Abstract Background and aims Systemic inflammation is an emerging target for secondary stroke prevention. As part of the European “CiRculating mEdiators of Stroke reCurrENce anD aetiOlogies” (CRESCENDO)-consortium, we investigated the role of the interleukin (IL)-1β-IL-6-c-reactive-protein (CRP)-axis for major adverse cardiovascular events (MACE) after acute ischemic stroke (AIS). Methods Serum samples from 4,390 patients were collected in Hannover (Germany), Barcelona/Seville (Spain) and Zurich/Basel (Switzerland) within 24 hours of AIS-onset. Associations of IL-1β, IL-6 and CRP with MACE (defined as recurrent AIS, myocardial infarction or TIA) and recurrent AIS were investigated using regression models adjusting for vascular risk factors, age, sex and the NIHSS-Score. We further stratified these analyses for stroke etiologies and previous anticoagulation status. Results At 90 days of follow-up, 119 patients suffered MACE, and 91 had another AIS. IL-1β was associated both with MACE and AIS (adjusted odds ratio (aOR)=1.38, 95%CI: 1.09-1.73 and aOR=1.34, 95%CI: 1.03-1.75). In contrast, no associations were found for IL-6 and CRP. The etiology-stratified analyses did not reveal substantial differences. Effect sizes of IL-1β for MACE were considerably higher in patients with previous anticoagulation (aOR=1.46, 95%CI: 1.00-2.14) versus without (aOR=1.16, 95%CI: 0.84-1.60). Conclusions The results of this large-scale collaboration reveal that early IL-1β, as an upstream mediator, is likely to play a particularly important role for recurrences across stroke etiologies. These effects were especially pronounced in cases with previous anticoagulation, pointing to inflammation as a key contributor to residual vascular risk in this population. Conflict of interest Nothing to disclose
Große et al. (Fri,) studied this question.