||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 fromthe Netherlands Study of
Depression and Anxiety. To compare the pattern of results, prospective analyses with ANS (during sleep, leisure time, and work) and inflammation
were conducted in two data sets from the Netherlands Twin Register measured for 4.9 years (n = 356) and 5.4 years (n = 472).
Autonomic nervous systemmeasures were heart rate (HR) and respiratory sinus arrhythmia (RSA). Inflammatory markers were C-reactive
protein (CRP) and interleukin (IL)-6.
Results: The Netherlands Study of Depression and Anxiety results showed that higher HR and lower RSAwere 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. The Netherlands Twin Register 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.