KR101007789B1 - Method for measuring artery stiffeness by using arterial wall stiffness index - Google Patents

Abstract

The present invention relates to a method for measuring the arterial wall hardening index using the arterial wall hardening index (AWSI) represented by the equation (16), the arterial wall hardening index (AWSI) of the present invention is a conventional purity (CC), hardening index ( β ), etc. By eliminating bias factors such as basal blood pressure and arterial size that are less affected by conventional arterial wall hardening indicators, the arterial wall stiffness index (AWSI) is a better understanding of the stage of arterial wall hardening with age. Can be used as a measure of predicting diseases related to arteries.

AWSI, CC

Description

Method for measuring aortic sclerosis using arterial wall hardening index {METHOD FOR MEASURING ARTERY STIFFENESS BY USING ARTERIAL WALL STIFFNESS INDEX}

The present invention relates to a method for measuring the degree of arterial wall hardening using the arterial wall hardening index (AWSI) represented by the following equation (16) to remove the bias element in measuring the degree of arterial wall hardening according to age.

The role of the arteries is to act as a buffer to maintain blood pressure in addition to merely serving as a blood supply passage. In addition, the aorta has two main roles: first, the function of fluid delivery to deliver blood to arteries far from the heart, and second, the function of absorption to absorb the pulsatile energy of blood flow from the heart, In other words, it has a function of storing blood for a short time during the systole. The aorta must have sufficient elasticity to support the function of energy absorption. The walls of healthy arteries have more than 40% of elasticity (elastin), which maintains elasticity, and the elasticity decreases toward the peripheral artery. In most cases, with aging, the elasticity is lost, so that it does not function properly. This is called arteriosclerosis, and fat deposits on the artery walls become hard, and the arterial diameter narrows gradually, leading to disorders of the blood flow. It starts as early as 20s and gradually progresses with age. Initially, it deposits on the inner wall of the artery to form a small fat half, and the deposition of fat increases, and the smooth muscle cells that make up the artery wall proliferate, narrowing the inner diameter of the artery, and impairing the blood flow, causing blood supply to peripheral tissues. It will not be smooth. In the early stages of atherosclerosis, vascular friction increases due to degeneration of endothelial cells, and as time passes, the medial layer of the vascular wall hardens due to hardening and loses its elasticity. Cure calcification and the like appear. At this stage, hemodynamic and morphological abnormalities appear. Methods to quantitatively and qualitatively analyze these abnormalities have been developed. One method is to measure the degree of stiffness of the arterial wall that changes with age.

In a healthy young age where the elasticity of the aorta is well maintained, the flow of the aorta flows at a slow rate, but when the age increases or atherosclerosis progresses due to various diseases, the aortic blood flow decreases rapidly. It is most accurate to directly touch hardened arteries as the hardening of the atherosclerosis proceeds, or to measure the degree of hardening directly by other digitized and accurate measuring methods, but this is difficult in reality and is measured by various indirect methods.

Several indicators are functional, including classical compliance (CC), Young's modulus of elastivity (Y), and stiffness index ( β ). (tangential stress), intima-media thickness (IMT), and the like.

Conventional purity (CC) is a method of calculating the elasticity in consideration of the change in diameter and blood pressure by measuring the diameter in the systolic and diastolic arteries of the carotid or aorta. That is, it is expressed as the ratio of the diameter or volume change of the blood vessel with the change in the expanding pressure.

D _s with D _d is the diameter of the systolic and diastolic, respectively, P _s with P _d is systolic and diastolic pressures, respectively.

If the ratio of the change in diameter to the change in blood pressure is large, the blood vessels can be easily stretched, so that the function of pulsating blood flow shock wave absorption in the aortic cavity can be well accommodated, and if the ratio is small, the blood vessels cannot be easily stretched, and the function of energy absorption is reduced.

In the hardening index β , the elastic modulus (E) of Equation 2 is a measure of the elastic properties of an arbitrary material, and is defined as a proportional coefficient between stress and strain over an arbitrary space position and time in the material. .

Per unit area, and Jung's modulus (Y), such as the equation (3) below to calculate the modulus of elasticity, in this respect is represented by the equation (4) of the coin surface is to β.

Where h is the arterial wall thickness.

Where D ₀ represents arterial diameter at normal blood pressure.

In recent years, the hardening index β independently predicts cardiovascular disease and is measured and calculated using computerized oscillometry. Although the relationship between the heart and the large vasculature and the effect of arterial stiffness on atherosclerosis is not well understood, the hardening indicator β , measured by simple automated techniques, is a measure of arterial stiffness and a cardiovascular risk measure. Used.

Pulse wave velocity (PWV) is a method of measuring the velocity of blood flow through a certain section of an artery. The pulse wave velocity (PWV) is obtained by dividing the distance between two points of the artery in which the pulse wave is recorded by the time difference Δt at which the pulse wave is transferred.

The pulse wave velocity is a method of measuring blood flow velocity in a certain section and reflects the change of the entire artery in the section, but it does not reflect the local change, that is, the presence of atherosclerotic plaque.

The augmentation index (AI) is a pulse wave analysis method that calculates arterial elasticity by measuring the incidence wave and the reflected wave generated when the heart is ejected.

P _s is the systolic pressure, P _d is the diastolic pressure, and P _i is the pressure at the inception point at which the upstroke of the reflected wave begins.

If atherosclerosis progresses and the reflected wave returns quickly, the forward pulse wave and the reflected wave merge together without increasing the pressure of the forward pulse wave, and the AI increases. However, AI is also affected by the resistance of peripheral arteries, even if blood vessel contractions occur in peripheral arteries without atherosclerosis.

Large, elastic artery walls harden with age, hypertension, or other cardiovascular disease. At the same time, the elasticity decreases and the pulse pressure of the blood pressure increases. The mathematical method devised by Frank. O explains the pulse wave propagation and the mechanical properties of the arteries. It is assumed that the arterial system has elasticity and diastolic blood pressure decreases exponentially with time constant determined by the resistance and elasticity of the entire artery where such elasticity exists. In this way, the elasticity of the entire blood vessels of the human was measured from pressure wave contour analysis of the decrease in arterial pressure of the dilator.

Recently, as functional changes in arteries with age have been studied, the changes in blood vessel diameter and blood pressure were measured using the conventional purity (CC), the elastic modulus of fusion, and the hardening index ( β ) among the indicators for measuring the aortic stiffness. It is also measured at the same time. However, since the aorta is deep in the chest, there is no technique for accurately measuring the change in the diameter of the aorta. In addition, results from the assumption that the pressure-volume relationship of blood vessels is linear include biased factors such as basal blood pressure, arterial size, arterial wall components, and cardiac function that change during the measurement, thus accurately measuring the degree of hardening of the arterial wall. There was a difficulty.

Therefore, the present inventors have carefully analyzed the pressure-volume relationship of blood vessels in order to remove the bias elements and to find a more direct measurement method of arterial wall sclerosis in measuring the indexes of the arterial wall sclerosis. As a result, the arterial wall stiffness index (AWSI), a new index to measure the degree of hardening of arterial walls, has been developed.

In the present invention, when measuring the degree of stiffness of the arterial wall, the arterial wall stiffness index (AWSI) that can measure the arterial wall stiffness at the same time to remove the bias elements shown in the indicators for measuring the degree of stiffness of the arterial wall at the same time The purpose is to provide.

The present invention relates to a method for measuring the degree of aortic sclerosis using the arterial wall hardening index (AWSI) represented by the following equation (16).

Specifically, the present invention is as follows.

First, it is necessary to measure the pressure-volume of the aorta before deriving the arterial wall hardening index (AWSI) of the present invention.

In the present invention, it is possible to use the pig aorta as a test subject to experimentally determine the pressure-volume relationship of the aorta. Specifically, eight pig aorta having a length of about 15 to 20 cm are extracted, and then mounted in a self-made apparatus within 6 hours, and then pressure and volume are measured (FIG. 1). At this time, by inserting a rod into the aorta as shown in Figure 1-c to fix both ends of the experimental instrument to limit the change in the length of the aorta. A latex band is used to prevent leakage through the aortic branch, and a hose clamp is used to securely connect the aorta and the instrument.

After fixing both ends of the aorta, change the pressure and volume by adding 0.2% of 0.9% physiological saline in the range of 20cc ~ 32cc through an intravenous infusion set. Pressure measurement uses a digital measuring instrument (24C OMNICARE, HEWLETT-PACKARD, Germany) that can measure blood pressure from 0mmHg to 360mmHg. The volume change is measured by the amount of 0.9% physiological saline injected.

Using the OriginPro 8 program, the average value of the data obtained by experimenting eight pig aorta in the same way was adjusted using OriginPro 8 program. The relationship between pressure and volume is an S-shape (Fig. 2). As shown in Equation 7 below.

Where V is volume, P is pressure, and a and b are any constants related to V and P.

Through the experimentally obtained pressure and volume relationship, arterial wall hardening index (AWSI) according to pressure change is obtained.

In order to obtain AWSI, first, a and b, which are values that are individually related to the test subjects, are obtained using the definition of conventional purity (CC).

Equation 8 below is a formula of CC, and Equation 9 below is a pressure-volume relationship obtained through the porcine aortic experiment at the systolic and diastolic stages.

Where V _s is the volume at the systolic phase, V _d is the volume at the diastolic phase, and P _s is Pressure at the systolic phase, P _d is the pressure at the diastolic stage.

By dividing both sides of Equation 9 above, a ² can be obtained through Equations 10 and 11, and the unit is the same as the unit of pressure.

In addition, by using the above equation (9) to calculate the difference between the volumetric relationship between the contraction pressure and the expansion pressure when the equation can be obtained, as shown in equation (13) from equation (12), the unit is the unit of the volume same.

Next, after differentiating both sides of Equation 8 with respect to pressure P, and substituting average blood pressure to overcome the bias factor for diastolic blood pressure, the modified purity C as shown in Equation 14 is obtained. You can get it.

Here, mBP means mean blood pressure.

This modified purity is obtained by overcoming the bias for diastolic blood pressure during measurement, and is obtained from the fact that the relationship between pressure and volume is an S-shaped waveform.

In order to overcome the bias on the size of blood vessels, the modified purity is divided by the volume at the expansion pressure, and the natural log is taken to adjust the ratio to obtain the arterial wall stiffness (AWS) of Equation 15 below. Finally, the absolute value of the following equation (15) is calculated, and the cubic root is taken to obtain the arterial wall hardening index (AWSI) expressed by the following equation (16).

Here, a ² and b are equations 11 and 13 calculated above.

The arterial wall hardening index (AWSI) of the present invention, based on the experimental results of the S-shaped waveform rather than the simple linear relationship between the arterial pressure and the volume, is higher than that of conventional arterial wall hardening indexes such as conventional purity (CC) or hardening index ( β ). By eliminating bias factors such as being less affected by basal blood pressure and arterial size, the degree of arterial wall stiffness, especially age, can be well understood. Furthermore, arterial wall hardening index (AWSI) can be used as a measure of predicting disease associated with the majority of arteries.

The following describes examples of the present invention and is not intended to limit the present invention to the following examples.

Example  One. AWSI  Clinical application of and other atherosclerosis metrics

Electron-beam computed tomography (EBCT) data from a population of 100 subjects were studied for clinical application of the AWSI of the present invention and other indicators to measure aortic sclerosis. .

The subject group consisted of normal volunteers in a regular health screening program, with a gender ratio of 65:35 for males to females and an average age of 60.51 years (Figures 3 and 4). Age groups were defined as 1 group under 41 years old, 2 groups under 41 years old and under 56 years old, 3 groups under 71 years old and over 56 years old, and 4 groups over 71 years old.

The blood pressure distributions of the test subjects were as shown in FIGS. 5 to 7, and the average of systolic blood pressure, diastolic blood pressure, and pulse pressure was 134.22 mmHg and 82.1 mmHgm 52.12 mmHg, respectively.

The EBCT scanning parameters in clinical applications were 360 × 360 matrix number, 8 mm section thickness, 50 msec time resolution, and the area of the contraction and dilation of the descending aorta was measured by metal injection of 60 mL contrast agent at a rate of 3 mL / sec. The diameter was calculated (FIG. 8).

In the present invention, the EBCT image is obtained from a cine image for a specific time, the blood pressure was measured before and after taking the EBCT, the average value was used as an input variable.

Thus, diastolic blood pressure, systolic blood pressure, and diastolic diameter of 100 subjects were measured, and the data were examined by CC, β , and AWSI mentioned above to analyze correlations based on age and age group. In addition, in order to know the reproducibility of each test method, one measurer repeated 10 measurements of five data to calculate a coeffocoent of variance (CV) corresponding to an intra observer error.

Experiment result

Comparing the experimentally obtained AWSI and CC, and β at blood pressure between 50mmHg and 360mmHg, the CV according to blood pressure of CC was 64.99%, CV of β was 25.26%, and CV of AWSI was 9.00% (Table 1 and Figures 9-11).

Conventional purity (CC) Curing index ( β ) Arterial Wall Hardening Index (AWSI) % Coefficient of variation 64.99 25.26 9.00 Meter error (%) 10.07 11.70 0.99

First, we compared CC, β , and AWSI based on age. In the linear regression analysis (p <0.001) based on age, the test statistic values F_ratio and the coefficient of determination R ² of CC were 38.42 and 0.28, respectively, and F_ratio and R ² of β were 83.61 and 0.46, respectively (Figs. 12 to 14).

Looking at Table 1 and Figure 9, it can be seen that the variation according to the blood pressure of the CC is very severe. The CC method does not rule out changes in blood pressure, and even if the diastolic and systolic pressures are different, the same value is calculated for the same pulse pressure. AWSI is relatively unaffected by pressure changes and can measure the degree of stiffness of the arterial wall.

Next, prior to conducting one way analysis of variance for the age group, the normality test was performed, the results are shown in Table 2.

Age
Colmogorov-Smirnov (a) Shapiro-Week statistics df Sig. statistics df Sig.
CC

One 0.182 12 0.200 (*) 0.958 12 0.762 2 0.170 20 0.134 0.967 20 0.692 3 0.159 38 0.017 0.890 38 0.001 4 0.131 30 0.200 (*) 0.857 30 0.001
β

One 0.143 12 0.200 (*) 0.970 12 0.908 2 0.297 20 0.000 0.532 20 0.000 3 0.273 38 0.000 0.609 38 0.000 4 0.225 30 0.000 0.747 30 0.000


AWSI One 0.135 12 0.200 (*) 0.932 12 0.405 2 0.192 20 0.051 0.908 20 0.059 3 0.127 38 0.125 0.960 38 0.196 4 0.098 30 0.200 (*) 0.976 30 0.709

(* Is the lower bound of actual importance.)

In the results of the normality test of Table 2, CC did not satisfy the normality for group 3, β did not satisfy the normality for groups 2, 3, and 4. In contrast, AWSI satisfied normality in all age groups. Based on the results of the normality test, AWSI implemented only a parametric approach. As a result of the Kruskal-Wallis test of the nonparametric approach according to age group of CC and β , the p-value is 0.000, which is less than 0.05, which is statistically significant. There was. In addition, as a result of one-way ANOVA of the parametric approaches according to CC, β , and AWSI age groups, the p-values were 0.000, 0.001, and 0.000, respectively, and were statistically significant. There was a difference. The distribution of values for the age group of CC, β , AWSI was as shown in Figs.

AWSI explains the steps to harden the arterial wall with age. In addition, the distribution of AWSI according to the age group satisfies normality for all age groups, and when compared to CC or β, almost no error lines overlapped in each age group (FIGS. 15 to 17). This fact shows that AWSI is the best at distinguishing the degree of arterial wall hardening by age group.

When acquiring clinical data, to measure the reliability of data measurement by each indicator, a measurer measured the aortic cross-sectional area five times for 10 subjects each time and compared the errors in the observers of CC, β and AWSI. As a result, the lowest AWSI was 10.07%, 11.70%, and 0.99%, respectively.

1 is a photograph of an experimental apparatus for experimentally identifying the pressure-volume relationship of arteries.

2 is a graph of the average pressure-volume relationship of eight porcine aorta measured using a pressure measuring device.

3 and 4 are graphs of the distribution of age and age groups of 100 test subjects.

5 to 7 are graphs of distribution of systolic blood pressure, diastolic blood pressure, and pulse pressure of 100 test subjects.

Figure 8 is a photograph of the diameter measured by EBCT scanning at the systolic and diastolic in the descending aorta.

9 to 11 are graphs of distributions according to the blood pressures of CC, β, and AWSI obtained using experimentally obtained blood pressures and volumes as input values.

12 to 14 are graphs of linear regression analysis of CC, β, and AWSI according to the age of 100 subjects.

15 to 17 are histograms and error lines of CC, β, and AWSI according to the ages of 100 test subjects.

Claims (4)

Method for measuring the degree of aortic sclerosis using the arterial wall hardening index (AWSI) represented by the equation (15) and (16). [Equation 15]

[Where AWS is arterial wall stiffness, a and b are any constants related to arterial volume (V) and pressure (P), Vd is volume at dilator, and mBP is mean blood pressure .] [Equation 16]

The method according to claim 1, wherein Equation 7, which is the pressure and volume relationship of the arteries obtained experimentally, Equation 8 of the conventional purity (CC), and Equation 9, which is the experimentally obtained pressure-volume relationship of the arteries at the systolic and diastolic stages, are obtained. Step (1), dividing both sides of the equation (9), respectively, to obtain a ² through (10) and (11), the equation of the volume relationship at the contraction pressure and the expansion pressure using the equation (9) Step (3) of calculating equation (b) of equation (13) from equation (12), differentiating both sides of equation (8) with respect to pressure P, and then calculating the average blood pressure to overcome the bias factor for diastolic blood pressure. Substituting and arranging to obtain the modified purity (C) of Equation 14 (4), dividing the modified purity by the volume at expansion pressure, and taking the natural log to adjust the ratio to obtain Equation 15 (5 ), And (15) Calculating the absolute value, by taking the cube root method for measuring the aortic degree of curing using the arterial wall hardening index (AWSI), characterized in that which is obtained through the step (6) to obtain the arterial wall hardening index (AWSI), which is represented by the equation (16): [Equation 7]

Where V is volume, P is pressure, and a and b are any constants related to V and P. [Equation 8]

[Equation 9]

[Where V _s is the volume at the systolic phase, V _d is the volume at the diastolic phase, and P _s is Pressure at the systolic phase, and P _d is the pressure at the diastolic phase.] [Equation 10]

[Equation 11]

[Equation 12]

[Equation 13]

[Equation 14]

[Where mBP means mean blood pressure] The method of claim 2, wherein Equation 7 in step (1) is a relationship between pressure and volume experimentally obtained using a pig aorta. The method according to claim 3, wherein in calculating Equation 7 in step (1), eight pig aorta having a length of about 15 to 20 cm are extracted, and rods are inserted into the aorta to fix both ends of the experimental instrument, and a hose clamp. Tightly connect the aorta and the instrument by using, and add 0.2% of 0.9% physiological saline in the range of 20cc ~ 32cc through the intravenous infusion set. By measuring within 6 hours and adjusting the average value of the obtained data using the OriginPro8 program.

Images