Affiliation:
1. Department of Neurology Seoul National University Hospital, Seoul National University College of Medicine Seoul South Korea
2. Genome Opinion Incorporation Seoul South Korea
3. Department of Neurology Seoul National University Healthcare System Gangnam Center Seoul South Korea
4. Division of Cardiology, Department of Internal Medicine Seoul National University Healthcare System Gangnam Center Seoul South Korea
5. Department of Neurology Uijeongbu Eulji Medical Center Uijeongbu‐si South Korea
6. Division of Hematology and Oncology, Department of Internal Medicine, Seoul National University College of Medicine Seoul National University Hospital Seoul South Korea
Abstract
ObjectiveThe effect of clonal hematopoiesis of indeterminate potential (CHIP) on the manifestation and clinical outcomes of acute ischemic stroke (AIS) has not been fully elucidated.MethodsPatients with AIS were included from a prospective registry coupled with a DNA repository. Targeted next‐generation sequencing on 25 genes that are frequently mutated in hematologic neoplasms was performed. The prevalence of CHIP was compared between patients with AIS and age‐matched healthy individuals. A multivariate linear or logistic regression model was used to assess the association among CHIP and stroke severity, hemorrhagic transformation, and functional outcome at 90 days.ResultsIn total, 380 patients with AIS (mean age = 67.2 ± 12.7 years; 41.3% women) and 446 age‐matched controls (mean age = 67.2 ± 8.7 years; 31.4% women) were analyzed. The prevalence of CHIP was significantly higher in patients with AIS than in the healthy controls (29.0 vs 22.0%, with variant allele frequencies of 1.5%, p = 0.024). PPM1D was found to be most significantly associated with incident AIS (adjusted odds ratio [aOR] = 7.85, 95% confidence interval [CI] = 1.83–33.63, p = 0.006). The presence of CHIP was significantly associated with the initial National Institutes of Health Stroke Scale (NIHSS) score (β = 1.67, p = 0.022). Furthermore, CHIP was independently associated with the occurrence of hemorrhagic transformation (65/110 clonal hematopoiesis positive [CH+] vs 56/270 CH negative [CH‐], aOR = 5.63, 95% CI = 3.24–9.77, p < 0.001) and 90‐day functional disability (72/110 [CH+] vs 99/270 [CH‐], aOR = 2.15, 95% CI = 1.20–3.88, p = 0.011).InterpretationCH was significantly associated with incident AIS. Moreover, particularly, sequence variations in PPM1D, TET2, and DNMT3A represent a new prognostic factor for AIS. ANN NEUROL 2023;94:836–847
Funder
Korea Disease Control and Prevention Agency
National Research Foundation of Korea
Subject
Neurology (clinical),Neurology
Cited by
3 articles.
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