Prognostic relevance of the interaction between short-term, metronome-paced heart rate variability, and inflammation: results from the population-based CARLA cohort study

Europace. 2017 Jan;19(1):110-118. doi: 10.1093/europace/euv333. Epub 2016 May 24.

Abstract

Aims: To determine the interaction between HRV and inflammation and their association with cardiovascular/all-cause mortality in the general population.

Methods and results: Subjects of the CARLA study (n = 1671; 778 women, 893 men, 45-83 years of age) were observed for an average follow-up period of 8.8 years (226 deaths, 70 cardiovascular deaths). Heart rate variability parameters were calculated from 5-min segments of 20-min resting electrocardiograms. High-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and soluble tumour necrosis factor-alpha receptor type 1 (sTNF-R1) were measured as inflammation parameters. The HRV parameters determined included the standard deviation of normal-to-normal intervals (SDNN), the root-mean-square of successive normal-interval differences (RMSSD), the low- and high-frequency (HF) power, the ratio of both, and non-linear parameters [Poincaré plot (SD1, SD2, SD1/SD2), short-term detrended fluctuation analysis]. We estimated hazard ratios by using covariate-adjusted Cox regression for cardiovascular and all-cause mortality incorporating an interaction term of HRV/inflammation parameters. Relative excess risk due to interactions (RERIs) were computed. We found an interaction effect of sTNF-R1 with SDNN (RERI: 0.5; 99% confidence interval (CI): 0.1-1.0), and a weaker effect with RMSSD (RERI: 0.4; 99% CI: 0.0-0.9) and HF (RERI: 0.4; 99% CI: 0.0-0.9) with respect to cardiovascular mortality on an additive scale after covariate adjustment. Neither IL-6 nor hsCRP showed a significant interaction with the HRV parameters.

Conclusion: A change in TNF-α levels or the autonomic nervous system influences the mortality risk through both entities simultaneously. Thus, TNF-α and HRV need to be considered when predicating mortality.

Keywords: CRP; Cardiovascular mortality; General population; Heart rate variability; Interleukin 6; Tumour necrosis factor-alpha.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Autonomic Nervous System / physiopathology*
  • C-Reactive Protein / analysis
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / physiopathology*
  • Cause of Death
  • Electrocardiography
  • Female
  • Germany
  • Heart / innervation*
  • Heart Rate*
  • Humans
  • Inflammation / blood
  • Inflammation / diagnosis
  • Inflammation / mortality
  • Inflammation / physiopathology*
  • Inflammation Mediators / blood
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Prospective Studies
  • Receptors, Tumor Necrosis Factor, Type I / blood
  • Risk Factors
  • Time Factors
  • Tumor Necrosis Factor-alpha / blood

Substances

  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-6
  • Receptors, Tumor Necrosis Factor, Type I
  • TNFRSF1A protein, human
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein