Heart Rate Variability Studies on Aging

Functional changes in autonomic nervous responses with ageing. Collins KJ, Exton-Smith AN, and other. Age Ageing. 1980 Feb; 9(1): 17-24.

 The effects of ageing on autonomic nervous responses have been investigated in 29 young adults, 64 healthy elderly in the age range 66 to 86 years, and 20 elderly in-patients with hypothermia, instability of bladder function or marked orthostatic hypotension. In the healthy elderly group, the beat-to-beat variation in response to postural change was significantly diminished, the vasoconstrictor response to cooling reduced and baroreflex sensitivity during lower-body negative pressure was decreased compared with young adults. Patients with an atronic bladder, determined by urodynamic tests, showed an even more marked decrease in baroreflex sensitivity. The multisystem nature of these autonomic disturbances suggests that physiological impairment may occur in autonomic neural pathways with ageing.

Age dependency of cardiovascular autonomic responses to head-up tilt in healthy subjects. Laitinen T, Niskanen L, and other. J.Appl.Physiol. 2004 Jun; 96(6):2333-40.

In elderly subjects, heart rate responses to postural change are attenuated, whereas their vascular responses are augmented. Altered strategy in maintaining blood pressure homeostasis during upright position may result from various cardiovascular changes, including age-related cardiovascular autonomic dysfunction. This exploratory study was conducted to evaluate impact of age on cardiovascular autonomic responses to head-up tilt (HUT) in healthy subjects covering a wide age range. The study population consisted of 63 healthy, normal-weight, nonsmoking subjects aged 23-77 yr. Five-minute electrocardiogram and finger blood pressure recordings were performed in the supine position and in the upright position 5 min after 70 degrees HUT. Stroke volume was assessed from noninvasive blood pressure signals by the arterial pulse contour method. Heart rate variability (HRV) and systolic blood pressure variability (SBPV) were analyzed by using spectral analysis, and baroreflex sensitivity (BRS) was assessed by using sequence and cross-spectral methods. Cardiovascular autonomic activation during HUT consisted of decreases in HRV and BRS and an increase in SBPV. These changes became attenuated with aging. Age correlated significantly with amplitude of HUT-stimulated response of the high-frequency component (r = -0.61, P < 0.001) and the ratio of low-frequency to high-frequency power of HRV (r = -0.31, P < 0.05) and indexes of BRS (local BRS: r = -0.62, P < 0.001; cross-spectral baroreflex sensitivity in the low-frequency range: r = -0.38, P < 0.01). Blood pressure in the upright position was maintained well irrespective of age. However, the HUT-induced increase in heart rate was more pronounced in the younger subjects, whereas the increase in peripheral resistance was predominantly observed in the older subjects. Thus it is likely that whereas the dynamic capacity of cardiac autonomic regulation decreases, vascular responses related to vasoactive mechanisms and vascular sympathetic regulation become augmented with increasing age.

Circadian profile of cardiac autonomic nervous modulation in healthy subjects: differing effects of aging and gender on heart rate variability. Bonnemeier H, Richardt G, and other. J Cardiovasc Electrophysiol. 2003 Aug;14(8):791-9.

Circadian Profile of 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 nycthemeral-dependent normal ranges for HRV assessment.

Standardized tests of heart rate variability: normal ranges obtained from 309 healthy humans, and effects of age, gender, and heart rate. Agelink MW, Malessa R, and other. Clin. Auton Res. 2001Apr;11(2):99-108.

The authors undertook this study to determine the effects of age, gender, and heart rate (HR) on the results of cardiac autonomic function tests for measuring heart rate variability (HRV) in a large sample of healthy subjects (n = 309). Conventional tests (deep breathing, maximum/minimum 30:15 ratio), and a standardized 5-minute resting study, including spectral analysis of HR, were used. The main findings included (1) the indices of all tests, except for the ratio of the low- (LF) to high-frequency (HF) spectral power (LF/HF ratio) and HR itself, are inversely related to age in both sexes; (2) the 5-minute spectral bands (except for the LF/HF ratio), the variation coefficient, expiratory-inspiratory ratio during deep breathing, and the maximum/minimum 30:15 ratio are independent of HR; (3) women up to the age of 55 years have a higher resting HR compared with men; (4) young and middle-aged women show a significantly lower LF power and LF/HF ratio compared with age-matched men, whereas no significant gender differences are observed in the absolute HF power. The authors computed age- and gender-dependent normal values for each of the HRV indices studied here and discuss the clinical consequences arising from gender differences in HRV.

Effect of aging on responses to autonomic cardiovascular tests. Raimondi G, Legramante JM, and other. J Gravit Physiol. 1999 Jul;6(1):141-2.

Cardiovascular deconditioning (CD) and orthostatic intolerance represent some of the major disturbances experienced by astronauts returning on Earth after micro-G exposure. The orthostatic intolerance observed in crew members after space missions has been hypothesized to be related to a disorder of the autonomic control of the cardiovascular system. There is evidence that advanced acing itself may alter the cardiovascular mechanism that underlie the CD. Due to involvement of elderly subjects in space flights it is mandatory to verify how age affects the cardiovascular autonomic neural regulation. In order to assess age-related differences in autonomic cardiovascular regulation our aim is to analyze the cardiovascular responses to 3 different autonomic tests that explore baroreceptor (tilt and deep breathing) and non-baroreceptor (isometric exercise) afferent pathways, in two goups of normal subjects characterized by significant different age.

Age-adjusted normal confidence intervals for heart rate variability in healthy subjects during head-up tilt. Piccirillo G, Fimognari FL,and other. Int J Cardiol. 1995 Jun 30;50(2):117-24.

PURPOSE: Aging leads to a decline in autonomic nervous system function. In this study, designed to assess the influence of age on neuroautonomic regulation of cardiac activity, heart rate variability was measured by power spectral analysis and normal ranges were determined in a population of healthy subjects. PATIENTS AND METHODS: In 83 healthy volunteers (42 men and 41 women; age range 25-85 years) autonomic nervous system function was assessed by autoregressive spectral analysis of heart rate variability in clinostatism and after passive orthostatic load (head-up tilt). The analysis considered two spectral components relevant to the study of the autonomic nervous system–high-frequency power (approximately 0.05 Hz) and low-frequency power (approximately 0.10 Hz)–and the ratio between them. Low-frequency spectral components, in particular the ratio between low- and high-frequency spectra, reflect sympathetic activity; high-frequency components reflect parasympathetic activity. RESULTS: For data comparison, the study group was subdivided into three age groups: 25 subjects (12 men and 13 women) under 44 years of age; 28 (15 men and 13 women) aged 44-64 years; and 30 (15 men and 15 women) over 64 years of age. The natural logarithms and normalized units of low- and high-frequency power, and the low-to-high power ratio were used to calculate 95% confidence intervals. Power spectral analysis at baseline and after postural tilt showed significantly higher low-frequency power of heart rate variability (P < 0.05), natural logarithm of power (P < 0.001) and normalized units (P < 0.001) in the two younger groups than in the oldest group. The two younger age-groups also had significantly increased high-frequency power (P < 0.05) and natural logarithm of power (P < 0.05). The oldest age group had significantly increased high-frequency power analyzed in normalized units (P < 0.001). CONCLUSION: The age-related lowering observed in nearly all the spectral frequency components of heart rate variability confirms in healthy subjects that autonomic nervous system function declines with age.

Autonomic function tests as related to age and gender in normal man. Gautschy B, Weidmann P, Gnadinger MP. Klin Wochenschr. 1986 Jun 2;64(11):499-505.

To obtain a comparative assessment of 5 different clinical autonomic function tests as related to age and gender in normal man, the beat-to-beat variation during deep breathing (BBV), orthostatic 30/15 R-R ratio, heart rate response to the Valsalva manoeuvre, blood pressure response to sustained handgrip and orthostatic blood pressure response were evaluated in 120 healthy subjects (60 women and 60 men) aged 22 to 92 yrs. Each of the functional parameters depending on cardiac parasympathetic integrity, i.e. the beat-to-beat variation, orthostatic 30/15 R-R ratio and Valsalva ratio, decreased (P less than 0.0001) progressively with increasing age. The blood pressure response to handgrip, which depends on the efferent sympathetic function, was unchanged, while the orthostatic response of systolic blood pressure, which depends on the function of the entire reflex arch, was augmented only minimally (P less than 0.001) with increasing age. No significant dependence on gender was noted, although blood pressure responses to handgrip tended to be slightly greater in men than women. Beat-to-beat variation expressed as the standard deviation of the mean R-R interval correlated with mean heart rate (P less than 0.05), while the coefficient of variation and the exspiration/inspiration ratio of beat-to-beat variation did not. The orthostatic 30/15 R-R ratio and beat-to-beat variation tended to be more closely interrelated (r = 0.56 to 0.63) than any of these tests with the Valsalva ratio (r = 0.51). The findings indicate that consideration of age may improve the diagnostic value of the orthostatic 30/15 R-R ratio.

Heart rate variability in healthy subjects: effect of age and the derivation of normal ranges for tests of autonomic function. O’Brien IA, O’Hare P, Corrall RJ. Br.Heart J. 1986 Apr;55(4):348-54.

The diagnosis of autonomic neuropathy frequently depends on results of tests which elicit reflex changes in heart rate. Few well-documented normal ranges are available for these tests. The present study was designed to investigate the effect of age upon heart rate variability at rest and in response to a single deep breath, the Valsalva manoeuvre, and standing. A computerised method of measurement of R-R interval variation was used to study heart rate responses in 310 healthy subjects aged 18-85 years. Heart rate variation during each procedure showed a skewed distribution and a statistically significant negative correlation with age. Normal ranges (90% and 95% confidence limits) for subjects aged 20-75 years were calculated for heart rate difference (max-min) and ratio (max/min) and standard deviation (SD). Heart rate responses were less than the 95th centile in at least one of the four procedures in 39 (12.6%) out of the 310 subjects, and were below this limit in two or more tests in five (1.6%) subjects. In view of the decline in heart rate variation with increasing age, normal ranges for tests of autonomic function must be related to the age of the subject.

Differential changes of autonomic nervous system function with age in man. Pfeifer MA, Weinberg CR and other. Am J Med. 1983 Aug;75(2):249-58.

To assess the relationship between aging and autonomic nervous system function, cardiovascular and pupillary autonomic nervous system reflexes were measured in subgroups of 103 normal male subjects ranging in age from 19 to 82 years (mean age = 39 years). Both the plasma norepinephrine level, a measure of cardiovascular sympathetic nervous system activity, and the mean arterial blood pressure increased with age (r = 0.68 and 0.67, respectively, both p less than 0.001). In contrast, the plasma epinephrine level, a measure of adrenomedullary sympathetic nervous system activity, was unrelated to age (r = 0.08, p = NS). Respiratory variation of heart rate during beta-adrenergic blockade, an index of cardiac parasympathetic nervous system activity, was reduced in older subjects (r = -0.54, p less than 0.001). Thus, there was evidence of an age-related increase of cardiovascular sympathetic nervous system activity and a reduction of cardiac parasympathetic nervous system activity. These findings are consistent with the hypothesis that there is sympathetic nervous system and parasympathetic nervous system compensation of cardiovascular function in response to an age-related decrease in baroreceptor sensitivity. However, dark-adapted pupil size during parasympathetic nervous system blockade, an index of iris sympathetic nervous system activity, declined with age (r = -0.81, p less than 0.001). The latency time for the pupillary response to a light stimulus, an index of iris parasympathetic nervous system activity, was prolonged in older subjects (r = 0.58, p less than 0.001). Thus, both sympathetic nervous system and parasympathetic nervous system inputs to the iris were diminished in older subjects, findings consistent with the generalized decrease of peripheral somatic nerve function that has been reported with aging in man. It is concluded that autonomic nervous system function also declines with aging, but that other age-related changes such as a decline of baroreceptor sensitivity may lead to compensatory autonomic nervous system response, which could mask underlying functional defects.

Aging of the autonomic nervous system. Shimazu T, Tamura N, Shimazu K. Nippon 2005 Jun;63(6):973-7.

Aging is associated with structural and functional changes in the autonomic nervous system (ANS), which innervates the whole body, and its altered function may influence almost all body systems. Changes related to aging are found in autonomic nerves and ganglia, and ANS controlled functions including cardiovascular functions. Much of the current knowledge about age-related changes in sympathetic nervous function is derived from studies of circulating catecholamine levels, norepinephrine kinetics and microneurographic recordings from sympathetic nerves of skeletal muscle. Significant evidence suggests that basal plasma noradrenaline levels increase with age. These data indicates that healthy aging is associated with elevated basal sympathetic nervous activity. In contrast, the reactivity of the sympathetic and the parasympathetic nervous activity are reduced with aging.

Aging of modulation of heart rate. C. Shannon, D. W. Carley and H. Benson. Heart and Circulatory Physiology, Vol 253, Issue 4 874-H877, 1987.

We postulated that measurements of autonomically mediated fluctuations in heart rate might provide a quantitative probe of biological aging. We used power spectrum analysis of instantaneous heart rate while 33 male subjects matched their breathing to a metronome at 15 breaths/min. Measurements were made in supine and standing position. Total power and its two major components, high- and low-frequency power, declined with age in both positions but at different rates. High-frequency power that represents parasympathetically mediated respiratory sinus arrhythmia declined linearly in supine position only in subjects 9-28 yr with a slope of -0.796, which was significantly different from zero at P = 0.0007. The absolute value of high-frequency power in standing position was approximately 60% of that in supine, a difference that was statistically significant (P = 0.01). Low-frequency power that represents beta-adrenergically mediated heart rate fluctuations, especially in standing position, declined linearly to 62 yr of age (P = 0.0001). Mean heart rate increased 17.2 beats/min, and diastolic blood pressure increased 8 mmHg in the entire group in the standing compared with supine position. There were no significant differences in these changes above and below 30 yr of age. We conclude that the influence of the two major mechanisms that modulate heart rate decline at significantly different rates with aging.

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