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Clonal hematopoiesis of indeterminate potential is associated with increased cardiovascular risk in chronic kidney
Jie Liu1, Shangjian Luo2, Zhiqiang Liu3
1Department of Nephrology, Metabolism and Immunology Laboratory for Urological Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Insights
Clonal hematopoiesis of indeterminate potential (CHIP) is common in chronic kidney disease (CKD) patients and independently linked to more severe coronary artery disease and increased cardiovascular event risk.
Area of Science:
- Cardiovascular Medicine
- Nephrology
- Hematology
Background:
- Chronic kidney disease (CKD) patients have a high prevalence of coronary artery disease (CAD).
- Clonal hematopoiesis of indeterminate potential (CHIP) shares risk factors with CKD, including aging and inflammation, potentially worsening vascular damage.
- The specific association between CHIP and coronary lesions in CKD, and its impact on cardiovascular events, requires further investigation.
Purpose of the Study:
- To investigate the association between CHIP and the characteristics of coronary artery lesions in patients with CKD.
- To determine if CHIP is an independent predictor of adverse cardiovascular events in this population.
Main Methods:
- Prospective study of 151 CKD patients undergoing coronary angiography.
- High-depth targeted sequencing to detect CHIP.
- Measurement of serum inflammatory factors and systematic follow-up for clinical events.
Main Results:
- CHIP was detected in 43.0% of CKD patients, increasing with age.
- CHIP patients exhibited higher rates of left circumflex stenosis, three-vessel disease, and Gensini scores.
- CHIP independently predicted three-vessel disease (OR 2.26) and major adverse cardiovascular events (HR 2.02).
Conclusions:
- CHIP is significantly associated with more severe coronary lesions in CKD patients.
- CHIP serves as an independent risk factor for adverse cardiovascular outcomes in individuals with CKD.
Background:
Patients with chronic kidney disease (CKD) exhibit an extremely high prevalence of coronary artery disease. Clonal hematopoiesis of indeterminate potential (CHIP) and CKD share pathological features such as aging, chronic inflammation, and accelerated atherosclerosis. Their coexistence can synergistically exacerbate vascular damage and increase coronary risk. However, the association between CHIP and specific coronary lesions in CKD populations has not been reported, and its relationship with cardiovascular events remains controversial.
Methods:
A total of 151 patients with CKD who underwent coronary angiography were prospectively included. To evaluate the status of CHIP, we utilized high-depth targeted sequencing, and measured serum inflammatory factor levels. Furthermore, we systematically followed up these patients to document the occurrence of adverse clinical events.
Results:
CHIP was identified in 65 (43.0%) CKD patients, with the carrier rate steadily rising with age. The CHIP subjects had higher rates of left circumflex stenosis, three-vessel disease, and Gensini scores than non-CHIP patients (all P < .05). After adjusting for relevant clinical risk factors, the presence of CHIP continued to show an independent association with three-vessel disease [odds ratio 2.26, 95% confidence interval (CI) 1.07-4.75; P = .032]. The survival analysis indicated that CHIP, along with non-DNMT3A mutations and a larger clone size (variant allele frequency ≥0.10), correlated with the primary composite endpoint (P < .01). Even after controlling for various clinical variables, the CHIP status still demonstrated an independent association with the primary composite endpoint (hazard ratio 2.02, 95% CI 1.11-3.67; P = .022).
Conclusions:
CHIP was associated with the severity of coronary lesions and unfavorable clinical outcomes in patients with CKD.
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