Age-related changes in carotid artery flow and pressure pulses: possible implications for cerebral microvascular disease.
ABSTRACT We sought to establish the relation between the pulsatile components of pressure and flow waveforms in the carotid artery and their change with age.
Distention (pressure) and axial flow velocity waveforms were recorded noninvasively and simultaneously from the common carotid artery of 56 healthy subjects aged 20 to 72 years.
There was a close relation between the time intervals of pressure and flow waves: from foot to first shoulder or peak, to second shoulder or peak, and to incisura (r=0.97, P<0.0001 for each), which approximated the line of identity. The peak and nadir of flow velocity decreased with age, but late systolic flow augmentation increased substantially (1.6 times in the older group); this can be attributed to earlier wave reflection from the lower body. Pressure augmentation index (PAI) and flow augmentation index (FAI) increased similarly with age (PAI (%) = 0.84 x age - 26.6; FAI (%) = 0.75 x age + 11.9; both P<0.0001).
Arterial stiffening with aging increases carotid flow augmentation and can explain the increasing flow fluctuations in cerebral blood vessels. Measurement of carotid FAI may provide a gauge for risk of cerebral microvascular damage, just as PAI provides a gauge for risk of left ventricular hypertrophy and failure.
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ABSTRACT: Excessive intracranial pulsatility is thought to damage the cerebral microcirculation, causing cognitive decline in elderly individuals. We investigated relationships between brain structure and measures related to intracranial pulsatility among healthy elderly. Thirty-seven stroke-free, non-demented individuals (62-82 years of age) were included. We assessed brain structure, invasively measured cerebrospinal fluid (CSF) pulse pressure, and magnetic resonance-quantified arterial and CSF flow pulsatility, as well as arterial pulse pressure. Using both multivariate partial least squares and ordinary regression analyses, we identified a significant pattern of negative relationships between the volume of several brain regions and measures of intracranial pulsatility. The strongest relationships concerned the temporal lobe cortex and hippocampus. These findings were also coherent with observations of positive relationships between intracranial pulsatility and ventricular volume. In conclusion, elderly subjects with high intracranial pulsatility display smaller brain volume and larger ventricles, supporting the notion that excessive cerebral arterial pulsatility harms the brain. This calls for research investigating altered intracranial cardiac-related pulsatile stress as a potential risk factor that may cause or worsen the prognosis in subjects developing cognitive impairment and dementia.Neurobiology of aging 09/2013; · 5.94 Impact Factor
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ABSTRACT: PurposeWe sought to noninvasively estimate aortic impedance indices from MR and tonometric data. Materials and MethodsMR aortic velocity-encoded and carotid applanation tonometry pressure data of 70 healthy subjects (19–79 years) were used to calculate the following indices from impedance spectrum: (i) characteristic impedance (Zc) reflecting pulsatile component of left ventricular (LV) afterload, (ii) frequency of the minimal impedance magnitude related to arterial compliance (FMIN), (iii) total peripheral resistance (TPR) related to steady LV load, (iv) impedance oscillatory index (ZINDEX) related to proximal reflections, and (v) reflection magnitude (RM). Associations with age and LV remodeling (LV mass/end-diastolic volume) were investigated using multivariate analysis. ResultsAll indices except Zc were associated with age independent of subjects characteristics and systolic blood pressures. They were all significantly associated with the well-established carotid-femoral pulse wave velocity (r ≥ 0.29; P < 0.01). However, such associations were not independent of age. Pulsatile index Zc was independently associated with carotid pulse pressure (r = 0.53, P < 0.001). Moreover, conversely to conventional stiffness indices, Zc and TPR were independently associated with LV remodeling (r = 0.30, r = 0.43, respectively, P < 0.01). Conclusion We estimated aortic impedance from velocity-encoded MR and tonometry data resulting in reliable impedance and reflection indices as confirmed by their significant and independent associations with age and LV remodeling. J. Magn. Reson. Imaging 2014. © 2014 Wiley Periodicals, Inc.Journal of Magnetic Resonance Imaging 03/2014; · 2.57 Impact Factor
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ABSTRACT: This study investigates the novel approach of placing a ventricular assist pump in the descending aorta in series configuration with the heart and compares it with the two traditional approaches of left-ventricle-to-ascending-aorta (LV-AA) and left-ventricle-to-descending-aorta (LV-DA) placement in parallel with the heart. Experiments were conducted by using the in-house simulator of the cardiovascular blood-flow loop (SCVL). The results indicate that the use of the LV-AA in-parallel configuration leads to a significant improvement in the systemic and pulmonic flow as the level of continuous flow is increased; however, this approach is considered highly invasive. The use of the LV-DA in-parallel configuration leads to an improvement in the systemic and pulmonic flow at lower levels of continuous flow but at higher levels of pump support leads to retrograde flow. In both in-parallel configurations, increasing the level of pump continuous flow leads to a decrease in pulsatility to a certain extent. The results of placing the pump in the descending aorta in series configuration show that the pressure drop upstream of the pump facilitates cardiac output as a result of afterload reduction. In addition, the pressure rise downstream of the pump may assist with renal perfusion. However, at the same time, the pressure drop generated at the proximal part of the descending aorta induces a slight drop in carotid perfusion, which would be autoregulated by the brain in a native cardiovascular system. The pulse wave analysis shows that placing the pump in the descending aorta leads to improved pulsatility in comparison with the traditional in-parallel configurations.Artificial Organs 05/2014; · 1.96 Impact Factor
Kozo Hirata, Toshio Yaginuma, Michael F. O'Rourke and Masanobu Kawakami
for Cerebral Microvascular Disease
Age-Related Changes in Carotid Artery Flow and Pressure Pulses : Possible Implications
Print ISSN: 0039-2499. Online ISSN: 1524-4628
Copyright © 2006 American Heart Association, Inc. All rights reserved.
is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
2006;37:2552-2556; originally published online August 31, 2006;
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Age-Related Changes in Carotid Artery Flow and
Possible Implications for Cerebral Microvascular Disease
Kozo Hirata, MD; Toshio Yaginuma, MD; Michael F. O’Rourke, MD, DSc; Masanobu Kawakami, MD
Background and Purpose—We sought to establish the relation between the pulsatile components of pressure and flow
waveforms in the carotid artery and their change with age.
Methods—Distention (pressure) and axial flow velocity waveforms were recorded noninvasively and simultaneously from
the common carotid artery of 56 healthy subjects aged 20 to 72 years.
Results—There was a close relation between the time intervals of pressure and flow waves: from foot to first shoulder or
peak, to second shoulder or peak, and to incisura (r?0.97, P?0.0001 for each), which approximated the line of identity.
The peak and nadir of flow velocity decreased with age, but late systolic flow augmentation increased substantially (1.6
times in the older group); this can be attributed to earlier wave reflection from the lower body. Pressure augmentation
index (PAI) and flow augmentation index (FAI) increased similarly with age (PAI (%)?0.84?age?26.6; FAI
(%)?0.75?age?11.9; both P?0.0001).
Conclusions—Arterial stiffening with aging increases carotid flow augmentation and can explain the increasing flow
fluctuations in cerebral blood vessels. Measurement of carotid FAI may provide a gauge for risk of cerebral
microvascular damage, just as PAI provides a gauge for risk of left ventricular hypertrophy and failure. (Stroke. 2006;
Key Words: carotid flow waveforms ? flow augmentation ? pulse wave encephalopathy ? wave reflection
pulsations. “Aortic” pulse wave velocity is determined from
the delay of the wave foot between carotid and femoral
sites.1,2The carotid pressure wave has been used as a
surrogate of the ascending aortic pressure wave in studies of
ascending aortic impedance, with change in age, in normal
populations, and in the presence of disease.3–6The carotid
pressure wave is also interpreted independently under differ-
ent pathological conditions from change in its late systolic
In contrast to the carotid pressure waveform, the clinical
significance of the pulsatile component of the carotid flow
wave is not fully understood, even though it is frequently
recorded as a part of population studies or for clinical
investigation of possible carotid disease. Although it is
accepted that upper-body flow waveforms are completely
different from wave patterns in the ascending aorta and in
lower-body arteries, such waves are known to show consid-
erable variability in normal human subjects2,9; their relation
with the carotid pressure wave and with subsequent disease
has not been considered.
ore often than not, noninvasive measures of arterial
stiffness in humans entail analysis of carotid artery
The present study was undertaken to establish the relation
between pulsatile components of the pressure/diameter wave
in the carotid artery and the accompanying flow wave in
normal subjects at different ages.
Seventy healthy, unmedicated volunteers were recruited during a
3-month period at a health awareness center at Omiya Medical
Center, Saitama, Japan. Fourteen subjects were excluded after
interview and examination on the basis of a history of hyperten-
sion, diabetes mellitus, hypercholesterolemia, or any cardiovas-
cular disease or from finding of a seated blood pressure after rest
of ?140/90 mm Hg, a fasting glucose value ?110 mg/dL, a
cholesterol value ?240 mg/dL, or some combination thereof. Fifty-
six subjects (mean?SD age, 48.2?14.3 years) were entered into the
study (Table 1). Informed consent was obtained from all subjects
according to institutional guidelines.
Blood Pressure Measurement
Brachial blood pressure was measured on the left arm in the supine
position, before carotid distention (pressure) and flow velocity
waveforms were recorded. Brachial mean blood pressure was calcu-
lated as diastolic blood pressure (DBP)?(0.33?pulse pressure).
Received May 22, 2006; accepted June 13, 2006.
From the Jichi Medical University Omiya Medical Center (K.H., M.K.), Saitama, Japan; Shizuoka City Hospital (T.Y.), Shizuoka, Japan; and
UNSW/St. Vincent’s Clinic (M.F.O’R.), Sydney, Australia.
Correspondence to M.F. O’Rourke, Suite 810, St. Vincent’s Clinic, 438 Victoria St, Darlinghurst, Sydney, NSW 2010, Australia. E-mail M.ORourke@
© 2006 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org DOI: 10.1161/01.STR.0000242289.20381.f4
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Measurements of Carotid Pressure and Flow
The distention and flow velocity waves of the right common carotid
artery were measured simultaneously with an ultrasound QFM1100
system (Hayashi Electric Co, Kawasaki, Japan), after the subjects
had rested in a supine position for 10 minutes. As previously
reported, this device determines the flow velocity waveform by the
continuous-wave Doppler method (frequency of probe, 5 MHz) and
the arterial internal diameter by the phase-locked echo-tracking
method (frequency of probe, 7.5 MHz), with good accuracy and
reproducibility.10,11Carotid distention waveforms were calibrated by
brachial mean blood pressure and DBP to obtain carotid pressure
values and were regarded as the carotid pressure waveform.5,12,13
Measured invasively, carotid distension and pressure waveforms are
virtually identical.14Tonometric measures of carotid pressure can be
inaccurate,15so that the distension waveform is preferred as a
noninvasive surrogate of carotid pressure.12,13
At least 5 carotid distention (pressure) and flow velocity wave-
forms obtained from a stable area of the record were analyzed to
determine the following parameters (Figure 1): peak systolic flow
velocity (Vs); end-diastolic flow velocity (Ved); peak flow velocity
of the secondary rise in the common carotid flow velocity waveform
(Vsr); and mean flow velocity (Vm). Pressure augmentation index
(PAI) of the distention (pressure) waveform was defined by the
following formula as reported by Laurent et al13: (P2?P1)/(P2?P0),
in which P2 is peak lumen diameter, P0 is minimal (end diastolic)
lumen diameter, and P1 is the lumen diameter at the inflection point
of the carotid distention (pressure) waveform. Flow augmentation
index (FAI) was defined similarly as (Vsr?Ved)/(Vs?Ved). Like
PAI, it is an index related to the amplitude and timing of wave
reflection.16?tp and ?tf were defined respectively as the time
between the wave foot and the peak of the initial rise in the carotid
distention (pressure) waveform (P1) and the flow velocity waveform
(Vs). ?TP and ?TF were defined as the time between the wave foot
and the peak of the secondary rise in the common carotid distention
(pressure) waveform (P2) and in the common carotid flow velocity
waveform (Vsr), respectively. EDpand EDfwere defined as the time
between the wave foot and the incisura of the carotid distention
(pressure) and flow waveforms, respectively. Flow volume was
calculated from the flow velocity and the corresponding internal
diameter of the vessel wall.
Statistical analysis was performed with StatView (version 5.0,
Abacus Concepts, Inc, Berkeley, Calif). The relation between 2
variables was determined by Pearson’s correlation coefficient. A
difference was considered significant at P?0.05. All data are
expressed as mean?SD.
Apart from age, which ranged from 20 to 72 years, and sex,
the population was homogeneous (Table 1). There was no
Figure 1. Definitions of measurements obtained from pressure
(top) and flow (bottom) waveforms in the common carotid artery.
Figure 2. Representative pressure (top) and flow velocity (bottom) in a healthy 23-year-old subject (A) and in a healthy 65-year-old
for Basic Characteristics vs Age
Basic Characteristics and Linear Regression Data
Body surface area, m2
Brachial systolic BP, mm Hg
Brachial DBP, mm Hg
pressure, mm Hg
Mean blood pressure, mm Hg
Heart rate, beats/min
NS indicates not significant.
Hirata et al Aging Changes in Carotid Pressure and Flow
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change in brachial systolic blood pressure or DBP with age,
but there was a small change in brachial pulse pressure and
The carotid pressure waveform was completely different
from the carotid flow waveform, and there were substantial
changes in both with age (Figure 2). The pressure waveform
was similar to that previously described2–7,17,18for the carotid
artery and proximal aorta, whereas the carotid flow wave was
different from that seen in other arteries with respect to 3
features: a sharp early systolic peak, a second late systolic
peak, and maintained high flow velocity at the end of diastole
(Figures 1 and 2). Despite such differences between pressure
and flow waveforms, there were close associations between
components of the waves and consistent patterns of change in
both with aging.
Associations between features of the pressure and flow waves
were so close and consistent as to indicate a functional
relation (Figure 3A). The time from wave foot to peak flow
(?tf) was the same as the time from wave foot to first pressure
inflection or peak (?tp), and the time to second systolic flow
peak (?TF) was the same as that to late systolic pressure
inflection or peak (?TP). The time to end systole was
likewise the same in pressure and flow waves, as gauged from
the wave foot to the sharp dip in pressure or flow wave, which
marked aortic valve closure (EDpand EDf).
There was also a close association (Figure 3B) between
carotid PAI as measured conventionally2,7,17and FAI, ex-
pressed as the amplitude of the difference between Vsr and
Ved, divided by the amplitude of the flow velocity pulse
(FAI; see Figure 1). PAI is accepted as a measure of wave
reflection from peripheral sites.2–8,17Similarities of FAI to
PAI indicate that the fluctuations in flow are likewise a
consequence of wave reflection from peripheral sites.
In this healthy cohort (Table 2), carotid systolic and pulse
pressure increased with age. The ?tp, ?tf, ?TP, and ?TF were
decreased, but EDpand EDfdid not change with age. There was
a progressive decrease in peak and end-diastolic flow velocity
expressed as flow volume (Table 2). In contrast to the falls in
peak and diastolic velocity with age, there was no change in Vsr
but an increase in Vsr?Ved. This was greater still when
flow waveforms with age were accompanied by increase in both
PAI and FAI (Table 2 and Figure 4).
Data presented here provide a firm basis for explaining the
shape of both flow and pressure waveforms in the carotid
artery of normal human subjects. Explanations support those
already provided for the innominate and brachial arteries.2,9,19
Figure 3. A, Relation between time-based indices derived from flow velocity (ordinate) and from pressure waveforms (abscissa).
Bottom left (closed circles); ?tf and ?tp, center (open rectangles); ?TF and ?TP, upper right (closed triangles); EDfand EDp.
Regression line for ?tf and ?tp: y?0.99x?0.74, P?0.0001. Regression line for ?TF and ?TP: y?0.99x?4.52, P?0.0001. Regres-
sion line for EDfand EDp: y?0.95x?17.10, P?0.0001. All values in ms. B, Relation between FAI (ordinate) and PAI (abscissa).
Regression line: y?0.97x?0.35.
TABLE 2. Flow and Pressure Waveform Indices of the Common Carotid Artery of the 56 Healthy Subjects
?40 14 101.8?9.829.3?6.45.87?0.57 68.6?7.7 1194.8?230.418.5?2.4 305.8?83.1 26.0?2.9440.6?95.633.3?5.1
40–5930 110.5?12.3 35.9?8.0 6.64?0.77 50.7?7.2 1043.2?262.615.4?6.4 313.1?60.224.2?4.2 493.9?91.032.2?4.9
?6012 109.3?14.241.1?5.7 6.71?0.7647.2?8.91010.8?257.413.5?2.7289.8?84.423.7?4.4504.7?151.333.1?6.5
All 56108.1?12.535.4?8.26.46?0.79 53.7?11.7 1074.2?259.315.7?3.1306.3?71.1 24.4?3.9 482.9?108.3 32.7?5.3
Abbreviations are defined in the text and expressed as mean?SD. n, No. of subjects investigated.
Symbols express significance of correlation between age and each parameter: *P?0.05; †P?0.01; ‡P?0.0001.
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The complex patterns of flow in upper-body arteries belie the
simple impedance patterns that result from a comparison of
frequency components of pressure and flow waves (supple-
mental Figure I, available online at http://stroke.ahajournals.
org), which imply the influence of a functionally discrete
reflecting site in the vascular bed beyond.2The unusual
patterns of flow in upper-body arteries can be explained on
the basis of an early return of wave reflection from local
upper-body sites and their interaction with later wave reflec-
tion coming in the opposite direction from sites in the lower
part of the body2,9,18(supplemental Figure II, available online
at http://stroke.ahajournals.org). The effects of aging are
readily explained on the basis of an earlier return of wave
reflection from the lower body, as a consequence of aortic
degeneration and increased aortic pulse wave velocity. The
only difference in carotid compared with innominate and
brachial flow2,9,19(Figures 1 and 2) is the continued high
velocity in end diastole, which is attributable to the vasodi-
lated brain being the major organ supplied by this artery.
Similar high-velocity flow at end diastole is seen in the renal
artery and in a peripheral artery during local vasodilation of
its vascular bed.2,20
Carotid tonometry is widely used to assess the effects of
wave reflection through measurement of PAI.2–4,6–8,12,21The
major problem in this measurement is detection of an inflec-
tion point on the wave that corresponds to the peak of carotid
flow.2–8,12,21–23Use of the method reported here simplifies
and increases the accuracy of measuring pressure augmenta-
tion, because the peak of the flow wave is unmistakable,
whereas the shoulder of the pressure wave is often indistinct,
especially as measured by carotid tonometry.23
The effects of carotid (and aortic) PAI with age are well
known and include increased left ventricular load, left ven-
tricular hypertrophy, left ventricular failure, and increased
severity and extent of coronary atherosclerosis.2,24Data
presented here show that this increased pressure augmenta-
tion with age is accompanied by increased late systolic flow
augmentation in the carotid artery as well (Figure 4 and Table
2). This is not immediately apparent on inspection of the
carotid flow velocity waveforms (Figure 2), nor through
consideration of difference between peak and nadir of the
flow velocity waveforms (Vs?Ved significantly decreased
with aging (P?0.0001); data not shown). Carotid dilation
with normal aging has already been reported, and the mag-
nitude was similar with our study result.25This and heart rate
increases are attributable to a velocity decrease in this study.
In the presence of microvascular rarefaction with age,
velocity fluctuations would be expected to increase in the
microvasculature, even if volume carotid flow pulsations
were unchanged. This has been confirmed.26,27However,
there is another factor as well. The early systolic flow peak,
a high-frequency component of the wave, attenuates in
arteries leading down to the cerebral microvasculature.2,28
In fact, fluctuations of flow in cerebral veins and capillar-
ies are of low frequency and, though delayed, appear to
correspond to late systolic flow augmentation in the
carotid or cerebral arteries rather than to an early systolic
flow peak with respect to timing and amplitude (ie, to
Vsr?Ved, not to Vs?Ved).29,30An increased amplitude of
such cerebral venous flow pulsations has been noted in older
persons and in those with vascular dementia27,29,30and has
been related to “pulse wave encephalopathy.”26,29,31
It has been shown that cerebral microvascular disease is
increased in the presence of aortic stiffening,32and it has been
hypothesized that such microvascular disease is caused by
increased pulsatile shear forces in these vessels from in-
creased pulsatile flow velocity.20Such a view is based on the
similarity of cerebral vascular lesions in humans33and exper-
imental animals34with aging and hypertension and with
lesions in human lungs when pulsatile blood flow is increased
over many years as a consequence of congenital heart disease
with left-to-right shunt.35It is also based on the calculated
yield stress of endothelial cells, which approaches values for
disruption in the presence of high pulsatile flow,2,36together
with an increase in permeability in the endothelial cells
Figure 4. Relation between FAI (solid circles, top) and carotid
PAI (open diamonds, bottom) with age. Regression line for FAI:
y?0.75x?11.9. Regression line for PAI: y?0.84x?26.6.
TABLE 2. Continued
639.0?178.114.7?5.0 333.3?121.7133.2?21.3132.0?18.7 256.1?36.6 260.6?39.2322.3?26.6321.4?23.9
751.5?136.617.0?3.5 438.5?97.5 103.2?22.9 103.8?22.0223.2?30.2 223.1?29.1308.7?27.8310.7?29.2 18.5?9.351.6?13.4
813.6?270.719.6?4.6 523.8?193.997.5?11.7 97.3?12.0215.8?37.5215.9?35.8316.0?28.0316.0?25.325.5?8.0 59.1?11.2
736.7?189.317.0?4.4 430.5?142.7 109.5?22.6109.4?21.7229.8?36.3231.0?37.1313.6?27.6314.5?27.013.8?15.5 47.9?16.6
Hirata et alAging Changes in Carotid Pressure and Flow
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