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Int J Environ Res Public Health. 2023 Jan; 20(1): 236. PMCID: PMC9819370
Published online 2022 Dec 23. doi: 10.3390/ijerph20010236 PMID: 36612558

Variations in the Second Derivative of a Photoplethysmogram with Age in Healthy

Korean Adults
Jungmi Choi1 and Min-Goo Park2,*

Paul B. Tchounwou, Academic Editor

Abstract

Second derivative of photoplethysmogram (SDPTG) indices correlate with aging and vascular
health. The trend of SDPTG indices with age has not yet been studied in the Korean population.
Various SDPTG indices were measured in 300 healthy Koreans (150 men and 150 women), aged
19–69 years, stratified into five age groups consisting of 60 people (30 men and 30 women) in each
age group from their 20s to 60s. The values of the SDPTG indices clearly showed distinct variations
with age in healthy Korean groups (p < 0.001 for all indices). b/a increased linearly with age (y =
0.0045x − 0.803), as did SDPTG aging index (SDPTG-AI) (y = 0.0162x − 1.1389). c/a decreased
linearly with age (y = −0.0044x + 0.1017), as did d/a (y = −0.0062x + 0.034) and e/a (y =
−0.001x + 0.2002). A significant sex difference was shown in b/a and e/a ratios and SDPTG-AI (p
< 0.001 for all indices); women had a higher b/a ratio (−0.55 ± 0.14 versus −0.65 ± 0.13) and
SDPTG-AI (−0.33 ± 0.3 versus −0.52 ± 0.33) and a lower e/a ratio (0.13 ± 0.06 versus 0.18 ±
0.07) than men. A linear regression model of diverse SDPTG indices was provided according to the
age of healthy Koreans, which may be valuable in preventing diseases related to vascular conditions
by estimating the degradation of arterial function.

Keywords: second derivative wave, photoplethysmogram, aging index, arterial distensibility,

healthy Koreans

1. Introduction
As the aging population of the world grows at an exponential rate, it becomes a great challenge for
public health care [1]. Therefore, the identification of reliable factors is necessary to prevent dis‐
eases related to aging [2]. Arterial conditions are a major risk factor for aging and may contribute to
hypertension, atherosclerosis, diabetes mellitus, and end-stage renal disease [2,3,4,5].

Pulse wave analysis is a well-established method for evaluating vascular load and vascular aging and
could thus be useful for assessing the vascular effects of hypertension, atherosclerosis, and aging
[2,6,7]. Photoplethysmography (PTG) is a simple, non-invasive technique for measuring changes in
blood volume [8,9,10,11]. Using this method, the pulse waveform reflecting arterial vessel elasticity
can be evaluated. However, because it is difficult to visually grasp detailed information of shape,
including the inflection point of the pulse, the second derivative of the finger photoplethysmogram
(SDPTG) has been used as an objective and reliable method of measurement [7,12,13,14].

In particular, SDPTG indices are useful for evaluating arterial deterioration as they show a distinc‐
tive trend that increases or decreases linearly with age [7,15,16]. In 2017, the SDPTG was intro‐
duced as a new aging index [17], and in 2021, the author of this study suggested that the SDPTG
aging index (SDPTG-AI), which involves performing measurements in the elderly with the same
instrument and protocol as in this study but with detection on the ear lobe rather than the fingertip,
showed a clear correlation with age in a multiple regression model [14].

SDPTG indices showed higher or lower values for women than for men in the same age group
[7,13]. This is attributed to the fact that women have a faster pulse wave velocity than males because
the arterial length and diameter in women are shorter and smaller, respectively than in men [18].
Therefore, SDPTG should be evaluated separately according to sex.

Studies on the SDPTG tendency with aging are concentrated in Japanese and Western populations
[2,5,7,12,13,19]. Only a few studies have been conducted in South Korea. Furthermore, each
SDPTG index could not be quantitatively predicted with functional age because the number of study
participants for each age group was small and varied [16,17]. The Japanese SDPTG has presented
quantitative SDPTG by sex and age [7]. However, considering the average height difference between
Japanese and Koreans [20], it will most likely not be applicable to Koreans.

Therefore, we presented a linear regression model of SDPTG indices that changed with age in
healthy Koreans by having a uniform number of study participants stratified by sex and age. We also
provided the reference range for SDPTG by sex and age group.

2. Materials and Methods

2.1. Subjects

A total of 300 healthy volunteers were recruited from the Clinical Trial Centre of Asan Medical
Centre (AMC, South Korea), stratified into five age groups consisting of 60 people each, between
the age groups of 20s to 60s. Participants were selected based on the following inclusion criteria:
1. Healthy Korean males and females aged between 19 and 69 years
2. Non-smokers
3. Non-pregnant woman
4. Subjects with a BMI (body mass index) of 18 to 30 kg/m2
5. Subjects who voluntarily decided to participate in this clinical trial for 2–3 h and gave their
written consent

However, subjects with the following criteria were excluded from the study:

1. Subjects who had consumed food other than water within 1 h of SDPTG measurements
2. Subjects who performed strenuous exercise within 1 h of SDPTG measurements
3. Subjects judged to be sleep deprived for less than 4 h the day before the measurements
4. Subjects who were expected to have a lot of hand movements because they could not control
their movements when measuring the SDPTG
5. Subjects who were taking drugs for the treatment of central nervous system or cardiovascular
diseases
6. Subjects taking medications for the treatment of hyperthyroidism or hypothyroidism
7. Patients suffering from diabetes for more than 10 years

This study was conducted as part of the quantitative photoplethysmogram (PTG) parameter statisti‐
cal standardization for healthy Koreans, a brain frontier project promoted by the Ministry of Educa‐
tion. Written consent was obtained from each participant prior to study participation. The study pro‐
tocol was approved by the Institutional Review Board (ASAN MEDICAL CENTER INSTITU‐
TIONAL REVIEW BOARD, IRB number: AMC-IRB-2007-0305). After gathering basic demo‐
graphic information, clinical research nurses examined the participants with the SDPTG. The study
was conducted in accordance with the guidelines of the Declaration of Helsinki.

2.2. SDPTG Measurements

All subjects sat in a comfortable position with their eyes open, and their pulse waves were measured
with a photoplethysmometer for 5 min [21]. A PTG sensor (Model: ubpulse T1 (Pulse Analyzer,
KFDA Certification No. 11-1296), LAXTHA Inc., Daejeon, South Korea) was placed on the left
index finger [21].

The hand with the sensor was placed on a table at the heart level, and nail polish or other foreign
objects on the finger with the sensor were removed [22]. In addition, items that put pressure on the
arms or fingers, such as sleeves, disposable bands, and rubber bands that fit the body, were removed.
Caution was taken not to breathe deeply or abdominally during measurements to prevent respiratory
sinus arrhythmias (RSA) [22].

With the device, PTG and second derivative PTG (SDPTG) measurements were performed simulta‐
neously, as shown in Figure 1. Each SDPTG waveform was displayed after the derivative of the
PTG in the device. The operator minimized data contamination by monitoring the signal shape and
ensuring that it was not corrupted by sensor or finger movements.

Figure 1

Photoplethysmogram (PTG) and second derivative PTG (SDPTG) signals.

2.3. Biomarkers and Calculations of SDPTG

The SDPTG is a waveform obtained by differentiating the PTG wave twice. It is easy to understand
the detailed information obtained from the PTG shape, such as inflection points; the PTG wave, is
also composed of several positive and negative peaks, as shown in Figure 1. Each peak of the
SDPTG consists of waves a, b, c, and d, which correspond to the systolic wave and the diastolic e
wave. They are defined as follows: (1) “a” wave is the large positive peak first appearing in an
SDPTG signal, (2) “b” wave is the negative peak immediately following the a wave, (3) “c” wave is
the positive peak immediately following the b wave, (4) “d” wave is the negative peak immediately
following the c wave, and (5) “e” wave is the positive diastolic peak that appears immediately after
the “d” wave.

As shown in Figure 1a–e waves represent the values corresponding to the amplitude of each peak,
and the SDPTG waveform analysis was utilized by converting the relative values of b, c, d, and e
waves based on the a wave. That is, b/a, c/a, d/a, and e/a ratios, which are the relative amplitude val‐
ues of b, c, d, and e waves to the wave amplitude, were used as the SDPTG indicators in this study.
The SDPTG-AI, the second derivative of the PTG aging index, was also used. This index reflects
the functional aging level of the artery and was calculated as b/a-c/a-d/a-e/a. This is combined by
setting the weights as +1 (proportional) and −1 (inversely proportional) to have a higher correlation
as the level of functional aging of blood vessels increases, based on the fact that the b/a ratio is pro‐
portional to age, while the c/a, d/a, and e/a ratios are inversely proportional to age. Therefore, the
SDPTG-AI is also commonly known as an early prediction index for arteriosclerosis, which is a rep‐
resentative condition of severe functional aging of blood vessels [7,23,24].
Arrhythmic events, ectopic beats, and noise effects may alter the estimation of the SDPTG [25].
Therefore, in our study, clean pulse data free of ectopy and noise were preferentially selected and
used to extract SDPTG indices.

2.4. Statistical Analysis

Simple regression analysis was performed to reveal the trend of SDPTG indices according to the age
of the subjects. An independent t-test was conducted to analyze the sex differences with respect to
SDPTG parameters in each age group. Statistical analysis was performed using SPSS ver. 23 (SPSS
Inc., Chicago, IL, USA, 2009). The significance level was set to α = 0.05 for all statistical tests
(two-tailed).

3. Results

This study included a total of 300 participants. Before analysis, two experts screened the data to re‐
move inappropriate samples that could not be analyzed due to measurement errors caused by finger
movements or an undistinguished pattern of the signals, leaving 292 participants (147 men and 145
women) for analysis, as shown in Table 1. Detailed SDPTG indices on the participants are described
in Table S1.

Table 1

Comparison of second derivative photoplethysmogram (SDPTG) indices between male and female participants in
each age group.
 20s 30s 40s 50s 60s Total
Variables
Male Female Male Female Male Female Male Female Male Female Male

Subjects,
30 29 30 29 27 30 30 27 30 30 147
n

24.3 ± 23.5 ± 35.1 ± 35.3 ± 44.6 ± 45.3 ± 54.4 ± 52.4 ± 63.1 ± 63.9 ± 44.3 ±
Age, y
2.5 3.2 2.7 2.9 2.9 2.9 2.7 2.2 † 2.4 2.6 14.1

−0.64 −0.59 −0.54 −0.48

−0.74 −0.74 −0.68 −0.55 −0.51 −0.56 −0.65
b/a ± 0.13 ± 0.11 ± 0.11 ± 0.17
± 0.08 †
± 0.11 †
± 0.1 ± 0.09 ± 0.12 ± 0.09 ‡
± 0.13
*

−0.13
−0.01 0.01 ± −0.01 −0.08 −0.08 −0.16 −0.16 −0.16 −0.16 −0.08
c/a ± 0.08
± 0.1 0.07 ± 0.13 ± 0.06 ± 0.09 ‡
± 0.1 ± 0.08 ± 0.08 ± 0.09 ± 0.12

−0.13
−0.07 −0.17 −0.2 ± −0.24 −0.28 −0.33 −0.31 −0.34 −0.36 −0.23
d/a ± 0.08 ‡
± 0.08 ‡
± 0.09 0.09 ± 0.07 ± 0.08 ± 0.09 ± 0.07 ± 0.12 ± 0.12 ± 0.14

0.20 ± 0.14 ± 0.17 ± 0.15 ± 0.18 ± 0.15 ± 0.18 ± 0.11 ± 0.14 ± 0.11 ± 0.18 ±
e/a † † ‡ ‡
0.1 0.05 0.07 0.05 0.05 0.06 0.07 0.05 * 0.06 0.06 0.07

−0.66 −0.46 −0.29 −0.07

SDPTG- −0.86 −0.73 −0.54 −0.24 −0.16 −0.22 −0.52
± 0.18 ± 0.22 ± 0.21 ± 0.28
AI ± 0.2 ± 0.20 ± 0.2 ± 0.19 ± 0.19 ± 0.24 ‡
± 0.33
* * *

Data are provided as number of participants or mean ± standard deviation (SD). p-values were derived using the
independent t-test considering sex differences (males vs. females) in each age group. * p < 0.05, † p < 0.01, ‡ p <
0.001. b/a, ratio of the height of b wave to that of a wave of SDPTG; c/a, ratio of the height of c wave to that of a
wave of SDPTG; d/a, ratio of the height of d wave to that of a wave of SDPTG; e/a, ratio of the height of e wave to
that of a wave of SDPTG; SDPTG-AI, SDPTG aging index calculated as (b-c-d-e)/a. Age was divided into groups:
20s (19–29 years), 30s (30–39 years), 40s (40–49 years), 50s (50–59 years), and 60s (60–69 years).

Figure 2 shows PTG and SDPTG signals measured for five participants aged in their 20s, 30s, 40s,
50s, and 60s. The SDPTG signals of the participants demonstrate how the b wave becomes less neg‐
ative and the d wave more negative with age. Accordingly, the SDPTG-AI and b/a increased to
−1.01 and −0.9, respectively, in a participant aged 20s, to −0.51 and −0.71 in one aged 40s, and to
−0.01 and −0.51 in one aged 60s. d/a decreased to −0.07 in a participant aged 20s, to −0.31 in one
aged 40s, and to −0.49 in one aged 60s.
 Figure 2

Photoplethysmogram (PTG) and second derivative PTG (SDPTG) measured for five participants aged in their 20s
(a), 30s (b), 40s (c), 50s (d) and 60s (e).

The values of the SDPTG indices (SDPTG-AI and b/a, c/a, d/a, e/a ratios) clearly showed a distinct
trend with age in healthy Korean groups, as shown in Figure 3 (p < 0.001 for all indices). b/a in‐
creased linearly with age (y = 0.0045x − 0.803, R2 = 0.2064), as did SDPTG-AI (y = 0.0162x −
1.1389, R2 = 0.4812), while c/a decreased linearly with age (y = −0.0044x + 0.1017, R2 = 0.3119),
as did d/a (y = −0.0062x + 0.034, R2 = 0.4792) and e/a (y = −0.001x + 0.2002, R2 = 0.0453).
 Figure 3

Variations in second derivative photoplethysmogram (SDPTG) indices with age in healthy Korean groups.

Figure 4 shows age-dependent changes in the main SDPTG indices in both the male and female
groups (p < 0.001 for all indices). b/a, a reflection of the aortal stiffness, increased with age in both
the male (y = 0.0053x − 0.8863, R2 = 0.3533) and female groups (y = 0.0038x − 0.722, R2 =
0.1549). Similarly, the SDPTG-AI, an aging index of arteries, also increased in both the male (y =
0.0177x − 0.1329, R2 = 0.5729) and female groups (y = 0.0147x − 0.9794, R2 = 0.4823). d/a de‐
creased with age in both the male (y = −0.0068x + 0.0738, R2 = 0.5088) and female groups (y =
−0.0056x − 0.0049, R2 = 0.4834).

Figure 4

Variations in major second derivative photoplethysmogram (SDPTG) indices between male and female groups.
Table 1 shows the sex differences in the SDPTG indices. Females had a higher b/a ratio (−0.55 ±
0.14 versus −0.65 ± 0.13, p < 0.001), a higher SDPTG-AI (−0.33 ± 0.3 versus −0.52 ± 0.33, p <
0.001) and a lower the e/a ratio (0.13 ± 0.06 versus 0.18 ± 0.07, p < 0.001) than males.

4. Discussion

A linear regression model of diverse SDPTG indices has been presented, which considers the age of
healthy Koreans, and reference ranges were provided for Korean females and males based on age
groups. The SDPTG indices clearly showed an increase in b/a and SDPTG aging index and a de‐
crease in c/a, d/a, and e/a with age. Each index exhibited a significant age-dependent trend (Figure 3
). This is consistent with the trend reported in previous studies of Japanese and Western people.
Takazawa et al., showed that the b/a ratio and SDPTG-AI rose with age, while the c/a, d/a, and e/a
ratios declined with age in 600 Japanese individuals [7]. Bortolotto et al., found that the SDPTG-AI
had a significant relationship with age, and was higher in participants aged > 60 years than in those
aged < 60 years in 524 French individuals [2]. Although a regression model of SDPTG with age has
not yet been provided, SDPTG parameters in Koreans also showed an age-dependent change consis‐
tent with those in Japanese people [16].

Among the SDPTG indices, the negative b/a ratio reflects the degree of aortic distensibility [6]. This
ratio increases if the vascular wall is well-stretched with a low vascular load when the aortic blood
volume is rapidly increased at the moment of cardiac output. Conversely, when the aortic vessel wall
is stiff, this negative ratio decreases. This means that the b/a ratio increases with age, which en‐
hances aortic stiffness, and reflects the vascular state of the aorta as the first vascular response when
blood is released from the left ventricle [7,13]. A negative d/a index reflects arterial compliance or
flexibility of the peripheral artery wall [13]. When there is functional vascular wall tension due to
high blood pressure or when arterial flexibility is reduced due
Back to to arteriosclerosis, the magnitude of
Top
the reflex wave in the peripheral arteries increases, and accordingly, this negative index increases.
Thus, the d/a ratio decreases with age [7,13]. c/a is a waveform which, along with changes in b and
d waves, reflects decreased arterial stiffness and decreases with age [7,26]. The e wave reflects the
initial rise of the diastolic wave that appears better in young and elastic vessels, and the e/a ratio
tends to decrease slightly with age [7]. SDPTG-AI is calculated as (b-c-d-e)/a and reflects functional
arterial aging [2,7]. It is commonly known as a parameter for assessing arteriosclerosis, which is
representative of severe functional arterial aging. Several previous studies have also reported that
patients with any history of arteriosclerotic diseases, including hypertension, diabetes mellitus, and
hypercholesterolemia, had higher SDPTG-AI values [2,7,27].

In particular, this study has presented a decisive linear regression model of diverse SDPTG indices,
such as b/a, d/a ratios, and SDPTG-AI in both male and female groups, in contrast with previous
studies which provided an age-dependent trend regardless of sex (Figure 4). b/a, d/a, and SDPTG-AI
were selected among the indices because b/a and SDPTG-AI are the most promising indices in the
assessment of arterial health as well as aging [7,26], and because the magnitude of the slope of the
trend line for the age of b/a, d/a, and SDPTG-AI was more extensive than that of c/a and e/a (
Figure 2). The R2 values in the regression model that assessed the relationship between b/a, d/a, and
SDPTG-AI with age for all participants were 0.2064, 0.4792, and 0.4812, respectively, whereas
those for the male participants were 0.3533, 0.5088, and 0.5729, respectively and for the female par‐
ticipants were 0.1549, 0.4634, and 0.4823, respectively (Figure 4). The correlation between aging
and each SDPTG index in the male participants was stronger than those of all participants but was
lesser or equal to that of female participants. Thus, the functional age of each SDPTG parameter can
be estimated quantitatively for each group (male or female). When the functional age calculated by
this model is older than the actual age (i.e., 10 years older), they will be included in a group requir‐
ing health management. Therefore, arterial health and age-related diseases like atherosclerosis, dia‐
betes, and end-stage renal disease could be prevented by recommending dietary management and
exercise.

Only a few studies have reported sex differences in SDPTG indices. Women had a higher b/a ratio
and SDPTG aging index and a lower e/a ratio than men in Japan [7]. Iketani et al., found that the
SDPTG-AI declined with age from 3 to 18 years and then increased in young men, while it declined
with age from 3 to 15 years and then increased in young women [13]. The entire Korean group in
this study showed sex differences in the b/a, e/a, and SDPTG-AI (Table 1), which showed a consis‐
tent trend to that seen in Japanese people aged 30 to 80 years. This study is also the first to investi‐
gate all SDPTG indices for sex differences in the Korean population.

SDPTG indices were known to be affected by hemodynamic, autonomic, adiposity and emotional
factors as well as ageing [2,7,28,29,30]. A recent study showed SDPTG indices had a significant
relationship with those factors except emotional factors [31]. In this study, to avoid introducing he‐
modynamic, autonomic or adiposity effects to the SDPTG indices, healthy people without hyperten‐
sion, obesity, or autonomic deterioration were recruited. In addition, SDPTG in the participants was
calculated accurately only when nervous system drugs, caffeinated drinks, food, and exercise had
not been administered 1 h before the assessment [32]

In conclusion, the distinct age-dependent trend of the SDPTG indices in this study will be valuable
in preventing diseases associated with aging or arterial function degradation, by providing defining
standards for its screening, with sensitive levels prior to typical symptoms related to arterial func‐
tional deterioration. Furthermore, the SDPTG is predicted to be used more actively to assess quanti‐
tative changes in sensitive levels before and after therapy or treatment, such as drugs, stimuli, and
exercise.

Acknowledgments

The authors thank Gyu-Jeong Noh (Asan Medical Center, Seoul, Korea), for clinical data acquisi‐
tion from healthy subjects.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/arti‐

cle/10.3390/ijerph20010236/s1, Table S1: The data on healthy Koreans’ SDPTG indices.
 Click here for additional data file.(94K, zip)

Funding Statement

This study was performed with funding from the Korean Ministry of Science and Technology [grant
numbers M103KV010019-06K2201-01910]. This study was also supported by the National Re‐
search Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. NRF-
2022R1F1A1074196).

Author Contributions

J.C. conceived and designed the manuscript. M.-G.P. wrote the first draft of this paper. J.C. and M.-
G.P. reviewed this paper. J.C. contributed to data acquisition. All authors have read and agreed to
the published version of the manuscript.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Insti‐
tutional Review Board of the ASAN MEDICAL CENTER (IRB number: AMC-IRB-2007-0305).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

All the data supporting the findings of this study are available from the corresponding authors upon
reasonable request.

Conflicts of Interest

The authors declare that the research was conducted in the absence of any commercial or financial
relationships that could be construed as a potential conflict of interest.

Footnotes
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those
of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) dis‐
claim responsibility for any injury to people or property resulting from any ideas, methods, instructions or prod‐
ucts referred to in the content.

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