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@ARTICLE{Zhang:285005,
      author       = {Zhang, Lanyue and Antabi, Mohamad Ali and Mattar, Jana and
                      El Bounkari, Omar and Fang, Rong and Waegemann, Karin and
                      Bode, Felix J and Stösser, Sebastian and Hermann, Peter and
                      Liman, Thomas G and Nolte, Christian and Ikenberg, Benno and
                      Bernkopf, Kathleen and Petzold, Gabor C and Bernhagen,
                      Jürgen and Dichgans, Martin and Georgakis, Marios K},
      collaboration = {Investigators, DEMDAS},
      othercontributors = {Endres, Matthias and Düzel, Emrah and Kerti, Lucia and
                          Neumann, Katja and Meißner, Julius N and Liman, Thomas G.
                          and Kerti, Lucia and Nolte, Christian H and Wittenberg,
                          Tatjana and Scheitz, Jan F and Prüß, Harald and Sperber,
                          Pia Sophie and Nave, Alexander H and Kufner Ibaroule, Anna
                          and Petzold, Gabor C and Bode, Felix and Stösser, Sebastian
                          and Meissner, Julius and Ebrahimi, Taraneh and Nordsiek,
                          Julia and Beckonert, Niklas and Kindler, Christine and Zerr,
                          Inga and Hermann, Peter and Schmitz, Matthias and Goebel,
                          Stefan and Bunck, Timothy and Schütte-Schmidt, Julia and
                          Nuhn, Sabine and Volpers, Corinna and Dechent, Peter and
                          Bähr, Mathias and Görtler, Michael and Glanz, Wenzel and
                          Perosa, Valentina and Dichgans, Martin and Wollenweber,
                          Frank and Georgakis, Marios and Fang, Rong and Janowitz,
                          Daniel and Waegemann, Karin and Tiedt, Steffen and
                          Wunderlich, Silke and Ikenberg, Benno and Bernkopf, Kathleen
                          and Huber, Christiane and Poppert, Holger and Düring, Marco
                          and Araque Caballero, Miguel Ángel and Gesierich, Benno and
                          Dewenter, Anna and Dobisch, Laura and Neumann, Katja and
                          Speck, Oliver and Spottke, Annika and Stöcker, Tony and
                          Bartenstein, Peter and Wagner, Michael},
      title        = {{C}irculating cytokine levels and 5-year vascular
                      recurrence after stroke: {A} multicenter prospective cohort
                      study.},
      journal      = {European stroke journal},
      volume       = {11},
      number       = {1},
      issn         = {2396-9873},
      address      = {London},
      publisher    = {Sage Publishing},
      reportid     = {DZNE-2026-00139},
      pages        = {23969873251360145},
      year         = {2026},
      abstract     = {Anti-inflammatory therapies are tested in randomized trials
                      for secondary stroke prevention. Detecting inflammatory
                      biomarkers that predict vascular recurrence could optimize
                      patient selection for these trials.In a multicenter
                      prospective cohort study, we measured plasma levels of 22
                      inflammatory cytokines in 486 acute stroke patients (474
                      ischemic strokes and 12 intracerebral hemorrhages; median
                      age 68 years, $34\%$ female, median 3 days post-stroke
                      onset). Patients were followed for over 5 years through
                      telephone and in-person interviews to record the occurrence
                      of the following outcomes: (1) recurrent stroke or transient
                      ischemic attack (TIA; primary outcome); (2) a composite of
                      recurrent vascular events (stroke, TIA, acute coronary
                      syndrome, hospital admission due to heart failure, and
                      death; secondary outcome). Associations between cytokine
                      levels and these outcomes were analyzed using Cox
                      proportional hazards models adjusted for demographic and
                      vascular risk factors.During the 5-year follow-up period, 59
                      patients $(12.1\%)$ experienced recurrent stroke or TIA, and
                      118 $(24.3\%)$ experienced recurrent vascular events. After
                      adjustments for demographic and vascular risk factors, and
                      correction for multiple comparisons, higher plasma levels of
                      CD62E (adjusted Hazard Ratio (aHR)/SD increment: 1.63,
                      $95\%CI$ 1.22-2.20) and MIF (aHR: 1.56, $95\%CI$ 1.18-2.06)
                      in the acute phase after stroke were statistically
                      significantly associated with increased risk of recurrent
                      stroke or TIA. The associations followed a dose-response
                      pattern across quartiles of CD62E and MIF levels. Adding
                      baseline CD62E and MIF levels to models including age, sex,
                      vascular risk factors, and baseline C-reactive protein (CRP)
                      levels led to significant improvements in the prediction of
                      5-year risk of recurrent stroke or TIA (ΔC-index
                      0.030-0.050).Among stroke patients, higher baseline levels
                      of CD62E and MIF improved prediction of 5-year risk of
                      recurrent stroke or TIA on top of vascular risk factors and
                      CRP levels. Whether assessment of these cytokines could
                      improve patient selection for secondary prevention trials of
                      anti-inflammatory treatments, should be explored in future
                      studies.},
      keywords     = {Humans / Female / Male / Aged / Prospective Studies /
                      Recurrence / Middle Aged / Cytokines: blood / Ischemic
                      Attack, Transient: blood / Biomarkers: blood / Stroke: blood
                      / Follow-Up Studies / Risk Factors / Ischemic Stroke: blood
                      / Cohort Studies / Stroke (Other) / cytokines (Other) /
                      inflammation (Other) / recurrence (Other) / risk prediction
                      (Other) / Cytokines (NLM Chemicals) / Biomarkers (NLM
                      Chemicals)},
      cin          = {Clinical Research (Munich) / AG Petzold / Clinical Research
                      (Bonn) / AG Endres / AG Dichgans},
      ddc          = {610},
      cid          = {I:(DE-2719)1111015 / I:(DE-2719)1013020 /
                      I:(DE-2719)1011001 / I:(DE-2719)1811005 /
                      I:(DE-2719)5000022},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41614521},
      doi          = {10.1093/esj/23969873251360145},
      url          = {https://pub.dzne.de/record/285005},
}