Association of clonal hematopoiesis with silent brain lesions and cognitive function in patients with atrial fibrillation
Bibliographic record
Abstract
Abstract Background Clonal hematopoiesis of indeterminate potential (CHIP) has been implicated in various cardiovascular diseases. However, the association of CHIP with clinically silent brain lesions and cognitive function in patients with atrial fibrillation (AF) is unclear. Purpose This study investigated whether CHIP mutations are associated with prevalent and incident silent brain lesions and longitudinal neurocognitive performance in a prospective AF cohort. Methods We analyzed 1,572 participants from the Swiss-AF study with targeted sequencing for CHIP-related mutations, brain magnetic resonance imaging (MRI), and standardized neurocognitive testing. Deep sequencing was performed to screen the entire genes for CHIP mutations at baseline. Large noncortical or cortical infarcts (LNCCIs), small noncortical infarcts (SNCIs), microbleeds, and white matter lesions (WML) were assessed at baseline and after 2 years. Cognitive function was evaluated over an 8-year follow-up using the Montreal Cognitive Assessment (MoCA) and the Swiss-AF Cognitive Construct (CoCo) score. Results CHIP mutations were present in 342 (22%) patients, with DNMT3A (49.4%) and TET2 (28.3%) being the most frequent. Compared to non-CHIP carriers, those with CHIP mutations had a significantly higher prevalence of SNCIs (Non-CHIP: 19.9%, DNMT3A: 22.2%, TET2: 27%, other genes: 32.3%; Pχ²=0.017), microbleeds (Non-CHIP: 19.9%, DNMT3A: 23.2%, TET2: 33.8%, other genes: 32.7%; Pχ²=0.002), and WML (Non-CHIP: 50.4%, DNMT3A: 61.3%, TET2: 73%, other genes: 68.7%; Pχ²<0.001). Multivariable regression revealed that CHIP is associated with increased odds of microbleeds (odds ratio (OR) = 1.45, 95% CI = [1.09-1.93], P=0.010) and WML (OR = 1.56, 95% CI = [1.20-2.04], P=0.001). In particular, mutations other than DNMT3A/TET2 were associated with SNCI (OR = 1.63, 95% CI = [1.02-2.54], P=0.03), microbleeds (OR = 1.70, 95% CI = [1.07-2.65], P=0.021), and WML (OR = 1.70, 95% CI = [1.07-2.74], P=0.03). Over the 2-year follow-up, patients with non-DNMT3A/TET2 CHIP mutations were at increased risk for new LNCCI (OR = 3.21, 95% CI = [1.03-8.35], P=0.030) and microbleeds (OR = 2.08, 95% CI = [1.07-3.78], P=0.020). CHIP carriers had no significant accelerated decline in cognitive function after adjustment (MoCA: beta = -0.08, 95% CI = [-0.29-0.13], P=0.47; CoCo: beta = -0.01, 95% CI = [-0.04-0.01], P=0.39). Conclusions CHIP is associated with a greater burden of silent brain lesions, particularly among patients with non-DNMT3A/TET2 mutations, but does not independently predict cognitive decline in patients with AF.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 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 | 0.000 | 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".