title: RR interval variability is inversely related to inflammatory markers: the CARDIA study.
abstract: Recent evidence reveals that the immune system is under the direct control of the vagus nerve via the "cholinergic anti-inflammatory pathway." Stimulation of vagus nerve activity significantly inhibits cytokine levels in animal models, and cholinergic agents inhibit cytokine release by human macrophages. Moreover, when vagus nerve activity is decreased or absent, cytokines are overproduced. Atherosclerosis is an inflammatory disease characterized by elevated levels of CRP and IL-6, but the relationship between cardiac vagal activity and cytokine levels in healthy humans is not well understood. Here we measured RR interval variability, an index of cardiac vagal modulation, and CRP and IL-6 in 757 subjects participating in a subset of the year 15 data collection in the CARDIA study of the evolution of risk factors in young adults. Univariate analysis revealed that all indices of RRV were strongly and inversely related to IL-6 (log pg/mL b=-0.08 and -0.17 for HF and LF power, P<0.001 respectively) and CRP (log mg/L b=-0.14 and -0.26 for HF and LF power, P<0.001 respectively) levels. In the multivariate model including gender, race, age, smoking, physical activity, SBP, BMI, and disease, the inverse relationship between RRV and inflammatory markers, although slightly attenuated, remained significant. These findings are consistent with the hypothesis that diminished descending vagal anti-inflammatory signals can allow cytokine overproduction in humans.
authors.affiliation: Behavioral Medicine Program, Department of Psychiatry, Columbia University Medical Center, New York, NY 10032, USA. rps7@columbia.edu
authors.forename: Richard P
authors.initials: RP
authors.lastname: Sloan
authors.forename: Heather
authors.initials: H
authors.lastname: McCreath
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Tracey
authors.forename: Stephen
authors.initials: S
authors.lastname: Sidney
authors.forename: Kiang
authors.initials: K
authors.lastname: Liu
authors.forename: Teresa
authors.initials: T
authors.lastname: Seeman
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000209:etiology / Q000503:physiopathology; D003430:Cross-Sectional Studies; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D015337:Multicenter Studies as Topic; D015999:Multivariate Analysis; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D014630:Vagus Nerve / Q000503:physiopathology; D044465:White People / Q000706:statistics & numerical data
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D002097:C-Reactive Protein