) were obtained from patients undergoing AVR. OxPC and LPA were extracted from pulverized aortic valves and analyzed using a targeted mass spectrometry approach. Lipid values are represented relative to an internal standard and normalized by homogenate and leaflet weights. The severity of calcification and aortic stenosis were measured anatomically by Echocardiographic calcification (ECC) score and hemodynamically by mean AV pressure gradient. Results: One-palmitoyl-2-(9-oxo)-nonanoyl- sn- glycero-3-phosphocholine (PONPC) was the most abundant OxPC among 58 OxPC molecules detected (49.3±3.8ng), in AV tissue. When valves were graded by ECC score, scores of 1 (no calcification) had observably attenuated amounts of mean total OxPC’s (135.3±39.3ng) compared to those with a score of 4 (severe calcification) (310.1±34.8 ng). Total valvular OxPC increased linearly with increased ECC score. Total non-fragmented OxPC’s were also significantly lower in valves with ECC scores of 1 and 2 compared to a score of 4 ( P =0.03). Six LPA species were also identified with 16:0 and 18:1 being the most prevalent. Mean AV pressure gradient had a significant, positive correlation with Total LPA amounts (r 2 =0.580, p <0.001), suggesting that elevated LPA concentrations in CAVS tissue is associated with disease severity. Conclusions: Our study is the largest lipidomics study of human aortic valve tissue demonstrating that OxPC and LPA molecules play a significant role in the etiology of CAVS and provides a novel therapeutic target for mitigating disease progression.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".