Assessment of Cardiovascular Autonomic Function: Age‐related Normal Ranges and Reproducibility of Spectral Analysis, Vector Analysis, and Standard Tests of Heart Rate Variation and Blood Pressure Responses

Abstract

To establish normal ranges for assessment of autonomic dysfunction, a battery of cardiovascular reflex tests was performed in 120 healthy subjects aged 15-67 years using a computer-based technique. Tests of heart rate variation (HRV) included 8 measures at rest: coefficient of variation (CV), root mean squared successive difference (RMSSD), spectral analysis of HRV in the low frequency, mid frequency, and high frequency bands in the supine and standing postures; 5 measures during deep breathing: CVb, RMSSDb, Expiration-Inspiration (E-I) difference, E/I ratio, and mean circular resultant of vector analysis; Valsalva ratio, and max/min 30:15 ratio. In addition, the change in systolic and diastolic blood pressure in response to standing and the diastolic blood pressure response to sustained handgrip were determined. The results of all measures, the blood pressure tests excepted, declined significantly with increasing age (r = -0.16 to -0.59; p less than 0.05). Moreover, RMSSD, RMSSDb, and E-I difference decreased considerably with increasing heart rate (r = -0.37 to -0.52; p less than 0.001). The longest and shortest R-R intervals in response to standing were distributed within beats 21-39 and 6-24, respectively. All tests were independent of sex. Log transformation was used to define the age-related lower limits of normal at the 2.3 centile for all tests of HRV, except for the E/I, Valsalva, and max/min 30:15 ratios. The results of these tests had to be analysed using a log(y-1) transformation. The intra-individual reproducibility determined on two consecutive days in 20 healthy subjects and 21 diabetic patients indicated that there were no major differences between the two groups regarding the day-to-day variation of test results, which was highest for the Valsalva ratio. We conclude that: (1) all indices of spectral and vector analyses of HRV are age-dependent and have the advantage of being independent of heart rate; (2) RMSSD, E-I difference, and the 30:15 ratio as it was used previously are not suitable for evaluation of autonomic dysfunction in diabetes; (3) log(y-1) transformation is required to determine age-dependent normal ranges and reproducibility for the three ratios.

Measures of cardiovascular autonomic nervous function: agreement, reproducibility, and reference values in middle age and elderly subjects

“…This association was both statistically and clinically significant for LF power and EI difference and appropriate sex-specific reference values were given. Also, the association between measures of autonomic function and age is consistent with previous findings [8,9,10,11,12,13], although we found slightly lower associations with age. This could be attributable to the older age of our subjects compared to previous studies.…”

“…Secondly, elderly people in general have more difficulties to correctly carry out certain tests (deep breathing and standing up quickly enough). This becomes apparent when comparing our reproducibility with other studies: somewhat higher reproducibility for the deep breathing test (EI difference and BRS) for slightly younger subjects [12,56,57,58]. Reproducibility of course might be improved by standardizing the conditions during measurements [56].…”

“…These Ewing test measures, and also HRV and BRS measures, are based on the autonomically mediated response of the heart rate to changes in blood pressure. Autonomic function has been reported to decrease in relation to age [8,9,10,11,12,13] and to differ between men and women [9,14,15]. Furthermore, diabetic patients have lower values on the Ewing battery [3,16,17,18,19], of the spectral analysis of HRV [4,16,20,21], and have a low BRS [5,22] in comparison with normal glucose tolerant control subjects.…”

Cardiovascular and cerebrovascular responses to lower body negative pressure in type 2 diabetic patients

“…In addition, we determined the minimum and maximum RR-intervals from the breathing cycle with the greatest difference between the maximum RR-interval during expiration and the minimum RR-interval during inspiration. As parameters of HRV, we calculated the difference between the maximum and minimum RR-intervals (E − I difference) as well as the ratio of maximum and minimum RR-intervals (E-I ratio) [16].…”

“…the 30:15 ratio and 5.) the Valsalva ratio exceeded age-related normal control values [16]. Based on the HRV findings, patients were classified in two subgroups (with or without CAN).…”