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@ARTICLE{Arends:275255,
      author       = {C. M. Arends and T. G. Liman and P. M. Strzelecka and A.
                      Kufner and P. Löwe and S. Huo and C. M. Stein and S. K.
                      Piper and M. Tilgner and P. S. Sperber and S. Dimitriou and
                      P. U. Heuschmann and R. Hablesreiter and C. Harms and L.
                      Bullinger$^*$ and J. E. Weber and M. Endres and F. Damm$^*$},
      title        = {{A}ssociations of clonal hematopoiesis with recurrent
                      vascular events and death in patients with incident ischemic
                      stroke},
      journal      = {Blood},
      volume       = {141},
      number       = {7},
      issn         = {0006-4971},
      address      = {Washington, DC},
      publisher    = {American Society of Hematology},
      reportid     = {DKFZ-2023-00702},
      pages        = {787 - 799},
      year         = {2023},
      abstract     = {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–Berlin 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
                      $≥1\%$ were identified in 236 of 581 patients $(41\%).$ CH
                      was associated with large-artery atherosclerosis stroke (P =
                      .01) and white matter lesion (P < .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 = .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 = .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.},
      cin          = {BE01},
      ddc          = {610},
      cid          = {I:(DE-He78)BE01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.1182/blood.2022017661},
      url          = {https://inrepo02.dkfz.de/record/275255},
}