Circadian profile of cardiac autonomic nervous modulation in healthy subjects: Differing effects of aging and gender on heart rate variability

Introduction: Although heart rate variability (HRV) has been established as a tool to study cardiac autonomic activity, almost no data are available on the circadian patterns of HRV in healthy subjects aged 20 to 70 years. Methods and Results: We investigated 166 healthy volunteers (81 women and 85 men; age 42 +/- 15 years, range 20-70) without evidence of cardiac disease. Time-domain HRV parameters were determined from 24-hour Holter monitoring and calculated as hourly mean values and mean 24-hour values. All volunteers were fully mobile, awoke around 7 A.M., and had 6 to 8 hours of sleep. Circadian profiles of vagus-associated HRV parameters revealed a marked day-night pattern, with a peak at nighttime and a plateau at daytime. The characteristic nocturnal peak and the day-night amplitude diminished with aging by decade. Estimates of overall HRV (geometric triangular index [TI], SD of NN intervals [SDNN]) and long-term components of HRV (SD of the averages of NN intervals for all 5-min segments [SDANN]) were low at nighttime and increased in the morning hours. There was a significant decline of 24-hour values of all HRV parameters (P < 0.001) and a strong negative correlation (P < 0.001) with increasing age. Mean 24-hour RR interval (P < 0.001), SDNN, mean SD of NN intervals for all 5-minute intervals (SDNNi), and SDANN (all P < 0.01) were significantly higher in men. Younger men also exhibited significantly higher values for vagus-associated parameters (root mean square successive difference [rMSSD], P < 0.05; SDNNi, P < 0.01); however, gender differences diminished with increasing age. Conclusion: Normal aging is associated with a constant decline of cardiac vagal modulation due to a significant decrease of nocturnal parasympathetic activity. The significant gender-related difference of HRV decreases with aging. These findings emphasize the need to determine age-, gender-, and nycthemeraldependent normal ranges for HRV assessment.