Prevalence and Therapeutic Implications of Clonal Hematopoiesis of Indeterminate Potential in Young Patients With Stroke

• Published in: Stroke (1970) 2023-04, Vol.54 (4), p.938-946
• Main Authors: Mayerhofer, Ernst, Strecker, Christoph, Becker, Heiko, Georgakis, Marios K., Uddin, Md Mesbah, Hoffmann, Michael M., Nadarajah, Niroshan, Meggendorfer, Manja, Haferlach, Torsten, Rosand, Jonathan, Natarajan, Pradeep, Anderson, Christopher D., Harloff, Andreas, Hoermann, Gregor
• Format: Article
• Language: English
• Subjects: Carotid Intima-Media Thickness; Clonal Hematopoiesis; Female; Hematologic Neoplasms - diagnosis; Hematologic Neoplasms - genetics; Hematopoiesis - genetics; Humans; Male; Mutation; Prevalence; Prospective Studies; Stroke - epidemiology; Stroke - genetics
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/STROKEAHA.122.041416

Undetermined stroke etiology hampers optimal secondary prevention in a large proportion of young patients. We explored whether genetic screening for clonal hematopoiesis of indetermined potential (CHIP), a novel risk factor for stroke, could identify patients with myeloid precursor lesions or covert myeloid neoplasm requiring specific treatment. We performed targeted sequencing on 56 genes recurrently mutated in hematologic neoplasms in a prospective cohort of patients with acute brain ischemia between 18 and 60 years. CHIP prevalence was compared with age-matched healthy controls from the Nijmegen Biomedical Study (n=1604) and the UK Biobank (n=101 678). Patients with suspicion of high-risk CHIP or myeloid neoplasm were invited for further hematologic evaluation. We included 248 consecutive patients (39% women) of whom 176 (71%) had cryptogenic stroke etiology. Fifty-one (21%) patients had CHIP, 3-fold more than in the general population (7.7% versus 2.6% for the Nijmegen Biomedical Study and 11.9% versus 4.1% for UK Biobank;