Photoplethysmography (PPG)-determined heart rate variability (HRV) and extracellular water (ECW) in the evaluation of chronic stress and inflammation

Hormones (Athens). 2022 Sep;21(3):383-390. doi: 10.1007/s42000-021-00341-y. Epub 2022 Jan 14.


Background: Heart rate variability (HRV) is the physiological variation in the time interval between consecutive heartbeats. Extracellular water (ECW) is the aqueous compartment surrounding cells and has been used as an inflammation index. Medically unexplained symptoms (MUS) refer to persistent psychosomatic bodily complaints, and their presence may be employed as a clinical index of chronic stress and inflammation, useful in distinguishing suffering patients from healthy subjects.

Aim: To evaluate the clinical performance of SDNN (standard deviation of intracardiac beat time interval of normal sinus beats) and RMSSD (square root of the mean squared differences of successive NN intervals) as indices of HRV, and their correlation with ECW and MUS.

Patients and methods: A large multicenter retrospective study was conducted in 37 Italian medical practices in Caucasian men and women aged 20 to 70 years. SDNN and RMSSD were measured with the PPG Stress Flow® device (BioTekna, Italy), while ECW was determined with the BIA-ACC® device (BioTekna, Italy). All subjects filled in a MUS® questionnaire with 19 "nonspecific" symptom questions. The study sample was stratified by decade of age into five groups.

Results: Data from 9246 subjects comprising 3127 males and 6119 females, with a median age of 47 years, were analyzed. HRV index SDNN and RMSSD distributions in the entire sample and in each of the five age groups were significantly greater in subjects with a limited number of MUS (0-5) than in subjects with six or more symptoms, while both distributions correlated negatively with ECW.

Conclusion: SDNN and RMSSD and ECW were predictors of MUS and were successfully used to objectively evaluate chronic stress and inflammation.

Keywords: Autonomic nervous system, ANS; Heart rate variability, HRV; Inflammation; Medically unexplained symptoms, MUS; Photoplethysmography, PPG; RMSSD, square root of the mean squared differences of successive NN intervals; SDNN, standard deviation of the intracardiac beat time intervals; Stress.

Publication types

  • Multicenter Study

MeSH terms

  • Female
  • Heart Rate / physiology
  • Humans
  • Inflammation / diagnosis
  • Male
  • Middle Aged
  • Photoplethysmography*
  • Retrospective Studies
  • Water*


  • Water