(Hypertension. 1997;30:803-808.)
© 1997 American Heart Association, Inc.
Articles |
Broadband Spectral Analysis of Blood Pressure and Heart Rate Variability in Very Elderly Subjects
From the Cattedra di Medicina Interna I, Ospedale S. Gerardo, Monza, Università di Milano; Istituto Scientifico Ospedale S. Luca, Istituto Auxologico Italiano, Milano; LaRC, Centro di Bioingegneria, Fondazione Pro Juventute, Milano; and Centro Fisiologia Clinica e Ipertensione, Università di Milano and Ospedale Maggiore, Milano, Italy.
Correspondence to Dr Gianfranco Parati, Centro Fisiologia Clinica e Ipertensione, Via F. Sforza 35, 20122 Milano, Italy.
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Abstract |
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Abstract Systolic blood pressure (SBP) variability is increased and R-R interval variability is reduced in the elderly. Little is known, however, about how SBP and R-R interval variabilities change in the very elderly. More important, however, it is not known which frequency components of SBP and R-R interval variability are affected significantly. We addressed this issue in subjects older than 70 years by broadband spectral analysis, which allows all variability components from the lowest to the highest frequency to be considered. In 20 very elderly normotensive subjects (mean±SD age, 78.1±6.8 years) and 28 normotensive adult subjects (36.1±7.1 years), noninvasive finger blood pressure and R-R intervals were recorded continuously for 30 minutes in the supine position and 15 minutes in the upright position. SBP and R-R interval power spectral densities were computed over the entire frequency region between 0.005 Hz (0.007 Hz in the upright position) and 0.5 Hz. Overall SBP variability (SD) was greater and overall R-R interval variability was less in very old subjects than in adult subjects. All spectral R-R interval powers were reduced significantly in very elderly individuals. The spectral SBP powers were greater in the very elderly group than in the adult group only in the very-low-frequency range (<0.04 Hz). This was true in the supine and the standing positions. With subjects in the standing position, the shape of the broadband spectra differed in the very old and adult subjects because in the former group the increase in SBP and R-R interval power around 0.1 Hz that was seen in the latter was blunted. Therefore, in very elderly subjects a reduction in overall R-R interval variability is accounted for by a reduction in all of its frequency components. The accompanying increase in overall BP variability, however, results from a nonhomogeneous behavior of its frequency components, which consists of an increase in the very low frequency and a concomitant reduction in the higher frequency powers. The mechanisms responsible for these changes may be complex, but at least they may in part reflect the baroreflex impairment and autonomic dysfunction that characterize aging.
Key Words: aging • broadband spectral analysis • blood pressure • heart rate • baroreflex
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Introduction |
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Blood pressure variability is increased and HR variability is reduced in elderly compared with middle-aged and young subjects.1 2 3 This is believed to depend on age-related abnormalities such as arterial stiffness, reduced effector responsiveness to neural stimuli, and baroreflex impairment.4 5 6 Baroreflex impairment is considered a major causal mechanism because of the important role of the baroreflex in reducing BP and enhancing HR oscillations.6 7
However, data on BP and HR variability in the elderly have been collected largely in subjects between 60 and 70 years old,6 8 and little is known about how these parameters change in subjects older than 70 years (ie, those who have been defined in clinical trials on antihypertensive treatment as "very elderly" individuals).9 10 Furthermore, in many studies BP and HR variability have been expressed either by a global index such as the SD around the mean value or by the spectral powers of relatively fast fluctuations (around 0.1 and 0.3 Hz2 3 11 ) that are now known to account for only a small part of the overall BP and HR variance.12 Therefore, the purpose of this study was to (1) measure BP and HR variability in subjects >70 years and up to 85 years old and (2) use the broadband spectral analysis approach to quantify all spectral components included in the variability phenomena.
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Methods |
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Our study was performed in 48 subjects (26 men, 22 women). Twenty subjects were older than 70 years (mean, 78.1±6.8 years), whereas the remaining 28 subjects were less than 45 years old (mean, 36.1±7.1 years). All subjects (Table
)
had normal BP, were in good health, and took no
cardiovascular or noncardiovascular
drugs. They agreed to participate in the study after an explanation of
its nature and purpose. The study protocol was approved by the ethics
committees of the institutions involved.
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Measurements
With the subject in the sitting position, BP was measured at the
outpatient clinic with a mercury sphygmomanometer to exclude
individuals with values 
140/90 mm Hg and therefore
hypertensive. In the adult group, average clinic BP was
121.3±2.3/79.0±1.0 mm Hg. In the very elderly group, the
average BP was 124.6±2.5/71.2±1.8 mm Hg. During the
experimental session, the BP signal was recorded beat to beat by a
noninvasive finger device (Finapres, Ohmeda, Colo). The device has been
shown previously to be capable of providing values similar to those of
intra-arterial devices (also during fast and marked BP
changes).13 HR was obtained from the R-R interval provided
by a continuous ECG recording.
Protocol
The study was performed in the morning after the collection of
clinic BP values, a light breakfast, and overnight abstinence from
smoking, alcohol, and coffee consumption. After the ECG electrodes
(V5 lead) and the finger cuff (middle or ring finger of the
nondominant arm) had been positioned and with the subject in the supine
position, a period of 30 minutes was permitted to elapse before data
were collected so that a steady state might be achieved. Data
collection consisted of 30 minutes of continuous recording with
the subject in the supine position followed by a 15-minute
recording with the subject in the standing position. A longer
recording time with the subject standing was not performed
because of the potentially limited orthostatic tolerance of
very elderly individuals. The finger-pressure device was calibrated
before data collection by connecting the Finapres transducer to a
mercury column via a Y tube and applying stepwise changes in mercury
pressure from 0 to 250 mm Hg. To ensure signal stability, the
automatic signal adjustment provided by the device was switched off and
only operated manually at 15-minute intervals with the subject in the
supine position and at 7.5-minute intervals with the subject in the
standing position. Throughout the recording time, the
instrumented finger was always kept at the heart level by an arm
support to prevent the occurrence of hydrostatic height differences
between the finger cuff and the heart.
Assessment of BP and R-R Interval Variability
The finger BP and the ECG signals were stored on tape
(RacalStore 4) for further analysis. For the BP signal, this
consisted of analog-to-digital conversion on 12 bits at 165 Hz,
purification from artifacts by an interactive procedure, and storage of
the digitized signal on a computer disk (Olivetti XP6 Computer). For
the ECG signal, it consisted of the same procedure except for the
sampling frequency, which was 600 Hz. The digitized signal was
processed further to obtain SBP for each pulse wave and R-R interval
for each two consecutive QRS complexes, which were stored in separate
time series. This allowed average SBP and R-R interval values to be
obtained separately for the supine and standing periods together with
the respective SDs, which were taken as global measures of variability
in the two positions. The splitting of this global variability into all
of its components was obtained by broadband spectral analysis.
To this aim, SBP and R-R interval series were interpolated by a cubic
spline and were subjected to antialiasing low-pass filtering. The
interpolated signals were resampled evenly at 2 Hz to prevent
distortion of the spectra caused by the inherent nonuniform sampling of
SBP and R-R interval series because of the
physiologically irregular sequence of
heartbeats with time. From each resampled series, a single spectrum was
computed by the fast Fourier transform method. This single spectrum
included all frequency components from 0.005 to 0.5 Hz with the subject
in the supine position and from 0.007 to 0.5 Hz with the subject in the
standing position without artificial subdivision into arbitrarily
defined frequency bands.14 The narrower frequency range
obtained with the subject in the standing position may be explained by
the shorter duration of the BP and R-R interval recording in
this posture.
Assessment of Baroreflex Sensitivity
Baroreflex sensitivity was assessed by the time-domain and
frequency-domain methods validated and described in detail in previous
articles.15 16 17 Computer analysis in the time
domain permitted the identification of sequences of contiguous heart-
beats characterized by progressive increases in SBP and R-R interval
(+RR/+SBP) or by progressive reductions in SBP and R-R interval
(-RR/-SBP). As performed for the laboratory technique based on
injection of vasoactive drugs, when the +RR/+SBP and -RR/-SBP
sequences showed a correlation coefficient .85, the slope of the
regression line between the SBP and R-R interval changes was taken as
an index of baroreflex sensitivity.15 16 In each subject,
the number of the +RR/+SBP and -RR/-SBP sequences was pooled and the
slope of the +RR/+SBP and -RR/-SBP sequences was averaged.
Computer analysis in the frequency domain was performed by
splitting the SBP and R-R interval signals into consecutive segments of
512 beats and by removing the segments containing nonstationarities. In
the segments in which around 0.1 Hz the SBP and R-R interval powers had
a coherence >0.5, the squared ratio between R-R interval and SBP
powers was computed. This was called the 
-coefficient and used as
another index of baroreflex sensitivity.17
Statistics
Data for individual subjects were averaged separately for adult
and very elderly individuals and for the supine (last 15 minutes) and
the standing positions (15 minutes). The statistical significance of
differences both between positions and between groups was tested by
two-way ANOVA. When the independent variables (age and/or position)
produced significant effects in the dependent variable, a post hoc
comparison was made by the least significant difference or planned
comparison test to verify separately the hypothesis of significant
differences between the two age groups and/or the two positions
(supine, standing).18 Moreover, in the case of power
spectra, a statistical analysis of the difference between adult
and very elderly subjects was performed for each spectral line. This
was done by computing the probability (P) of a significant
result of the t test for unpaired observations at each
frequency (f) of the spectrum. A logarithmic
transformation of the spectra was applied previously to obtain
distributions close to normal. The probability (P) was
plotted as a function of the frequency
(f).14 A value of
P<.05 was taken as the level of statistical significance
unless otherwise indicated.
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Results |
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As shown in Fig 1
, with subjects in
the supine position there were no significant differences in either SBP
or R-R interval mean values between the adult and very elderly
subjects. This was also true for SBP SDs, whereas R-R interval SDs were
markedly reduced in the very elderly. Compared with the supine position
values, those for standing were characterized by a small increase in
SBP, a somewhat more evident reduction in R-R interval, and little
change in SBP and R-R interval SDs. With the exception of the SBP SDs
(which became larger in the very elderly than in younger subjects), the
between-group differences or similarities were unchanged in the
standing position versus the supine position.
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The broadband spectral data are illustrated in Fig 2. In both adult and elderly individuals
and in the supine and the standing positions, both the SBP and the R-R
interval spectral powers increased progressively going from the highest
to the lowest frequencies included in the analysis. In either
the supine or the standing position, the BP spectral powers were
greater in the elderly than in the adult group in the
very-low-frequency range (<0.04 Hz) (Fig 2, top panels), whereas the
R-R interval spectral powers were markedly less in the elderly than in
the adult group throughout the frequency range considered in our study
(Fig 2, bottom panels). Furthermore, in the standing position the shape
of the BP spectra was somewhat different in adult and very elderly
subjects. In adult subjects in the standing position, the shape of the
BP spectra was associated with the appearance of a clear peak of BP
around 0.1 Hz that was not evident in elderly subjects. This was also
true for the R-R interval spectra.
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The baroreflex data are shown in Fig 3.
In very elderly subjects, there was a striking reduction of the
sequence number in both the supine and the standing positions. Compared
with adults, the sequence slope in elderly individuals was markedly
reduced in the supine position and less reduced in the standing
position. In both positions, the number of coherent segments (ie, the
segments in which the coherence between SBP and R-R interval powers
around 0.1 Hz was >0.5) was significantly reduced in the elderly who
also showed a marked reduction in the -coefficient. Again, the
reduction was more evident in the supine position than in the standing
position.
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Discussion |
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In our subjects who were >70 years old (average, 78 years), the SD of SBP was greater than that in subjects <45 years old, although the difference was statistically significant in the standing position only. Furthermore, in these very elderly subjects, both the supine and the standing R-R interval SDs were markedly less compared with younger individuals. This confirms previous findings that aging is accompanied by an increase in overall BP variability and a decrease in overall HR variability.1 2 3 11 19 This study confirms these findings to be true for very elderly subjects.
The most important new observation of our study, however, concerns the age-related changes in the various components of BP and HR oscillations that can be identified by broadband spectral analysis. Our data show that in subjects >70 years old the reduction of R-R interval variability involved all of its frequency components. In contrast, the frequency components of BP variability were superimposable in elderly and adult individuals for a large portion of the frequency spectrum, and it was only in the very-low-frequency range that elderly individuals showed a variability greater than that in adult individuals. Once again, the variability was greater in the standing position than in the supine position. Therefore, whereas all components of HR variability show a uniform age-dependent reduction, the age-dependent changes in BP variability are characterized by a considerable dishomogeneity (ie, by a selective increase in variability only in the lowest portion of the frequency spectrum). Because BP spectral powers always increase progressively with the reduction in their frequency (ie, the slower the oscillation the greater its power) according to a 1/f pattern,20 the increase in very- low-frequency components with aging is responsible for an age-related change in the slope of the 1/f BP pattern, a phenomenon previously described for HR.19 21
Three other points in our article should be mentioned. First, our study does not clarify the mechanisms responsible for the increased SBP powers in the lowest portion of the broadband spectrum. Previous data in animals and humans have suggested that in this very-low-frequency region, BP fluctuations may depend on modulation of vasomotor tone by humoral substances such as angiotensin II.22 23 However, it is unlikely that angiotensin II accounts for an increase in very-low-frequency BP powers at an old age because the renin-angiotensin system is less active in the elderly.24 Other data also suggest that very-low-frequency powers of BP or HR depend on physical activity.25 However, this mechanism cannot explain our findings because the positions used in our experiment (supine, standing) were strictly standardized. A third and more likely mechanism involves an alteration of neural cardiovascular influences and especially an impairment of baroreflex control of circulation. This explanation is supported by the evidence that (1) baroreflex sensitivity was markedly impaired in our elderly subjects (see below); (2) in conscious cats, sinoaortic denervation is accompanied by an increase in the magnitude of BP oscillations that is particularly evident in the very-low-frequency region20 26 ; (3) this intervention causes a marked reduction in HR variability across the entire frequency range, which is similar to the reduction of all R-R interval spectral powers seen in very elderly subjects; and (4) in humans, baroreflex sensitivity is inversely related to overall BP variability (which depends primarily on the lowest-frequency powers) and directly related to overall R-R interval variability.7 This implies that baroreflex influences are not limited to fast BP and HR fluctuations but extend to the low and very low frequency fluctuations as well.20 26
The second point involves the quantitative and qualitative differences in BP and R-R interval spectra of subjects >70 years and <45 years old. The broadband spectral analysis showed that there were not only quantitative but also qualitative differences in the BP and R-R interval spectra of subjects >70 years and <45 years old. It was shown that in subjects <45 years old, standing was accompanied by the appearance of a clear peak around 0.1 Hz of the BP spectrum, whereas in subjects >70 years such a peak was lost with an increased power in the spectrum only at lower frequencies. The loss of the 0.1-Hz peak also characterized the R-R interval spectrum in elderly subjects in the upright position. Because an increase in 0.1-Hz BP power on shifting from lying to standing reflects to a considerable extent an increase in sympathetic vasomotor modulation, whereas an increase in this R-R interval power indicates an increase in cardiac sympathetic activity and a reduction in cardiac vagal modulation,21 27 these changes may provide additional evidence of an alteration of autonomic cardiovascular modulation in very old individuals.28
The third point involves our time- and frequency-domain assessment of the baroreflex which provided evidence that spontaneous control of the heart by baroreceptors is markedly impaired in very old individuals. As mentioned above, this impairment may be involved in the increase in the very-low-frequency BP powers and in the reduction of all R-R interval powers. It may also be involved in the blunting of the 0.1-Hz peak in the BP and R-R interval spectra when the subject changes from a lying position to a standing position, because the autonomic components of these spectra probably originate from a baroreflex modulation, which may amplify both powers by a resonance phenomenon.21 29
Our study has two potential limitations. One possible limitation is that, because scanty validation of the finger BP signal by simultaneous intra-arterial recording was performed in very elderly subjects, the possibility exists that the greater low-frequency powers of our very elderly individuals are caused by finger BP distortion. However, (1) in two very elderly individuals, in whom it was possible to record both finger and intra-arterial BP, the between-method discrepancy was not obviously different from that observed in younger subjects; (2) in a previous large study on subjects of variable age, Imholz30 reported no major effect of aging on the difference between the finger and the more proximal intra-arterial signal; (3) in a smaller study carried out in very elderly individuals by Rongen et al,31 no significant differences between intra-arterial and finger BP tracings were observed when focusing on BP variations; and (4) it is also unlikely that the greater very-low-frequency powers of our very elderly subjects originated from an amplification of BP waveforms in the finger, because age per se does not exaggerate but instead reduces the pulse waveform amplification from central to peripheral arteries.32
The second potential limitation is that our study focused on a relatively short recording time in two static laboratory settings. This prevented an extension of the analysis to the even lower spectral frequencies, which are detectable by longer recording periods, and possibly underestimated the age-dependent alterations in BP and R-R interval variability that occur in daily life.8 Application of the broadband spectral analysis method to 24-hour beat-to-beat BP monitoring periods is the demanding approach necessary to remove this limitation.
In conclusion, our data obtained by broadband spectral analysis provide the first evidence on the alterations of a broad range of components of overall BP and HR variability in the very elderly. The aging-related reduction in overall HR variability reflects a reduction in all of its components. This is not the case for the aging-related increase in BP variability, in which the various variability components have a more dishomogeneous behavior. The use of broadband spectral analysis therefore permitted us to discover complex alterations in variability phenomena, which are not evident when a crude overall index of variability, such as the one provided by the standard deviation, is used.
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Selected Abbreviations and Acronyms |
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Received September 5, 1996; first decision October 29, 1996; accepted March 5, 1997.
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