Optimal time for brachial artery occlusion of periphral artiral volume to assess endothelial function
YuanqiaoLiu
MD
1YananZhao
MD
1RunkanZhu1
ZihanLi
MD
1TingtingLi
MD
1TingxunLiu1
PingYang
MD PhD
1DaoyuanSi
MD PhD
1,3✉Phone(+86)431-84995339Emailsidaoyuan@jlu.edu.cnYuQiu2
1Department of Cardiology, Jilin Provincial Engineering Laboratory for Endothelial Function and Genetic Diagnosis of Cardiovascular DiseaseUnion Hospital of Jilin UniversityChangchunJilinChina, Japan, China
2Department of Rehabilitation Medicine, Shandong Provincial Third HospitalShandong UniversityJinanShandongChina
3Department of Cardiology, Jilin Provincial Engineering Laboratory for Endothelial Function and Genetic Diagnosis of CardiovascularUnion Hospital of Jilin UniversityDisease Xiantai Street NO.126ChangchunJilinChina, Japan, China
Yuanqiao Liu1, MD, Yanan Zhao1, MD, Runkan Zhu1, Zihan Li1 MD,Tingting Li1 MD, Tingxun Liu1, Ping Yang1, MD PhD ,Daoyuan Si1*, MD PhD and Yu Qiu2*
1,Department of Cardiology, China-Japan Union Hospital of Jilin University, Jilin Provincial Engineering Laboratory for Endothelial Function and Genetic Diagnosis of Cardiovascular Disease, Changchun, Jilin, China
2,Department of Rehabilitation Medicine, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, China
Daoyuan Si* and Yu Qiu* are co-corresponding author.
Address for Correspondence:
Daoyuan Si, MD PhD
Department of Cardiology, China-Japan Union Hospital of Jilin University, Jilin Provincial Engineering Laboratory for Endothelial Function and Genetic Diagnosis of Cardiovascular Disease
Xiantai Street NO.126, Changchun, Jilin, China
Ph:(+ 86)431-84995339
Fax: (+ 86)431-84995091
Email:sidaoyuan@jlu.edu.cn
Abstract
Backgroud:
The aim of the study was to evaluate PAV technique in clinical work scenario, which was a novel fingertip non-invasive detection, defined the optimal brachial artery blocking time on the basis of selecting the best reactive hyperaemic index. With the extension of brachial artery blocking time, the degree of reactive hyperemia will increased gradually and tended to be stable. This study will evaluate the different brachial artery blocking time to assess the optimal reactive hyperaemic index(RHI), so as to define the optimal brachial artery blocking time of PAV technology.
Methods:
A
Four PAV tests were performed at the same day in 447 subjects who met the inclusion criteria. The brachial artery occlusion time was set at 1,3,5,7 minutes respectively, to define the optimal duration time of blood occlusion to obtain maximum reactive hypermia. The relationship between the ratio of reactive hyperaemic index at the each time period (that is the precentage of RHI measured at 7 minutes) and the measurement time was plotted to evaluate the general trend. RHI were recorded in each group and each time period, and bar charts were drawn according to the mean RHI and standard deviation to analyse whether there were differences of RHI in each group. The PAV measured value obtained in each group and each time period were used to draw dot plots, and the dispersion degree of PAV obtained in each group was analyzed.Results:
According to the PAV block time-reactive congestion curve chart, when the block time lasted for 3, 5 and 7 minutes, the curve graph showed an upward trend and tended to be stable. In total data, the average RHI results of 1-minute were significantly different from that of 3-minute, 5-minute and 7-minute(1.29 vs 1.44, p < 0.0001;1.29 vs 1.41, p < 0.0005; 1.29 vs 1.38, p < 0.0080). The PAV had the smallest degree of dispersion and similar coefficients of variation when the blocking time was 3 minutes(31%, 31%, 30%, 29%).
Conclusion:
At the time of maximum reactive congestion index, combined with the time tolerance of cuff compression acceptable to the subjects, 3-minute was recommended as the optimal time for brachial artery occlusion.
Keywords:
periphral artiral volume
endothelial function
methodology
A
Backgroud:
A
Endothelial cells are crucial for maintaining homeostasis. They not only regulate vascular permeability but also meet the stability of hemodynamics by adapting to the diameter of blood vessels. Among them, endothelial cells in arteries can adjust vascular tension by adapting to the increase in shear stress levels and through auxiliary vasodilators such as nitric oxide. Endothelial cells in veins play a crucial role in cell transport and inflammation. Endothelial cells in capillaries mediate the transfer of oxygen, nutrients and metabolic wastes between blood and surrounding tissues. When endothelial function is impaired, endothelium-dependent vasodilation dysfunction occurs due to reduced nitric oxide utilization capacity and increased vascular permeability. This pathophysiological mechanism is an important participant in the pathogenesis of cardiovascular diseases. Cardiovascular diseases (CVDs) are one of the most important causes of morbidity and mortality worldwide. Therefore, identifying patients with cardiovascular injury at the subclinical stage are critical in order to implement appropriate therapeutic interventions as early as possible and to optimally control modifiable cardiovascular risk factors.[1]Endothelial dysfunction was an important marker of the occurrence
and development of CVDs, especially in the process of atherosclerosis’ formation, most studies have shown that it can also be an independent predictor of cardiovascular disease. Therefore, detection of vascular endothelial function was very neccessery. For the moment, there were varieties of methods for detecting vascular endothelial function, in addition to the “gold” standard measurement, FMD[2], the newly developed technology was the fingertip non-invasive endothelial funtion detections, which mainly include peripheral arterial tonometry(PAT), periphral artiral volume(PAV).
A
Studies have reported the reproducibility of FMD, 5-minute was defined the best brachial artery occlusion time on the basis of the optimal reactive hyperaemic index. However, FMD, as the "gold" standard for detecting endothelial function, had inevitable subjective and objective errors in the measurement process, because it was operator-dependent in the measurement process, and the acquisition of final data will be affected by different operators, therefore, its repeatability may be affected. The researches on PAT were also reported that RHI varied with brachial artery occlusion time. The lower RHI was associated with the short occlusion time. Nevertheless, relevant studies showed that there was no difference in RHI between 5 minutes and 8 minutes as the maintenance time of the forearm occlusion, furthermore, longer cuff pressure times may cause intolerance in the subject. PAV technique could avoid the situation. As a novel fingertip technique, PAV could avoid subjective dependence and objective experimental errors caused by venous stasis which the basic principle of this technology were: A) Hemoglobin was light absorbent to infrared light; B) Only the hemoglobin in the arteries pulsated. The correlation between PAV and CAD, PAV and FMD had been confirmed by previous studies, and it had been proved that PAV could have good reproducibility. It could be seen that PAV technology has a promising clinical application prospect. The purpose of this study was to select the maximum reactive hyperaemic index at different blocking times, so as to define the optimal time of brachial artery blocking.Methods:
Study participants
A total of 447 subjects were included in the study who met the inclusion criteria. Patients with negative coronary angiography after admission, and no CAD risk factors such as hypertension, diabetes, hyperlipidemia, smoking were completely healthy people. The patients with PCI after coronary angiography were CAD people. Subjects who were younger than 45 years were defined as young people, those who were older or equal to 45 years were defined as middle age. Exclusion included people who were in acute coronary syndrome(ACS), cardiac insufficiency, persistent atrial fibrillation, severe vavular disease, Reno's disease or raynaud phenomenon, endocrine and kidney disease, and those participating in another clinical trial or the drug for which the treatment was administered may affect the final result of research.
A
This study in accordance with the Helsinki Declaration of 1975 as revised in 2013.A
The study was performed at the China-Japan Union Hospital of Jilin University Follow-up Center for Cardiology, using PAV to assess included subjects’ endothelial function, informed consent of patients was obtained before use of the device. Although the theory of PAV was similar to PAT, the difference was that PAV technique detected changes in hemoglobin flow before and after brachial artery blood flow obstruction through optical plethysmography probes placed on the tips of subjects' two index fingers, and thus reflects changes in peripheral artery volume. Before the test day, subjects were asked to refrain from eating for at least 6 hours, smoking, coffee or tea at least 12 hours. The subjects were asked to take the test next day if they had eaten, smoked, tea or coffee before the test day. Before starting the test, subjects should rest in a qiuet environment for at least 5 minutes, keeping temperature between 21℃~25℃. The interval of each measurement was recommended to exceed at least 2 hours, so as to avoid the hyperaemic effect left over from the previous measurement affecting the next test result. Meanwhile, the subjects were asked to avoid taking drugs that may affect the vascular activity, such as nitroglycerin. Four PAV tests were performed on the same day, with the cuff compression brachial artery occlusion times of 1, 3, 5, and 7 minutes, respectively, to establish the optimal duration of blood flow occlusion for maximum hyperaemia effect. All patient details had been de-identified and the reporting of this study conforms to STROBE guidelines[3].Periphral artiral volume
PAV testing was operated by one examiner, each subject was assessed by the same examiner four separate times on the same day. Prior to the test day, subjects were abstain from consuming food at least 6 hours, cigarettes, coffee, or tea for at least 12 hours and rest at least 5 minutes in a quiet, indoor enviroment with a temperature of 21℃ to 25℃, with a recommended interval of at least 2 hours between each measurement. The PAV device consisted of a photo-plethysmographically based index finger probe, a pressure cuff and a computer terminal to measure digital arterial volume changes in hemoglobin flow with pulse waves when the pressure was applied to the finger surface, which is primarily evaluated by a photosensor and light-emitting diode (940 nm). Before measuring, subjects were required to keep in a supine position with the cuff placed 2cm above the left elbow joint, and the opposite arm as control group, while PAV probes were fixed to the fingertips of both index fingers so that changes in hemoglobin flow could be observed through the computer terminal, PAV value could be obtained finally. PAV measurement process: A stable period of 5 minutes was taken as the baseline measurement, then the cuff was inflated to a pressure higher than systolic pressure 50mmHg, causing brachial artery blood occlusion on the pressurized side. The duration was set based on the brachial artery blood occlusion time set for the experiment, the cuff was quickly deflated when reaching the required blocking time to cause reactive hypereamia, PAV signals obtained from the two fingertips on the pressurized side and the non-pressurized side respectively were recorded by the computer terminal automaticall. After the cuff was deflated, 5 minutes was also taken as the stable period of brachial artery blood flow after the cuff is deflate, the terminal was recorded RHI automatically and the non-pressurized fingertip measurement was used as control value, finally PAV value was calculated by the instrument terminal. The RHI was defined as the ratio of the average pulse wave amplitude(PWA) over a 40-second period beginning 40 seconds after reactive hepereamia and the average baseline PWA over a 40-second period beginning 40 seconds after the baseline before occlusion, then was automatically normalized to the opposite arm, the results of PAV were calculated by computer algorithm at length.
Study design:
A
A
During the measurement, the PAV measuring probes were placed on the fingertips of the index finger of both hands of the subjects to continuously record the PAV signal. After a 7-minute stably period as the baseline measurement, the blood pressure cuff was inflated firstly to maintain brachial artery blood flow blocking for 7 minutes, and then the cuff was deflated, the changes of hemoglobin flow during this period were continuously recorded through the PAV computer terminal, and the 7-minute stability period of brachial artery blood flow after the cuff was deflated was taken as the baseline measurement. The PAV value with pressure time of 7 minutes was obtained by terminal calculation. After the interval of 2 hours, the subjects were tested again, the 7-minute stable period was also taken as the baseline measurement value, so that the blocking time of brachial artery blood flow was maintained for 5 minutes, and the PAV value with pressure time of 5 minutes was finally obtained through the terminal calculation. The time interval was still 2 hours. After recording the baseline measurement value of the stabilization period of 7 minutes, the brachial artery blood flow blockade time was set to last 3 minutes and the cuff was deflated. The brachial artery blood flow stabilization period after the cuff deflated was still set to 7 minutes, and the PAV value of the compression time was finally obtained by terminal calculation. The same method was applied to the subjects to detect the brachial artery blood flow blocking time for 1 minute, the PAV value of 1 minute compression time was finally obtained through terminal calculation. A
A
The study protocol adhered to the ethical principles outlined in the Declaration of Helsinki and was approved by the ethical review board of the China-Japan Union Hospital of Jilin University. The study was also registered with the Chinese Clinical Trial Registry (ChiCTR-DDD-17011214). A
All patients provided written informed consent. This study received project support(2020SCZ52).*Date of Registration was 2017-04-22, the clinical trial number was not applicable.
Statistical analysis:
Data were reported as mean value, standard deviation. Comparsion among the data was conducted with normality test firstly, statistical description was conducted with mean ± standard deviation for normal distribution. Independent sample t test was used for homogeneity of variances, and t' test was used for variance differences, p < 0.05 has significant difference. The median was used to describe the non-conforming distribution and the rank-sum test was used to analyze the non-conforming distribution. The difference between the measured values of the data conformed to the normal distribution, and the paired t-test was used for statistical analysis. All statistical analyses were performed in SPSS 26.
Results:
Subject characteristics
A total of 447 patients were inclued in this study (power value had calculated was ≥ 80%), 149 hospitalized patients who underwent PCI after coronary angiography were divided into middle-aged coronary heart disease group, 56.8% of whom were male, 298 ocompletely healthy patient, that is, the result of coronary angiography were negative, with no history of smoking, no risk factors for coronary heart disease such as hyperlipidemia, hypertension and diabetes. Subjects who were ≥ 45 years old divided into middle-aged healthy group, <45 years old were divided into young healthy group, with 149 cases in each group. Table.1 showed the charactoristics of study groups, including age, sex, systolic blood pressure, diostolic blood pressure. Among them, 56.8% were males and the mean age was 52.7 years old. The mean ± standard deviation values of the systolic and diastolic blood pressure were 132.9 ± 12.2 mmHg and 86.3 ± 10.9 mmHg respectively.
Table.1 Charactoristics of study groups
n | Age(years) | Sex(male) | Systolic blood pressure (mmHg) | Diostolic blood pressure(mmHg) | |
|---|---|---|---|---|---|
Young healthy group | 149 | 37.2 ± 4.2 | 80(53.7%) | 129.4 ± 10.6 | 83.4 ± 8.8 |
Middle-aged healthy group | 149 | 57.7 ± 8.9 | 88(59.0%) | 134.1 ± 11.8 | 89.4 ± 9.1 |
Middle-aged CAD group | 149 | 63.1 ± 10.2 | 86(57.7%) | 135.4 ± 13.4 | 86.0 ± 13.6 |
Total | 447 | 52.7 ± 13.8 | 254(56.8%) | 132.9 ± 12.2 | 86.3 ± 10.9 |
Values were expressed as mean ± standard deviation or percentage.
Comparison of PAV and average RHI in different blocking time groups
PAV blocking time-reactive hyperamic index line plot was drawn acccording to PAV blocking time and reactive hyperamic index. The percentage of RHI and that at 7 minutes was 92.7% when the blocking time was 1 minute, which was significantly lower than that at 3,5,7 minutes(percentages were 100%, 100% and 100% respectively, as shown in Figure.1), the trend was stabe when the blocking time was 3 minute to 5 minute.
In the overall data, the average RHI was 1.29 when the blocking time was 1 minute, which is significantly lower than that when the blocking time was 3, 5 and 7 minutes, the average RHI were 1.44(p < 0.0001), 1.41 (p = 0.0005), 1.38 (p = 0.008), as shown in Fig. 2A, it could be seen that the average RHI when the blocking time was 1-minute was significantly different from the average RHI when the blocking time was 3-minute, 5-minute, 7-minute. There was a significant difference in the average RHI results between the 3-minute and 7-minute blocking times (p = 0.047). However, no significant differences were observed between the 3-minute vs 5-minute or 5-minute vs 7-minute blocking times(p = 0.263, p = 0.390). Meanwhile, the coefficient of variation of PAV values for different groups of blocking times were calculated. In total data, when the blocking time was 1, 3, 5, and 7 minutes, the coefficients of variation were 31%, 31%, 30%, and 29% respectively, there was no statistically significant difference in the coefficient of dispersion.
In the young healthy group, the mean RHI was 1.44 when the
blocking time was 1-minute, RHIs were 1.67, 1.58, and 1.54 when the blocking time was 3, 5, and 7-minute, respectively, as shown in Fig. 2. When the blocking time was 1 minute, the RHI showed statistically significant differences compared with those at 3 minutes, 5 minutes, and 7 minutes respectively(p < 0.0001, p = 0.0083, p = 0.04). However, there were no significant differences in RHI results between 3-minute vs 5-minute and 3-minute vs 7-minute blocking times. In this group, when the blocking time was 1, 3, 5, and 7 minutes, the coefficients of variation were 39%, 31%, 35%, and 37% respectively, there was no statistically significant difference in the coefficient of dispersion either.
In the middle-aged healthy group, the average RHI was 1.43 when
the blocking time was 1 minute. With blocking times was 3, 5, and
7minutes, the average RHI values were 1.55, 1.55, and 1.50 respectively,
as shown in Fig. 2C. The RHI results at 1 minute showed significant
differences compared to those at 3, 5, 7 minutes(p = 0.038, p = 0.048, p
= 0.25). However, no significant differences were obseverdbetween the
average RHI results of 3-minute vs 5-minute and 3-minute vs 7-minute
blocking times. In this group, the coefficients of variation were 39%,
31%, 35%, and 37% when the blocking times were 1, 3, 5, and 7
minutes respectively. It can be seen that there was no significant
difference among the results.
In the middle-aged CAD group, the average RHI was 0.99 when the blocking time was 1 minute, compared to at 3, 5, and 7 minutes were 1.12, 1.00, and 1.09, respectively (Fig. 2). Significant differences were found between the 1-minute and the 3-minute (p = 0.014), 1-minute and 5-minute (p = 0.043), 1-minute and 7-minute (p = 0.040) blocking times. The average RHI results of the blocking time for 3-minute vs 5-minute and 7-minute, there were no significant differences between them(p = 0.98, p = 0.38). The average RHI results of 5-minute blocking time vs 7 min blocking time were significant difference either(p = 0.40). In this group, the coefficients of variation were 43%, 41%, 38%, and 39% when the blocking times were 1, 3, 5, and 7 minutes respectively, and there was no significant difference among them.
A
The degree of dispersion of PAV in different groups is shown in the Fig. 3. In the young healthy group, the PAV distribution was concentrated when the blocking time were 1-minute, 3-minute and 5-minute. In the middle-aged healthy group, PAV distribution was also concentrated at 1-minute and 3-minute and 5-minute. In the group of middle-aged coronary heart disease, the degree of dispersion was more concentrated at 3-minute. In total data, the dispersion of PAV were similar.
PAV blocking time - reactive hyperemia line chart
Fig. 1
X was brachial artery occlusion time, which is 1, 3, 5, 7 minutes respectively. Y was the percentage of RHI and RHI measured at 7 minutes at each time period.
Comparison of the average RHI of three groups in different blocking time periods
Fig. 2
A was the difference of mean RHI at different occlusion time when the sample size was total data. B was the difference of mean RHI at different occlusion time in young healthy group. C was the difference of mean RHI at different occlusion time in middle-aged healthy group. D was the difference of mean RHI at different occlusion time in middle-aged CAD group.
Dispersion of PAV in different time periods
Figure 3.(1) was the dispersion of PAV in young healthy group. (2) was the dispersion of PAV in middled-aged healthy group. (3) was the dispersion of PAV in middle-aged CAD group.(4) was the dispersion of PAV in total group.A was the deviation of PAV measured when the blocking time was 1-minute and 7-minute; B was the deviation of PAV measured when the blocking time is 3-minute and 7-minute; C was the deviation of PAV measured when the blocking time is 5-minute and 7-minute.
Discussion:
As an early sign and intiation of atherosclerosis, ED was closely related to cardiovascular diseases, especially CAD. The onset of atherosclerosis began in childhood, in children at high risk of atherosclerosis, asympotamic young and middle-aged, invasive endothelial function detection, such as coronary angiography, was obviously not suitable for large-scale population. Therefore, non-invasive detections have been gradually developed, and its gold standard, FMD technology has been widely used in clinical applications and lots of studies. However, FMD technology still has measurement errors, which may lead to bias in the final result, fingertip non-invasive detection technology came into being. Such technology avoid subjective measurement errors, such as PAT, which may not avoid objective errors caused by venous stasis when measuring, and PAV technology avoids such errors, making the measurement results more accurate.
In previous studies, the optimal blocking time of FMD technique and PAT technique has been confirmed, and it has been found that the blocking time of 5 minutes was a common method for assessing adult endothelial function by FMD technology. As a novel technique for fingertip non-invasive endothelial function detection, its relationship with coronary heart disease has been confirmed by previous studies, and its repeatability studies have also been effectively verified. However, the definition of the optimal blocking time of PAV technology remains to be studied. The purpose of this study was to establish the optimal blocking time of blood flow occlusion to obtain the maximum congestion reaction. By applying PAV detection technology, the study evaluated vascular endothelial function in healthy people and patients with coronary heart disease, and found that the optimal RHI value could be obtained within the time range of 3 minutes to 5 minutes after blood flow occlusion. If it was assumed that the maximum reactive hyperemia occured at any time point or in any time window, resulting in an error in the final value, it was considered that such results may exist in independent measurements or in the detection of endothelial function by catheter, and was not a common phenomenon. During the measurement, it was found that although there was no significant difference in RHI between 3 minutes and 5 minutes of block time in the overall sample data, it was found that the duration of cuff compression was 3 minutes, which was more acceptable to subjects and may be more applicable to large-scale clinical applications.
Studies have shown that blood flow occlusion duration of 5 minutes was a common blocking time used by FMD to evaluate vascular endothelial function, and its blocking time was relatively long, which will inevitably cause some measurement errors in the detection process. In the absence of continuous diameter measurement, the true peak diameter may have fallen between these discrete measurement intervals. This may miss all true peak diameters. Studies have shown that blood flow occlusion duration of 5 minutes was a common blocking time used by FMD to evaluate vascular endothelial function, and its blocking time was relatively long, which will inevitably cause some measurement errors in the detection process. Moreover, relevant research on another non-invasive fingertip detection technology, PAT, can confirm that RHI gradually stabilizes when the blocking time is 3 minutes, and there is no significant statistical difference in RHI when the blocking time is 5 minutes and 8 minutes. [4–9] In the absence of continuous diameter measurement, the true peak diameter may have fallen between these discrete measurement intervals. This may miss all true peak diameters. The PAV research team led by Ping Yang found that the RHI value of patients with coronary heart disease was weakened by PAV measurement, which indicated that PAV technology could be used as a non-invasive fingertip test to assess vascular endothelial function[10–11]. This study was part of the further evaluation of this method. The study showed that the RHI measured by PAV could change with the different time of brachial artery blood flow blockade, and did not find that RHI gradually decreased with the increase of the time of blockage. The percentage of RHI at 1 minute was 92.7% as compared to RHI results at 7 minutes, indicating that the RHI results were unstable, but the results of RHI when the blocking time at 3 minutes and 5 minutes were similar to 7 minutes in the overall sample collected in this study. It is indicated that when the blocking time is 3 minutes, the RHI has become relatively stable and can be used as the optimal time for brachial artery blocking when measuring PAV. This indicated that RHI had a marginal effect, that was, after reaching a certain time peak, due to the influence of brachial artery diameter, the final value would no longer increase. At the same time, the average RHI value of each group when the blocking time was 1 minute, 3 minutes, 5 minutes and 7 minutes were analyzed. From the overall data, it was found that the average RHI value when the blocking time was 1 minute was significantly different from that when the blocking time were 3 minutes, 5 minutes and 7 minutes. It was also found that the RHI values at 1 minute were significantly different from those at 3, 5, and 7 minutes, regardless of whether they were in the young healthy group, the middle-aged healthy group, or the middle-aged CAD group. This indicated that when the blocking time was 1 minute, the RHI results were unstable and insufficient to serve as the optimal blocking time for PAV measurement. Moreover, by drawing the PAV scatter plot, it was found that in the young healthy group, the PAV dispersion was relatively small when the blocking time was 3 minutes. The same result was also found in the middle-aged healthy group and the middle-aged CAD group. It was observed in the overall data that when the blocking time was 3 minutes, the PAV dispersion was relatively small, indicating that the measurement results were more stable at a blocking time of 3 minutes. Compared with a longer brachial artery blocking time, 3 minutes was more recommended as the optimal brachial artery blocking time. Moreover, the information was collected about the time tolerance of the subjects to cuff compression during the measurement process. It was found that most subjects had good tolerance when the occlusion time was 3 minutes. Therefore, 3 minutes could be recommended as the optimal blocking time when using PAV to evaluate vascular endothelial function. This observation is similar to a study using the FMD technique and PAT technique[12–13].
This study detected the changes in hemoglobin by non-invasively detecting endothelial function through the fingertip using a new technology and measuring the changes in pulse flow during congestion with a finger probe similar to a blood oxygen meter. Although the reactive congestion index gradually stabilized with the extension of brachial artery occlusion time, this study still cannot completely rule out the possibility that the longer brachial artery occlusion time may have affected the PAV value that ultimately reflects endothelial function. However, for longer occlusion times, such as 5 minutes or 7 minutes, some patients experienced intolerance during the measurement process. The subjects tolerated it well at 3 minutes. On the other hand, in PAV- blocking time reactive hyperemia line chart, it can be seen from the blocking time-reactive hyperemia line chart that, however, in the actual statistics of the young healthy group, middle-aged healthy group, and middle-aged CAD group, except for the lower PAV caused by CAD or increased age, no decrease in PAV was found with the increase of blocking time, which might also be an advantage of PAV. Combining the previously reported relationship between PAV and CAD, there is reason to believe that PAV can serve as a new technique for measuring endothelial function through fingertips to screen for coronary heart disease risk.
Limitation and Prospect:
Obesity was also a risk factor for cardiovascular disease. In this study, the differences in the healthy group and middle-aged group, healthy and CAD group may be related to the relatively higher arm circumference. Although the coefficient of variation of PAV results was similar among the three groups of patients when the blocking time was 1 minute, it could still be seen that there was a statistically significant difference between the SD value of the brachial artery blocking time at 1 minute and the average RHI value at 3 minutes, 5 minutes, and 7 minutes, and the results were relatively unstable. Therefore, for some people with excessive BMI, the cuff length can be appropriately increased or the RHI can be measured multiple times when the blocking time was 3 minutes. Among the three sets of data, it was found that many PAV values were relatively discrete. The possible reasons for this difference are believed to be related to the following two situations: 1) The clinical sample size can be expanded on this basis, and the optimal time of brachial artery occlusion can be continuously corrected on the basis of reaching the maximum reactive congestion index; 2) Slight movements of the elbows and arms of the person being measured may lead to final measurement errors. The inevitable errors caused by the slight movements of the person being measured during the measurement process can be gradually corrected through multiple measurements. In this study, differences in lipid or blood sugar control among young people, the elderly and healthy subjects cannot be ruled out. However, among all the healthy subjects in this study, no one was diagnosed with any risk factors or cardiovascular diseases, nor was anyone taking any type of medication. These findings suggest that the average RHI values obtained vary, which may be related to age. This might be because the elasticity of the aorta gradually decreases with age.
According to the relevant research on PAV and this study, the final indicators obtained by PAV measurement technology are close to the gold standard FMD for non-invasive endothelial function detection technology. This indicates that PAV can be used as a more convenient non-invasive technique for endothelial function detection at the fingertip. To conduct early screening for coronary heart disease in healthy individuals, assess endothelial function in people with coronary heart disease, those at high risk of coronary heart disease, and those undergoing recovery treatment after PCI, thereby providing a new direction for clinical treatment.
Conclusion:
Our research indicates that when achieving the maximum RHI, the optimal time for brachial artery occlusion is recommended to be 3 minutes, which is also the most suitable cuff compression time for the majority of subjects. This suggests that PAV may become a new type of non-invasive endothelial function detection technology, that is, it can be applied in clinical practice to screen the endothelial function of patients with early endothelial insufficiency, patients with coronary heart disease, and those with coronary heart disease risk factors, providing a new non-invasive diagnosis and treatment method for targeted treatment of endothelial insufficiency in clinical practice.
Abbreviations:
PAV
periphral artiral volume
RHI
reactive hyperaemic index
CVDS
cardiovascular diseases
PAT
peripheral arterial tonometry
CAD
coronary artery disease
ACS
acute coronary syndrome
PCI
percutaneous coronary intervention
FMD
Flow-mediated dilation
BMI
Body mass index
Declarations
Ethics approval and consent to participate
A
This study was approved by the ethical review board of China-Japan UnionHospital of Jilin University (2018092805). All individuals signed the
written informed consents to the use of their clinical data for the
purpose of research in the study.
A
Data Availability
The datasets used and/or analyzed during the current study are availablefrom the corresponding author on reasonable request.
A
Author Contribution
Yuanqiao Liu has drawn the manuscript and conducted the data analysis. Daoyuan Si and Yu Qiu have guided this article together. Ping Yang has been responsible for reviewing this article. Yanan Zhao, Zihan Li, Tingting Li, Tingxun Liu and Runkan Zhu participated in data collection.
Competing interests:
Author Ping Yang has been a consultant for Saintyear Medical Ltd.,
which owns patent rights to PAV technique. Other authors have nothing to
disclose.
A
Funding:
This work was supported by grants from the Jilin Province Health Research Talent Special Project. (No. 2020SCZ52)
Acknowledgements:
Thank you to all the authors and hospitals for their participation and support. At the same time, thank you to the patients for their active cooperation and contribution to the medical industry.
Reference:
1.
Jvon Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med. 2007;147:573–7.
2.
Jakubiak GK. Cardiac Troponin Serum Concentration Measurement Is Useful Not Only in the Diagnosis of Acute Cardiovascular Events[J]. J Pers Med. 2024;3(14):230.
3.
Elm EV, Altman DG. et.al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies.[J]. Int J Surg 2014, Dec;12(12):1495–9.
4.
Dobbiea LJ, Mackina ST, Hogartha K, et al. Validation of semi- automated flow-mediated dilation measurement in healthy volunteers[J]. Blood Press Monit. 2020;25:216–23.
5.
Wisloff U, Stoylen A, Loennechen JP, et al. Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study[J]. Circulation. 2007;115:3086–94.
6.
Heiss C, Keymel S, Niesler U, et al. Impaired progenitor cell activity in age-related endothelial dysfunction[J]. J Am Coll Cardiol. 2005;45:1441–8.
7.
Koh KK, Quon MJ, Lee Y, et al. Additive beneficial cardiovascular and metabolic effects of combination therapy with ramipril and candesartan in hypertensive patients[J]. Eur Heart J. 2007;28:1440–7.
8.
Kathiresan S, Gona P, Larson MG, et al. Crosssectional relations of multiple biomarkers from distinct biological pathways to brachial artery endothelial function[J]. Circulation. 2006;113:938–45.
9.
Koh KK, Shin MS, Sakuma I, et al. Effects of conventional or lower doses of hormone replacement therapy in postmenopausal women[J]. Arterioscler Thromb Vasc Biol. 2004;24:1516–21.
10.
Si D, Ni L, Wang Y, et al. A new method for the assessment of endothelial function with peripheral arterial volume[J]. BMC Cardiovasc Disord. 2018;18(1):81.
11.
Du B, Si D, Zhao D, et al. A new peripheral endothelial function measurement improves prediction of symptomatic coronary artery disease[J]. J Int Med Res. 2020;48(6):300060520932818.
12.
Faizi AK, Kornmo DW, Agewall S. Evaluation of endothelial function using finger plethysmography[J]. Clin Physiol Funct Imaging. 2009;29(5):372–5.
13.
Black MA, Cable NT, Thijssen DH, et al. Importance of Measuring the Time Course of Flow-Mediated Dilatation in Humans[J]. Hypertension. 2008;51(2):203–10.