Journal of Human Hypertension (2015) 29, 663–668

© 2015 Macmillan Publishers Limited All rights reserved 0950-9240/15

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ORIGINAL ARTICLE
The relationship between heart-carotid pulse transit time and
carotid intima-media thickness in hypertensive patients
C Li1,2,8, H Xiong3,8, W Wu1,2,8, X Tian4, Y Wang5, D Wu1,2, W-H Lin1,2, F Miao1,2, H Zhang1,2, W Huang6 and Y-T Zhang1,2,7

The study aimed to investigate the relationship between heart-carotid pulse transit time and carotid intima-media thickness (CIMT)
in hypertensive patients, and whether including the pre-ejection period (PEP) in heart-carotid pulse transit time would affect this
correlation. A total of 62 hypertensive patients were included in this study. They were divided into the normal CIMT group (n = 33,
CIMT ⩽ 0.8 mm) and the thickened CIMT group (n = 29, CIMT40.8 mm). The noninvasive ultrasound method was used to measure
CIMT, electrocardiogram R-wave-based heart-carotid pulse transit time (rcPTT) and PEP. Aortic valve-carotid artery pulse transit time
(acPTT) was calculated by subtracting PEP from rcPTT. Simple linear analysis showed that CIMT was negatively associated with rcPTT
and acPTT (r = − 0.57, Po 0.0001; r = − 0.41, P = 0.016) in the normal CIMT group as well as in the thickened CIMT group (r = − 0.50,
P = 0.0053; r = − 0.59, P = 0.001). These relationships were eliminated in the normal CIMT group after adjusting for age, gender,
smoking behaviour, systolic blood pressure, diastolic blood pressure and cholesterol levels. However, rcPTT and acPTT still showed
significant correlations with CIMT in the thickened CIMT group. In conclusion, rcPTT and acPTT were associated with CIMT,
independent of well-known clinical confounders in thickened CIMT hypertensive patients. Therefore, rcPTT and acPTT might be
useful markers for atherosclerosis evaluation.

Journal of Human Hypertension (2015) 29, 663–668; doi:10.1038/jhh.2015.11; published online 12 March 2015

INTRODUCTION stiffness during steady-state exercise. Traditionally, PTT was

Many studies have proven that hypertension can aggravate the defined as the time taken for the pulse pressure wave to travel
development of atherosclerosis.1–3 Hypertensive patients have a between two different arterial sites. For convenience, this method
higher risk for coronary, cerebral and peripheral arterial diseases has been gradually replaced by obtaining the time interval
compared with normotensive subjects. Therefore, it is important between the occurrence of the electrocardiogram (ECG) R wave
to evaluate the development of atherosclerosis in hypertensive and the occurrence of some specified feature of the pulse
patients for better predicting cardiovascular events. waveform at a peripheral arterial site for that cardiac cycle.
Carotid artery intima-media thickness (CIMT), which can be Therefore, PTT measured by the latter method includes two
easily obtained by ultrasonography, is a widely used marker of components: the cardiac pre-ejection period (PEP) and the true
atherosclerosis. It can provide prognostic information in asympto- transit time of a pulse wave. Although PTT has been studied in
matic individuals and recurrent events in patients with cardio- different scenarios (obstructive sleep apnea,14 anesthesia15 and
vascular diseases, independent of traditional risk factors.4–6 The tracking blood pressure16), the relationship between heart-carotid
research by Lorenz et al.7 showed that when the value of CIMT PTT and CIMT has not yet been examined. Furthermore, the effect
increased by 0.1 mm the risk of suffering from myocardial of PEP on this relationship remains unknown.
infarction increased by 10–15% and the chance of stroke As atherosclerosis can increase the stiffening of aorta and major
increased by 13–18%. arteries,17–20 we hypothesize that thickened CIMT would be
Pulse transit time (PTT) has recently shown its ability for negatively correlated with heart-carotid PTT in hypertensive
assessing changes in arterial stiffening.8–13 Zhang et al.11 found patients. Thus, this study was designed to investigate whether
that radial PTT is highly correlated with age in both men and heart-carotid PTT could be a useful index of atherosclerosis in
women, which indicated that radial PTT could be an age- hypertensive patients and whether including the PEP in heart-
dependent index of arterial stiffness. Peulic et al.12 built a finite carotid PTT would affect this evaluation.
elements model to simulate the effects of arterial stiffness on PTT
under four different breathing patterns, and they reported that
PTT measurement could be used for noninvasive assessment of SUBJECTS AND METHODS
arterial stiffness. The finding by Kounalakis and Geladas13 Subjects
suggested that brachial PTT could be a convenient measure for A total of 62 hypertensive patients, aged from 28 to 77 years, were
reflecting alterations in blood pressure, cardiac output and arterial recruited into this study. They were divided into two groups as follows: (1)

1
Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; 2Key Laboratory for Health
Informatics of the Chinese Academy of Sciences, Shenzhen, China; 3Departments of Ultrasound, The Second People’s Hospital of Shenzhen, Shenzhen, China; 4Cardiac
Electrocardiogram Room, The Second People’s Hospital of Shenzhen, Shenzhen, China; 5Clinical Laboratory, The Second People’s Hospital of Shenzhen, Shenzhen, China;
6
Institute of Clinical Anatomy, Southern Medical University, Guangzhou, China and 7Department of Electronic Engineering, Joint Research Centre for Biomedical Engineering, The
Chinese University of Hong Kong, Hong Kong, China. Correspondence: Dr H Zhang, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology,
Chinese Academy of Sciences, 1068 Xueyuan Avenue, Shenzhen University Town, Shenzhen 518055, China.
E-mail: [email protected]
8
These authors contributed equally to this work.
Received 24 August 2014; revised 7 January 2015; accepted 12 January 2015; published online 12 March 2015
 Relationship between heart-carotid PTT and CIMT
C Li et al
664

Figure 1. PEP measured at the aortic valve (left) and rcPTT measured at the carotid artery (right) gating with ECG in three consecutive cardiac
cycles for hypertensive patients.

Table 1. Clinical characteristics of the study population Table 2. Parameters of rcPTT, PEP, acPTT and CIMT in the hypertensive
groups
Parameters Hypertensive patients P-value
Parameters Hypertensive patients P-value
CIMT40.8 mm CIMT ⩽ 0.8 mm
N = 29 N = 33 CIMT40.8 mm, N = 29 CIMT ⩽ 0.8 mm, N = 33

Male/female 19/10 14/19 0.073 rcPTT, ms 90.20 (15.51) 93.39 (16.27) 0.047
Age, years 57.24 (11.02) 51.58 (12.95) 0.071 PEP, ms 68.38 (12.55) 66.63 (13.42) 0.60
Height, cm 166.38 (8.69) 164.73 (8.73) 0.46 acPTT, ms 21.83 (12.48) 26.76 (9.79) 0.033
Weight, kg 69.62 (12.33) 67.42 (9.76) 0.44 CIMT, mm 1.03 (0.13) 0.72 (0.084) o0.0001
Smokers (n) 15 7 0.012
HR, b.p.m. 70.55 (7.11) 69.52 (9.54) 0.48 Abbreviations: acPTT, aortic valve-carotid pulse transit time; CIMT, the
LVEF, % 65.89 (2.47) 66.59 (2.72) 0.49 intima-media thickness of left common carotid artery pressure; PEP, pre-
HDL-C, mmol l − 1 1.20 (0.22) 1.22 (0.26) 0.46 ejection period; rcPTT, ECG R-wave-based carotid pulse transit time.
LDL-C, mmol l − 1 2.86 (0.59) 3.14 (0.64) 0.085 Po0.05: statistically significant.
SBP, mm Hg 144.55 (7.19) 146.79 (9.81) 0.29
DBP, mm Hg 91.93 (10.52) 90.85 (11.14) 0.71
MAP, mm Hg 110.22 (8.0) 108.75 (7.49) 0.83 heart diseases or history of cancer were excluded from this study. This
PP, mm Hg 54.86 (13.73) 53.70 (14.03) 0.70 protocol was approved by the ethics committee in the Second People’s
Duration of 2 (7.5) 1.67 (5.25) 0.52 Hospital of Shenzhen, China, and written informed consent was obtained
hypertension, years from each patient before the start of the experiment.
Abbreviations: CIMT, carotid intima-media thickness; DBP, diastolic blood
pressure; HDL-C, high-density lipoprotein cholesterol; HR, heart rate; Measurements of CIMT
LDL-C, low-density lipoprotein cholesterol; LVEF, left ventricular ejection The research by Banga and coworkers23 found that variability in CIMT
fraction; MAP, mean arterial pressure; PP, pulse pressure; SBP, systolic blood. measurements was lowest when determining the mean CIMT in different
Gender, smoking behaviour and duration of hypertension were compared directions. Therefore, we scanned the left common carotid artery from
using the Wilcoxon test and expressed as median (interquartile range). three angles (lateral, anterior and posterior), according to the suggestion in
Po0.05: statistically significant. the study by Banga et al. An ultrasound technician with 23 years of
experience performed all examinations using a 7.5 MHz linear array probe.
The CIMT was determined using a high-resolution Doppler device (iU22,
the normal CIMT group with CIMT ⩽ 0.8 mm (n = 33, aged from 28 to 77 Philips Ultrasound, Bothell, WA, USA). Each participant was examined in the
years) and (2) the thickened CIMT group with CIMT40.8 mm (n = 29, aged supine position, with the head over-extended and turned 45° away from
from 35 to 77 years). The reason for choosing 0.8 mm as the threshold the examined side. The CIMT was defined as the distance between the
value to distinguish between normal and thickened CIMT patients is that leading edge of the lumen–intima interface and the leading edge of the
the occurrence of CIMT40.8 mm is always accompanied by a significant media–adventitia interface.24 The CIMT was measured on the far wall of
increase in arterial stiffness21 as well as by the presence of plaque in one of the left common carotid artery, at a distance of 1.0–2.0 cm proximal to the
the bifurcations of the common carotid or common femoral arteries.22 carotid bifurcation. Specially, if a plaque exists at the CIMT measuring
In this study, hypertension was defined as systolic blood pressure point, an appropriate adjacent site is chosen. The average of intima-media
(SBP) and/or diastolic blood pressure (DBP) consistently higher than thickness measurements from three angles was calculated as the value
140/90 mm Hg. All subjects participated in carotid ultrasound and clinical of CIMT.
examinations. Brachial blood pressure and heart rate were measured three
times, at 2-min intervals, using an Oscar 2 device (SunTech Medical,
Morrisville, NC, USA) after at least a 5-min rest. The average of three Measurements of heart-carotid PTT, PEP
measurements was used in the analysis. Pulse pressure was calculated Because the ultrasound Doppler system has been demonstrated to have
as SBP–DBP, and the mean arterial pressure was calculated as DBP the same performance with the complior and applanation tonometry
+(SBP − DBP)/3. Left ventricular ejection fraction (LVEF) was measured with method25–27 in measuring PTT, we use the same ECG-synchronized
a Doppler ultrasound device (iU22, Philips Ultrasound, Bothell, WA, USA). ultrasound Doppler system to measure the CIMT and PTT parameters to
High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein reduce the time and complexity for both patients and doctors. Doppler
cholesterol (LDL-C) were measured by a Hitachi 7600 auto biochemistry waveform was measured separately and nonsimultaneously at the aortic
instrument (Hitachi, Tokyo, Japan). Age, gender, smoking behaviour and valve and left carotid artery (Figure 1). PEP was measured as the time
medical history were obtained using a questionnaire. Patients with obvious difference between the ECG R-wave and the foot of the Doppler waveform

Journal of Human Hypertension (2015) 663 – 668 © 2015 Macmillan Publishers Limited
 Relationship between heart-carotid PTT and CIMT
C Li et al
665

Figure 2. Relationship between rcPTT, PEP and acPTT with CIMT in the thickened CIMT hypertensive group (a, c and e) and the normal CIMT
hypertensive group (b, d and f). P o0.05: statistically significant.

obtained at the aortic valve. The ECG R-wave-based carotid PTT (rcPTT) was pressure, HDL-C, LDL-C, heart rate, LVEF and duration of
defined as the time interval from the R-wave to the foot of the Doppler hypertension between the normal CIMT group and the thickened
spectral envelope at the left carotid artery. The aortic valve-carotid PTT CIMT group. However, a significant difference was found in
(acPTT) was calculated by subtracting PEP from rcPTT, i.e., acPTT = rcPTT − smoking behaviour between the two hypertensive groups. In
PEP. All of the measurements were measured under the best resting
conditions to avoid the effect of heart rate. Additionally, all measurements
addition, in both groups, the LVEF fell within the ranges that are
were averaged over three consecutive cardiac cycles. considered normal.

Statistical analysis The parameters of rcPTT, PEP, acPTT and CIMT

The data were expressed as mean (s.d.) or median (interquartile range). CIMT, rcPTT, PEP and acPTT of the two hypertensive groups are
Comparisons of difference in mean values between the two hypertensive shown in Table 2. The thickened CIMT group showed significantly
groups were performed using the Student t-test or the Wilcoxon test lower rcPTT and acPTT compared with the normal CIMT group
method. Simple linear regression based on the least squares method was (P o 0.05). Moreover, no significant differences were found in PEP
used to examine the linear correlations of CIMT with rcPTT, PEP and acPTT between the two hypertensive groups. Additionally, CIMT
in the hypertensive groups. Three multiple linear regression models were
measurement in the normal CIMT hypertensive patients was
used separately to detect whether CIMT was independently associated
with rcPTT, PEP and acPTT in two hypertensive groups. Specifically, model significantly lower than that in the thickened CIMT hypertensive
1 used rcPTT, age, gender, SBP, DBP, smoking behaviour, HDL-C and LDL-C patients (P o0.0001).
as independent variables. In model 2, rcPTT was replaced by acPTT, and in
model 3 rcPTT was replaced by PEP. To investigate whether the inclusion The correlations of CIMT with rcPTT, acPTT and PEP
of PEP could improve the accuracy of atherosclerosis estimation,
Figure 2 shows the linear correlations of rcPTT, PEP and acPTT with
we performed partial correlation analysis28 to calculate the correlation
between CIMT and rcPTT, between CIMT and acPTT, as well as PEP, with CIMT in each group. The results showed that CIMT was negatively
adjustments for the effects of age, gender, SBP and DBP, smoking correlated with rcPTT and acPTT (r = − 0.50, P = 0.0053,
behaviour and cholesterol levels. CIMT = 1.4281–0.0044 × rcPTT; r = − 0.59, P = 0.001, CIMT = 1.1732–
0.0064 × acPTT, respectively) in the thickened CIMT group.
Similarly, CIMT showed negative relationships with rcPTT, PEP
RESULTS and acPTT (r = − 0.57, P o 0.0001, CIMT = 0.9943–0.003 × rcPTT;
Baseline characteristics r = − 0.39, P = 0.026, CIMT = 0.8809–0.0024 × PEP; r = − 0.41,
Table 1 summarizes the clinical characteristics of the study groups. P = 0.016, y = 0.8138–0.0036 × acPTT, respectively) in the normal
No significant differences were found in age, gender, blood CIMT group.

© 2015 Macmillan Publishers Limited Journal of Human Hypertension (2015) 663 – 668
 Relationship between heart-carotid PTT and CIMT
C Li et al
666
Table 3. The determinants of CIMT in multiple linear regression Table 4. Partial correlation analyses of rcPTT, acPTT and PEP with CIMT
models after adjusting control factors

β Err. Sig. Parameters r P-value

Model 1 Hypertensive patients with CIMT40.8 mm (N = 29)

Hypertensive patients with CIMT40.8 mm (N = 29) rcPTT − 0.51 0.01
rcPTT − 0.003 0.001 0.009 PEP − 0.16 0.49
Age 0.007 0.001 o0.0001 acPTT − 0.46 0.03
Smoking 0.08 0.031 0.016
Hypertensive patients with CIMT ⩽ 0.8 mm (N = 33) Hypertensive patients with CIMT ⩽ 0.8 mm (N = 33)
Age 0.004 0.001 o0.0001 rcPTT − 0.26 0.20
Smoking − 0.058 0.028 0.046 PEP − 0.18 0.61
HDL-C − 0.099 0.052 0.069 acPTT −0.11 0.79

Model 2 Abbreviations: acPTT, aortic valve-carotid pulse transit time; PEP, pre-
Hypertensive patients with CIMT40.8 mm (N = 29) ejection period; rcPTT, ECG R-wave-based carotid pulse transit time.
acPTT − 0.004 0.001 0.017 Control factors include age, gender, SBP, DBP, smoking behaviour, HDL-C
Age 0.007 0.002 o0.0001 and LDL-C.
Smoking 0.064 0.033 0.062
Hypertensive patients with CIMT ⩽ 0.8 mm (N = 33)
Age 0.004 0.001 o0.0001
Smoking − 0.058 0.028 0.046 DISCUSSION
HDL-C − 0.099 0.052 0.069 To the best of our knowledge, this is the first study exploring the
correlation between heart-carotid PTT and CIMT in hypertensive
Model 3
patients. Our main finding is that rcPTT and acPTT could be useful
Hypertensive patients with CIMT40.8 mm (N = 29)
Age 0.008 0.002 o0.0001 indexes of atherosclerosis in thickened-carotid-wall hypertensive
Smoking 0.085 0.035 0.022 patients, independent of age, gender, SBP, DBP, smoking
Hypertensive patients with CIMT ⩽ 0.8 mm (N = 33) behaviour, HDL-C and LDL-C. Additionally, PEP could be included
Age 0.004 0.001 o0.0001 in heart-carotid PTT if heart-carotid PTT was used to evaluate the
Smoking − 0.058 0.028 0.046 development of atherosclerosis.
HDL-C − 0.099 0.052 0.069 Statistically significant differences were found in acPTT between
Abbreviations: acPTT, aortic valve-carotid pulse transit time; CIMT, the the thickened CIMT (CIMT40.8 mm) hypertensive group and
intima-media thickness of left common carotid artery pressure; Err., standard normal CIMT (CIMT ⩽ 0.8 mm) hypertensive group. This may be
error; HDL-C, high-density lipoprotein cholesterol; rcPTT, ECG R-wave-based because long-term hypertension could lead to remodeling of the
carotid pulse transit time; Sig., statistical significance. CIMT was the arterial wall, which increases arterial stiffness and accelerates the
dependent variable in these models. Model 1: using rcPTT, age, gender, propagation of pulse wave, thereby decreasing the transit time.
SBP, DBP, smoking behaviour, HDL-C and LDL-C as independent variables. The results of linear regression analysis showed that rcPTT and
Model 2: using acPTT, age, gender, SBP, DBP, smoking behaviour, HDL-C and
acPTT had significant and negative relations with CIMT in both
LDL-C as independent variables. Model 3: using PEP, age, gender, SBP, DBP,
smoking behaviour, HDL-C and LDL-C as independent variables.
normal and thickened CIMT hypertensive groups. However, the
results of multiple linear regression analysis suggested that the
relationships of CIMT with rcPTT and acPTT were eliminated in the
normal thickness hypertensive group after correcting for the effect
of possible confounding factors (age, gender, SBP, DBP, smoking
Three multiple linear regression models using the backward
behaviour, HDL-C and LDL-C). By contrast, CIMT still correlated
selection method were conducted separately to examine the significantly with rcPTT and acPTT in the thickened CIMT group.
independence of the observed associations of rcPTT, PEP and Therefore, we concluded that CIMT is associated with rcPTT and
acPTT with CIMT in both of the hypertensive groups (Table 3). The acPTT, independent of well-known clinical confounders in the
results revealed that rcPTT and acPTT were independently thickened CIMT hypertensive group, whereas the relationships of
associated with CIMT in the thickened CIMT hypertensive group CIMT with rcPTT and acPTT in the normal thickness hypertensive
after adjusting for confounding factors (age, gender, SBP, group may be caused by the effect of confounding factors.
DBP, smoking behaviour, HDL-C and LDL-C). However, those Moreover, most studies to date have proven that CIMT is an
statistical significances were not found in the normal CIMT independent marker for indicating the presence of atherosclerosis
hypertensive patients. Moreover, the results of model 3 showed and cardiovascular events. The research by Veller et al.22 reported
that PEP was not a significant factor of CIMT in the two that, among individuals whose CIMT was greater than 0.8 mm,
hypertensive groups. 95.5% had plaque in their aorta. The research by Lundberg et al.29
suggested that CIMT was related to overall stenoses in the body,
Partial correlation analysis of CIMT with rcPTT, acPTT and PEP even after adjustment for traditional risk factors, confirming CIMT
as an indicator of general atherosclerosis. Taken together, the
Because the results of univariate regression are always mediated independent correlation between CIMT and PTT in the thickened
by covariables, partial correlation analysis was used to investigate CIMT hypertensive group may suggest that rcPTT and acPTT could
whether the inclusion of PEP in heart-carotid PTT would affect the be useful adjunctive markers in reflecting the degree of
relationships of rcPTT, PEP and acPTT with CIMT (Table 4). We took atherosclerosis. Although we did not include healthy subjects in
age, gender, SBP, DBP, smoking behaviour, HDL-C and LDL-C as our study, the research by Jogestrand et al.30 has shown that CIMT
control factors, and no multicollinearity was found among them was not significantly related with arterial stiffness, measured by
(variance inflation factor o5). After correcting the effect of stiffness parameter beta, in the common carotid arteries of
confounding factors, the CIMT presented a stronger correlation healthy individuals.
with rcPTT (r = − 0.51, P = 0.01) than with acPTT (r = − 0.46, P = 0.03) We also found that PEP had an indirect negative relationship
in the thickened CIMT hypertensive group. with CIMT in normal CIMT hypertensive patients. PEP is the time

Journal of Human Hypertension (2015) 663 – 668 © 2015 Macmillan Publishers Limited
 Relationship between heart-carotid PTT and CIMT
C Li et al
667
interval between the onset of electrical depolarization of the left What is known about this topic?
ventricle and the opening of the aortic valve. Because the change ● Carotid intima-media thickness (CIMT) is a widely used marker of
in electrical depolarization in various diseases is minimal, the atherosclerosis.
variation of PEP mainly reflects a change in isovolumetric ● Pulse transit time (PTT) could be a useful index of arterial stiffness.
contraction time.31 We speculate that the reason for the negative However, little is known about the relationship between heart-
relationship between CIMT and PEP in normal CIMT hypertensive carotid PTT and CIMT in hypertensive patients.
patients is that the decreased arterial compliance in hypertensive
What does this study add?
patients would result in a decreased aortic diastolic pressure, ● ECG R-wave-based heart-carotid PTT (rcPTT) and aortic valve-
thereby leading to a shortened isovolumetric contraction time to carotid PTT (acPTT) could be useful and independent markers for
researching the lower aortic diastolic pressure before ventricular evaluating atherosclerosis in thickened CIMT hypertensive patients.
ejection commences. The lack of statistical significance for the ● The inclusion of the pre-ejection period (PEP) in the heart-carotid
thickened CIMT hypertensive group may be because the abnormal PTT measurement might improve the accuracy of atherosclerosis
stiffening and thickening affected this linear relationship. evaluation in thickened CIMT hypertensive patients.
The research by Zhang and coworkers32 reported that the
inclusion of PEP in the upper-body PTT measurement could
improve the accuracy of cuffless blood pressure estimation after
CONFLICT OF INTEREST
exercise. This may indicate that including PEP in PTT could better
The authors declare no conflict of interest.
reflect the change of vessel states. However, they measured the
accuracy with Pearson's correlation coefficient, which can be
affected by covariables.28 Therefore, we performed partial ACKNOWLEDGEMENTS
correlation analysis to calculate the correlations of CIMT with
This work was supported in part by the Guangdong Innovation Research Team Fund
rcPTT, acPTT and PEP, investigating whether including PEP could for Low-cost Health-care Technologies in China, the Key Lab for Health Informatics of
improve the accuracy of atherosclerosis estimation. The results of Chinese Academy of Sciences, the Enhancing Program of Key Laboratories of
the partial correlation analysis were substantially consistent with Shenzhen City (ZDSY20120617113021359), the National High-tech R&D Program (863
multiple linear regression analysis, as follows: the correlations of Program, No.2012AA02A603), Shenzhen Development and Reform Commission’s
rcPTT, PEP and acPTT with CIMT were eliminated in the normal Stroke Screening and Prevention Public Service Platform, the External Cooperation
thickness hypertensive group; CIMT was significantly associated Program of the Chinese Academy of Sciences (No. GJHZ1212), and Shenzhen
with rcPTT and with acPTT in the thickened CIMT hypertensive Innovation Funding (JCYJ20140414170821190).
group after correcting for the effects of age, gender, SBP, DBP,
smoking behaviour, HDL-C and LDL-C. Moreover, the results REFERENCES
suggested that CIMT presented a stronger correlation with rcPTT
1 Dahlöf B. Cardiovascular disease risk factors: epidemiology and risk assessment.
(r = − 0.51, P = 0.01) than with acPTT (r = − 0.46, P = 0.03). This Am J Cardiol 2010; 105(Suppl 1): 3A–9A.
finding might indicate that the inclusion of PEP in the heart- 2 Feng XL, Pang M, Beard J. Health system strengthening and hypertension
carotid PTT measurements could improve the accuracy of awareness, treatment and control: data from the China Health and Retirement
atherosclerosis evaluation in the thickened CIMT hypertensive Longitudinal Study. Bull World Health Organ 2014; 92: 29–41.
group. However, large-scale experiments are needed in the future 3 Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the
to confirm this phenomenon. biology of atherosclerosis. Nature 2011; 473: 317–325.
The present study has several limitations. First, although 4 Lim TK, Lim E, Dwivedi G, Kooner J, Senior R. Normal Value of Carotid Intima-
Media Thickness-A Surrogate Marker of Atherosclerosis: Quantitative Assessment
statistically significant results were obtained in our study, the
by B-Mode Carotid Ultrasound. J Am Soc Echocardiogr 2008; 21: 112–116.
number of subjects could still be too small to extrapolate the 5 Kullo IJ, Malik AR. Arterial ultrasonography and tonometry as adjuncts to
study findings to the general population. Second, generally, PEP is cardiovascular risk stratification. J Am Coll Cardiol 2007; 49: 1413–1426.
measured by subtracting the left ventricular ejection time from 6 Nichols W, O'Rourke MF (eds). McDonald’s blood flow in arteries: theoretical.
the total electrical mechanical systole. However, the present study Experimental and Clinical Principles. 6th edn Hodder Arnold: London, 2011.
measured PEP as the time difference between the ECG R-wave 7 Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical
and the foot of the Doppler waveform obtained at the aortic valve, cardiovascular events with carotid intima-media thickness: a systematic review
which could have a time delay in the blood flow. Third, although and meta-analysis. Circulation 2007; 115: 459–467.
8 Foo JY, CS L. Pulse transit time as an indirect marker for variations in cardiovas-
our data suggest that the value of CIMT 40.8 mm marks the
cular related reactivity. Technol Health Care 2006; 14: 97–108.
threshold of thickened CIMT, this figure must not be considered 9 Sharwood-Smith G, Bruce J, Drummond G. Assessment of pulse transit time to
absolutely, because of the variability of CIMT in different research indicate cardiovascular changes during obstetric spinal anaesthesia. Br J Anaesth
populations. Finally, we did not investigate the relationship 2006; 96: 100–105.
between heart-carotid PTT and CIMT in healthy individuals, and 10 Nichols WW. Clinical measurement of arterial stiffness obtained from noninvasive
this may reduce the significance of our findings. pressure waveforms. Am J Hypertens 2005; 18: 3S–10S.
11 Zhang YL, Zheng YY, Ma ZC, Sun YN. Radial pulse transit time is an index of
arterial stiffness. Hypertens Res 2011; 34: 884–887.
CONCLUSION 12 Peulic A, Jovanov E, Radovic M, Saveljic I, Zdravkovic N, Filipovic N. Arterial
stiffness modeling using variations of pulse transit time. 2011 10th International
In conclusion, both rcPTT and acPTT are significantly associated Workshop on Biomedical Engineering. IEEE: 2011.
with CIMT after adjusting for age, gender, SBP, DBP, smoking 13 Kounalakis SN, Geladas ND. The role of pulse transit time as an index of arterial
behaviour, HDL-C and LDL-C in thickened CIMT hypertensive stiffness during exercise. Cardiovasc Eng 2009; 9: 92–97.
patients. Our findings suggest that rcPTT and acPTT could be 14 Nisbet LC, Yiallourou SR, Nixon GM, Biggs SN, Davey MJ, Trinder J et al. Char-
useful and independent markers of atherosclerosis in thickened acterization of the acute pulse transit time response to obstructive apneas and
CIMT hypertensive patients. Moreover, the partial correlation hypopneas in preschool children with sleep-disordered breathing. Sleep Med
shows that CIMT has a stronger correlation with rcPTT than with 2013; 14: 1123–1131.
15 Singham S, Voss L, Barnard J, Sleigh J. Nociceptive and anaesthetic-induced
acPTT in thickened CIMT hypertensive patients, which might
changes in pulse transit time during general anaesthesia. Br J Anaesth 2003; 91:
indicate that the inclusion of PEP in the heart-carotid PTT 662–666.
measurement could improve the accuracy of atherosclerosis 16 Gesche H, Grosskurth D, Kuchler G, Patzak A. Continuous blood pressure
evaluation. However, additional clinical experiments are needed measurement by using the pulse transit time: comparison to a cuff-
to confirm this phenomenon. based method. Eur J Appl Physiol 2012; 112: 309–315.

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 Relationship between heart-carotid PTT and CIMT
C Li et al
668
17 Oleary DH, Polak JF, Kronmal RA, Savage PJ, Borhani NO, Kittner SJ et al. Thick- 25 Calabia J, Torguet P, Garcia M, Garcia I, Martin N, Guasch B et al. Doppler ultra-
ening of the carotid wall—a marker for atherosclerosis in the elderly? Stroke 1996; sound in the measurement of pulse wave velocity: agreement with the
27: 224–231. Complior method. Cardiovasc Ultrasound 2011; 9: 13.
18 Nakashima Y, Wight TN, Sueishi K. Early atherosclerosis in humans: role of diffuse 26 Jiang B, Liu B, McNeill KL, Chowienczyk PJ. Measurement of pulse wave velocity
intimal thickening and extracellular matrix proteoglycans. Cardiovasc Res 2008; using pulse wave Doppler ultrasound: comparison with arterial tonometry.
79: 14–23. Ultrasound Med Biol 2008; 34: 509–512.
19 Stefanadis C, Stratos C, Boudoulas H, Kourouklis C, Toutouzas P. Distensibility of 27 Baguet JP, Kingwell BA, Dart AL, Shaw J, Ferrier KE, Jennings GL. Analysis of the
the ascending aorta: comparison of invasive and non-invasive techniques in healthy regional pulse wave velocity by Doppler: methodology and reproducibility. J Hum
men and in men with coronary artery disease. Eur Heart J 1990; 11: 990–996. Hypertens 2003; 17: 407–412.
20 Giannattasio C, Failla M, Emanuelli G, Grappiolo A, Boffi L, Corsi D et al. Local 28 Kendall MG, Stuart A. The Advanced Theory of Statistics, 3rd end, 1973,
effects of atherosclerotic plaque on arterial distensibility. J Hypertens 2001; 38: pp: 330-360.
1177–1180. 29 Lundberg C, Hansen T, Ahlstrom H, Lind L, Wikstrom J, Johansson L. The rela-
21 Riley WA, Evans GW, Sharrett AR, Burke GL, Barnes RW. Variation of common tionship between carotid intima-media thickness and global atherosclerosis. Clin
carotid artery elasticity with intimal-medial thickness: the ARIC study. Ultrasound Physiol Funct Imaging 2014; 34: 457–462.
Med Biol 1997; 23: 157–164. 30 Jogestrand T, Eiken O, Nowak J. Relation between the elastic properties and
22 Veller MG, Fisher CM, Nicolaides AN, Renton S, Geroulakos G, Stafford NJ et al. intima-media thickness of the common carotid artery. Clin Physiol Funct Imaging
Measurement of the ultrasonic intima-media complex thickness in normal sub- 2003; 23: 134–137.
jects. J Vasc Surg 1993; 17: 719–725. 31 Hamada M, Hiwada K, Kokubu T. Clinical significance of systolic time intervals in
23 Kanters S, Algra A, vanLeeuwen MS, Banga JD. Reproducibility of in vivo carotid hypertensive patients. Eur Heart J 1990; 11: 105–113.
intima-media thickness measurements: a review. Stroke 1997; 28: 665–671. 32 Wong MYM, Pickwell-MacPherson E, Zhang YT, Cheng JCY. The effects
24 Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE. Common carotid of pre-ejection period on post-exercise systolic blood pressure estimation
intima-media thickness and risk of stroke and myocardial infarction: the using the pulse arrival time technique. Eur J Appl Physiol 2011; 111:
Rotterdam Study. Circulation 1997; 96: 1432–1437. 135–144.

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