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

      Doehner, Wolfram; von Haehling, Stephan; Suhr, Jennifer; Ebner, Nicole; Schuster, Andreas; Nagel, Eike; Melms, Arthur; Wurster, Thomas; Stellos, Konstantinos; Gawaz, Meinrad; et al. (American College of Cardiology, 2012-07)
      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.
    • Midregion prohormone adrenomedullin and prognosis in patients presenting with acute dyspnea: results from the BACH (Biomarkers in Acute Heart Failure) trial

      Maisel, Alan; Mueller, Christian; Nowak, Richard M; Peacock, W. Frank; Ponikowski, Piotr; Mockel, Martin; Hogan, Christopher; Wu, Alan H.B.; Richards, Mark; Clopton, Paul; et al. (American College of Cardiology, 2011-08-30)
      The aim of this study was to determine the prognostic utility of midregion proadrenomedullin (MR-proADM) in all patients, cardiac and noncardiac, presenting with acute shortness of breath.
    • Ursodeoxycholic acid in patients with chronic heart failure: a double-blind, randomized, placebo-controlled, crossover trial

      von Haehling, Stephan; Schefold, Joerg C.; Jankowska, Ewa A.; Springer, Jochen; Vazir, Ali; Kalra, Paul R.; Sandek, Anja; Fauler, Günter; Stojakovic, Tatjana; Trauner, Michael; et al. (American College of Cardiology, 2012-02-07)
      This study sought to assess the effects of ursodeoxycholic acid (UDCA) on endothelial function and inflammatory markers in patients with chronic heart failure (CHF).