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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 55:M744-M749 (2000)
© 2000 The Gerontological Society of America

A 15-Year Longitudinal Follow-Up Study of Heart Rate and Heart Rate Variability in Healthy Elderly Persons

Hirofumi Tasakia, Takumi Seritaa, Akiko Iritaa, Osamu Hanoa, Ivan Ilieva, Chiaki Ueyamaa, Kouei Kitanoa, Shinji Setoa, Motonobu Hayanoa and Katsusuke Yanoa

a The Third Department of Internal Medicine, Nagasaki University School of Medicine, Japan

Hirofumi Tasaki, The Third Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501 Japan E-mail: mikan{at}net2.nagasaki-u.ac.jp.

Decision Editor: John E. Morley, MB, BCh


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 References
 
Background. Few researchers have conducted heart rate (HR) studies in healthy very elderly subjects aged 70 years or older, and there are no longitudinal follow-up studies in this population. The objective of this study was to evaluate long-term changes in HR and heart rate variability (HRV) with aging in healthy elderly persons by means of comparison between two Holter monitor recordings obtained at an interval of 15 years.

Methods. The study population consisted of 15 healthy elderly persons (10 women and 5 men) aged 64 to 80 years (mean 70 ± 4.1) at the first recording, and 79 to 95 years old (mean 85 ± 4.1 years) at the second recording 15 years later. Nighttime (midnight to 5 AM) and daytime (noon to 5 PM) HR and HRV were obtained, and paired t tests were performed to assess the differences in each parameter of nighttime and daytime HR and HRV between the two (15-year interval) Holter monitor recordings.

Results. The results of the t-test comparisons were as follows: there was a significant increase in minimal, maximal, and average HRs (nighttime, p < .01; daytime, p < .05, respectively). On the other hand, with regard to HRV, there was a significant nighttime decrease in the SDNN index (mean of standard deviations of normal RR intervals between adjacent QRS complexes resulting from sinus node depolarizations for all 5-minute segments) (p = .0086), and a significant daytime increase in the NN50 (number of adjacent normal RR intervals >50 milliseconds) per hour (p = .0425). Moreover, there was a significant decrease in the low-frequency (LF) component (nighttime, p = .0151; daytime, p = .0032), and a significant decrease in the LF/HF ratio (nighttime, p = .0270; daytime, p = .0371), but there was no significant change in the nighttime or daytime high-frequency (HF) component.

Conclusions. HR increased with age over the 15-year period in the healthy elderly persons. As for concurrent changes in HRV, however, the parameters of sympathetic modulation decreased, and the parameters of parasympathetic modulation were unchanged or slightly increased.

ALTHOUGH cardiac automaticity is intrinsic to various pacemaker tissues, heart rate (HR) and rhythm are largely under the control of the autonomic nervous system (ANS) (1) (2) (3) (4). Recently, heart rate variability (HRV) has been used to evaluate activities of the ANS and to elucidate prognoses of various heart diseases or cardiac events (5) (6) (7). At the same time, studies of interrelation between age and HR or HRV have been accumulating. From these studies, it has been suggested that average maximal HR (8) and ANS activities (9) (10) (11) (12) (13) decline with age in healthy adults. However, most of the preceding studies were conducted in healthy subjects aged 70 years or younger (9) (10) (11) (12) (13), and all were cross-sectional. Few researchers have conducted studies in healthy very elderly subjects aged 70 years or older (14) (15) (16), and there are no longitudinal follow-up studies in this population.

The objective of this study was to evaluate changes in HR and HRV with aging in healthy elderly persons by means of comparison between two Holter monitor recordings obtained at a 15-year interval.


   Methods
Top
 Abstract
 Methods
Results
 Discussion
 References
 
Study Population
The study was conducted in 15 healthy elderly persons (10 women and 5 men) who were volunteers from a club for senior citizens located in the countryside in Japan. Two Holter monitor recordings were obtained for each subject, with an interval of 15 years between the two recordings. The subjects were 64 to 80 years old (mean 70 ± 4.1 years) at the first recording and 79 to 95 years old (mean 85 ± 4.1 years) at the second recording 15 years later. The study participants had no specific abnormalities in past history, thoracic roentogenography, electrocardiography, or blood biochemical analyses, and were not receiving any medication. They maintained the activity level expected for their age.

Processing of Holter Monitor Recordings
Holter monitor recordings were conducted in leads CM1 and CM5 (corresponding to modified V1 and V5, respectively) using a Holter recorder (Model 445, Der Mar Avionics Inc., Irvine, CA), and an analyzing system (DMW4000, Fukuda Denshi Co., Ltd., Tokyo, Japan) was used for analysis. The sequential RR interval data were downloaded to a personal computer, and statistical analysis was conducted using software prepared by Fukuda Denshi Co., Ltd. We obtained nighttime (midnight to 5 AM, when almost all subjects are thought to have been in the supine position from the records of behavior) and daytime (noon to 5 PM, when almost all subjects are thought to have been in the standing or sitting position) average HR and HRV on the basis of diurnal data.

We obtained minimal, maximal, and average HR values. For HRV, we obtained the parameters in time domain analysis (i.e., SDNN index [mean of the standard deviations of all normal RR intervals for all 5-minute segments in nighttime or daytime measured in milliseconds] and the NN50 [number of instances where the difference between adjacent normal RR intervals exceeds 50 milliseconds] per hour) and the parameters in frequency domain analysis calculated using fast Fourier transform (i.e., low-frequency [LF: 0.039 to 0.148 Hz] component, high-frequency [HF: 0.148 to 0.398 Hz] component, and the LF/HF ratio).

Statistical Methods
Paired t tests were performed to assess the differences in each parameter of nighttime and daytime HR and HRV between the two 15-year interval Holter monitor recordings. Differences of p < .05 were taken to be significant.


   Results
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 Abstract
 Methods
 Results
Discussion
 References
 
Heart Rate
We compared minimal, maximal, and average HRs between the first and the second recordings obtained 15 years apart.

Minimal HR.-- Minimal HR increased significantly for both nighttime (49.2 ± 5.4 vs 55.3 ± 8.2 bpm; mean ± SD; p = .0018) and daytime (59.6 ± 9.1 vs 64.1 ± 9.1 bpm; p = .0048) with age ( Fig. 1).



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  		Figure 1. Changes of minimal heart rate and maximal heart rate with age over a 15-year period in healthy elderly persons during nighttime (midnight to 5 AM) and daytime (noon to 5 PM). bpm = beats per minute.

 
Maximal HR.-- Maximal HR increased significantly for both nighttime (67.7 ± 6.6 vs 73.8 ± 11.7 bpm; p = .0099) and daytime (86.0 ± 11.3 vs 92.4 ± 15.6 bpm; p = .0114) with age ( Fig. 1).

Average HR.-- Average HR increased significantly for both nighttime (53.6 ± 5.6 vs 59.5 ± 9.7 bpm; p = .0054) and daytime (67.8 ± 9.8 vs 72.5 ± 9.9 bpm; p = .0119) with age.

Heart Rate Variability
Time domain analysis.-- The nighttime SDNN index decreased significantly (53 ± 16 vs 45 ± 13 milliseconds; p = .0086), and we noted a decreased tendency in the daytime SDNN index (53 ± 19 vs 44 ± 14 milliseconds; p = .0574) as a result of aging 15 years ( Fig. 2).



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  		Figure 2. Changes of the SDNN index and NN50 with age over a 15-year period in healthy elderly persons during nighttime (midnight to 5 AM) and daytime (noon to 5 PM). SDNN index = mean of standard deviations of normal RR intervals for all 5-minute segments; NN50 = number of adjacent normal RR intervals >50 milliseconds per hour; /h = number per hour.

 
We noted an increased tendency in nighttime NN50 (39.7 ± 35.1 vs 50.1 ± 55.9/h; p = .2393) and a significant increase in daytime NN50 (22.9 ± 17.0 vs 44.5 ± 41.7/h; p = .0425) ( Fig. 2).

Frequency domain analysis.-- The LF component decreased significantly for both nighttime (339.26 ± 290.63 vs 222.49 ± 213.52 millisecond2; p = .0151) and daytime (246.76 ± 170.54 vs 145.19 ± 112.10 millisecond2; p = .0032) recordings as a result of aging 15 years ( Fig. 3).



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  		Figure 3. Changes of the low-frequency (LF) component and the high-frequency (HF) component with age over a 15-year period in healthy elderly persons during nighttime (midnight to 5 AM) and daytime (noon to 5 PM).

 
We noted an increased tendency in the nighttime HF component (296.76 ± 229.95 vs 407.15 ± 467.04 millisecond2; p = 0.1932); however, there was no significant change in the daytime HF component (171.63 ± 153.81 vs 196.33 ± 194.72 millisecond2; p = .3398) ( Fig. 3).

The LF/HF ratio decreased significantly for both nighttime (1.295 ± 0.665 vs 0.818 ± 0.531; p = .0270) and daytime (1.923 ± 0.910 vs 1.281 ± 0.951; p = .0371) recordings ( Fig. 4).



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  		Figure 4. Changes of LF/HF ratio with age over a 15-year period in healthy elderly persons during nighttime (midnight to 5 AM) and daytime (noon to 5 PM). LF = low-frequency component; HF = high-frequency component.

 

   Discussion
Top
 Abstract
 Methods
 Results
 Discussion
References
 
We conducted a 15-year longitudinal follow-up study to evaluate age-related changes in HR and HRV based on Holter monitor recordings in healthy elderly persons aged 64 to 80 years (mean 70 ± 4.1 years) at the time of the first recording. We report that the results differ from those of previous cross-sectional studies on healthy persons aged 70 years or younger.

Senile Changes in HR in Healthy Elderly Persons
It was suggested in the cross-sectional study of subjects aged 70 years or younger conducted by Kostis and colleagues (8) that there was a negative correlation between age and average maximal HR during daytime and nighttime and between age and maximal exercise HR, but that there was no correlation between age and minimal or average HR (8). Umetani and colleagues (16) also demonstrated that 24-hour HR declined with age in a cross-sectional study of healthy subjects aged 10 to 99 years. However, since most of the previous cross-sectional studies have been conducted on elderly persons who are relatively young and include only a few who are very elderly, the correlation between age and HR in healthy elderly persons aged 70 years or older is still unknown (16). Moreover, there have been no long-term follow-up studies performed to assess the relation between HR and aging in healthy very elderly persons.

Thus we conducted a 15-year longitudinal follow-up study of a population of healthy, very elderly individuals with a mean age of 70 ± 4.1 years at the first recording, and demonstrated that nighttime and daytime minimal, maximal, and average HRs significantly increased with age over 15 years, unlike the results of the preceding studies conducted with elderly persons aged 70 years or younger.

Fleg and colleagues (17) conducted a study to evaluate the correlation between age and blood catecholamine levels and demonstrated that blood epinephrine levels at rest and blood epinephrine and norepinephrine levels under exercise loading were significantly higher in the elderly (68–77 years) than in the younger population, although HR was not in proportion to blood catecholamine levels in their study. Pfeifer and colleagues (18) also stated that plasma norepinephrine levels increase with age. On the other hand, Goldberger (19) proposed that the RR interval is the most suitable index among the indices of sympathovagal balance.

Consequently, the results in our longitudinal follow-up study and the three studies described above may indicate that the age-related increase in blood catecholamine level is involved in increase in HR with age over a 15-year period in the very elderly. Other phenomena, such as the sluggish rate of norepinephrine removal from the neuroeffector gaps (20), might also contribute to this age-related increase in HR, that is, the rate of norepinephrine removal from the neuroeffector gaps might slow down with age, which may result from senile decline in metabolism. Contrary to our results and expectations, some previous studies on the effect of aging on adrenoceptor response have revealed reduced ß-adrenergic responsivity with age (21) (22) (23).

In addition to neurohormonal changes, other age-related changes (e.g., decrease in circulating plasma volume, decline in cardiac function, decline in respiratory function, arteriosclerosis, and senile changes in mechanisms at the receptors and within the myocardial cell) have been reported. These changes might also be related to the increase in HR to some extent, if we take into account the concurrent changes in HRV with aging seen in our study.

Senile Changes in HRV in Healthy Elderly Persons
Bigger and colleagues conducted a study in patients after acute myocardial infarction using Holter monitoring, which revealed significant positive correlations between the SDNN index, the mean of the standard deviations of all normal RR intervals for all 5-minute segments of a 24-hour ECG recording (5) (16) (24), and the LF component, a mixed vagal and sympathetic signal (5) (24). Umetani and colleagues (16) reported that the SDNN index closely correlated with aging, exhibiting a linear decrease over the life span.

We assessed the data from nighttime and daytime 5-hour recordings in healthy elderly persons in a longitudinal follow-up study. There was a significant decrease in nighttime SDNN index, a decreased tendency in daytime SDNN index, and, at the same time, a significant decrease in the LF component and in the LF/HF ratio, a parameter of sympathovagal balance or sympathetic activity (4) (5). However, we saw either no change or a slight increase in the HF component, a parameter of parasympathetic neural activity (4) (5). Consequently, a decrease in the SDNN index with aging was similar to concurrent changes in the LF component or the LF/HF ratio in our study. The correlation of the SDNN index to the LF component and the change in the SDNN index with aging in our study agree with the findings of Bigger and colleagues (24) and Umetani and colleagues (16), respectively.

It is suggested in cross-sectional studies conducted in healthy subjects aged 70 years or younger that the LF component, which is accepted as a parameter of cardiac sympathetic modulations especially when expressed in normalized units, decreases with age (5) (9) (10) (11) (12) (13). In our 15-year longitudinal follow-up study, both the nighttime and daytime LF components decreased significantly with age. These results indicate that the LF component decreases as a result of aging not only in healthy persons aged 70 years or younger but also in healthy elderly persons aged 70 years or older. This may be attributed partly to an age-related decline in sensitivity of the ß-adrenergic receptors of automatistic cells in the sinus node to sympathetic stimulation (21) (22) (23) or partly to negative feedback of increased blood catecholamine levels resulting from senile decline in metabolism to the cardiovascular sympathetic nerve (17). Moreover, the rate of norepinephrine removal from the neuroeffector junction of the sinus node (20) might possibly slow with age in elderly subjects. This change might possibly interfere with periodical norepinephrine removal from the neuroeffector junction, which might directly attenuate sympathetic neural modulation and therefore decrease the LF component.

It is suggested that NN50 and HF are parameters of cardiac parasympathetic neural activities (5). Liao and colleagues (25) suggest in a study of HRV conducted in healthy adults aged 70 years or younger that population levels of HF are lower in the older (55–64 years) than in the younger (45–54 years) age groups. Similar data on the parasympathetic activities are shown in other cross-sectional studies conducted in healthy persons aged 70 years or younger (9) (12) (13). In our 15-year longitudinal follow-up study in healthy elderly persons with a mean age of 70 ± 4.1, however, an increased tendency in nighttime NN50 and a significant increase in daytime NN50 were seen as a result of aging. There was a tendency for nighttime HF to increase, and there was no change in daytime HF. These facts agree with the findings of other parameters in time domain analysis, corresponding to HF or NN50, in a few studies in healthy subjects aged 70 years or older as well as younger (15) (16).

Consequently, these results indicate that NN50 and HF stop decreasing with age at approximately 70 years and remain at the same level or slightly increase after the age of 70. This may be attributed to feedback of the age-related increase in catecholamine levels in blood (17) (18) or norepinephrine levels at the neuroeffector gaps (20) in the ANS, that is to say, inhibition of sympathetic neural modulation and activation of parasympathetic neural modulation in elderly persons.

This longitudinal follow-up study in healthy elderly persons has revealed a significant decrease in the nighttime and daytime LF/HF ratio, a parameter of sympathovagal balance or sympathetic activity (5). These results differ from preceding cross-sectional studies in persons aged approximately 70 years or under (11) (12), and is thought to reflect a significant age-related decrease in the LF component and an unchanged or slightly increased HF. This appears to indicate, when measured by HRV, that the center of the balance between sympathetic activities and parasympathetic activities has been dislocated to the side of parasympathetic neural activities in healthy elderly persons with aging.

Conclusions
We conducted a 15-year longitudinal follow-up study in healthy very elderly persons with a mean age of 70 ± 4.1 years at the first recording. The results demonstrated an age-related increase in HR in these subjects over the 15-year interval, contrary to a previous study conducted in subjects aged 70 years or younger (8). As for concurrent changes in HRV, however, the parameters reflecting sympathetic neural activity such as the LF component and LF/HF ratio decreased, and the parameters reflecting parasympathetic neural activity such as NN50 and HF component maintained the same level or slightly increased. There was a discrepancy between changes in HR and the parameters of ANS activities measured by HRV along with aging for the 15 years in healthy elderly persons.

Therefore, we suggest that these age-related changes in HR and HRV may be characteristic of the very elderly and, therefore, should be taken into consideration in assessing the data from the elderly persons aged 70 years or older. In addition, assessing this discrepancy between changes in HR and HRV with age might facilitate the interpretation of the complicated sympathovagal balance of the ANS.

Received January 12, 2000

Accepted February 7, 2000


   References
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 Abstract
 Methods
 Results
 Discussion
 References
 

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