Biomarkers of Immune Capacity, Infection and Inflammation Are Associated with Poor Outcome and Mortality After Stroke - the PREDICT Study

Overview

Journal BMC Neurol

Publisher Biomed Central

Specialty Neurology

Date 2019 Jul 5

PMID 31269910

Citations 20

Authors

A Mengel

L Ulm

B Hotter

H Harms

S K Piper

U Grittner

J Montaner

C Meisel

A Meisel

S Hoffmann

Affiliations

Soon will be listed here.

Abstract

Background: Almost 40% of stroke patients have a poor outcome at 3 months after the index event. Predictors for stroke outcome in the early acute phase may help to tailor stroke treatment. Infection and inflammation are considered to influence stroke outcome.

Methods: In a prospective multicenter study in Germany and Spain, including 486 patients with acute ischemic stroke, we used multivariable regression analysis to investigate the association of poor outcome with monocytic HLA-DR (mHLA-DR) expression, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha) and lipopolysaccharide-binding protein (LBP) as markers for immunodepression, inflammation and infection. Outcome was assessed at 3 months after stroke via a structured telephone interview using the modified Rankin Scale (mRS). Poor outcome was defined as a mRS score of 3 or higher which included death. Furthermore, a time-to-event analysis for death within 3 months was performed.

Results: Three-month outcome data was available for 391 patients. Female sex, older age, diabetes mellitus, atrial fibrillation, stroke-associated pneumonia (SAP) and higher National Institute of Health Stroke Scale (NIHSS) score as well as lower mHLA-DR levels, higher IL-6 and LBP-levels at day 1 were associated with poor outcome at 3 months in bivariate analysis. Furthermore, multivariable analysis revealed that lower mHLA-DR expression was associated with poor outcome. Female sex, older age, atrial fibrillation, SAP, higher NIHSS score, lower mHLA-DR expression and higher IL-6 levels were associated with shorter survival time in bivariate analysis. In multivariable analysis, SAP and higher IL-6 levels on day 1 were associated with shorter survival time.

Conclusions: SAP, lower mHLA-DR-expression and higher IL-6 levels on day one are associated with poor outcome and shorter survival time at 3 months after stroke onset.

Trial Registration: www.clinicaltrials.gov, NCT01079728 , March 3, 2010.

Citing Articles

Gut Microbiota, Bacterial Translocation, and Stroke: Current Knowledge and Future Directions.

Granados-Martinez C, Alfageme-Lopez N, Navarro-Oviedo M, Nieto-Vaquero C, Cuartero M, Diaz-Benito B Biomedicines. 2025; 12(12.

PMID: 39767686 PMC: 11673227. DOI: 10.3390/biomedicines12122781.

Promotes Stroke-Induced Neurogenesis and Neuronal Repair in Young and Aged Mice.

Khan D, Bock D, Liu H, Muhammad S Int J Mol Sci. 2024; 25(22).

PMID: 39596503 PMC: 11594625. DOI: 10.3390/ijms252212440.

Exploring functional abilities and competing risks among stroke patients: a longitudinal and survival analysis study at Felege Hiwot Referral Hospital, Ethiopia.

Berehan H, Dessie Z, Tesfaw L BMJ Open. 2024; 14(5):e073384.

PMID: 38697761 PMC: 11086538. DOI: 10.1136/bmjopen-2023-073384.

Stroke-induced changes to immune function and their relevance to increased risk of severe COVID-19 disease.

McCulloch L, Mouat I, South K, McColl B, Allan S, Smith C Discov Immunol. 2024; 1(1):kyac004.

PMID: 38566903 PMC: 10917238. DOI: 10.1093/discim/kyac004.

Risk factors for stroke-related functional disability and mortality at Felege Hiwot Referral Hospital, Ethiopia.

Tento T, Kume A, Kumaso S BMC Neurol. 2023; 23(1):393.

PMID: 37907867 PMC: 10617073. DOI: 10.1186/s12883-023-03444-8.

References

Wolk K, Docke W, Von Baehr V, Volk H, Sabat R . Impaired antigen presentation by human monocytes during endotoxin tolerance. Blood. 2000; 96(1):218-23. View

Baird A, Dambrosia J, Janket S, Eichbaum Q, Chaves C, Silver B . A three-item scale for the early prediction of stroke recovery. Lancet. 2001; 357(9274):2095-9. DOI: 10.1016/s0140-6736(00)05183-7. View

Weimar C, Kurth T, Kraywinkel K, Wagner M, Busse O, Haberl R . Assessment of functioning and disability after ischemic stroke. Stroke. 2002; 33(8):2053-9. DOI: 10.1161/01.str.0000022808.21776.bf. View

Appelros P, Nydevik I, Viitanen M . Poor outcome after first-ever stroke: predictors for death, dependency, and recurrent stroke within the first year. Stroke. 2003; 34(1):122-6. DOI: 10.1161/01.str.0000047852.05842.3c. View

Katzan I, Cebul R, Husak S, Dawson N, Baker D . The effect of pneumonia on mortality among patients hospitalized for acute stroke. Neurology. 2003; 60(4):620-5. DOI: 10.1212/01.wnl.0000046586.38284.60. View

Frank R, Hargreaves R . Clinical biomarkers in drug discovery and development. Nat Rev Drug Discov. 2003; 2(7):566-80. DOI: 10.1038/nrd1130. View

Glader E, Stegmayr B, Norrving B, Terent A, Hulter-Asberg K, Wester P . Sex differences in management and outcome after stroke: a Swedish national perspective. Stroke. 2003; 34(8):1970-5. DOI: 10.1161/01.STR.0000083534.81284.C5. View

Villar J, Maca-Meyer N, Perez-Mendez L, Flores C . Bench-to-bedside review: understanding genetic predisposition to sepsis. Crit Care. 2004; 8(3):180-9. PMC: 468916. DOI: 10.1186/cc2863. View

Paolucci S, Bragoni M, Coiro P, De Angelis D, Fusco F, Morelli D . Is sex a prognostic factor in stroke rehabilitation? A matched comparison. Stroke. 2006; 37(12):2989-94. DOI: 10.1161/01.STR.0000248456.41647.3d. View

10.

Gargano J, Reeves M . Sex differences in stroke recovery and stroke-specific quality of life: results from a statewide stroke registry. Stroke. 2007; 38(9):2541-8. DOI: 10.1161/STROKEAHA.107.485482. View

11.

Harms H, Prass K, Meisel C, Klehmet J, Rogge W, Drenckhahn C . Preventive antibacterial therapy in acute ischemic stroke: a randomized controlled trial. PLoS One. 2008; 3(5):e2158. PMC: 2373885. DOI: 10.1371/journal.pone.0002158. View

12.

Saposnik G, Hill M, ODonnell M, Fang J, Hachinski V, Kapral M . Variables associated with 7-day, 30-day, and 1-year fatality after ischemic stroke. Stroke. 2008; 39(8):2318-24. DOI: 10.1161/STROKEAHA.107.510362. View

13.

Klehmet J, Harms H, Richter M, Prass K, Volk H, Dirnagl U . Stroke-induced immunodepression and post-stroke infections: lessons from the preventive antibacterial therapy in stroke trial. Neuroscience. 2008; 158(3):1184-93. DOI: 10.1016/j.neuroscience.2008.07.044. View

14.

Flaherty M, Karlawish J, Khoury J, Kleindorfer D, Woo D, Broderick J . How important is surrogate consent for stroke research?. Neurology. 2008; 71(20):1566-71. DOI: 10.1212/01.wnl.0000316196.63704.f5. View

15.

Wahlgren N, Ahmed N, Eriksson N, Aichner F, Bluhmki E, Davalos A . Multivariable analysis of outcome predictors and adjustment of main outcome results to baseline data profile in randomized controlled trials: Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST). Stroke. 2008; 39(12):3316-22. DOI: 10.1161/STROKEAHA.107.510768. View

16.

Hong K, Kang D, Koo J, Yu K, Han M, Cho Y . Impact of neurological and medical complications on 3-month outcomes in acute ischaemic stroke. Eur J Neurol. 2008; 15(12):1324-31. DOI: 10.1111/j.1468-1331.2008.02310.x. View

17.

Feuerstein G, Chavez J . Translational medicine for stroke drug discovery: the pharmaceutical industry perspective. Stroke. 2008; 40(3 Suppl):S121-5. DOI: 10.1161/STROKEAHA.108.535104. View

18.

Kissela B, Lindsell C, Kleindorfer D, Alwell K, Moomaw C, Woo D . Clinical prediction of functional outcome after ischemic stroke: the surprising importance of periventricular white matter disease and race. Stroke. 2008; 40(2):530-6. PMC: 2766300. DOI: 10.1161/STROKEAHA.108.521906. View

19.

Eriksson M, Glader E, Norrving B, Terent A, Stegmayr B . Sex differences in stroke care and outcome in the Swedish national quality register for stroke care. Stroke. 2009; 40(3):909-14. DOI: 10.1161/STROKEAHA.108.517581. View

20.

Urra X, Cervera A, Obach V, Climent N, Planas A, Chamorro A . Monocytes are major players in the prognosis and risk of infection after acute stroke. Stroke. 2009; 40(4):1262-8. DOI: 10.1161/STROKEAHA.108.532085. View