Elevated plasma levels of neuropeptide proenkephalin A predict mortality and functional outcome in ischemic stroke
von Haehling, Stephan
AffiliationCharité Universitätsmedizin Berlin
Immunochemical Intelligence GmbH
King's College London
Johann Wolfgang Goethe University Frankfurt
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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.
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):346
PublisherAmerican College of Cardiology
SponsorsThe 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.
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