title: Elevated Plasma C-Terminal Endothelin-1 Precursor Fragment Concentrations Are Associated with Less Anxiety in Patients with Cardiovascular Risk Factors. Results from the Observational DIAST-CHF Study.
abstract: BACKGROUND
  The role of endothelin-1 (ET-1) in the neurobiology of anxiety is unknown, therefore, we assessed in the observational multicenter DIAST-CHF study whether the C-terminal ET-1 precursor fragment (CT-proET-1) is linked to anxiety.
  
  
  METHODS
  Plasma concentrations of CT-proET-1 were measured in a total of 1,410 patients presenting with cardiovascular risk factors (mean age 66.91±8.2 years, 49.3% males, mean left ventricular ejection fraction 60.0±8.2%) who had completed the Hospital Anxiety and Depression Scale (HADS) questionnaire.
  
  
  RESULTS
  Among the total study cohort (n = 1,410), there were 118 subjects (8.4%) with an HADS anxiety score above the cut-off level of 11 suggestive of clinically relevant anxiety. Plasma CT-proET-1 levels were significantly lower in the group of anxious patients as compared to non-anxious patients (p = 0.013). In regression models adjusted for sex, age, systolic blood pressure, and diameters of left atrium and ventricle, plasma CT-proET-1 was again linked to anxiety (Exp(β) = 0.247, 95%-confidence interval [95%-CI] = 0.067-0.914, p = 0.036). Given the high prevalence of depressive disorders in anxious patients, we additionally included the HADS depression score as an independent variable in the models and found that CT-proET-1 remained a significant predictor of anxiety, independent of comorbid depression (Exp(β) = 0.114, 95%-CI = 0.023-0.566, p = 0.008).
  
  
  CONCLUSIONS
  Our data from a population-based study in outpatients with cardiovascular risk factors revealed that circulating CT-proET-1 levels are negatively associated with anxiety. Further investigations are required to clarify the putative anxiolytic effect of ET-1 or its precursor molecules in humans and to decipher its mechanistic pathways.
authors: Department of Psychosomatic Medicine and Psychotherapy, University of Göttingen, Göttingen, Germany; German Centre for Cardiovascular Research, partner site Göttingen, Göttingen, Germany.
authors: Thomas
authors: T
authors: Meyer
authors: Department of Psychosomatic Medicine and Psychotherapy, University of Göttingen, Göttingen, Germany; German Centre for Cardiovascular Research, partner site Göttingen, Göttingen, Germany.
authors: Mira-Lynn
authors: ML
authors: Chavanon
authors: Department of Psychosomatic Medicine and Psychotherapy, University of Göttingen, Göttingen, Germany; German Centre for Cardiovascular Research, partner site Göttingen, Göttingen, Germany.
authors: Christoph
authors: C
authors: Herrrmann-Lingen
authors: Department of Psychosomatic Medicine and Psychotherapy, University of Göttingen, Göttingen, Germany.
authors: Maren
authors: M
authors: Roggenthien
authors: Department of Cardiology and Pneumology, University of Göttingen, Göttingen, Germany.
authors: Kathleen
authors: K
authors: Nolte
authors: Department of Internal Medicine and Cardiology, Charité University Medicine, Berlin, Germany; German Center for Cardiovascular Research, partner site Berlin, Berlin, Germany.
authors: Burkert
authors: B
authors: Pieske
authors: Department of Cardiology and Pneumology, University of Göttingen, Göttingen, Germany; German Center for Cardiovascular Research, partner site Berlin, Berlin, Germany.
authors: Rolf
authors: R
authors: Wachter
authors: Department of Cardiology and Pneumology, University of Göttingen, Göttingen, Germany; Department of Internal Medicine and Cardiology, Charité University Medicine, Berlin, Germany; German Center for Cardiovascular Research, partner site Berlin, Berlin, Germany.
authors: Frank
authors: F
authors: Edelmann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001007:Anxiety / Q000097:blood* / Q000523:psychology; D003324:Coronary Artery Disease / Q000097:blood / Q000523:psychology*; D003863:Depression / Q000097:blood* / Q000523:psychology; D019332:Endothelin-1 / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D045265:Natriuretic Peptides / Q000097:blood; D010446:Peptide Fragments / Q000097:blood* / Q000235:genetics; D012307:Risk Factors; D015398:Signal Transduction; D013318:Stroke Volume; D011795:Surveys and Questionnaires
chemical_list: C557077:C-terminal proendothelin-1; D019332:Endothelin-1; D045265:Natriuretic Peptides; D010446:Peptide Fragments