Elevated plasma levels of neuropeptide proenkephalin A predict mortality and functional outcome in ischemic stroke

2.50
Hdl Handle:
http://hdl.handle.net/10547/593445
Title:
Elevated plasma levels of neuropeptide proenkephalin A predict mortality and functional outcome in ischemic stroke
Authors:
Doehner, Wolfram; von Haehling, Stephan; Suhr, Jennifer; Ebner, Nicole; Schuster, Andreas; Nagel, Eike; Melms, Arthur; Wurster, Thomas; Stellos, Konstantinos; Gawaz, Meinrad; Bigalke, Boris
Abstract:
Objectives The purpose of this study was to investigate neuropeptides in patients presenting with symptoms of acute cerebrovascular disease. Background The precursor neuropeptides proenkephalin A (PENK-A) and protachykinin (PTA) are markers of blood-brain barrier integrity and have been recently discussed in vascular dementia and neuroinflammatory disorders. Methods In a prospective observational study, we measured plasma PENK-A and PTA concentrations in 189 consecutive patients who were admitted with symptoms of acute stroke. Plasma concentrations were determined by sandwich immunoassay; lower detection limits were 15.6 pmol/l (PENK-A) and 22 pmol/l (PTA). Clinical outcome was assessed at 3 months for mortality, major adverse cerebro/cardiovascular events, and functional outcome (modified Rankin scale). Results PENK-A was significantly elevated in patients with ischemic stroke (n = 124; 65.6%) compared to patients with transient ischemic attack (n = 16; 8.5%) and to patients with nonischemic events (n = 49; 25.9%): median (interquartile range), stroke 123.8 pmol/l (93 to 160.5); transient ischemic attack 114.5 pmol/l (85.3 to 138.8); and nonischemic event 102.8 pmol/l (76.4 to 137.6; both groups vs. stroke p < 0.05). High concentrations of PENK-A, but not PTA, were related to severity of stroke as assessed by National Institutes of Health Stroke Scale (NIHSS [r = 0.225; p = 0.002]) and to advanced functional disability (modified Rankin Scale score 3 to 6 vs. 0 to 2: 135.1 pmol/l [99.2 to 174.1] vs. 108.9 pmol/l [88.6 to 139.5]; p = 0.014). After adjusting for age, NIHSS, and brain lesion size (computed tomography), PENK-A predicted mortality (hazard ratio [HR] for log-10 PENK-A in pmol/l: 4.52; 95% confidence interval [CI]: 1.1 to 19.0; p < 0.05) and major adverse cerebro/cardiovascular events (HR: 6.65; 95% CI: 1.8 to 24.9; p < 0.05). Patients in the highest quartile of PENK-A (cutoff >153 pmol/l) had an increased risk of mortality (HR: 2.40; 95% CI: 1.02 to 5.40; p < 0.05) and of major adverse cerebro/cardiovascular events (HR: 2.23; 95% CI: 1.10 to 4.54; p < 0.05). Conclusions PENK-A is a prognostic biomarker in the acute phase of ischemic stroke. Elevated PENK-A concentrations are associated with ischemic stroke, severity of cerebral injury, and may have prognostic value for fatal and nonfatal events.
Affiliation:
Charité Universitätsmedizin Berlin; Immunochemical Intelligence GmbH; King's College London; Eberhard-Karls-Universität Tübingen; Johann Wolfgang Goethe University Frankfurt
Citation:
Doehner, W. et al (2012) 'Elevated Plasma Levels of Neuropeptide Proenkephalin A Predict Mortality and Functional Outcome in Ischemic Stroke' Journal of the American College of Cardiology 60 (4):346
Publisher:
American College of Cardiology
Journal:
Journal of the American College of Cardiology
Issue Date:
Jul-2012
URI:
http://hdl.handle.net/10547/593445
DOI:
10.1016/j.jacc.2012.04.024
PubMed ID:
22813614
Additional Links:
http://linkinghub.elsevier.com/retrieve/pii/S0735109712016385
Type:
Article
Language:
en
ISSN:
0735-1097
Sponsors:
The study was supported by the grants of the German Cardiac Society (DGK) “Molecular Imaging of Atherosclerotic Plaques” to Dr. Bigalke, and in part by Sonderforschungsbereich/Transregio19 “Molecular Pathogenesis and Therapy” and Klinische Forschergruppe KFO274 “Platelets, Molecular Mechanisms and Translational Medicine” to Drs. Stellos and Gawaz (DFG Li849/3-1; SFB-TR19-B8N). Dr. Doehner received support from the German Ministry of Education and Research (No. 01 EO 0801) and from the Verein der Freunde und Förderer der Berliner Charité. Drs. Doehner and von Haehling received support from the European Commission under the Seventh Framework Programme 439 (FP7/2007–2013, grant agreement no. 241558; SICA-HF). Dr. von Haehling is a consultant for B.R.A.H.M.S. GmbH, Henningsdorf, Germany. Jennifer Suhr is employed by Immunochemical Intelligence GmbH. The other authors have reported they have no relationships relevant to the contents of this paper to disclose.
Appears in Collections:
IHR Institute for Health Research

Full metadata record

DC FieldValue Language
dc.contributor.authorDoehner, Wolframen
dc.contributor.authorvon Haehling, Stephanen
dc.contributor.authorSuhr, Jenniferen
dc.contributor.authorEbner, Nicoleen
dc.contributor.authorSchuster, Andreasen
dc.contributor.authorNagel, Eikeen
dc.contributor.authorMelms, Arthuren
dc.contributor.authorWurster, Thomasen
dc.contributor.authorStellos, Konstantinosen
dc.contributor.authorGawaz, Meinraden
dc.contributor.authorBigalke, Borisen
dc.date.accessioned2016-01-14T11:51:37Zen
dc.date.available2016-01-14T11:51:37Zen
dc.date.issued2012-07en
dc.identifier.citationDoehner, W. et al (2012) 'Elevated Plasma Levels of Neuropeptide Proenkephalin A Predict Mortality and Functional Outcome in Ischemic Stroke' Journal of the American College of Cardiology 60 (4):346en
dc.identifier.issn0735-1097en
dc.identifier.pmid22813614en
dc.identifier.doi10.1016/j.jacc.2012.04.024en
dc.identifier.urihttp://hdl.handle.net/10547/593445en
dc.description.abstractObjectives The purpose of this study was to investigate neuropeptides in patients presenting with symptoms of acute cerebrovascular disease. Background The precursor neuropeptides proenkephalin A (PENK-A) and protachykinin (PTA) are markers of blood-brain barrier integrity and have been recently discussed in vascular dementia and neuroinflammatory disorders. Methods In a prospective observational study, we measured plasma PENK-A and PTA concentrations in 189 consecutive patients who were admitted with symptoms of acute stroke. Plasma concentrations were determined by sandwich immunoassay; lower detection limits were 15.6 pmol/l (PENK-A) and 22 pmol/l (PTA). Clinical outcome was assessed at 3 months for mortality, major adverse cerebro/cardiovascular events, and functional outcome (modified Rankin scale). Results PENK-A was significantly elevated in patients with ischemic stroke (n = 124; 65.6%) compared to patients with transient ischemic attack (n = 16; 8.5%) and to patients with nonischemic events (n = 49; 25.9%): median (interquartile range), stroke 123.8 pmol/l (93 to 160.5); transient ischemic attack 114.5 pmol/l (85.3 to 138.8); and nonischemic event 102.8 pmol/l (76.4 to 137.6; both groups vs. stroke p < 0.05). High concentrations of PENK-A, but not PTA, were related to severity of stroke as assessed by National Institutes of Health Stroke Scale (NIHSS [r = 0.225; p = 0.002]) and to advanced functional disability (modified Rankin Scale score 3 to 6 vs. 0 to 2: 135.1 pmol/l [99.2 to 174.1] vs. 108.9 pmol/l [88.6 to 139.5]; p = 0.014). After adjusting for age, NIHSS, and brain lesion size (computed tomography), PENK-A predicted mortality (hazard ratio [HR] for log-10 PENK-A in pmol/l: 4.52; 95% confidence interval [CI]: 1.1 to 19.0; p < 0.05) and major adverse cerebro/cardiovascular events (HR: 6.65; 95% CI: 1.8 to 24.9; p < 0.05). Patients in the highest quartile of PENK-A (cutoff >153 pmol/l) had an increased risk of mortality (HR: 2.40; 95% CI: 1.02 to 5.40; p < 0.05) and of major adverse cerebro/cardiovascular events (HR: 2.23; 95% CI: 1.10 to 4.54; p < 0.05). Conclusions PENK-A is a prognostic biomarker in the acute phase of ischemic stroke. Elevated PENK-A concentrations are associated with ischemic stroke, severity of cerebral injury, and may have prognostic value for fatal and nonfatal events.en
dc.description.sponsorshipThe study was supported by the grants of the German Cardiac Society (DGK) “Molecular Imaging of Atherosclerotic Plaques” to Dr. Bigalke, and in part by Sonderforschungsbereich/Transregio19 “Molecular Pathogenesis and Therapy” and Klinische Forschergruppe KFO274 “Platelets, Molecular Mechanisms and Translational Medicine” to Drs. Stellos and Gawaz (DFG Li849/3-1; SFB-TR19-B8N). Dr. Doehner received support from the German Ministry of Education and Research (No. 01 EO 0801) and from the Verein der Freunde und Förderer der Berliner Charité. Drs. Doehner and von Haehling received support from the European Commission under the Seventh Framework Programme 439 (FP7/2007–2013, grant agreement no. 241558; SICA-HF). Dr. von Haehling is a consultant for B.R.A.H.M.S. GmbH, Henningsdorf, Germany. Jennifer Suhr is employed by Immunochemical Intelligence GmbH. The other authors have reported they have no relationships relevant to the contents of this paper to disclose.en
dc.language.isoenen
dc.publisherAmerican College of Cardiologyen
dc.relation.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0735109712016385en
dc.rightsArchived with thanks to Journal of the American College of Cardiologyen
dc.subjectneuropeptideen
dc.subjectProenkephalin Aen
dc.subjectischemic strokeen
dc.titleElevated plasma levels of neuropeptide proenkephalin A predict mortality and functional outcome in ischemic strokeen
dc.typeArticleen
dc.contributor.departmentCharité Universitätsmedizin Berlinen
dc.contributor.departmentImmunochemical Intelligence GmbHen
dc.contributor.departmentKing's College Londonen
dc.contributor.departmentEberhard-Karls-Universität Tübingenen
dc.contributor.departmentJohann Wolfgang Goethe University Frankfurten
dc.identifier.journalJournal of the American College of Cardiologyen

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