title: Lower heart rate variability predicts increased level of C-reactive protein 4 years later in healthy, nonsmoking adults.
abstract: BACKGROUND
  Inflammation and vagally mediated heart rate variability (vmHRV) have been implicated in a number of conditions including diabetes and cardiovascular disease. Consistent with the inflammatory reflex termed the 'cholinergic anti-inflammatory pathway', numerous cross-sectional studies have demonstrated negative associations between vmHRV and inflammatory markers such as C-reactive protein (CRP). The only prospective study, however, showed the opposite: higher CRP at baseline predicted higher high-frequency heart rate variability (HF-HRV) at follow-up. Thus, additional studies are needed to examine the prospective association between vmHRV and CRP.
  
  
  METHODS
  Healthy employees participated in a voluntary on-site health assessment. Blood samples and ambulatory heart rate recordings were obtained, and night-time HF-HRV was calculated. Useable heart rate data were available in 2007 for 106 nonsmoking employees (9% women; age 44.4 ± 8 years), all of whom returned for an identical follow-up health assessment in 2011. Bootstrapped (500 replications) bivariate (r) and partial Pearson's correlations (ppc) adjusting for sex, age and body mass index at baseline (2007) were calculated.
  
  
  RESULTS
  Zero-order correlations indicated that higher HF-HRV was associated with lower levels of CRP at both time-points (2007: r = -0.19, P < 0.05; 2011: r = -0.34, P < 0.001). After adjustment, HF-HRV remained a significant predictor of CRP (ppc = -0.20, P < 0.05).
  
  
  CONCLUSIONS
  In this study, we have provided in vivo support for the cholinergic anti-inflammatory pathway in humans. Cardiac vagal modulation at baseline predicts level of CRP 4 years later. Our findings have important implications for the role of vmHRV as a risk factor for cardiovascular disease morbidity and mortality. Interventions targeted at vmHRV might be useful in the prevention of diseases associated with elevated systemic inflammation.
authors.affiliation: Mannheim Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, Heidelberg University, Mannheim, Germany.
authors.forename: M N
authors.initials: MN
authors.lastname: Jarczok
authors.forename: J
authors.initials: J
authors.lastname: Koenig
authors.forename: D
authors.initials: D
authors.lastname: Mauss
authors.forename: J E
authors.initials: JE
authors.lastname: Fischer
authors.forename: J F
authors.initials: JF
authors.lastname: Thayer
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood / Q000503:physiopathology; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D014630:Vagus Nerve / Q000502:physiology; D055815:Young Adult
chemical_list: D002097:C-Reactive Protein
keywords: C-reactive protein; cardiac autonomic function; heart rate variability; prospective studies; systemic inflammation