Normal ranges and reproducibility of statistical, geometric, frequency domain, and non-linear measures of 24-hour heart rate variability

Diabetic cardiovascular autonomic neuropathy (CAN) carries an increased ris k of mortality. The early detection and characterization of CAN has traditi onally been based on the results of autonomic reflex tests (AFTs). A variet y of different measures to quantify 24-hour heart rate variability (HRV) ha ve recently been introduced, but their normal ranges, reliability, and vali dity in patients with CAN have not been adequately studied. We established the normal ranges of statistical (SDNN index, CV, SNN50, RMSSD), geometric (triangular index (TI), triangular interpolation (TINN), top angle index [T AI]), frequency domain (spectral power in the VLF, LF, and HF bands, LF/HF ratio, LF in normalized units [NU]), and non-linear measures (CV1 and CV2 o f the Poincare plot) of 24-hour HRV in 94 healthy control subjects. Day-to- day reproducibility was evaluated on two occasions in 17 healthy subjects a nd 9 diabetic patients. The parameters of HRV were computed over time perio ds representing the day (6:00-24:00 hours), night (00:00-6:00 hours), and 2 4 hours in total. The results of all indexes, except for the LF/HF ratio an d LF-NU, declined significantly with increasing age (p < 0.05), but were in dependent of sex and BMI. The statistical, geometric, and non-linear measur es (p < 0.05), but not the frequency-domain parameters decreased significan tly with increasing heart rate. Since the HRV data showed log normal distri bution, log transformation was used to define the age-related lower limits of normal at the 2.5th centile. Intraindividual reproducibility was highest for the geometric measures. The nonlinear and statistical parameters also showed high reliability, except for the SNN50. The repeatability of the fre quency domain measures was somewhat lower but still satisfactory. Reproduci bility was lower in the diabetic than in the control group, higher during t he day than during the night, and better than that reported previously for the AFTs. In conclusion, in healthy subjects the measures of 24-h HRV are n ot related to sex or BMI, but strongly dependent on age and heart rate, the latter except for the frequency domain measures. The majority of the HRV m easures, in particular the geometric parameters, show a relatively high int raindividual reproducibility which underlines their suitability for the use in prospective studies.