From The Second Department of Internal Medicine, Tokyo Medical College,
Tokyo, Japan.
Correspondence to Kenji Takazawa, MD, The Second Department of Internal Medicine, Tokyo Medical College Hospital, 6–7-1, Nishishinjuku Shinjuku Tokyo 160, Japan.
Abstract
Abstract—To evaluate the clinical
application of the second derivative of the fingertip
photoplethysmogram waveform, we performed drug administration studies
(study 1) and epidemiological studies (study 2). In study 1, ascending
aortic pressure was recorded simultaneously with the
fingertip photoplethysmogram and its second derivative in 39 patients
with a mean±SD age of 54±11 years. The augmentation index was defined
as the ratio of the height of the late systolic peak to that of
the early systolic peak in the pulse. The second derivative
consists of an a, b, c, and d wave in systole and an e wave in
diastole. Ascending aortic pressure increased after
injection of 2.5 µg angiotensin from 126/74 to
160/91 mm Hg and decreased after 0.3 mg sublingual
nitroglycerin to 111/73 mm Hg. The d/a, the ratio
of the height of the d wave to that of the a wave, decreased after
angiotensin from -0.40±0.13 to -0.62±0.19 and increased
after nitroglycerin to -0.25±0.12
(P<0.001 and P<0.001, respectively).
The negative d/a increased with increases in plethysmographic and
ascending aortic augmentation indices (r=0.79,
P<0.001, and r=0.80,
P<0.001, respectively). The negative d/a reflects the
late systolic pressure augmentation in the ascending aorta and
may be useful for noninvasive evaluation of the effects of vasoactive
agents. In study 2, the second derivative of the plethysmogram waveform
was measured in a total of 600 subjects (50 men and 50 women in each
decade from the 3rd to the 8th) in our health assessment center. The
b/a ratio increased with age, and c/a, d/a, and e/a ratios decreased
with age. Thus, the second derivative aging index was defined as
b-c-d-e/a. The second derivative wave aging index (y)
increased with age (x) (r=0.80,
P<0.001,
y=0.023x-1.515). The second derivative
aging index was higher in 126 subjects with any history of diabetes
mellitus, hypertension, hypercholesterolemia,
and ischemic heart disease than in age-matched subjects without
such a history (-0.06±0.36 versus -0.22±0.41,
P<0.01). Women had a higher aging index than men
(P<0.01). The b-c-d-e/a ratio may be useful for
evaluation of vascular aging and for screening of arteriosclerotic
disease.
Noninvasive pulse
wave analysis is useful for evaluation of vascular load and
vascular aging.1 It is usually measured at the
palpable artery, including carotid, femoral, and radial
arteries.2 These pulse wave tracings provide more
precise information concerning blood pressure changes than
systolic and diastolic pressures
only.3 The basic idea of the augmentation index
was first described by Murgo et al4 in 1980 in
relation to the reflection return point in the ascending aorta. Kelly
et al2 first used the term "augmentation
index" in their 1989 study evaluating age-related changes in AIs.
They showed age-related increase in AIs at carotid and radial arteries.
Ascending aortic pressure can be divided into 2 components at the
anacrotic notch, where maximal flow velocity is
observed.2 The early systolic component
is caused mainly by left ventricular ejection, and the
second component is augmented by peripheral reflection
wave.5 PTG detects the changes in the amount of
light absorbed by hemoglobin, which reflects changes in blood volume.
Wiederhelm et al6 showed pulsatile pressure
changes in vessel down to meta-arteriole size that corresponded to
pulse tracing. PTG has been used to evaluate arterial
compliance in relation to changes in the amplitude of
wave,7 but the wave contour itself is not
usually used. The SDPTG has been developed to allow more accurate
recognition of the inflection points on the original plethysmographic
wave, ie, anacrotic or dicrotic notches. In 1972, Ozawa
recorded the first and second derivative waves of PTG and reported
(in Japanese) that the first derivative wave had characteristic wave
contours. In 1978, he further reported that the second derivative wave
had characteristic contours that facilitated the interpretation of the
original waves. The conventional PTG measurements came to be performed
less frequently because of difficulties in analysis and
reading, and most clinicians made recordings of the second
derivative wave alone because of the simplicity of evaluating the
heights of each wave and the ease of recognition of the changes in the
waveforms. The purpose of the present studies was to determine the
wave changes in SDPTG immediately after administration of vasoactive
agents (study 1) and age-related changes in different age groups (study
2).
Methods
Study 1
All procedures were approved by the ethics committee of Tokyo
Medical College Hospital. Informed consent was obtained from all
patients.
Study 2
Results
Study 1
Study 2
Table 2
Discussion
In study 1, we found marked changes in the d/a ratio of SDPTG
before and after administration of vasoactive agents without any
significant changes in b/a, c/a, and e/a ratios. This may have been
caused by changes in the reflection wave, which increased with
vasoconstriction produced by AGT and decreased through vasodilation
produced by NTG. AGT produced a marked increase in both
systolic and diastolic pressures in the ascending
aorta through vasoconstriction of peripheral
arteriole,8 which elevated the mean pressure and
increased pulse wave velocity, resulting in early return of
peripheral reflection wave. Increase in reflection wave
after administration of AGT caused the increase in aortic pressure AI
and PTG AI. On the other hand, after NTG administration, marked
reductions were observed in the AIs for aortic pressure and PTG.
Vasodilation by NTG produced a marked reduction in the ascending aortic
late systolic component without significant change in
diastolic pressure, which was brought about by reduction in
peripheral reflection wave through dilation of muscular
arteries.9 Despite the PTG
representing a flow/volume pulse measured from an
extremity, a similarity between the aortic pressure AI and the PTG AI
was observed both at baseline and after hemodynamic
alterations. The values of PTG AI from our data would appear to fall
between values of radial and carotid AIs obtained from the studies of
Kelly et al.2 The late systolic component
of PTG is relatively higher than that of the radial artery, and this
may reflect the complex anatomy of arterioles in which the
timing of wave propagations can vary. Another important issue is
that the signal from the device is a function of red cell density, with
the relation between blood volume and signal output being more likely a
logarithmic function according to the Lambert-Beer
equation.10
In study 2, SDPTG shows the increase in b/a and decrease in c/a, d/a
and e/a ratios. Each wave ratio had significant
age-related change. The b wave became shallower in
relation to the a wave (increased b/a), and the a and b waves are
included in the early systolic component where the effect of
reflection wave is less; therefore, the b/a ratio may reflect
the large arterial stiffness. The b/a ratio was higher in
women than in men. The epidemiological study on pulse wave velocity
reported by London et al11 showed that pulse wave
velocity in women was higher than that in men. Similar data were
reported by Hayward et al12: the AI obtained by
carotid pulse was also higher in women than in men. In both of these
studies, it was assumed that the body structure (ie, relatively short
limbs and small diameter of ascending aorta) in women contributed to
the results. In our study, women were also shorter than men in height.
Age-related changes in the shallower b wave relative to the a wave
might be caused by decreasing distensibility of the aorta. On the other
hand, deepened d wave relative to a wave is caused mainly by increased
reflection wave from the periphery. The reflection wave from the
periphery increases with age because of arterial stiffness
and early return of wave reflection as a consequence of increased pulse
wave velocity. The meaning of the c/a ratio was not understood; c/a
ratio usually moves with association with the b or the d wave. The e
wave reflects the initial rise of the diastolic wave. The
e/a ratio decreased with age and was lower in women than in men. The
subjects who had any history of arteriosclerotic
disease showed a higher SDPTG aging index. Characteristic
arterial waveforms of patients with
arteriosclerosis were reported by Lax and
Feiburg13 and Dawber et
al.14 Both reports focused on diminution of the
dicrotic notch. Lax and Feiburg also found diminution of the
dicrotic notch in the characteristic arterial pulse of
young diabetic subjects, which might be related to our findings of an
age-related decrease in the e wave.
Limitations
The acute effect of vasoconstriction and vasodilation with increase and
decrease in blood pressure could be assessed by the d/a ratio. Nichols
et al16 reported an increase in fundamental
impedance (impedance at one harmonic), which is one of the potent
indicators of left ventricular afterload, associated with
increasing pressure augmentation. The negative d/a increased with
increases in the AIs of PTG and ascending aortic pressure wave, which
indicates that the negative d/a ratio should be a useful index for the
evaluation of vasoactive agents, as well as an index of left
ventricular afterload. The SDPTG aging index may be useful
for evaluation of vascular aging and screening of
arteriosclerotic patients.
Selected Abbreviations and Acronyms
Acknowledgments
The authors are indebted to Professor Patrick Barron of the
International Medical Communications Center of Tokyo Medical College
for his review of this manuscript. We thank Yumiko Itayama, Hiroshi
Okano, and Professor Emelitus Kenjirou Itoh of our Health Assessment
Center for collecting the data in study 2. We thank Dr Masaharu
Yoshimura, the past president of Dokkyo Medical College, for his
important suggestions.
Received January 24, 1998;
first decision February 8, 1998;
accepted April 7, 1998.
References
1.
O'Rourke MF, Kelly RP, Avolio AP. History.
In: Pine JW Jr, ed. The Arterial Pulse.
Philadelphia, Pa: Lea & Febiger; 1992:3–14.
2.
Kelly RP, Hayward CS, Avolio AP, O'Rourke MF.
Noninvasive determination of age-related changes in the human
arterial pulse. Circulation. 1989;80:1652–1659.
3.
Takazawa K, Tanaka N, Takeda K, Kurosu F, Ibukiyama C.
Underestimation of vasodilator effects of nitroglycerin
by upper limb blood pressure. Hypertension. 1995;26:520–523.
4.
Murgo JP, Westerhof N, Giolma JP, Altobeli SA.
Aortic input impedance in normal man: relationship to pressure wave
forms. Circulation. 1980;62:105–116.
5.
Westerhof P, Sipkema G, Van den Bos C, Elzinga G.
Forward and backward waves in the arterial system.
Cardiovasc Res. 1972;6:648–656.[Medline]
[Order article via Infotrieve]
6.
Wiederhelm CA, Woodbury JW, Kirk S, Rushmer RF.
Pulsatile pressure on the microcirculation of frog's mesentery.
Am J Physiol. 1964;207:173–176.
7.
Fichett D. Forearm arterial compliance: a
new measure of arterial compliance? Cardiovasc
Res. 1984;18:651–656.[Medline]
[Order article via Infotrieve]
8.
Ross J Jr, Braunwald E. The study of left
ventricular function in man by increasing resistance to
ventricular ejection with angiotensin.
Circulation. 1964;29:739–749.
9.
Yaginuma T, Takazawa K, O'Rourke MF. Effects of
nitroglycerin on ascending aortic impedance and on left
ventricular load in normal subjects and patients with
coronary artery disease. In: O'Rourke MF, Safar ME, Dzau VJ,
eds. Arterial Vasodilation: Mechanisms and
Therapy. London, UK: Edward Arnold; 1993:78–90.
10.
Jeperson LR, Pederson OL. The quantitative aspect of
photoplethysmography revisited. Heart Vessels. 1986;2:186–190.[Medline]
[Order article via Infotrieve]
11.
London M, Guerin AP, Pannier B, Marchais SJ, Stimpel M.
Influence of sex on arterial hemodynamics
and blood pressure role of body height. Hypertension. 1995;26:514–519.
12.
Hayward CS, Kelly RP. Gender-related differences in the
central arterial pressure waveform. J Am Coll
Cardiol. 1997;30:1863–1871.[Abstract]
13.
Lax H, Feiburg AW. Abnormalities of the
arterial pulse wave in young diabetic subjects.
Circulation. 1959;20:1106–1110.
14.
Dawber TR, Thomas HE, McNamara PM. Characteristic
of the dicrotic notch of the arterial pulse wave in
coronary heart disease. Angiology. 1973;24:244–255.
15.
Kawarada A, Shimazu A, Ito H, Yamakoshi K. Noninvasive
measurement of arterial elasticity in various human limbs.
Med Biol Eng Comput. 1988;26:641–646.[Medline]
[Order article via Infotrieve]
16.
Nichols WW, O'Rourke MF, Avolio AP, Yaginuma T, Murgo
JP, Pepine CJ, Conti R. Effects of age on ventricular
vascular coupling. Am J Cardiol. 1985;55:1179–1184.[Medline]
[Order article via Infotrieve]
© 1998 American Heart Association, Inc.
Third Workshop on Structure and Function of Large
Arteries: Part II
Assessment of Vasoactive Agents and Vascular Aging by the Second Derivative of Photoplethysmogram Waveform
Key Words: photoplethysmography • second derivative wave • augmentation index • vasoactive agents • vascular aging • angiotensin • nitroglycerin
Thirty-nine patients (34 men, 5 women) with a mean±SD age of
54±11 years who underwent diagnostic cardiac
catheterization were studied: there were 19 cases of
myocardial infarction, 17 cases of angina pectoris, and 3 cases of
chest pain syndrome without organic cardiac abnormalities. Ascending
aortic pressure was measured by a microtip catheter (SPC or SVPC
series, Millar Instruments), and PTG and SDPTG were measured by a
photoplethysmograph equipped with double differentiation circuits
(PT-400, Fukuda Denshi), with the sensor located at the cuticle of the
second digit of the left hand. Measurements were performed in the
control state and when systolic blood pressure was increased by
30% after intravenous injection of 2.5 µg AGT. After
systolic pressure returned to control levels, 0.3 mg sublingual
NTG was administered; measurement was made 5 minutes later. Figure 1
shows the analysis of each
wave. The negative d/a (-d/a) was used for adjustment of polarity to
be compared with the AI.
View larger version (24K):
[in a new window]
Figure 1. Measurement of wave. Ascending aortic pressure
(AoP) AI was defined as
P2-P0/P1-P0, where
P2 is ascending aortic late peak systolic pressure,
P0 is ascending aortic diastolic pressure, and
P1 is ascending aortic early peak systolic
pressure. The AI of PTG was defined as PT2/PT1,
where PT2 is amplitude of the late systolic
component, and PT1 is amplitude of the early
systolic component. SDPTG includes 4 systolic waves and
1 diastolic wave: a wave, initial positive wave; b wave,
early negative wave; c wave, re-increasing wave; d wave, re-decreasing
wave; and diastolic e wave. The ratios of the height of
each wave to that of the a wave were measured (b/a, c/a, d/a, and
e/a).
The study included a total of 600 subjects (50 men and 50
women in each decade from the 3rd to the 8th) in our health assessment
center. PTG and SDPTG were measured in subjects in the sitting position
at the cuticle of the second digit of the left hand by digital PTG
(FCP-3166 Fukuda Denshi). The FCP-3166 contained automatic
analyses of each SDPTG wave, and total frequency response was
adjusted to 10 Hz for the PT-400 model used in study 1. Some subjects
had a history of disease: diabetes mellitus (n=12), hypertension
(n=117), ischemic heart disease (n=4), and
hypercholesterolemia (n=12).
Figure 2 shows a sample tracing.
Results are shown in Table 1, with
descriptive statistics of ANOVA and Scheffé's F test. Compared
with the control state, b/a, c/a, and e/a ratios did not change
significantly after AGT or NTG. The d/a ratio decreased significantly
after AGT and increased after NTG (P<0.001 and
P<0.001, respectively). Figure 3 shows the relationship between AIs and
the negative d/a. The negative d/a (-d/a) increased with increasing
PTG AI and aortic pressure AI (r=0.79,
P<0.001, and r=0.81, P<0.001,
respectively). PTG AI increased with increasing aortic pressure AI
(r=0.86, P<0.001).
View larger version (19K):
[in a new window]
Figure 2. Tracings show results of administration of
vasoactive agents. An increase in the late systolic component
of aortic pressure (AoP) and PTG after intravenous
injection of 2.5 µg AGT and a deepened d wave in relation to the
height of the a wave (decreased d/a) are seen in SDPTG. On the other
hand, NTG produces marked reduction in late systolic components
of aortic pressure and PTG, with d wave becoming shallower in relation
to the height of a wave (increased d/a). AoF indicates ascending aortic
flow velocity.
View this table:
[in a new window]
Table 1. Descriptive Statistics and Results of ANOVA and
Scheffé's F Test
View larger version (18K):
[in a new window]
Figure 3. Relationship between the negative d/a and AIs.
Negative d/a increased with increases in PTG AI (left) and aortic
pressure (AoP) AI (right). 
indicates control; 
, after AGT; and
x, after NTG.
Figure 4 shows age-related changes
for each SDPTG ratio. The b/a ratio increased with age
(r=0.75, P<0.001); c/a (r=-0.67,
P<0.001), d/a (r=-0.72, P<0.001),
and e/a (r=0.25, P<0.001) ratios decreased with
age. From the above results, the equation of b-c-d-e/a was defined as
the SDPTG aging index. Figure 5 shows the
relationship between SDPTG aging index and age. SDPTG aging index
(y) increased with age (x) (r=0.80,
P<0.001; y=0.023x-1.515). The SDPTG
aging index was higher in 126 subjects with any history of the diseases
listed above than in age-matched subjects without any such history
(-0.06±0.36 versus -0.22±0.41, P<0.01).
View larger version (34K):
[in a new window]
Figure 4. Relationship between each wave ratio and
age. The b/a ratio increased with age, and c/a, d/a, and e/a ratios
decreased with age.
View larger version (25K):
[in a new window]
Figure 5. Relationship between SDPTG aging index and age.
SDPTG aging index (b-c-d-e/a) (Y) increased with age (X);
Y=0.023X-1.515 (P<0.001, r=0.80). shows the gender difference of
parameters. Women had a higher b/a ratio than men
(-0.59±0.18 versus -0.64±0.18, P<0.001). The e/a ratio
was lower in women than men (0.16±0.07 versus 0.19±0.09,
P<0.001). PTG AI was higher in women than men (1.11±0.22
versus 1.07±0.21, P<0.05). SDPTG aging index was higher
in women than men (-0.32±0.47 versus -0.43±0.47,
P<0.01).
View this table:
[in a new window]
Table 2. Demographics of Study 2 Subjects With Results of
Student's Unpaired t
Test
The amplitude of PTG was thought to reflect the volume of
blood, but it really reflects the changes in blood volume. The
amplitude of PTG reflects blood volume changes from the basal
to highest; if the basal blood volume is different, the amplitude of
height does not indicate the same amount of blood. Kawarada et
al15 introduced quantitative PTG volume signals
in conjunction with calibration counterpressure to derive elastic
modulus curves as a function of transmural pressure. We used the
relative ratio of PTG and SDPTG waves for comparison of each subject,
which gave us more accurate information on pulse wave contours in
relation to ascending aortic pressure wave. The other important issue
is frequency response of PTG and SDPTG. We recorded a final
frequency response of 10 Hz in SDPTG. This relatively lower frequency
of derivative method is convenient for tracing pulse wave contour and
eliminating noise, but it is not used for the determination of rate of
wave rise such as dP/dt.
AGT
=
angiotensin
AI
=
augmentation index
NTG
=
nitroglycerin
PTG
=
photoplethysmography
SDPTG
=
second derivative wave of fingertip photoplethysmography
This article has been cited by other articles:
 |
|
 |
|
  J. Hashimoto and S. Ito Some mechanical aspects of arterial aging: physiological overview based on pulse wave analysis Therapeutic Advances in Cardiovascular Disease, October 1, 2009; 3(5): 367 - 378. [Abstract] [PDF]
|
|
|
|
 |
|
 J. G. Kips, E. R. Rietzschel, M. L. De Buyzere, B. E. Westerhof, T. C. Gillebert, L. M. Van Bortel, and P. Segers Evaluation of Noninvasive Methods to Assess Wave Reflection and Pulse Transit Time From the Pressure Waveform Alone Hypertension, February 1, 2009; 53(2): 142 - 149. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. O'Rourke and J. Hashimoto Mechanical Factors in Arterial Aging: A Clinical Perspective J. Am. Coll. Cardiol., July 3, 2007; 50(1): 1 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Laurent, J. Cockcroft, L. Van Bortel, P. Boutouyrie, C. Giannattasio, D. Hayoz, B. Pannier, C. Vlachopoulos, I. Wilkinson, H. Struijker-Boudier, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications Eur. Heart J., November 1, 2006; 27(21): 2588 - 2605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Hsu, P. T. Chao, H. Hsiu, W. K. Wang, S. P. Li, and Y. Y. L. Wang Organ-specific ligation-induced changes in harmonic components of the pulse spectrum and regional vasoconstrictor selectivity in Wistar rats Exp Physiol, January 1, 2006; 91(1): 163 - 170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. G Brillante, M. T Johnstone, and L. G Howes Effects of Intravenous PD 123319 on Haemodynamic and Arterial Stiffness Indices in Healthy Volunteers Journal of Renin-Angiotensin-Aldosterone System, June 1, 2005; 6(2): 102 - 106. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Scholze, C. Rinder, J. Beige, R. Riezler, W. Zidek, and M. Tepel Acetylcysteine Reduces Plasma Homocysteine Concentration and Improves Pulse Pressure and Endothelial Function in Patients With End-Stage Renal Failure Circulation, January 27, 2004; 109(3): 369 - 374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X J Jiang, M F O'Rourke, W Q L Jin, L S Liu, C W Li, P C Tai, X C Zhang, and S Z Liu Quantification of glyceryl trinitrate effect through analysis of the synthesised ascending aortic pressure waveform Heart, August 1, 2002; 88(2): 143 - 148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Millasseau, F. G. Guigui, R. P. Kelly, K. Prasad, J. R. Cockcroft, J. M. Ritter, and P. J. Chowienczyk Noninvasive Assessment of the Digital Volume Pulse : Comparison With the Peripheral Pressure Pulse Hypertension, December 1, 2000; 36(6): 952 - 956. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Chowienczyk, R. P. Kelly, H. MacCallum, S. C. Millasseau, T. L. G. Andersson, R. G. Gosling, J. M. Ritter, and E. E. Anggard Photoplethysmographic assessment of pulse wave reflection: Blunted response to endothelium-dependent beta2-adrenergic vasodilation in type II diabetes mellitus J. Am. Coll. Cardiol., December 1, 1999; 34(7): 2007 - 2014. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||