Decreased heart rate variability is associated with higher levels of inflammation in middle-aged men

Am Heart J. 2008 Oct;156(4):759.e1-7. doi: 10.1016/j.ahj.2008.07.009.


Background: Many traditional risk factors for coronary artery disease (CAD) are associated with altered autonomic function. Inflammation may provide a link between risk factors, autonomic dysfunction, and CAD. We examined the association between heart rate variability (HRV), a measure of autonomic function, and inflammation, measured by C-reactive protein (CRP) and interleukin-6 (IL-6).

Methods: We examined 264 middle-aged male twins free of symptomatic CAD. All underwent ambulatory electrocardiogram monitoring and 24-hour ultra low, very low, low, and high-frequency power were calculated using power spectral analysis. C-reactive protein and IL-6 were measured, and risk factors including age, smoking, hypertension, lipids, diabetes, body mass index (BMI), depression, and physical activity were assessed.

Results: Physical activity, BMI, high-density lipoprotein cholesterol, smoking, depression, and hypertension were directly associated with CRP and IL-6 and inversely associated with one or more HRV variables. There was a graded inverse relationship between all HRV parameters (except high frequency) and CRP and IL-6. After adjustment for age, BMI, activity, high-density lipoprotein, smoking, hypertension, depression, and diabetes, ultra low frequency and very low frequency remained significant predictors of CRP (P < .01).

Conclusions: C-reactive protein is associated with decreased HRV, even after controlling for traditional CAD risk factors. Autonomic dysregulation leading to inflammation may represent one pathway through which traditional risk factors promote development of CAD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Twin Study

MeSH terms

  • Autonomic Nervous System / physiopathology
  • C-Reactive Protein / analysis*
  • Coronary Artery Disease / epidemiology
  • Cross-Sectional Studies
  • Electrocardiography, Ambulatory
  • Heart Rate / physiology*
  • Humans
  • Inflammation / blood
  • Inflammation / physiopathology*
  • Interleukin-6 / analysis*
  • Male
  • Middle Aged
  • Risk Factors


  • Interleukin-6
  • C-Reactive Protein