Elevated plasma levels of neuropeptide proenkephalin A predict mortality and functional outcome in ischemic stroke
Name:
Publisher version
View Source
Access full-text PDFOpen Access
View Source
Check access options
Check access options
Authors
Doehner, Wolframvon Haehling, Stephan
Suhr, Jennifer
Ebner, Nicole
Schuster, Andreas
Nagel, Eike
Melms, Arthur
Wurster, Thomas
Stellos, Konstantinos
Gawaz, Meinrad
Bigalke, Boris
Affiliation
Charité Universitätsmedizin BerlinImmunochemical Intelligence GmbH
King's College London
Eberhard-Karls-Universität Tübingen
Johann Wolfgang Goethe University Frankfurt
Issue Date
2012-07
Metadata
Show full item recordAbstract
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.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):346Publisher
American College of CardiologyPubMed ID
22813614Additional Links
http://linkinghub.elsevier.com/retrieve/pii/S0735109712016385Type
ArticleLanguage
enISSN
0735-1097Sponsors
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.ae974a485f413a2113503eed53cd6c53
10.1016/j.jacc.2012.04.024
Scopus Count
Collections
Related articles
- Neuropeptide proenkephalin A is associated with in-hospital mortality in patients with acute intracerebral hemorrhage.
- Authors: Yang XG, An HL, Zhang JM
- Issue date: 2014 Aug
- Proenkephalin and prognosis after acute myocardial infarction.
- Authors: Ng LL, Sandhu JK, Narayan H, Quinn PA, Squire IB, Davies JE, Bergmann A, Maisel A, Jones DJ
- Issue date: 2014 Jan 28
- Midregional pro-atrial natriuretic peptide and outcome in patients with acute ischemic stroke.
- Authors: Katan M, Fluri F, Schuetz P, Morgenthaler NG, Zweifel C, Bingisser R, Kappos L, Steck A, Engelter ST, Müller B, Christ-Crain M
- Issue date: 2010 Sep 21
- C-reactive protein predicts further ischemic events in transient ischemic attack patients.
- Authors: Purroy F, Montaner J, Molina CA, Delgado P, Arenillas JF, Chacon P, Quintana M, Alvarez-Sabin J
- Issue date: 2007 Jan
- Computed tomography and computed tomography angiography findings predict functional impairment in patients with minor stroke and transient ischaemic attack.
- Authors: Coutts SB, O'Reilly C, Hill MD, Steffenhagen N, Poppe AY, Boyko MJ, Puetz V, Demchuk AM, Calgary CTA study group
- Issue date: 2009 Dec