Somatic mutation contributing to clonal haematopoiesis is a risk factor of recurrent stroke in first-ever acute ischaemic stroke: a prospective cohort study.

Autor:	Qiu X; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing, China., Dai Y; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing, China., Cheng S; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing, China., Gu HQ; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing, China., Jiang Y; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing, China., Meng X; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing, China., Wang Y; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China., Zhao X; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China., Jiang Y; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing, China., Xu Z; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing, China., Huang X; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing, China., Wang M; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing, China., Lyu TJ; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing, China., Wang Y; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China., Weng J; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China., Cui L; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China., Shangguan Y; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China., Li H; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; China National Clinical Research Center for Neurological Diseases, Beijing, China., Wang Y; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China lizixiao2008@hotmail.com yongjunwang@ncrcnd.org.cn.; China National Clinical Research Center for Neurological Diseases, Beijing, China.; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.; Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, China.; Center for Excellence in Brain Science and Intelligence Technology Shanghai, Chinese Academy of Sciences, Shanghai, China., Li Z; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China lizixiao2008@hotmail.com yongjunwang@ncrcnd.org.cn.; China National Clinical Research Center for Neurological Diseases, Beijing, China.; Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, China.; Chinese Institute for Brain Research, Beijing, China.
Jazyk:	angličtina
Zdroj:	Stroke and vascular neurology [Stroke Vasc Neurol] 2023 Apr; Vol. 8 (2), pp. 103-110. Date of Electronic Publication: 2022 Sep 21.
DOI:	10.1136/svn-2022-001756
Abstrakt:	Background: Somatic mutation contributes to clonal haematopoiesis of indeterminate potential (CHIP) is related to age and associated with a higher risk of stroke and atherosclerotic cardiovascular disease. Here, we investigated the prognostic significance of CHIP in a large first-ever acute ischaemic stroke (AIS) cohort and explored the underlying mechanisms. Methods: We studied a prospective cohort of 6016 patients who had a first-ever AIS in China. Whole-genome sequencing was performed to identify CHIP. High-sensitivity C reactive protein (hs-CRP) levels above 3 mg/L at baseline were defined as hyperinflammation. Recurrent stroke during the 3-month follow-up was the primary outcome. Results: Among the 6016 patients who had a first-ever AIS, with a median age was 62 years (IQR, 54.0‒70.0), 3.70% were identified as CHIP carriers. The most common mutations occurred in the DNMT3A (30.0%) and TET2 (11.4%) genes. During a follow-up of 3 months, the presence of CHIP was associated with recurrent stroke (HR 1.62, 95% CI 1.04 to 2.51, p=0.03), recurrent ischaemic stroke (HR 1.64, 95% CI 1.04 to 2.58, p=0.03) and combined vascular events (HR 1.58, 95% CI 1.02 to 2.44, p=0.04) after adjusting for hsCRP levels at baseline in patients who had a first-ever AIS. Subgroup analysis demonstrated that CHIP was only associated with recurrent stroke when patients under hyperinflammation (OR 3.10, 95% CI 1.92 to 5.00, p<0.001) but not in those without hyperinflammation (OR 0.18, 95% CI 0.03 to 1.04, p=0.06, P interaction =0.002). Conclusion: Our results suggest that somatic mutations contributing to CHIP increase the risk of short-term recurrent stroke in patients who had a first-ever AIS. Hyperinflammation may be important in the relationship between CHIP and recurrent stroke. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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