Associations Between Clonal Hematopoiesis of Indeterminate Potential and Cardiovascular Disease in Three Prospective CKD Patient Cohorts
Bibliographic record
Abstract
Background: Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition characterized by the clonal expansion of blood cells carrying somatic mutations to specific driver genes. Although CHIP has been established as an important contributor to cardiovascular diseases (CVD) in the general population, its association with CVD in a pro-inflammatory chronic kidney disease (CKD) setting has not been examined. Methods: We examined prospective associations between CHIP status and CVD events in three cohorts that included a total of 3,414 CKD patients: the Chronic Renal Insufficiency Cohort (CRIC), the African American Study of Kidney Disease (AASK), and the Canadian study of prediction of death, dialysis and interim cardiovascular events (CanPREDDICT). Primary analyses tested associations between CHIP status and a composite CVD endpoint of myocardial infarction (MI), stroke, congestive heart failure (CHF), or peripheral artery disease (PAD). Cox proportional hazards regression models were used, adjusting for demographic, lifestyle, and clinical covariables, including cardiovascular risk factors. Secondary analyses investigated individual CVD endpoints. Random-effect meta-analyses were employed to combine effects across studies. Results: Study participants had an average age of 68.8 years and a mean eGFR of 40.2 ml/min/1.73m2. As expected, participants had a high frequency of hypertension (95%) and diabetes (49%), with CHIP identified in 25% of participants. Those with large CHIP clone size (VAF≥10%) and a non-DNMT3A CHIP gene mutation exhibited 38% (95% CI:2%-85%) and 42% (95% CI: 6%-90%) higher risks of the composite CVD endpoint, respectively, compared to noncarriers. Compared to non-CHIP status, large clone size was further associated with incident CHF (HR: 1.53, 95% CI: 1.13-2.00). Conclusions: CHIP carrier status may be an important risk factor for CVD among CKD patients, with associations mirroring those observed in the general population. Funding: NIDDK Support, Government Support - Non-U.S.
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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 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.003 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".