title: Behavioural modification of the cholinergic anti-inflammatory response to C-reactive protein in patients with hypertension.
abstract: OBJECTIVE
  A central hypothesis of the cholinergic anti-inflammatory reflex model is that innate immune activity is inhibited by the efferent vagus. We evaluated whether changes in markers of tonic or reflex vagal heart rate modulation following behavioural intervention were associated inversely with changes in high-sensitivity C-reactive protein (hsCRP) or interleukin-6 (IL-6).
  
  
  METHODS
  Subjects diagnosed with hypertension (n = 45, age 35-64 years, 53% women) were randomized to an 8-week protocol of behavioural neurocardiac training (with heart rate variability biofeedback) or autogenic relaxation. Assessments before and after intervention included pro-inflammatory factors (hsCRP, IL-6), markers of vagal heart rate modulation [RR high-frequency (HF) power within 0.15-0.40 Hz, baroreflex sensitivity and RR interval], conventional measures of lipoprotein cholesterol and 24-h ambulatory systolic and diastolic blood pressure.
  
  
  RESULTS
  Changes in hsCRP and IL-6 were not associated with changes in lipoprotein cholesterol or blood pressure. After adjusting for anti-inflammatory drugs and confounding factors, changes in hsCRP related inversely to changes in HF power (β = -0.25±0.1, P = 0.02), baroreflex sensitivity (β = -0.33±0.7, P = 0.04) and RR interval (β = -0.001 ± 0.0004, P = 0.02). Statistically significant relationships were not observed for IL-6.
  
  
  CONCLUSIONS
  Changes in hsCRP were consistent with the inhibitory effect of increased vagal efferent activity on pro-inflammatory factors predicted by the cholinergic anti-inflammatory reflex model. Clinical trials for patients with cardiovascular dysfunction are warranted to assess whether behavioural interventions can contribute independently to the chronic regulation of inflammatory activity and to improved clinical outcomes.
authors.affiliation: University Health Network and University of Toronto, ON, Canada. rnolan@uhnres.utoronto.ca
authors.forename: R P
authors.initials: RP
authors.lastname: Nolan
authors.forename: J S
authors.initials: JS
authors.lastname: Floras
authors.forename: L
authors.initials: L
authors.lastname: Ahmed
authors.forename: P J
authors.initials: PJ
authors.lastname: Harvey
authors.forename: N
authors.initials: N
authors.lastname: Hiscock
authors.forename: H
authors.initials: H
authors.lastname: Hendrickx
authors.forename: D
authors.initials: D
authors.lastname: Talbot
mesh_terms: D000328:Adult; D001326:Autogenic Training; D017704:Baroreflex / Q000276:immunology*; D032763:Behavior Control / Q000379:methods; D001676:Biofeedback, Psychology / Q000502:physiology*; D015415:Biomarkers; D001794:Blood Pressure / Q000276:immunology; D002097:C-Reactive Protein / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D006321:Heart / Q000294:innervation / Q000503:physiopathology; D006339:Heart Rate / Q000276:immunology; D006801:Humans; D006973:Hypertension / Q000276:immunology / Q000503:physiopathology / Q000523:psychology; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D012063:Relaxation / Q000502:physiology*; D014630:Vagus Nerve / Q000276:immunology
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D002097:C-Reactive Protein; D002784:Cholesterol