Bidirectional prospective associations between cardiac autonomic activity and inflammatory markers

Mandy Xian Hu*, Femke Lamers, Melanie Neijts, Gonneke Willemsen, Eco J.C. De Geus, Brenda W.J.H. Penninx

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

53 Downloads (Pure)


OBJECTIVE: Autonomic nervous system (ANS) imbalance has been cross-sectionally associated with inflammatory processes. Longitudinal studies are needed to shed light on the nature of this relationship. We examined cross-sectional and bidirectional prospective associations between cardiac autonomic measures and inflammatory markers.

METHODS: Analyses were conducted with baseline (n=2823), 2-year (n=2099), and 6-year (n=1774) data from the Netherlands Study of Depression and Anxiety (NESDA). To compare the pattern of results, prospective analyses with ANS (during sleep, leisure time and work) and inflammation were conducted in two datasets from the Netherlands Twin Register (NTR) measured over 4.9 years (n=356) and 5.4 years (n=472). ANS measures were heart rate (HR) and respiratory sinus arrhythmia (RSA). Inflammatory markers were C-reactive protein (CRP) and interleukin(IL)-6.

RESULTS: NESDA results showed that higher HR and lower RSA were cross-sectionally significantly associated with higher inflammatory levels. Higher HR predicted higher levels of CRP (B=.065; p<.001) and IL-6 (B=.036; p=.014) at follow-up. Higher CRP levels predicted lower RSA (B=-.024; p=.048) at follow-up. NTR results confirmed that higher HR was associated with higher CRP and IL-6 levels 4.9 years later. Higher IL-6 levels predicted higher HR and lower RSA at follow-up.

CONCLUSIONS: Autonomic imbalance is associated with higher levels of inflammation. Independent data from two studies converge in evidence that higher HR predicts subsequent higher levels of CRP and IL-6. Inflammatory markers may also predict future ANS activity, but evidence for this was less consistent.

Original languageEnglish
Pages (from-to)475-482
Number of pages8
JournalPsychosomatic Medicine
Issue number5
Early online date7 May 2018
Publication statusPublished - Jun 2018


Source of Funding and Conflicts of Interest: This work was supported by the Geestkracht program of the Netherlands Organisation for Health Research and Development (Zon-Mw, Grant Number 10-000-1002), by the FP7-Marie Curie Grant (PCIG12-GA-2012-334065 to F.L.), and by participating universities (VU University Medical Center, Leiden University Medical Center, University Medical Center Groningen). The authors report no conflicts of interest.

FundersFunder number
FP7-Marie CuriePCIG12-GA-2012-334065


    • ANS = autonomic nervous system
    • Autonomic nervous system
    • BMI = body mass index
    • CAD = coronary artery disease
    • CRP = C-reactive protein
    • ECG = electrocardiogram
    • ELISA = enzyme-linked immunosorbent assay
    • Inflammation
    • Longitudinal
    • Vagal activity


    Dive into the research topics of 'Bidirectional prospective associations between cardiac autonomic activity and inflammatory markers'. Together they form a unique fingerprint.

    Cite this