Comparison between pulse wave velocities measured using Complior and measured using Biopac

Comparison between pulse wave velocities measured using Complior and measured using Biopac Arterial stiffness is a reliable prognostic parameter for cardiovascular diseases. The effect of change in arterial stiffness can be measured by the change of the pulse wave velocity (PWV). The Complior system is widely used to measure PWV between the carotid and radial arteries by means of piezoelectric clips placed around the neck and the wrist. The Biopac system is an easier to use alternative that uses ECG and simple optical sensors to measure the PWV between the heart and the fingertips, and thus extends a bit more to the peripheral vasculature compared to the Complior system. The goal of this study was to test under various conditions to what extent these systems provide comparable and correlating values. 25 Healthy volunteers, 20–30 years old, were measured in four sequential position: sitting, lying, standing and sitting. The results showed that the Biopac system measured consistently and significantly lower PWV values than the Complior system, for all positions. Cor - relation values and Bland–Altman plots showed that despite the difference in PWV magnitudes obtained by the two systems the measurements did agree well. Which implies that as long as the differences in PWV magnitudes are taken into account, either system could be used to measure PWV changes over time. However, when basing diagnosis on absolute PWV values, one should be very much aware of how the PWV was measured and with what system. Keywords Arterial stiffness · Pulse wave velocity · Cardiovascular disease · Non-invasive 1 Introduction atherosclerosis. Most of these phenomena are related to an increase in arterial stiffness. Arterial stiffness is a reliable prognostic parameter for car - Arterial stiffness is a measure of the capability of an diovascular morbidity and mortality in adults. In particu- artery to expand and contract in response to local blood pres- lar, this is the case in patients with renal disease, diabe- sure changes and is the inverse of arterial compliance. The tes mellitus or hypertension and in elderly patients [1–4]. compliance, and therefore the volume change in response Cardiovascular disease (CVD) is worldwide the number to a blood pressure change, in a stiff vessel is reduced one cause of death. Smoking, unhealthy diet, physical inac- compared to a healthy vessel. The effect of reduced com- tivity and harmful use of alcohol are the most important pliance is a decreased propagation time of pressure pulse behavioural risk factors of CVD. These behavioural risks waves (PWs) through the vessels and thus an increase of may lead to hypertension, diabetes, obesity, heart failure, or the velocity of the PW. The relationship between this pulse wave velocity (PWV) and the compliance of the vessel wall is described in the MoensKorteweg equation [5]: * Marit H. N. van Velzen m.v.velzen@jbz.nl E ⋅ h inc PWV = , (1) Laboratory of Experimental Anesthesiology, Department 2r ⋅ of Anesthesiology, Erasmus University Medical Center, Rotterdam, The Netherlands where E is the incremental elastic modulus, h is the wall inc Department of BioMechanical Engineering, Faculty 3mE, thickness, and r the radius of the vessel. The symbol ρ rep- Delft University of Technology, Delft, The Netherlands resents the density of blood. Department of Medical Information Communication PWV measurements are widely used as an index of arte- Technology MICT, Jeroen Bosch Ziekenhuis, PO Box 90153, rial stiffness [6 ] and for the evaluation of cardiovascular 5200 ME ’s Hertogenbosch, The Netherlands Vol.:(0123456789) 1 3 Journal of Clinical Monitoring and Computing risk. PWV measurements are generally simple, accurate and different devices for the same purpose provides the same highly reproducible [7, 8]. In clinical practice, several inva- outcome. One would never accept it if measuring a heart sive and non-invasive measurement techniques are readily rate using ECG versus using a pulse oximeter on the finger available to measure PWV. Two of such techniques, equally would provide a 30 bpm difference. Therefore, the goal of often used in clinical practice by the Erasmus Medical Cen- this health technology assessment was to test under various tre in Rotterdam, the Netherlands, are the Complior (Alam conditions to what extent these systems provide comparable Medical, Vincennes, France), using piezoelectric sensors values and to what extent these values correlate. [9], and the Biopac (Biopac Systems, Inc, USA), using a photoplethysmography (PPG) sensor and ECG. These tech- niques are generally used to non-invasively measure the 2 Method PWV in the big arteries over a long trajectory. The Complior system is used to measure PWV between 2.1 Study population the carotid and radial arteries by means of piezoelectric-clips placed around the neck and the wrist. The Biopac system Twenty-five healthy volunteers, 20–30 years old, without is an easier-to-use alternative to the Complior system, but any known history of atherosclerosis associated diseases it measures the PWV between the heart and the fingertips, (such as diabetes mellitus, hypertension, coronary artery and thus extends a bit more to the peripheral vasculature. disease, stroke, renal disorder), or injuries at the upper limbs One may expect that the two systems show good agreement, were included in this study after obtaining written informed because the majority of the trajectory (sternoclavicular joint consent from the subject. This study was approved by the to wrist) of the arterial trajectories over which the Biopac medical ethics committee of Erasmus University Medical and Complior systems measure PWV are identical. However, Center Rotterdam, The Netherlands (MEC-2012-139). the trajectory for the Biopac system additionally includes the wrist-fingertip vasculature. Furthermore, the Biopac 2.2 Protocol includes the heart-sternoclavicular trajectory, whereas with the Complior one takes the sternoclavicular-carotid tra- The transit time of a PW traveling from within the heart to jectory as an approximation for the heart-sternoclavicular easily accessible locations, such as the extremities or the trajectory. neck, consists of two components: the PW propagationtime While both systems are supposed to measure or approxi- from the heart through the artery to the PW measurement mate a PWV value for the more or less the same trajectory location, and the isometric contraction time of the heart from the heart to the hand, the potentially differing physi- (pre-ejection period, PEP). The PEP is known to vary with ological responses of the carotid and the peripheral arteries cardiac preload and heart rate [11–13]. Therefore, all meas- may cause different PWV measurement outcomes. The baro- urements were conducted in a quiet room under tranquil con- receptor reflex is one of the body’s homeostatic mechanisms ditions at a room temperature of 22.4 °C (SD 0.5 °C). To that helps to maintain blood pressure at nearly constant lev- further minimize any influences of a varying PEP or cardiac els [10] by detecting blood pressure using the baroreceptors output during the measurement, the subjects were instructed located in the walls of the carotid arteries. If one suddenly not to talk or move during the measurement for each posi- rises from a lying position, gravity pulls the blood in the tion. Because caffeine, tobacco and alcohol influence the direction of the legs, which could endanger the blood flow heart rate and cardiac output, all subjects were asked to not to the brain. As a response, the baroreceptor reflex causes take any caffeine, tobacco or alcohol for at least 3 h prior to the peripheral veins to be squeezed and the carotid arteries the experiment. to be widened to aid the blood flow to the brain. Therefore The measurements were conducted 4 times for each sub- one may expect that depending on the measurement situa- ject, each time in a different body position. In the first posi- tions the PWV change measured with the Complior system tion, the subject sat on a chair with both hands resting on a will oppose the PWV measured with the Biopac system if table. In the second position, the subject lied on a bed with the baroreceptor reflex is invoked. both arms and hands resting along his/her body. In the third So while both systems are aimed at providing a similar position, the subject stood upright with both hands hang- measure of vascular condition and while the trajectories over ing down along his/her body. The fourth position was the which they measure PWV largely overlap, there are various same as the first position, to check if the PWV-value was reasons why it is unclear whether they will provide similar reproducible. measurement outcomes. To the best of our knowledge, there Before the start of each measurement in each position are no reports about the agreement between PWV values the subject was kept at rest for 60 s in the requested posi- measured using the Complior system or the Biopac system. tion. The PWV values were recorded with both of the tested Yet, in clinical practice it is crucial to know whether using 1 3 Journal of Clinical Monitoring and Computing systems simultaneously during the entire measurement, “Complior SP” software. The distance between the sensors, which lasted up to 60 s. measured in a straight line from the sternoclavicular joint to the styloid process of the radius, was used to approximate 2.3 Pulse wave velocity measurements the arterial distance travelled by the PWs. Using the “Com- and analyses plior SP” software, the foot of the PW measured at both locations was used to calculate the mean PWV once per 5 s. The PWV was measured between the carotid and radial The system used for measuring the PWV between the arteries using the Complior system (Alam Medical, Vin- carotid artery and the left index finger tip consisted of a cennes, France) and between the carotid artery and the left measuring device and analysis software. The measurement index finger tip using ECG and PPG (described below). The device contained one PPG-sensor (TSD200 with the Complior system measures the PWV using piezoelectric PPG100C amplifier, Biopac Systems, Inc, Goleta, USA), sensors. For measuring the PWs on the carotid artery, a clip positioned on the left index finger, and three external ECG- containing a piezoelectric sensor was placed on the left side leads (ECG100C amplifier, Biopac Systems, Inc, Goleta, of the neck. For measuring the PWs on the radial artery, a USA) (see Fig. 1). The three ECG-leads were placed on the clip containing a piezoelectric sensor was placed on the left subject’s both wrists and right ankle. The PPG- and ECG- wrist (see Fig. 1). Both sensor signals were recorded by the signals were simultaneously converted to digital signals using AcqKnowledge version 3.7.3 software (Biopac Sys- tems, Inc, Goleta, USA), at a sampling frequency of 2 kHz. The PPG-signal was filtered with a fourth-order low pass Butterworth filter with a cut-off frequency of 9 Hz using Matlab R2010a (The MathWorks, Inc., Matick, MA, USA). The PWV was determined by dividing the distance between the PPG-sensor on the left index finger and the sternoclav - icular joint (D) by the calculated time-difference between the time instance of the R-peak of the ECG t (n) ECG R−peak and the foot of the PW measured at the left index finger tip t (n) : PPG foot PWV (n)= , biopac (2) t (n)− t (n) PPG ECG foot R−peak where n is the sequence number of the heartbeats. The R-peaks in the ECG were found using the off-the-shelf Mat- lab function ‘R-peakdetect’ [14]. The maximum of the sec- ond derivative of each PW was taken as the foot of the PW (PPG ) and the corresponding time was indicated as foot t (n) [15]. The utilized PPG-sensor was quite sensi- PPG foot tive for motion and positioning artefacts, which sometimes distorted the shapes of the PWs in a way that they were rendered unsuitable for further analysis. Therefore, a cus- tom-made Matlab algorithm, called ‘7Step PW-Filter’, was implemented in the data analysis to filter out any PWs that strongly deviated in shape from a suitable PW [16] .If more than 50% of the PWs were filtered out for being too dis- torted, the data-set was excluded from further analysis. 2.4 Statistical analysis The mean PWVs +/− standard deviation (SD) over 60 s were calculated for each measurement technique for each body position. The Shapiro–Wilk test was used to check Fig. 1 Schematic view of placement of the both measurement sys- tems 1 3 Journal of Clinical Monitoring and Computing if the data was normally distributed. PWV values obtained Table 2 Mean and standard deviation of the PWV using the Complior and Biopac system were compared using Position PWV (m/s) PWV (m/s) Paired sampled t-test complior biopac a paired samples t-test and a Bland–Altman plot was used to Sitting 1 10.2 ± 1.4 3.0 ± 0.2 t(21) = − 24.442, analyse the agreement between the two different PWV meas - p < 0.001 urement techniques. Correlation between both sitting posi- Lying 9.3 ± 1.6 3.1 ± 0.2 t(19) = − 18.654, tions (Position 1 and Position 4) were analysed using a Pear- p < 0.001 son Correlation test. A significance level of p -value < 0.05 Standing 9.8 ± 2.2 3.2 ± 0.2 t(13) = − 16.178, was used. A repeated measurement ANOVA with Green- p < 0.001 houseGeisser correction and a post hoc test with Bonferroni Sitting 2 10.2 ± 1.1 3.0 ± 0.2 t(21) = − 31.704, correction was used to test for any effects of the repeated p < 0.001 measurements. All statistical analyses were performed using SPSS version 22.0 (SPSS, Inc., Chicago, IL, USA). Figure  3 and Table  3 present the Bland–Altman value and plot showing good agreement between the two PWV 3 Results measurement techniques. The Pearson correlation between sitting Positions 1 and Twenty-five subjects, (11 male, 14 female) were included in 4 proved to be high and significant for PWV (0.778, biopac p < 0.001). For PWV there was no significant correla- this study. The data of one male and one female subject were complior excluded from the analysis because there was too much noise tion (0.141, p = 0.541). The repeated measures ANOVA indicated that the in the signals to obtain any usable PWs. Table 1 presents the characteristic of the remaining study population. For posi- four body positions were rated equally [F(3,45) = 2.47, p = 0.074], for the Complior. For the Biopac, the four body tions 1, 2 and 4 (sitting 1, lying, sitting 2) the ‘7Step PW- Filter’ filtered out none of the PWs. For Position 3 (standing) positions were not rated equally [F(3,39) = 13,1, p = 0.000]. The post hoc tests of the Biopac-data revealed that Position there were 8 datasets with over 50% unsuitable PWs, which were therefore excluded from further analysis. In the remain- 2 (lying) and Position 3 (standing) resulted in significantly higher PWV compared to Position 1 (sitting 1) (p = 0.000, ing 15 datasets, the median percentage of unsuitable PWs that were filtered out was 2.2% (Q = 0% and Q = 36.6%). p = 0.025, respectively). There was no significantly differ - 1 3 ence between Position 2 (lying) and Position 3 (standing) The means and SDs for the PWV and PWV complior biopac for the four different positions are listed in Table  2, as well (p = 1.000). as the results of the paired samples t-test. Significant dif- ferences were found for each position between PWV complior and PWV . biopac Figure 2 shows a boxplot of PWV and PWV complior biopac for each position. The data consistently showed that PWV was much lower than PWV . biopac complior Table 1 Characteristics of the study population Variable Mean ± SD (n = 23) Gender (m/f) 10/13 Age (years) 25 ± 3 Weight (kg) 72 ± 9 Height (m) 1.77 ± 0.08 Body mass index (kg/m ) 23.03 ± 2.72 Blood pressure (mmHg)  Systolic 127 ± 11  Diastolic 80 ± 9 Heart rate (bpm) 77 ± 14 Smoker, yes (%) 2 [8, 33] Distance from sternoclavicular to wrist (cm) 69 ± 3 Fig. 2 Boxplot of the PWV and PWV , with the median as biopac complior Distance from wrist to fingertip (cm) 17 ± 1 red line and the minimum and maximum value 1 3 Journal of Clinical Monitoring and Computing Fig. 3 Bland–Altman plots of PWV and PWV by the four positions. The dotted lines represent the 95% limits of agreement and the complior biopac straight mean difference (bias) between PWV and PWV complior biopac between PWV and PWV may more likely be Table 3 Bland–Altman biopac complior explained by the difference in vessel compliance between Position BIAS ± CI (m/s) % of overall the two trajectories. More peripheral vessels are narrower, mean PWV thinner walled and more compliant. Because the more (%) peripherally measured PWV showed to be lower, it biopac Sitting 1 7.2 ± 2.7 37.6 is hypothesized that the reduced vessel stiffness and wall Lying 6.2 ± 2.9 47.0 thickness (both reducing PWV) outweigh the reduced vas- Standing 6.6 ± 4.3 64.4 cular radii (which would increase the PWV). However, Sitting 2 7.3 ± 2.1 29.0 the PWV -values agree with values reported in other complior studies. The mean PWV -values (10.2 ± 1.4 m/s) were complior in the same range as those reported by Rajzer et al. [17] (10.1 ± 1.7 m/s). Although Raizer et al. measured PWV over 4 Discussion the carotid-femoral trajectory, it is expected that PWVs over that trajectory will be similar to those in the carotid-radial This study compared PWV values measured over the trajectory, because of similar lengths and because the effects carotid-radial artery trajectory using the Complior system of differences in vessel radii and wall thicknesses are likely with PWV values measured between the R-peak of the ECG to cancel each other out, according to Eq. 1. Furthermore, and the arrival of the PW in the left index finger tip using the current results also agree with those of McEleavy, who the Biopac system in healthy volunteers in three body posi- measured a PWV of 9.01 ± 1.2 m/s in the carotid-radial tra- tions: sitting, lying and standing. The PWV values biopac jectory [18]. For the PWV no other studies reporting biopac were considerably lower than the PW V -values, and complior PWV between the heart and a fingertip were found, however this effect persisted in each position. This absolute differ - the time between the R-peak of the ECG and arrival of the ence might be explained for a minor part by the fact that foot of the PW at the fingertip (called pulse transit time) PWV includes the PEP, whereas PWV does not. biopac complior (283 ± 21 ms) was in the same range as reported previously However, the PEP could account for no more than 1 m/s by van Velzen et al. (273 ± 20 ms) [16] and by Kortekaas of the PWV . Therefore, the large absolute difference biopac et al. (271 ± 28 ms) [13]. 1 3 Journal of Clinical Monitoring and Computing Table 2 shows that the PWV was consistently and could benefit patients and clinical practice. Although the biopac significantly lower than PWV for all positions (1–4). ‘7Step PW-Filter’ algorithm used to eliminate distorted complior However, the Bland–Altman plots (Fig. 3) show that the bias PWs functioned well, the availability of a PPG-sensor is small and the values are scattered around the mean, lead- less sensitive to disturbances and not requiring measur- ing to the conclusion that there is a good agreement between ing sensor distances, would greatly simplify measuring the PWV and PWV values, but they simply differ PWs in awake and moving patients. Obviously, this is less complior biopac in magnitude. relevant when measuring PWs in patients under general The PWV was slightly, but significantly higher when lying anaesthesia. or standing as compared to sitting (with no significant dif- In conclusion, this study demonstrated that PWV values ference between lying and standing), when measured by the were consistently and significantly lower when measured Biopac system over the heart-fingertip trajectory. PWV may with the Biopac system than when measured with the Com- increase when vessels become stiffer and narrower due to plior system. Yet, despite the difference in absolute PWV contraction, but although this effect could be induced when values, the two systems did agree fairly well. This suggests standing up, it is less likely to happen when lying down. that as long as the difference in PWV magnitudes are taken There was no significant effect of the different positions for into account, either system could be used to measure PWV the PWV , which suggests that the PWV is less changes in time. However, when basing diagnosis on abso- complior complior suitable to detect such small PWV changes or it is less sensi- lute PWV values, one should be very much aware of how tive to changing positions. The Pearson correlation results the PWV was measured and with what system. In the future, show much better agreement between repetitions of the sit- clinical practice could greatly benefit if software for calcu- ting position at different moments for the Biopac system lating PWV is embedded in the commonly used anaesthesia than for the Complior system. This suggests that when doing monitors, enabling PWV measurements using a standard longitudinal PWV measurements, the Biopac system should ECG and a standard pulse oximeter. This might allow PWV be preferred, provided that the same position is consistently measurements to become a widely available diagnostic tool, used during successive measurements. and an easy-to-use, noninvasive, safe and quick method for When using the Biopac system, the measured PWV objectively assessing arterial stiffness as a reliable prognos - includes the PEP. The PEP is known to vary during posi- tic parameter for cardiovascular morbidity and mortality. tion changes. PEP variations caused by subject movement or Acknowledgements The authors would like to express their gratitude stress were avoided during the current study. Kortekaas et al. to all the volunteers who participated in this study. showed a variability of the PEP in healthy volunteers in rest of 58.5 ± 13.0 ms [13]. Over the distances travelled by the Open Access This article is distributed under the terms of the Crea- PWs in the current study, these PEP durations could account tive Commons Attribution 4.0 International License (http://creat iveco mmons.or g/licenses/b y/4.0/), which permits unrestricted use, distribu- for no more than 1 m/s of the PWV . Consequently, PEP biopac tion, and reproduction in any medium, provided you give appropriate variations are unlikely to explain any variations in this study. credit to the original author(s) and the source, provide a link to the Limitations of the two tested techniques include the Creative Commons license, and indicate if changes were made. challenge of accurately positioning the sensors, and the discrepancy between the measured distance between the sensors and the actual path length travelled by the PWs. When measuring the PWV more locally, such as between References the wrist and a position at the lower arm, the discrepancy 1. Cruickshank K, Riste L, Anderson SG, Wright JS, Dunn G, Gos- between the distance between the sensors and the actual ling RG. Aortic pulse-wave velocity and its relationship to mor- path length travelled by the PWs should diminish. tality in diabetes and glucose intolerance: an integrated index of Furthermore, the utilized piezoelectric sensors in the vascular function? Circulation. 2002;106(16):2085–90. Complior and PPG-sensors in the Biopac system were 2. Blacher J, Guerin AP, Pannier B, Marchais SJ, Safar ME, London GM. Impact of aortic stiffness on survival in end-stage renal dis- quite sensitive to motion and positioning disturbances. ease. Circulation. 1999;99(18):2434–9. This sensitivity to disturbances poses a potential limitation 3. Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize on the usability of these techniques in clinical practice. L, Ducimetiere P, Benetos A. Aortic stiffness is an independent Moreover, the Complior system is not always comfort- predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension. 2001;37(5):1236–41. able for the subject: use of the clip on the neck was some- 4. Avolio AP, Chen SG, Wang RP, Zhang CL, Li MF, O’Rourke times experienced as uncomfortable, whereas the sensor MF. Effects of aging on changing arterial compliance and left required for the Biopac system a photoplethysmography ventricular load in a northern Chinese urban community. Circula- sensor on the finger and three ECG-leads on the wrists and tion. 1983;68(1):50–8. right ankle are more comfortable than the Complior sensor and are generally available in hospitals. Using this system 1 3 Journal of Clinical Monitoring and Computing 5. Bramwell JC, Hill AV. The velocity of the pulse wave in man. 13. Kortekaas MC, van Velzen MHN, Grüne F, Niehof SP, Stolker Proc R Soc Lond Ser B. 1922;93(652):298–306. https ://doi. RJ, Huygen FJPM. Small intra-individual variability of the pre- org/10.2307/81045 . ejection period justifies the use of pulse transit time as approxima- 6. Asmar R, Benetos A, Topouchian J, Laurent P, Pannier B, Brisac tion of the vascular transit. Submitted to PLoS One. 2018 AM, Target R, Levy BI. Assessment of arterial distensibility by 14. Clifford GD. Rpeakdetect function (ECG toolbox). 2008 automatic pulse wave velocity measurement: validation and clini- 15. Van Velzen MHN, Loeve AJ, Kortekaas MC, Niehof SN, Mik cal application studies. Hypertension. 1995;26(3):485–90. EG, Stolker RJ. Effect of heat-induced pain stimuli on pulse tran- 7. Wilkinson IB, Fuchs SA, Jansen IM, Spratt JC, Murray GD, Cock- sit time and pulse wave amplitude in healthy volunteers. Physiol croft JR, Webb DJ. Reproducibility of pulse wave velocity and Meas. 2015;37(1):52–66. augmentation index measured by pulse wave analysis. J Hyper- 16. van Velzen MHN, Loeve AJ, Niehof SP, Mik EG. (2017) Increas- tens. 1998;16(12 SUPPL.):2079–84. ing accuracy of pulse transit time measurements by automated 8. Safar H, Mourad JJ, Safar M, Blacher J. Aortic pulse wave veloc- elimination of distorted photoplethysmography waves. Med Biol ity, an independent marker of cardiovascular risk. Arch Mal Coeur Eng Compu:1–12. https ://doi.org/10.1007/s1151 7-017-1642-x. Vaiss. 2002;95(12):1215–8. 17. Rajzer MWMMW.. Comparison of aortic pulse wave velocity 9. Jatoi NA, Mahmud A, Bennett K, Feely J. Assessment of arterial measured by three techniques: Complior, SphygmoCor and Arte- stiffness in hypertension: Comparison of oscillometric (arterio- riograph. J Hypertens. 2008;26(10):2001–7. graph), piezoelectronic (Complior) and tonometric (SphygmoCor) 18. McEleavy OD, McCallum RW, Petrie JR, Small M, Connell techniques. J Hypertens. 2009;27(11):2186–91. JMC, Sattar N, Cleland SJ. Higher carotid-radial pulse wave 10. Heesch CM. Reflexes that control cardiovascular function. Am J velocity in healthy offspring of patients with Type 2 diabe- Physiol. 1999;277(6 Pt 2):S234–43. tes. Diabet Med. 2004;21(3):262–6. https ://doi.or g/10.111 11. Weissler AM, Harris WS, Schoenfeld CD. Systolic time intervals 1/j.1464-5491.2004.01127 .x. in heart failure in man. Circulation. 1968;37(2):149–59. 12. Newlin DB, Levenson RW. Pre-ejection period: measuring beta-adrenergic influences upon the heart. Psychophysiology. 1979;16(6):546–53. 1 3 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Clinical Monitoring and Computing Springer Journals

Comparison between pulse wave velocities measured using Complior and measured using Biopac

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Abstract

Arterial stiffness is a reliable prognostic parameter for cardiovascular diseases. The effect of change in arterial stiffness can be measured by the change of the pulse wave velocity (PWV). The Complior system is widely used to measure PWV between the carotid and radial arteries by means of piezoelectric clips placed around the neck and the wrist. The Biopac system is an easier to use alternative that uses ECG and simple optical sensors to measure the PWV between the heart and the fingertips, and thus extends a bit more to the peripheral vasculature compared to the Complior system. The goal of this study was to test under various conditions to what extent these systems provide comparable and correlating values. 25 Healthy volunteers, 20–30 years old, were measured in four sequential position: sitting, lying, standing and sitting. The results showed that the Biopac system measured consistently and significantly lower PWV values than the Complior system, for all positions. Cor - relation values and Bland–Altman plots showed that despite the difference in PWV magnitudes obtained by the two systems the measurements did agree well. Which implies that as long as the differences in PWV magnitudes are taken into account, either system could be used to measure PWV changes over time. However, when basing diagnosis on absolute PWV values, one should be very much aware of how the PWV was measured and with what system. Keywords Arterial stiffness · Pulse wave velocity · Cardiovascular disease · Non-invasive 1 Introduction atherosclerosis. Most of these phenomena are related to an increase in arterial stiffness. Arterial stiffness is a reliable prognostic parameter for car - Arterial stiffness is a measure of the capability of an diovascular morbidity and mortality in adults. In particu- artery to expand and contract in response to local blood pres- lar, this is the case in patients with renal disease, diabe- sure changes and is the inverse of arterial compliance. The tes mellitus or hypertension and in elderly patients [1–4]. compliance, and therefore the volume change in response Cardiovascular disease (CVD) is worldwide the number to a blood pressure change, in a stiff vessel is reduced one cause of death. Smoking, unhealthy diet, physical inac- compared to a healthy vessel. The effect of reduced com- tivity and harmful use of alcohol are the most important pliance is a decreased propagation time of pressure pulse behavioural risk factors of CVD. These behavioural risks waves (PWs) through the vessels and thus an increase of may lead to hypertension, diabetes, obesity, heart failure, or the velocity of the PW. The relationship between this pulse wave velocity (PWV) and the compliance of the vessel wall is described in the MoensKorteweg equation [5]: * Marit H. N. van Velzen m.v.velzen@jbz.nl E ⋅ h inc PWV = , (1) Laboratory of Experimental Anesthesiology, Department 2r ⋅ of Anesthesiology, Erasmus University Medical Center, Rotterdam, The Netherlands where E is the incremental elastic modulus, h is the wall inc Department of BioMechanical Engineering, Faculty 3mE, thickness, and r the radius of the vessel. The symbol ρ rep- Delft University of Technology, Delft, The Netherlands resents the density of blood. Department of Medical Information Communication PWV measurements are widely used as an index of arte- Technology MICT, Jeroen Bosch Ziekenhuis, PO Box 90153, rial stiffness [6 ] and for the evaluation of cardiovascular 5200 ME ’s Hertogenbosch, The Netherlands Vol.:(0123456789) 1 3 Journal of Clinical Monitoring and Computing risk. PWV measurements are generally simple, accurate and different devices for the same purpose provides the same highly reproducible [7, 8]. In clinical practice, several inva- outcome. One would never accept it if measuring a heart sive and non-invasive measurement techniques are readily rate using ECG versus using a pulse oximeter on the finger available to measure PWV. Two of such techniques, equally would provide a 30 bpm difference. Therefore, the goal of often used in clinical practice by the Erasmus Medical Cen- this health technology assessment was to test under various tre in Rotterdam, the Netherlands, are the Complior (Alam conditions to what extent these systems provide comparable Medical, Vincennes, France), using piezoelectric sensors values and to what extent these values correlate. [9], and the Biopac (Biopac Systems, Inc, USA), using a photoplethysmography (PPG) sensor and ECG. These tech- niques are generally used to non-invasively measure the 2 Method PWV in the big arteries over a long trajectory. The Complior system is used to measure PWV between 2.1 Study population the carotid and radial arteries by means of piezoelectric-clips placed around the neck and the wrist. The Biopac system Twenty-five healthy volunteers, 20–30 years old, without is an easier-to-use alternative to the Complior system, but any known history of atherosclerosis associated diseases it measures the PWV between the heart and the fingertips, (such as diabetes mellitus, hypertension, coronary artery and thus extends a bit more to the peripheral vasculature. disease, stroke, renal disorder), or injuries at the upper limbs One may expect that the two systems show good agreement, were included in this study after obtaining written informed because the majority of the trajectory (sternoclavicular joint consent from the subject. This study was approved by the to wrist) of the arterial trajectories over which the Biopac medical ethics committee of Erasmus University Medical and Complior systems measure PWV are identical. However, Center Rotterdam, The Netherlands (MEC-2012-139). the trajectory for the Biopac system additionally includes the wrist-fingertip vasculature. Furthermore, the Biopac 2.2 Protocol includes the heart-sternoclavicular trajectory, whereas with the Complior one takes the sternoclavicular-carotid tra- The transit time of a PW traveling from within the heart to jectory as an approximation for the heart-sternoclavicular easily accessible locations, such as the extremities or the trajectory. neck, consists of two components: the PW propagationtime While both systems are supposed to measure or approxi- from the heart through the artery to the PW measurement mate a PWV value for the more or less the same trajectory location, and the isometric contraction time of the heart from the heart to the hand, the potentially differing physi- (pre-ejection period, PEP). The PEP is known to vary with ological responses of the carotid and the peripheral arteries cardiac preload and heart rate [11–13]. Therefore, all meas- may cause different PWV measurement outcomes. The baro- urements were conducted in a quiet room under tranquil con- receptor reflex is one of the body’s homeostatic mechanisms ditions at a room temperature of 22.4 °C (SD 0.5 °C). To that helps to maintain blood pressure at nearly constant lev- further minimize any influences of a varying PEP or cardiac els [10] by detecting blood pressure using the baroreceptors output during the measurement, the subjects were instructed located in the walls of the carotid arteries. If one suddenly not to talk or move during the measurement for each posi- rises from a lying position, gravity pulls the blood in the tion. Because caffeine, tobacco and alcohol influence the direction of the legs, which could endanger the blood flow heart rate and cardiac output, all subjects were asked to not to the brain. As a response, the baroreceptor reflex causes take any caffeine, tobacco or alcohol for at least 3 h prior to the peripheral veins to be squeezed and the carotid arteries the experiment. to be widened to aid the blood flow to the brain. Therefore The measurements were conducted 4 times for each sub- one may expect that depending on the measurement situa- ject, each time in a different body position. In the first posi- tions the PWV change measured with the Complior system tion, the subject sat on a chair with both hands resting on a will oppose the PWV measured with the Biopac system if table. In the second position, the subject lied on a bed with the baroreceptor reflex is invoked. both arms and hands resting along his/her body. In the third So while both systems are aimed at providing a similar position, the subject stood upright with both hands hang- measure of vascular condition and while the trajectories over ing down along his/her body. The fourth position was the which they measure PWV largely overlap, there are various same as the first position, to check if the PWV-value was reasons why it is unclear whether they will provide similar reproducible. measurement outcomes. To the best of our knowledge, there Before the start of each measurement in each position are no reports about the agreement between PWV values the subject was kept at rest for 60 s in the requested posi- measured using the Complior system or the Biopac system. tion. The PWV values were recorded with both of the tested Yet, in clinical practice it is crucial to know whether using 1 3 Journal of Clinical Monitoring and Computing systems simultaneously during the entire measurement, “Complior SP” software. The distance between the sensors, which lasted up to 60 s. measured in a straight line from the sternoclavicular joint to the styloid process of the radius, was used to approximate 2.3 Pulse wave velocity measurements the arterial distance travelled by the PWs. Using the “Com- and analyses plior SP” software, the foot of the PW measured at both locations was used to calculate the mean PWV once per 5 s. The PWV was measured between the carotid and radial The system used for measuring the PWV between the arteries using the Complior system (Alam Medical, Vin- carotid artery and the left index finger tip consisted of a cennes, France) and between the carotid artery and the left measuring device and analysis software. The measurement index finger tip using ECG and PPG (described below). The device contained one PPG-sensor (TSD200 with the Complior system measures the PWV using piezoelectric PPG100C amplifier, Biopac Systems, Inc, Goleta, USA), sensors. For measuring the PWs on the carotid artery, a clip positioned on the left index finger, and three external ECG- containing a piezoelectric sensor was placed on the left side leads (ECG100C amplifier, Biopac Systems, Inc, Goleta, of the neck. For measuring the PWs on the radial artery, a USA) (see Fig. 1). The three ECG-leads were placed on the clip containing a piezoelectric sensor was placed on the left subject’s both wrists and right ankle. The PPG- and ECG- wrist (see Fig. 1). Both sensor signals were recorded by the signals were simultaneously converted to digital signals using AcqKnowledge version 3.7.3 software (Biopac Sys- tems, Inc, Goleta, USA), at a sampling frequency of 2 kHz. The PPG-signal was filtered with a fourth-order low pass Butterworth filter with a cut-off frequency of 9 Hz using Matlab R2010a (The MathWorks, Inc., Matick, MA, USA). The PWV was determined by dividing the distance between the PPG-sensor on the left index finger and the sternoclav - icular joint (D) by the calculated time-difference between the time instance of the R-peak of the ECG t (n) ECG R−peak and the foot of the PW measured at the left index finger tip t (n) : PPG foot PWV (n)= , biopac (2) t (n)− t (n) PPG ECG foot R−peak where n is the sequence number of the heartbeats. The R-peaks in the ECG were found using the off-the-shelf Mat- lab function ‘R-peakdetect’ [14]. The maximum of the sec- ond derivative of each PW was taken as the foot of the PW (PPG ) and the corresponding time was indicated as foot t (n) [15]. The utilized PPG-sensor was quite sensi- PPG foot tive for motion and positioning artefacts, which sometimes distorted the shapes of the PWs in a way that they were rendered unsuitable for further analysis. Therefore, a cus- tom-made Matlab algorithm, called ‘7Step PW-Filter’, was implemented in the data analysis to filter out any PWs that strongly deviated in shape from a suitable PW [16] .If more than 50% of the PWs were filtered out for being too dis- torted, the data-set was excluded from further analysis. 2.4 Statistical analysis The mean PWVs +/− standard deviation (SD) over 60 s were calculated for each measurement technique for each body position. The Shapiro–Wilk test was used to check Fig. 1 Schematic view of placement of the both measurement sys- tems 1 3 Journal of Clinical Monitoring and Computing if the data was normally distributed. PWV values obtained Table 2 Mean and standard deviation of the PWV using the Complior and Biopac system were compared using Position PWV (m/s) PWV (m/s) Paired sampled t-test complior biopac a paired samples t-test and a Bland–Altman plot was used to Sitting 1 10.2 ± 1.4 3.0 ± 0.2 t(21) = − 24.442, analyse the agreement between the two different PWV meas - p < 0.001 urement techniques. Correlation between both sitting posi- Lying 9.3 ± 1.6 3.1 ± 0.2 t(19) = − 18.654, tions (Position 1 and Position 4) were analysed using a Pear- p < 0.001 son Correlation test. A significance level of p -value < 0.05 Standing 9.8 ± 2.2 3.2 ± 0.2 t(13) = − 16.178, was used. A repeated measurement ANOVA with Green- p < 0.001 houseGeisser correction and a post hoc test with Bonferroni Sitting 2 10.2 ± 1.1 3.0 ± 0.2 t(21) = − 31.704, correction was used to test for any effects of the repeated p < 0.001 measurements. All statistical analyses were performed using SPSS version 22.0 (SPSS, Inc., Chicago, IL, USA). Figure  3 and Table  3 present the Bland–Altman value and plot showing good agreement between the two PWV 3 Results measurement techniques. The Pearson correlation between sitting Positions 1 and Twenty-five subjects, (11 male, 14 female) were included in 4 proved to be high and significant for PWV (0.778, biopac p < 0.001). For PWV there was no significant correla- this study. The data of one male and one female subject were complior excluded from the analysis because there was too much noise tion (0.141, p = 0.541). The repeated measures ANOVA indicated that the in the signals to obtain any usable PWs. Table 1 presents the characteristic of the remaining study population. For posi- four body positions were rated equally [F(3,45) = 2.47, p = 0.074], for the Complior. For the Biopac, the four body tions 1, 2 and 4 (sitting 1, lying, sitting 2) the ‘7Step PW- Filter’ filtered out none of the PWs. For Position 3 (standing) positions were not rated equally [F(3,39) = 13,1, p = 0.000]. The post hoc tests of the Biopac-data revealed that Position there were 8 datasets with over 50% unsuitable PWs, which were therefore excluded from further analysis. In the remain- 2 (lying) and Position 3 (standing) resulted in significantly higher PWV compared to Position 1 (sitting 1) (p = 0.000, ing 15 datasets, the median percentage of unsuitable PWs that were filtered out was 2.2% (Q = 0% and Q = 36.6%). p = 0.025, respectively). There was no significantly differ - 1 3 ence between Position 2 (lying) and Position 3 (standing) The means and SDs for the PWV and PWV complior biopac for the four different positions are listed in Table  2, as well (p = 1.000). as the results of the paired samples t-test. Significant dif- ferences were found for each position between PWV complior and PWV . biopac Figure 2 shows a boxplot of PWV and PWV complior biopac for each position. The data consistently showed that PWV was much lower than PWV . biopac complior Table 1 Characteristics of the study population Variable Mean ± SD (n = 23) Gender (m/f) 10/13 Age (years) 25 ± 3 Weight (kg) 72 ± 9 Height (m) 1.77 ± 0.08 Body mass index (kg/m ) 23.03 ± 2.72 Blood pressure (mmHg)  Systolic 127 ± 11  Diastolic 80 ± 9 Heart rate (bpm) 77 ± 14 Smoker, yes (%) 2 [8, 33] Distance from sternoclavicular to wrist (cm) 69 ± 3 Fig. 2 Boxplot of the PWV and PWV , with the median as biopac complior Distance from wrist to fingertip (cm) 17 ± 1 red line and the minimum and maximum value 1 3 Journal of Clinical Monitoring and Computing Fig. 3 Bland–Altman plots of PWV and PWV by the four positions. The dotted lines represent the 95% limits of agreement and the complior biopac straight mean difference (bias) between PWV and PWV complior biopac between PWV and PWV may more likely be Table 3 Bland–Altman biopac complior explained by the difference in vessel compliance between Position BIAS ± CI (m/s) % of overall the two trajectories. More peripheral vessels are narrower, mean PWV thinner walled and more compliant. Because the more (%) peripherally measured PWV showed to be lower, it biopac Sitting 1 7.2 ± 2.7 37.6 is hypothesized that the reduced vessel stiffness and wall Lying 6.2 ± 2.9 47.0 thickness (both reducing PWV) outweigh the reduced vas- Standing 6.6 ± 4.3 64.4 cular radii (which would increase the PWV). However, Sitting 2 7.3 ± 2.1 29.0 the PWV -values agree with values reported in other complior studies. The mean PWV -values (10.2 ± 1.4 m/s) were complior in the same range as those reported by Rajzer et al. [17] (10.1 ± 1.7 m/s). Although Raizer et al. measured PWV over 4 Discussion the carotid-femoral trajectory, it is expected that PWVs over that trajectory will be similar to those in the carotid-radial This study compared PWV values measured over the trajectory, because of similar lengths and because the effects carotid-radial artery trajectory using the Complior system of differences in vessel radii and wall thicknesses are likely with PWV values measured between the R-peak of the ECG to cancel each other out, according to Eq. 1. Furthermore, and the arrival of the PW in the left index finger tip using the current results also agree with those of McEleavy, who the Biopac system in healthy volunteers in three body posi- measured a PWV of 9.01 ± 1.2 m/s in the carotid-radial tra- tions: sitting, lying and standing. The PWV values biopac jectory [18]. For the PWV no other studies reporting biopac were considerably lower than the PW V -values, and complior PWV between the heart and a fingertip were found, however this effect persisted in each position. This absolute differ - the time between the R-peak of the ECG and arrival of the ence might be explained for a minor part by the fact that foot of the PW at the fingertip (called pulse transit time) PWV includes the PEP, whereas PWV does not. biopac complior (283 ± 21 ms) was in the same range as reported previously However, the PEP could account for no more than 1 m/s by van Velzen et al. (273 ± 20 ms) [16] and by Kortekaas of the PWV . Therefore, the large absolute difference biopac et al. (271 ± 28 ms) [13]. 1 3 Journal of Clinical Monitoring and Computing Table 2 shows that the PWV was consistently and could benefit patients and clinical practice. Although the biopac significantly lower than PWV for all positions (1–4). ‘7Step PW-Filter’ algorithm used to eliminate distorted complior However, the Bland–Altman plots (Fig. 3) show that the bias PWs functioned well, the availability of a PPG-sensor is small and the values are scattered around the mean, lead- less sensitive to disturbances and not requiring measur- ing to the conclusion that there is a good agreement between ing sensor distances, would greatly simplify measuring the PWV and PWV values, but they simply differ PWs in awake and moving patients. Obviously, this is less complior biopac in magnitude. relevant when measuring PWs in patients under general The PWV was slightly, but significantly higher when lying anaesthesia. or standing as compared to sitting (with no significant dif- In conclusion, this study demonstrated that PWV values ference between lying and standing), when measured by the were consistently and significantly lower when measured Biopac system over the heart-fingertip trajectory. PWV may with the Biopac system than when measured with the Com- increase when vessels become stiffer and narrower due to plior system. Yet, despite the difference in absolute PWV contraction, but although this effect could be induced when values, the two systems did agree fairly well. This suggests standing up, it is less likely to happen when lying down. that as long as the difference in PWV magnitudes are taken There was no significant effect of the different positions for into account, either system could be used to measure PWV the PWV , which suggests that the PWV is less changes in time. However, when basing diagnosis on abso- complior complior suitable to detect such small PWV changes or it is less sensi- lute PWV values, one should be very much aware of how tive to changing positions. The Pearson correlation results the PWV was measured and with what system. In the future, show much better agreement between repetitions of the sit- clinical practice could greatly benefit if software for calcu- ting position at different moments for the Biopac system lating PWV is embedded in the commonly used anaesthesia than for the Complior system. This suggests that when doing monitors, enabling PWV measurements using a standard longitudinal PWV measurements, the Biopac system should ECG and a standard pulse oximeter. This might allow PWV be preferred, provided that the same position is consistently measurements to become a widely available diagnostic tool, used during successive measurements. and an easy-to-use, noninvasive, safe and quick method for When using the Biopac system, the measured PWV objectively assessing arterial stiffness as a reliable prognos - includes the PEP. The PEP is known to vary during posi- tic parameter for cardiovascular morbidity and mortality. tion changes. PEP variations caused by subject movement or Acknowledgements The authors would like to express their gratitude stress were avoided during the current study. Kortekaas et al. to all the volunteers who participated in this study. showed a variability of the PEP in healthy volunteers in rest of 58.5 ± 13.0 ms [13]. Over the distances travelled by the Open Access This article is distributed under the terms of the Crea- PWs in the current study, these PEP durations could account tive Commons Attribution 4.0 International License (http://creat iveco mmons.or g/licenses/b y/4.0/), which permits unrestricted use, distribu- for no more than 1 m/s of the PWV . Consequently, PEP biopac tion, and reproduction in any medium, provided you give appropriate variations are unlikely to explain any variations in this study. credit to the original author(s) and the source, provide a link to the Limitations of the two tested techniques include the Creative Commons license, and indicate if changes were made. challenge of accurately positioning the sensors, and the discrepancy between the measured distance between the sensors and the actual path length travelled by the PWs. When measuring the PWV more locally, such as between References the wrist and a position at the lower arm, the discrepancy 1. 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Journal of Clinical Monitoring and ComputingSpringer Journals

Published: Jun 6, 2018

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