{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:11:50Z","timestamp":1791256310563,"version":"4.1.0"},"reference-count":50,"publisher":"American Society of Hematology","issue":"7","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,2,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Clonal hematopoiesis (CH) is common among older people and is associated with an increased risk of atherosclerosis, inflammation, and shorter overall survival. Age and inflammation are major risk factors for ischemic stroke, yet the association of CH with risk of secondary vascular events and death is unknown. We investigated CH in peripheral blood DNA from 581 patients with first-ever ischemic stroke from the Prospective Cohort With Incident Stroke\u2013Berlin study using error-corrected targeted sequencing. The primary composite end point (CEP) consisted of recurrent stroke, myocardial infarction, and all-cause mortality. A total of 348 somatic mutations with a variant allele frequency \u22651% were identified in 236 of 581 patients (41%). CH was associated with large-artery atherosclerosis stroke (P\u00a0= .01) and white matter lesion (P\u00a0&amp;lt; .001). CH-positive patients showed increased levels of proinflammatory cytokines, such as interleukin-6 (IL-6), interferon gamma, high-sensitivity C-reactive protein, and vascular cell adhesion molecule 1. CH-positive patients had a higher risk for the primary CEP (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.04-2.31; P\u00a0= .03), which was more pronounced in patients with larger clones. CH clone size remained an independent risk factor (HR, 1.30; 95% CI, 1.04-1.62; P\u00a0= .022) in multivariable Cox regression. Although our data show that, in particular, larger and TET2- or PPM1D-mutated clones are associated with increased risk of recurrent vascular events and death, this risk is partially mitigated by a common germline variant of the IL-6 receptor (IL-6R p.D358A). The CH mutation profile is accompanied by a proinflammatory profile, opening new avenues for preventive precision medicine approaches to resolve the self-perpetuating cycle of inflammation and clonal expansion.<\/jats:p>","DOI":"10.1182\/blood.2022017661","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T15:40:18Z","timestamp":1669650018000},"page":"787-799","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":101,"title":["Associations of clonal hematopoiesis with recurrent vascular events and death in patients with incident ischemic stroke"],"prefix":"10.1182","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4417-4750","authenticated-orcid":false,"given":"Christopher M.","family":"Arends","sequence":"first","affiliation":[{"name":"1Department of Hematology, Oncology, and Cancer Immunology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"},{"name":"2Berlin Institute of Health at Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Liman","sequence":"additional","affiliation":[{"name":"2Berlin Institute of Health at Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Berlin, Germany"},{"name":"3Department of Neurology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"},{"name":"4Center for Stroke Research Berlin, Department of Experimental Neurology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"},{"name":"5German Center for Neurodegenerative Diseases (Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen), Partner 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Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"},{"name":"9Institute of Medical Informatics, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3196-6214","authenticated-orcid":false,"given":"Marlon","family":"Tilgner","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Oncology, and Cancer Immunology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia S.","family":"Sperber","sequence":"additional","affiliation":[{"name":"4Center for Stroke Research Berlin, Department of Experimental Neurology, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate 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