title: The association between autonomic dysfunction, inflammation and atherosclerosis in men under investigation for carotid plaques.
abstract: BACKGROUND
  Autonomic dysfunction is a risk factor for cardiovascular disease (CVD), however, the exact mechanism linking autonomic dysfunction to cardiovascular disease is not known. In this study we hypothesized that autonomic dysfunction increases inflammation, which subsequently accelerates atherosclerosis. The aim of the current study was to investigate the association between autonomic tone, inflammation and atherosclerosis.
  
  
  METHODS
  124 men under investigation for carotid atherosclerosis were examined for autonomic function (heart rate variability; HRV and baroreflex sensitivity; BRS), inflammatory markers (white blood cell count; WBCC and C-reactive protein; CRP) and degree of carotid atherosclerosis. The direct or indirect associations between autonomic function, inflammatory parameters and carotid plaque area were investigated with multiple linear regressions.
  
  
  RESULTS
  Male subjects with prevalent CVD showed larger carotid plaque area, higher WBCC, and reduced BRS compared to subjects with no history of CVD. Further, BRS was inversely associated with carotid plaque area (r = -0.21, p = 0.018) as well as inflammatory parameters WBCC and CRP (r = -0.29, p = 0.001, and r = -0.23, p = 0.009, respectively), whereas HRV only was inversely associated with WBCC (r = -0.22, p = 0.014). To investigate if inflammation could provide a link between autonomic function and carotid atherosclerosis we adjusted the associations accordingly. After adjusting for WBCC and CRP the inverse association between BRS and carotid plaque area was attenuated and did not remain significant, while both WBCC and CRP remained significantly associated with carotid plaque area, indicating that low-grade inflammation can possibly link BRS to atherosclerosis. Also, after adjusting for age, antihypertensive treatment and cardiovascular risk factors, BRS was independently inversely associated with both WBCC and CRP, and HRV independently inversely associated with WBCC. WBCC was the only inflammatory marker independently associated with carotid plaque area after adjustment.
  
  
  CONCLUSIONS
  We demonstrate that autonomic dysfunction is associated with atherosclerosis and that inflammation could play an important role in mediating this relationship.
authors.affiliation: Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Ulleryd
authors.affiliation: Department of Molecular and Clinical Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Ulrica
authors.initials: U
authors.lastname: Prahl
authors.affiliation: Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Johannes
authors.initials: J
authors.lastname: Börsbo
authors.affiliation: Department of Molecular and Clinical Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Caroline
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Department of Mathematical Statistics, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.affiliation: Department of Molecular and Clinical Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Bergström
authors.affiliation: Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Maria E
authors.identifier: http://orcid.org/0000-0002-2569-2977
authors.initials: ME
authors.lastname: Johansson
mesh_terms: D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000150:complications* / Q000503:physiopathology; D001342:Autonomic Nervous System Diseases / Q000150:complications* / Q000503:physiopathology; D017704:Baroreflex; D002097:C-Reactive Protein / Q000378:metabolism; D016893:Carotid Stenosis / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology; D006339:Heart Rate; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D002097:C-Reactive Protein