Elevated Serum Inflammatory Markers in Subacute Stroke Are Associated With Clinical Outcome but Not Modified by Aerobic Fitness Training: Results of the Randomized Controlled PHYS-STROKE Trial
Background: Inflammatory markers, such as C-reactive Protein (CRP), Interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha and fibrinogen, are upregulated following acute stroke. Studies have shown associations of these biomarkers with increased mortality, recurrent vascular risk, and poor function...
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Frontiers Media S.A.
2021-08-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2021.713018/full |
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DOAJ |
language |
English |
format |
Article |
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DOAJ |
author |
Bernadette Kirzinger Andrea Stroux Torsten Rackoll Torsten Rackoll Torsten Rackoll Matthias Endres Matthias Endres Matthias Endres Matthias Endres Matthias Endres Matthias Endres Agnes Flöel Agnes Flöel Martin Ebinger Martin Ebinger Alexander Heinrich Nave Alexander Heinrich Nave Alexander Heinrich Nave Alexander Heinrich Nave |
spellingShingle |
Bernadette Kirzinger Andrea Stroux Torsten Rackoll Torsten Rackoll Torsten Rackoll Matthias Endres Matthias Endres Matthias Endres Matthias Endres Matthias Endres Matthias Endres Agnes Flöel Agnes Flöel Martin Ebinger Martin Ebinger Alexander Heinrich Nave Alexander Heinrich Nave Alexander Heinrich Nave Alexander Heinrich Nave Elevated Serum Inflammatory Markers in Subacute Stroke Are Associated With Clinical Outcome but Not Modified by Aerobic Fitness Training: Results of the Randomized Controlled PHYS-STROKE Trial Frontiers in Neurology stroke inflammation outcome IL-6 crp TNF-alpha |
author_facet |
Bernadette Kirzinger Andrea Stroux Torsten Rackoll Torsten Rackoll Torsten Rackoll Matthias Endres Matthias Endres Matthias Endres Matthias Endres Matthias Endres Matthias Endres Agnes Flöel Agnes Flöel Martin Ebinger Martin Ebinger Alexander Heinrich Nave Alexander Heinrich Nave Alexander Heinrich Nave Alexander Heinrich Nave |
author_sort |
Bernadette Kirzinger |
title |
Elevated Serum Inflammatory Markers in Subacute Stroke Are Associated With Clinical Outcome but Not Modified by Aerobic Fitness Training: Results of the Randomized Controlled PHYS-STROKE Trial |
title_short |
Elevated Serum Inflammatory Markers in Subacute Stroke Are Associated With Clinical Outcome but Not Modified by Aerobic Fitness Training: Results of the Randomized Controlled PHYS-STROKE Trial |
title_full |
Elevated Serum Inflammatory Markers in Subacute Stroke Are Associated With Clinical Outcome but Not Modified by Aerobic Fitness Training: Results of the Randomized Controlled PHYS-STROKE Trial |
title_fullStr |
Elevated Serum Inflammatory Markers in Subacute Stroke Are Associated With Clinical Outcome but Not Modified by Aerobic Fitness Training: Results of the Randomized Controlled PHYS-STROKE Trial |
title_full_unstemmed |
Elevated Serum Inflammatory Markers in Subacute Stroke Are Associated With Clinical Outcome but Not Modified by Aerobic Fitness Training: Results of the Randomized Controlled PHYS-STROKE Trial |
title_sort |
elevated serum inflammatory markers in subacute stroke are associated with clinical outcome but not modified by aerobic fitness training: results of the randomized controlled phys-stroke trial |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neurology |
issn |
1664-2295 |
publishDate |
2021-08-01 |
description |
Background: Inflammatory markers, such as C-reactive Protein (CRP), Interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha and fibrinogen, are upregulated following acute stroke. Studies have shown associations of these biomarkers with increased mortality, recurrent vascular risk, and poor functional outcome. It is suggested that physical fitness training may play a role in decreasing long-term inflammatory activity and supports tissue recovery.Aim: We investigated the dynamics of selected inflammatory markers in the subacute phase following stroke and determined if fluctuations are associated with functional recovery up to 6 months. Further, we examined whether exposure to aerobic physical fitness training in the subacute phase influenced serum inflammatory markers over time.Methods: This is an exploratory analysis of patients enrolled in the multicenter randomized-controlled PHYS-STROKE trial. Patients within 45 days of stroke onset were randomized to receive either four weeks of aerobic physical fitness training or relaxation sessions. Generalized estimating equation models were used to investigate the dynamics of inflammatory markers and the associations of exposure to fitness training with serum inflammatory markers over time. Multiple logistic regression models were used to explore associations between inflammatory marker levels at baseline and three months after stroke and outcome at 3- or 6-months.Results: Irrespective of the intervention group, high sensitive CRP (hs-CRP), IL-6, and fibrinogen (but not TNF-alpha) were significantly lower at follow-up visits when compared to baseline (p all ≤ 0.01). In our cohort, exposure to aerobic physical fitness training did not influence levels of inflammatory markers over time. In multivariate logistic regression analyses, increased baseline IL-6 and fibrinogen levels were inversely associated with worse outcome at 3 and 6 months. Increased levels of hs-CRP at 3 months after stroke were associated with impaired outcome at 6 months. We found no independent associations of TNF-alpha levels with investigated outcome parameters.Conclusion: Serum markers of inflammation were elevated after stroke and decreased within 6 months. In our cohort, exposure to aerobic physical fitness training did not modify the dynamics of inflammatory markers over time. Elevated IL-6 and fibrinogen levels in early subacute stroke were associated with worse outcome up to 6-months after stroke.Clinical Trial Registration:ClinicalTrials.gov, NCT01953549. |
topic |
stroke inflammation outcome IL-6 crp TNF-alpha |
url |
https://www.frontiersin.org/articles/10.3389/fneur.2021.713018/full |
work_keys_str_mv |
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doaj-32d7f519e6be47f6b5b6bee88ed3292b2021-08-26T08:41:42ZengFrontiers Media S.A.Frontiers in Neurology1664-22952021-08-011210.3389/fneur.2021.713018713018Elevated Serum Inflammatory Markers in Subacute Stroke Are Associated With Clinical Outcome but Not Modified by Aerobic Fitness Training: Results of the Randomized Controlled PHYS-STROKE TrialBernadette Kirzinger0Andrea Stroux1Torsten Rackoll2Torsten Rackoll3Torsten Rackoll4Matthias Endres5Matthias Endres6Matthias Endres7Matthias Endres8Matthias Endres9Matthias Endres10Agnes Flöel11Agnes Flöel12Martin Ebinger13Martin Ebinger14Alexander Heinrich Nave15Alexander Heinrich Nave16Alexander Heinrich Nave17Alexander Heinrich Nave18Center for Stroke Research Berlin, Charité – Universitätsmedizin Berlin, Berlin, GermanyInstitute of Biometry and Clinical Epidemiology, Charité – Universitätsmedizin Berlin, Berlin, GermanyCenter for Stroke Research Berlin, Charité – Universitätsmedizin Berlin, Berlin, GermanyBerlin Institute of Health QUEST Center for Transforming Biomedical Research Berlin, Charité – Universitätsmedizin Berlin, Berlin, GermanyNeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, Berlin, GermanyCenter for Stroke Research Berlin, Charité – Universitätsmedizin Berlin, Berlin, GermanyNeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, Berlin, GermanyKlinik Und Hochschulambulanz für Neurologie, Charité – Universitätsmedizin Berlin, Berlin, GermanyGerman Center for Cardiovascular Research, Partner Site Berlin, Berlin, GermanyGerman Center for Neurodegenerative Diseases, Partner Site Berlin, Berlin, GermanyBerlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, GermanyDepartment of Neurology, University Medicine Greifswald, Greifswald, Germany0German Center for Neurodegenerative Diseases, Partner Site Rostock/Greifswald, Greifswald, GermanyCenter for Stroke Research Berlin, Charité – Universitätsmedizin Berlin, Berlin, Germany1Medical Park Berlin Humboldtmühle, Berlin, GermanyCenter for Stroke Research Berlin, Charité – Universitätsmedizin Berlin, Berlin, GermanyKlinik Und Hochschulambulanz für Neurologie, Charité – Universitätsmedizin Berlin, Berlin, GermanyGerman Center for Cardiovascular Research, Partner Site Berlin, Berlin, GermanyBerlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, GermanyBackground: Inflammatory markers, such as C-reactive Protein (CRP), Interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha and fibrinogen, are upregulated following acute stroke. Studies have shown associations of these biomarkers with increased mortality, recurrent vascular risk, and poor functional outcome. It is suggested that physical fitness training may play a role in decreasing long-term inflammatory activity and supports tissue recovery.Aim: We investigated the dynamics of selected inflammatory markers in the subacute phase following stroke and determined if fluctuations are associated with functional recovery up to 6 months. Further, we examined whether exposure to aerobic physical fitness training in the subacute phase influenced serum inflammatory markers over time.Methods: This is an exploratory analysis of patients enrolled in the multicenter randomized-controlled PHYS-STROKE trial. Patients within 45 days of stroke onset were randomized to receive either four weeks of aerobic physical fitness training or relaxation sessions. Generalized estimating equation models were used to investigate the dynamics of inflammatory markers and the associations of exposure to fitness training with serum inflammatory markers over time. Multiple logistic regression models were used to explore associations between inflammatory marker levels at baseline and three months after stroke and outcome at 3- or 6-months.Results: Irrespective of the intervention group, high sensitive CRP (hs-CRP), IL-6, and fibrinogen (but not TNF-alpha) were significantly lower at follow-up visits when compared to baseline (p all ≤ 0.01). In our cohort, exposure to aerobic physical fitness training did not influence levels of inflammatory markers over time. In multivariate logistic regression analyses, increased baseline IL-6 and fibrinogen levels were inversely associated with worse outcome at 3 and 6 months. Increased levels of hs-CRP at 3 months after stroke were associated with impaired outcome at 6 months. We found no independent associations of TNF-alpha levels with investigated outcome parameters.Conclusion: Serum markers of inflammation were elevated after stroke and decreased within 6 months. In our cohort, exposure to aerobic physical fitness training did not modify the dynamics of inflammatory markers over time. Elevated IL-6 and fibrinogen levels in early subacute stroke were associated with worse outcome up to 6-months after stroke.Clinical Trial Registration:ClinicalTrials.gov, NCT01953549.https://www.frontiersin.org/articles/10.3389/fneur.2021.713018/fullstrokeinflammationoutcomeIL-6crpTNF-alpha |