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

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.
AuthorsWolfram Doehner, Stephan von Haehling, Jennifer Suhr, Nicole Ebner, Andreas Schuster, Eike Nagel, Arthur Melms, Thomas Wurster, Konstantinos Stellos, Meinrad Gawaz, Boris Bigalke
JournalJournal of the American College of Cardiology (J Am Coll Cardiol) Vol. 60 Issue 4 Pg. 346-54 (Jul 24 2012) ISSN: 1558-3597 [Electronic] United States
PMID22813614 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Biomarkers
  • Enkephalins
  • Protein Precursors
  • Tachykinins
  • proenkephalin
  • protachykinin
Topics
  • Aged
  • Aged, 80 and over
  • Biomarkers (blood)
  • Brain Damage, Chronic (blood, mortality)
  • Brain Ischemia (blood, mortality)
  • Cause of Death
  • Cerebral Infarction (blood, mortality)
  • Disability Evaluation
  • Enkephalins (blood)
  • Female
  • Follow-Up Studies
  • Humans
  • Intracranial Arteriosclerosis (blood, mortality)
  • Ischemic Attack, Transient (blood, mortality)
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Protein Precursors (blood)
  • Tachykinins (blood)

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