Increased heart rate and reduced heart-rate variability are associated with subclinical inflammation in middle-aged and elderly subjects with no apparent heart disease

Eur Heart J. 2004 Mar;25(5):363-70. doi: 10.1016/j.ehj.2003.12.003.


Aim: Elevation of inflammation markers, high heart rate, and reduced heart-rate variability are all strong markers of mortality in a broad spectrum of patients. The association between these markers has not been clarified thoroughly. We investigated the associations between markers of inflammation, heart rate, and heart-rate variability.

Methods and results: Six hundred and forty-three healthy men and women between 55 and 75 years of age and with no prior history of cardiovascular disease or stroke were included in the study. The baseline study included a physical examination, fasting laboratory tests, and 24-h ambulatory ECG monitoring. We selected the time-domain components of heart-rate variability for further analyses. C-reactive protein concentration and white blood cell count were selected as markers of inflammation. After identifying parameters related to measures of heart-rate variability, we used regression analyses to evaluate independent associations. Heart-rate variability, as measured by the standard deviation of the time between normal-to-normal complexes or the standard deviation of the average of normal-to-normal intervals for each 5-min period, was negatively associated with smoking, C-reactive protein, white blood cell count, blood sugar and triglyceride concentration, female gender, and diabetes. In contrast, physical activity was strongly associated with higher heart-rate variability. In multivariate regression analyses, increased heart-rate and reduced heart-rate variability were significantly and independently related to white blood cell count or C-reactive protein concentration.

Conclusion: Increased heart rate and reduced heart-rate variability are associated with subclinical inflammation in healthy middle-aged and elderly subjects. The increased mortality that has been reported in these settings may thus have a common aetiology. An autonomic imbalance in favour of the sympathetic system may interact with inflammatory processes to play a more important role in the process of atherosclerosis than previously thought.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arrhythmias, Cardiac / etiology*
  • C-Reactive Protein / analysis
  • Electrocardiography, Ambulatory
  • Female
  • Heart Rate / physiology
  • Humans
  • Leukocyte Count
  • Male
  • Middle Aged
  • Myocarditis / complications*
  • Myocarditis / physiopathology


  • C-Reactive Protein