Trimethylamine-N-oxide (TMAO) is associated with cardiovascular mortality and vascular brain lesions in patients with atrial fibrillation
Bibliographic record
Abstract
Abstract Introduction Trimethylamine-N-oxide (TMAO) is a well characterized pro-atherogenic metabolite derived from the microbial processing of phosphatidylcholine and carnitine (usually present in red meat) and subsequent hepatic oxydation, which promotes endothelial dysfunction, platelet activation and thrombosis initiation. Its role concerning cerebral and cardiovascular adverse events has been assessed in various patient subpopulations but not for long term in patients with atrial fibrillation. Methods Baseline TMAO plasma levels were measured by high-performance liquid chromatography/mass spectrometry in plasmas of 2,379 subjects from our multicentric study. Among them, 1,722 participants at time of recruitment underwent brain MRI. Participants were stratified into TMAO tertiles and Cox PH models, linear mixed effect models or logistic mixed effect models were employed adjusting for several risk factors (age, sex, BMI, active and past smoke habit, cystatin c levels, heart failure, diabetes mellitus, hypertension, coronary artery disease and history of TIA/stroke). Subjects were prospectively followed with a median observation time of 4 years. Results Subjects in the highest tertile of TMAO were older (75.4 vs. 70.6 years in low tertile p<0.001) and had significantly more often comorbidities, (26.9% of subjects were diabetic vs. 9.1% in low tertile p<0.001), with higher BMI (28.1 vs 27.0, p<0.001) and worse renal function as assessed by serum cystatin C (1.46 vs 1.07, mg/dl; p<0.001). Heart failure was present in 37.9% participants in the upper compared to 15.8% in the lower tertile. (p<0.001). As shown in Figure 1, Kaplan Meier estimates showed increased cardiovascular mortality with increasing TMAO tertiles (p<0.0001). After adjustment for the abovementioned factors the upper tertile (T3) had an increased hazard ratio (HR) compared to the lowest one (HR 2.36 95% CI 1.56–3.58 p<0.01). Similar trends for global and ischemic stroke occurrences were not found although TMAO levels positively weakly correlated with NIHSS severity (Spearman's coefficient 0.31 p=0.02). Concerning brain MRI findings, TMAO tertiles identified individuals with different prevalence of small non-cortical infarcts (30.5%, 18.1% and 17.4% in high, middle and low tertiles respectively; p<0.001) and when present, larger white matter lesions volumes (5061 mm3, 4158 mm3 and 2970 mm3; p<0.001). After adjustment, the association with small non-cortical infarcts with TMAO levels remained significant in the highest tertile (T3) (OR 1.48 95% CI 1.07–2.05; p=0.02) and a trend towards larger white matter lesions volumes was observed (estimate 1307 95% CI −90–2705; p=0.07). Conclusions TMAO represents a robust prognostic independent biomarker identifying multimorbid, high risk patients for cardiovascular mortality and brain damage. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Swiss National Science Foundation (SNSF) and Theodor und Ida Herzog-Egli Foundation Figure 1. CV mortality according to TMAOFigure 2. Brain lesions assessment
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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.002 | 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".