Device, method and program for calculating blood pressure index or blood flow index

Abstract

To provide a device for calculating a blood pressure index of a subject to be examined, which can evaluate the cardiovascular system simply and with high accuracy.SOLUTION: A device for calculating a blood pressure index of a subject to be examined comprises: a residual pressure waveform generation unit 42 configured to fit a diastolic portion of a blood pressure waveform with respect to the time variation of a peripheral artery of the subject to be examined to an exponential decay curve, thereby generating a residual pressure waveform having a first negative peak and a subsequent positive peak; and a diastolic blood pressure variation index calculation unit 43 configured to calculate a diastolic blood pressure variation index using a pressure at the negative and positive peaks of the residual pressure waveform and the pulse pressure of the peripheral artery.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a device, method, and program for calculating a blood pressure index or a blood flow index. [Background technology]

[0002] In healthy individuals, the central aorta is the softest part of the artery, while the more peripheral it is, the stiffer it becomes. This causes a phenomenon called pulse pressure amplification, in which peripheral pulse pressure is greater than central aortic pulse pressure. Measurement of pulse pressure amplification has been widely used to evaluate a subject's cardiovascular system, particularly the degree of arterial stiffness (Non-Patent Document 1).

[0003] However, measuring pulse pressure amplification requires measuring two points, aortic blood pressure and peripheral blood pressure, which makes the measurement complicated. Moreover, since aortic blood pressure is located deep in the trunk, it is difficult to measure directly, and in most cases, blood pressure waveforms at the arm and wrist are measured and estimated using a transfer function (Non-Patent Document 2). It would be desirable to have blood pressure and / or blood flow indices that can be easily evaluated. It would also be even more desirable if pulse pressure amplification and aortic blood pressure could be measured more easily. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Avolio AP et al., Hypertension 2009; 54: 375-383 [Non-patent document 2] Williams B et al. Circulation 2006; 113: 1213-1225 Summary of the Invention [Problem to be solved by the invention]

[0005] The problem to be solved by the present invention is to provide a device, method, and program for calculating a blood pressure index and / or a blood flow index that can more easily and accurately evaluate the cardiovascular system. [Means for solving the problem]

[0006] As a result of extensive research into solving the above problems, the inventors of the present invention have unexpectedly found that they focused on the diastolic waveform of peripheral arteries, and calculated the diastolic blood pressure variability index (PFI) using the first negative peak and the next positive peak of a curve obtained by fitting a blood pressure waveform to an exponential decay curve. d ) and found that this blood pressure index is an index that can be used to evaluate the cardiovascular system easily and accurately, leading to the completion of the present invention. Furthermore, surprisingly, the diastolic blood flow variability index (FFI) was calculated using the negative peak in the blood flow waveform and the subsequent positive peak in the diastolic phase. d ) is calculated It has been found that even in such cases, such a blood flow index is an index that can easily and accurately evaluate the cardiovascular system.

[0007] The present invention encompasses the embodiments described below.

[0008] Item 1. A device for calculating blood pressure indicators of a subject, a residual pressure waveform generator that fits the diastolic portion of the blood pressure waveform of the peripheral artery under test with an exponential decay curve to generate a residual pressure waveform having an initial negative peak and a subsequent positive peak; The pressure at the negative peak of the residual pressure waveform is P R1 , the pressure at the positive peak P R2 , peripheral arterial pulse pressure PP Peri In this case, the diastolic blood pressure change expressed by the following equation (1) Dynamic index (PFI) d ) a diastolic blood pressure variability index calculation unit;

[0009]

number

[0010] A blood pressure index calculation device comprising:

[0011] Item 2. The blood pressure index calculation device according to Item 1, further comprising a pulse pressure amplification estimation unit that estimates pulse pressure amplification based on the diastolic blood pressure variability index.

[0012] Item 3. The blood pressure index calculation device according to Item 1, further comprising a central aortic blood pressure estimation unit that estimates central aortic blood pressure based on the diastolic blood pressure variability index.

[0013] Item 4. A blood pressure index calculation device according to Item 1, further comprising a vascular stiffness evaluation unit that evaluates the stiffness of the blood vessels of the test subject based on the diastolic blood pressure variability index.

[0014] Item 5. A device for calculating a blood flow index of a test subject, The blood flow velocity at the maximum positive peak of the systolic blood flow velocity waveform with respect to time change of the peripheral artery of the test subject is V FW , the blood flow velocity at the negative peak is V BW , and the blood flow velocity at the next positive peak in the diastolic phase is V FW2 In this case, the diastolic blood flow variability index (FFI) is calculated as follows: d ) diastolic blood flow variability index calculation section

[0015]

number

[0016] A blood flow index calculation device comprising:

[0017] Item 6. The blood flow index calculation device according to Item 5, further comprising a pulse pressure amplification estimation unit that estimates pulse pressure amplification based on the diastolic blood flow variability index.

[0018] Item 7. The blood flow index calculation device according to Item 5, further comprising a central aortic blood pressure estimation unit that estimates central aortic blood pressure based on the diastolic blood flow variability index.

[0019] Item 8. The blood flow index calculation device according to Item 5, further comprising a vascular stiffness evaluation unit that evaluates the stiffness of the blood vessels of the test subject based on the diastolic blood flow variability index.

[0020] Item 9. A method for calculating a blood pressure index of a test subject, comprising: a residual pressure waveform generating step of fitting a diastolic portion of the blood pressure waveform of the peripheral artery under test with an exponential decay curve to generate a residual pressure waveform having an initial negative peak and a subsequent positive peak; The pressure at the negative peak of the residual pressure waveform is P R1 , where P is the pressure at the positive peak R2 , peripheral arterial pulse pressure PP Peri In this case, the diastolic blood pressure variability index (PFI) is calculated as follows: d ) a diastolic blood pressure variability index calculation step;

[0021]

number

[0022] A blood pressure index calculation method including:

[0023] Item 10. A blood pressure index calculation method according to Item 9, further comprising a pulse pressure amplification estimation step of estimating pulse pressure amplification based on the diastolic blood pressure variability index.

[0024] Item 11. A blood pressure index calculation method according to Item 9, further comprising a central aortic blood pressure estimation step of estimating central aortic blood pressure based on the diastolic blood pressure variability index.

[0025] Item 12. A method for calculating a blood flow index in the diastolic phase of a test subject, comprising: The blood flow velocity at the maximum positive peak of the systolic blood flow velocity waveform with respect to time change of the peripheral artery of the test subject is V FW , the blood flow velocity at the negative peak is V BW , and the blood flow velocity at the next positive peak in the diastolic phase is VFW2 In this case, the blood flow velocity change expressed by the following equation (3) Dynamic index (FFI d ) a blood flow velocity variability index calculation step;

[0026]

number

[0027] A blood flow calculation method comprising:

[0028] Item 13. A blood flow index calculation method according to Item 12, further comprising a pulse pressure amplification estimation step of estimating pulse pressure amplification based on the diastolic blood flow variability index.

[0029] Item 14. The blood flow index calculation method according to Item 12, further comprising a central aortic blood pressure estimation unit that estimates central aortic blood pressure based on the diastolic blood flow variability index.

[0030] Item 15. A program for causing a computer to execute a process for calculating a blood pressure index of a test subject, Computer, a residual pressure waveform generator that fits a diastolic portion of the blood pressure waveform of the peripheral artery under test with an exponential decay curve to generate a residual pressure waveform having an initial negative peak and a subsequent positive peak; The pressure at the negative peak of the residual pressure waveform is P R1 , where P is the pressure at the positive peak R2 , peripheral arterial pulse pressure PP Peri In this case, the diastolic blood pressure variability index (PFI) is calculated as follows: d ) diastolic blood pressure variability index calculation section

[0031]

number

[0032] A blood pressure index calculation program that functions as a

[0033] Item 16. A program for causing a computer to execute a process for calculating a blood flow index of a test subject, Computer, The blood flow velocity at the maximum positive peak of the systolic blood flow velocity waveform with respect to time change of the peripheral artery of the test subject is V FW , the blood flow velocity at the negative peak is V BW Then the next diastolic positive The peak blood flow velocity is V FW2 In this case, the blood flow velocity variability index (FFI) is calculated as follows: d ) Blood flow velocity variation index calculation section

[0034]

number

[0035] A blood flow index calculation program that functions as a

[0036] Item 17. A computer-readable recording medium on which the program according to item 15 or 16 is recorded. [Effects of the Invention]

[0037] According to the present invention, the cardiovascular system of a subject can be evaluated simply and accurately. [Brief explanation of the drawings]

[0038] [Figure 1] 1 is a schematic diagram of the configuration of a blood pressure index calculation system. [Figure 2] 4 is a flowchart showing the operation of a processing unit of the blood pressure index calculation device. [Figure 3] 1 is a schematic diagram of the configuration of a blood flow index calculation system. [Figure 4] 10 is a flowchart showing the operation of a processing unit of the blood flow index calculation device. [Figure 5](a) Graph of femoral artery blood pressure pulse waveform, (b) graph of diastolic residual pressure, (c) graph of blood flow velocity. Symbols in parentheses represent coordinates (x, y). T is time, P is pressure, V is velocity, FW is peak systolic forward flow, BW is peak retrograde (backward) flow, and FW2 is peak diastolic forward flow. [Figure 6] Relationship between diastolic blood flow variability and pressure variability in the femoral artery (n = 592). (a) Bland-Altman histograms for the time from systolic onset to peak backward (reverse) velocity (TBW) and end-systole (TES) estimated from the pressure inflection point. The x-axis shows the mean ([TES + TBW] / 2), the y-axis shows the difference (TES - TBW), and the z-axis shows the number of observations. The mean and 2SD difference are -0.002 and 0.046 s, respectively. (b) Graph showing the correlation between diastolic blood flow variability index and diastolic pressure variability index. (c) Bland-Altman histograms for the time from systolic onset to peak forward diastolic velocity (TFW2) and the second (positive) residual pressure peak (TR2). The x-axis shows the mean ([TR2 + TFW2] / 2), the y-axis shows the difference (TR2 - TFW2), and the z-axis shows the number of observations. The mean and 2SD difference are 0.071 and 0.091s, respectively. [Figure 7] The effect of the arterial-limb arterial stiffness gradient [(a) PWVFD / PWVCF ratio] or pulse pressure amplification [(b) PPD / PPA ratio] on the diastolic pressure variability index (PFId) mediated by the diastolic flow variability index (FFId). For each mediation model, the effect is given as the standardized regression coefficient. The model number (i = 1, 2...) is indicated by a subscript (e.g., ai), ai, bi, and ci indicate the direct effect, ci is the total effect, and ai*bi is the indirect effect. Solid and dotted lines indicate significant and non-significant associations, respectively. **P less than 0.01, ***P less than 0.001. DETAILED DESCRIPTION OF THE INVENTION

[0039] (First embodiment) First, we will explain the configuration of a blood pressure index calculation system 1 including a device for calculating a blood pressure index of a test subject according to the first embodiment of the present invention. The blood pressure index calculation system 1 includes a blood pressure pulse wave measuring device 10 that measures the blood pressure waveform of the subject's peripheral artery, a blood pressure measuring device 20 that measures the subject's arterial blood pressure, and a blood pressure index calculation device 30 that includes a computer or the like that stores and processes data received from the blood pressure pulse wave measuring device 10 and the blood pressure measuring device 20.

[0040] The blood pressure index calculation device 30 includes a CPU (Central Processing Unit), a GPU (Graphics Processing Unit), an ASIC (Application Specific Integrated Circuit), and the like that performs calculations or judgments based on various data received from the blood pressure pulse wave measurement device 10 and the blood pressure measurement device 20 and / or data stored or generated internally. Processing devices such as FPGAs (Field Programmable Gate Arrays) and FPGAs (Field Specific Integrated Circuits) The system is equipped with a processor 40, a storage device 50 such as a ROM, RAM, or hard disk for storing various data, and a display device 52 for displaying the results of calculations performed by the processor 40.

[0041] The blood pressure pulse wave measuring device 10 may be any blood pressure pulse wave measuring device capable of measuring a blood pressure waveform from a peripheral artery of a subject, and examples thereof include pulse pressure sensors such as a tonometer and a pulse oximeter. Peripheral arteries that can be measured with the blood pressure pulse wave measuring device 10 include, but are not limited to, the brachial artery, radial artery, carotid artery, femoral artery, and / or dorsalis pedis artery. The arterial blood pressure measured with the blood pressure pulse wave measuring device 10 includes the blood pressure waveform and pulse pressure of the peripheral artery.

[0042] The blood pressure waveform stored in the blood pressure pulse wave measuring device 10 for a certain period of time (for example, 5 to 30 seconds) is used as a blood pressure indicator. The blood pressure index calculation device 30 stores the data in its storage device 50. In a preferred embodiment, a user of the blood pressure index calculation system 1 (hereinafter referred to as the user), who is a medical professional such as a doctor or nurse, can select data from a time period (e.g., 10 seconds) that the user determines to be stable from the stored blood pressure waveform data displayed on the time series axis on the display device 52, and select the data for subsequent calculation processing. In another preferred embodiment, the blood pressure waveform data to be transmitted from the blood pressure pulse wave measuring device 10 to the blood pressure index calculation device 30 is automatically selected by the blood pressure index calculation device 30.

[0043] The blood pressure measurement device 20 may be any device capable of measuring the arterial blood pressure of a subject, such as a cuff-type oscillometer or a tonometer. Peripheral arteries that can be measured by the blood pressure measurement device 20 include, but are not limited to, the brachial artery, radial artery, and / or lower limb arteries. The arterial blood pressure measured by the blood pressure measurement device 20 includes the systolic blood pressure, diastolic blood pressure, mean blood pressure, and / or heart rate of the peripheral artery. Such blood pressure measurement methods are well known and can be performed by those skilled in the art. The blood pressure data measured by the blood pressure measurement device 20 is transmitted to the blood pressure index calculation device 30 and stored in the storage device 50 of the blood pressure index calculation device 30. In a preferred embodiment, the user of the blood pressure index calculation system 1 can select and / or average blood pressure data determined by the user to be stable from the stored blood pressure data displayed on the display device 52 and use the selected blood pressure data for subsequent calculation processing. In another preferred embodiment, the selection of blood pressure data transmitted from the blood pressure measurement device 20 to the blood pressure index calculation device 30 is automatically performed by the blood pressure index calculation device 30.

[0044] The processing device 40 of the blood pressure index calculation device 30 includes an averaged blood pressure waveform generating unit 41 that takes an ensemble average of blood pressure waveform data received from the blood pressure pulse wave measuring device 10 over a predetermined period to generate an averaged blood pressure waveform, a residual pressure waveform generating unit 42 that fits the diastolic portion of the blood pressure waveform with respect to time change of the blood pressure waveform data of the peripheral artery of the test subject generated by the averaged blood pressure waveform generating unit 41 to an exponential decay curve to generate a residual pressure waveform having a first negative peak and a subsequent positive peak, and a residual pressure waveform generating unit 43 that calculates the pressure at the first negative peak of the residual pressure waveform as P R1 , the pressure at the next positive peak is P R2 , peripheral arterial pulse pressure PP Peri In this case, the diastolic blood pressure variability index (PFI) is calculated as follows: d ) is provided.

[0045]

number

[0046] In the examples described below, an example is explained in which the diastolic blood pressure variability index is calculated using blood pressure waveform data of the femoral artery. Figure 5(a) is a graph of an averaged arterial waveform obtained by taking the ensemble average of blood pressure waveform data of the femoral artery of a subject measured by the blood pressure pulse wave measuring device 10, and Figure 5(b) is a graph of an averaged arterial waveform obtained by taking the ensemble average of blood pressure waveform data of the femoral artery of a subject measured by the blood pressure pulse wave measuring device 10. 5(b) is a graph of the residual pressure waveform that remains when the diastolic portion of the blood pressure waveform data of FIG. 5(a) is fitted to an exponential decay curve.

[0047] Symbols in brackets represent coordinates (x, y), T is time, and P is pressure. ES is end systole, DN is dicrotic notch, and DW is dicrotic wave peak, which are well known to those skilled in the art of hemodynamics.

[0048] While previous studies have often focused on the systolic phase, this disclosure focuses on the diastolic phase of the blood pressure waveform.

[0049] If the diastolic pressure of the blood pressure waveform is approximated by an exponential decay curve, the residual pressure is expressed as (TR1 , P R1 ) first negative peak, (T R2 , P R2 ) second positive peak, (T R3 , P R3 ) appears, and the third negative peak appears at (T DN , P DN ) and (T DW , P DW ) in Figure 5(b) (T R1 , P R1 ) and (T R2 , P R2 ) in Figure 5(b). R1 , P R1 ) and (T R2 , P R2 ) was observed in all subjects examined in the examples. These facts were discovered for the first time by the inventors of the present application. ES , P ES ) was the boundary between the systolic and diastolic periods, but in equation (1) (T ES , P ES ) pressure P at two different points R1 , P R2 It is characterized by measuring peripheral arterial pulse pressure (PP) Peri is the difference between the maximum systolic value and the minimum diastolic value of the averaged arterial waveform (in Figure 5(a), 130mmHg - 70mmHg is approximately 60mmHg). Peri can be obtained manually or automatically from the signal of the blood pressure pulse wave measuring device 10.

[0050] Curve fitting of the exponential decay can be performed using the well-known equation (2) (Liu, Z. et al. al., Am J Physiol 1986;251 (3 pt 2):H588-600. and Kottenberg-Assenmacher E et al., Anesthesiology 2009;110:370-379.), using the Levenberg-Marquardt algorithm. can be optimized.

[0051]

number

[0052] where t is the time from end-systole, P(t) is the exponential pressure waveform at t, P0 is the estimated (optimized) pressure at end-systole, and P ∞ is the optimization asymptotic pressure, and τ (tau) is the optimization time constant. τ can be a variable or a finite value, but it is important to choose the optimal value to get a better fit. It is preferable to set it to a finite value in order to ∞ =0 may also be used.

[0053] Surprisingly, the diastolic blood pressure variability index (PFI) calculated by Equation (1) d has a strong correlation with pulse pressure amplification. Measurement of pulse pressure amplification requires measurements at two points, aortic blood pressure and peripheral blood pressure, which makes the measurement complicated. However, the diastolic blood pressure variability index (PFI) disclosed in the present invention can be used to measure pulse pressure amplification. d The diastolic blood pressure variability index (PFI) of the present disclosure can be calculated simply by measuring one point on a peripheral artery. d By using this method, the cardiovascular system of a subject can be evaluated more easily and accurately.

[0054] In addition, the diastolic blood pressure variability index PFI of the present disclosure d By using this, pulse pressure amplification and aortic blood pressure can be easily estimated without using a transfer function.

[0055] Furthermore, pulse wave velocity (PWV) is well known as an index of vascular arteriosclerosis (Townsend RR et al. Hypertension 2015;66:698-722), but the diastolic blood pressure variability index (PFI) of the present disclosure d There is also a strong correlation between the PWV ratio of two peripheral arteries. The diastolic blood pressure variability index (PFI) of the present disclosure can be easily calculated without measuring the seeding rate. d is used to evaluate the degree of hardening. It is also possible to do so.

[0056] The processing device 40 of the blood pressure index calculation device 30 calculates the diastolic blood pressure variability index PFI d The apparatus may further include a pulse pressure amplification estimation unit 44 that estimates the pulse pressure amplification based on the above.

[0057] Specifically, the diastolic blood pressure variability index (PFI) d is the peripheral arterial pulse pressure (PP) peri Central aortic pulse pressure (PP) A Ratio of (PP peri / PP A ), which has a strong correlation with pulse pressure amplification, d From this, pulse pressure amplification can be estimated.

[0058] In one example, the storage device 50 stores a diastolic blood pressure variability index (PFI d and pulse pressure amplification PP peri / PP A The pulse pressure amplification estimator 44 calculates the pulse pressure amplification PP of a certain subject from the diastolic blood pressure variability index of the subject using the function. peri / PP A can be estimated.

[0059] In another example, the storage device 50 stores a diastolic blood pressure variability index (PFI d The reference value and pulse pressure amplification PP peri / PP A and the reference value of the diastolic blood pressure variability index PFI d If the pulse pressure amplification of the subject is higher than the reference value, the pulse pressure amplification PP peri / PP A It can be estimated that the diastolic blood pressure variability index (PFI) is higher than the standard value. d Reference value and pulse pressure amplification PP peri / PP A The reference values for the diastolic blood pressure variability index (PFI) for healthy individuals are d Average value and pulse pressure amplification PP peri / PP Aor the diastolic blood pressure variability index (PFI) of heart disease patients. d Average value and pulse pressure amplification PP peri / PP A It may be the average value of

[0060] In another example, the storage device 50 stores a diastolic blood pressure variability index (PFI d The reference value and pulse pressure amplification PP peri / PP A and the reference value of the diastolic blood pressure variability index PFI d If the pulse pressure amplification of the subject is equal to or less than the reference value of PP peri / PP A It can be estimated that the diastolic blood pressure variability index (PFI) is below the reference value. d Reference value and pulse pressure amplification PP peri / PP A The reference values for the diastolic blood pressure variability index (PFI) for healthy individuals are d Average value and pulse pressure amplification PP peri / PP A or the diastolic blood pressure variability index (PFI) of heart disease patients. d Average value and pulse pressure amplification PP peri / PP A It may be the average value of

[0061] In yet another example, the storage device 50 stores a diastolic blood pressure variability index (PFI d The reference value and pulse pressure amplification PP peri / PP A The pulse pressure amplification estimation unit 44 stores the reference values of the diastolic blood pressure variability index and the diastolic blood pressure variability index PFI d and the relationship between the reference value and pulse pressure amplification PP peri / PP A The estimated value of the pulse pressure amplification of the subject can be calculated from the reference value of the diastolic blood pressure variability index (PFI). d Reference value and pulse pressure amplification PP peri / PP A The reference values for the diastolic blood pressure variability index (PFI) for healthy individuals are dAverage value and pulse pressure amplification PP peri / PP A or the diastolic blood pressure variability index (PFI) of heart disease patients. d Average value and pulse pressure amplification PP peri / PP A It may be the average value of

[0062] The processing device 40 of the blood pressure index calculation device 30 calculates the diastolic blood pressure variability index PFI d The central aortic blood pressure may further include a central aortic blood pressure estimation unit 45 that estimates the central aortic blood pressure based on the central aortic pulse pressure PP A , central aortic systolic blood pressure, etc.

[0063] Specifically, the diastolic blood pressure variability index (PFI) d is pulse pressure amplification PP peri / PP A Because of its strong correlation with d and peripheral arterial pulse pressure (PP) peri From the value of , the central aortic pulse pressure PP A Seeking Furthermore, since the diastolic pressure of the peripheral arteries and the central aorta is considered to be the same, the central aortic pulse pressure PP A The central aortic systolic pressure can be estimated from the peripheral arterial pulse pressure (PP). peri teeth , can be measured by the blood pressure pulse wave measuring device 10 and transmitted to the blood pressure index calculation device 30. In addition, peripheral arterial pulse pressure PP peri When using brachial pulse pressure as the BP, it can be obtained directly from brachial cuff blood pressure measurement, etc. Peripheral arterial pulse pressure (PP) can be measured on arteries other than the brachial artery, such as the femoral artery. peri Looking for When measuring peripheral arterial pulse pressure (PP), the mean and diastolic blood pressures obtained by brachial blood pressure measurement, etc. are used as calibration blood pressures, assuming that the mean and diastolic blood pressures are equivalent in all peripheral arteries. peri can be obtained.

[0064] In one example, the storage device 50 stores a diastolic blood pressure variability index (PFI d , peripheral arterial pulse pressure PP peri , and central aortic pulse pressure PP A The central aortic blood pressure estimation unit 45 stores the function of The central aortic pulse pressure PP of the subject can be calculated from the diastolic blood pressure variability index and peripheral arterial pulse pressure using, for example, such a function. A can be estimated.

[0065] Pulse pressure amplification PP peri / PP A = a×log(PFI d ) + b × age + c × heart rate + d × BMI (a, b, c, and d are constants that take unique values depending on the location of the peripheral artery.) central aortic pulse pressure PP A =PP peri ÷Pulse pressure amplification Central aortic systolic pressure = (PP peri ÷ pulse pressure amplification) + peripheral arterial diastolic pressure

[0066] In another example, the storage device 50 stores a diastolic blood pressure variability index (PFI d Reference values for peripheral arterial pulse pressure (PP) peri and the central aortic pulse pressure PP A The reference value of the central aortic blood pressure is stored. The unit 45 calculates the central aortic pulse pressure PP of a subject from the diastolic blood pressure variability index and the peripheral arterial pulse pressure of the subject. A However, central aortic pulse pressure PP A It is possible to estimate whether the diastolic blood pressure variability index (PFI) is higher than the reference value. d Reference values for peripheral arterial pulse pressure (PP) peri Reference values for PP and central aortic pulse pressure A The reference values for the diastolic blood pressure variability index (PFI) for healthy individuals are d Average value of peripheral arterial pulse Pressure PP peri and central aortic pulse pressure PP A It can be the average of the averages of Diastolic blood pressure variability index (PFI) in patients with cardiovascular disease d Average value of peripheral arterial pulse pressure (PP) peri and central aortic pulse pressure PP A It may be the average value of

[0067] In yet another example, the storage device 50 stores a diastolic blood pressure variability index (PFI d Reference values for peripheral arterial pulse pressure (PP) peri Reference values for PP and central aortic pulse pressure A The reference value of central aortic blood pressure is stored. The pressure estimation unit 45 calculates the diastolic blood pressure variability index and the diastolic blood pressure variability index PFI of a certain subject. d The relationship between the reference values of the subject's peripheral arterial pulse pressure and peripheral arterial pulse pressure PP peri and the relationship between the reference values of central aortic pulse pressure PP A From the reference value of the subject, the central aortic pulse pressure PP A It is possible to estimate the diastolic blood pressure variability index (PFI) d Reference values for peripheral arterial pulse pressure (PP) peri Reference values for PP and central aortic pulse pressure A The reference values for the diastolic blood pressure variability index (PFI) for healthy individuals are d Average value of peripheral artery Pulse pressure (PP) peri and central aortic pulse pressure PP A It can be the average value of Diastolic Blood Pressure Variability Index (PFI) in patients with vascular disease d Average value of peripheral arterial pulse pressure (PP) peri and central aortic pulse pressure PP A It may be the average value of

[0068] central aortic pulse pressure PP A = peripheral arterial pulse pressure PP peri / pulse pressure amplification, Central aortic systolic pressure = central aortic pulse pressure PP A + Peripheral arterial diastolic blood pressure, Central aortic systolic blood pressure = (peripheral arterial pulse pressure PP peri / pulse pressure amplification) + peripheral arterial diastolic blood pressure , From this equation, the central aortic blood pressure estimator 45 calculates the central aortic pulse pressure PP A From central aortic constriction The blood pressure can be estimated.

[0069] The processing device 40 of the blood pressure index calculation device 30 may further include a vascular stiffness evaluation unit 46 that evaluates the stiffness of the blood vessels of the test subject based on the diastolic blood pressure variability index.

[0070] In one example, the storage device 50 stores a diastolic blood pressure variability index (PFI d The vascular stiffness evaluation unit 46 stores the reference value of the diastolic blood pressure variability index PFI d If the value is equal to or lower than the reference value, it can be estimated that the subject is likely to have advanced vascular sclerosis. The diastolic blood pressure variability index PFI can be displayed on the display device 52 in the following format. d The reference value for the diastolic blood pressure variability index (PFI) in patients with arteriosclerosis is d It may be the average value of

[0071] In another example, the storage device 50 stores a diastolic blood pressure variability index (PFI d The vascular stiffness evaluation unit 46 stores the reference value of the diastolic blood pressure variability index PFI d If the value is equal to or higher than the reference value, it can be estimated that the possibility of the subject having advanced vascular sclerosis is low. The low possibility can be displayed on the display device 52 in the form of a display to that effect, a ranking, a probability, etc. d The reference value for the diastolic blood pressure variability index (PFI) for healthy individuals is d It may be the average value of

[0072] 2 is a flowchart showing the main operations of the processing device 40 of the blood pressure index calculation device 30 for calculating the blood pressure index of the subject. In step S1, the averaged blood pressure waveform generation unit 41 generates an averaged blood pressure waveform from the blood pressure waveform data of the subject's peripheral artery. In step S2, the residual pressure waveform generation unit 42 fits the diastolic portion of the blood pressure waveform data received from the averaged blood pressure waveform generation unit 41 to an exponential decay curve to generate a residual pressure waveform having a first negative peak and a subsequent positive peak. In step S3, the diastolic blood pressure variability index calculation unit 43 calculates the pressure at the first negative peak of the residual pressure waveform as P. R1 , the next positive The pressure at the peak is P R2 , peripheral arterial pulse pressure PP Peri In this case, the following equation (1) Diastolic Blood Pressure Variability Index (PFI) d ) is calculated.

[0073]

number

[0074] Optionally, in step S4, the pulse pressure amplification estimator 44 calculates a diastolic blood pressure variability index PFI d Based on this, the pulse pressure amplification is estimated.

[0075] Optionally, in step S5, the central aortic blood pressure estimator 45 calculates a diastolic blood pressure variability index PFI d The central aortic blood pressure is estimated from the pulse pressure amplification estimated based on the mean blood pressure (or systolic blood pressure) and diastolic blood pressure obtained by brachial blood pressure measurement.

[0076] Optionally, in step S6, the vascular stiffness assessment unit 46 calculates a diastolic blood pressure variability index PFI d Based on this, the degree of hardening of the blood vessel of the test subject is evaluated.

[0077] According to the method for calculating a blood pressure index of a test subject of the first embodiment, the diastolic blood pressure variability index, which is a blood pressure index, can be calculated easily. Furthermore, using this diastolic blood pressure variability index, the cardiovascular system of the test subject, pulse pressure amplification, central aortic blood pressure, and vascular stiffness of the test subject can be evaluated simply and accurately.

[0078] In the above first embodiment, a blood pressure index calculation device 30 and a blood pressure index calculation method for a test subject were described, but the present invention is not limited to this and also includes a program for causing a computer to function as a processing device 40 of the above blood pressure index calculation device 30, and a computer-readable recording medium on which the program is recorded.

[0079] The first embodiment can be modified as follows. When measuring blood pressure waveform data, the measurement time may be determined manually by the user, but it is also possible to preset a certain time period (for example, 5 to 30 seconds) and measure the time within that period. All steps may be automatically measured by the processing device 22 so that the measurement is started and finished automatically. Alternatively, the device may be configured so that the user can switch between manual and automatic operation. Instead of measuring blood pressure and blood flow separately, the blood pressure and blood flow of the subject may be measured simultaneously, and both sets of data may be synchronized and imported into a personal computer for automatic processing. In this case, more precise measurements are possible. In the first embodiment, the blood pressure pulse wave measuring device 10 and the blood pressure measuring device 20 are described as separate devices. However, the blood pressure pulse wave measuring device 10 and the blood pressure measuring device 20 may be the same device. That is, a single device may measure the blood pressure waveform from the subject's peripheral artery and the subject's arterial blood pressure. In the first embodiment, the mean blood pressure waveform generating unit 41, the residual pressure waveform generating unit 42, the diastolic blood pressure variability index calculating unit 43, the pulse pressure amplification estimating unit 44, the central aortic blood pressure estimating unit 45, and the vascular stiffness evaluating unit 46 of the processing device 40 are all located within the processing device 40. However, the units 41, 42, 43, 44, 45, and 46 may be located in separate, physically separate processing devices. That is, the scope of the present invention includes not only cases where the units within the processing device 40 are located within the same hardware processor, but also cases where they are located separately within different hardware processors. In the first embodiment, the blood pressure index calculation device 30 includes the storage device 50 and the display device 52. However, the storage device 50 and / or the display device 52 may be provided separately from the processing device 40 outside the blood pressure index calculation device 30 and communicated via a communication line such as a LAN (Local Area Network) or the Internet. The storage device 50 may be configured to be communicatively connected to the processing device 40 via a communication line. In this case, for example, the storage device 50 can store data processed in each step of the processing device 40, including the steps shown in Fig. 2. The storage device 50 may also store data generated by the blood pressure pulse wave measuring device 10, the blood pressure measurement device 20, or both, and send such data to the processing device 40 for later processing in the processing device 40, including the steps shown in Fig. 2.

[0080] (Second embodiment) Next, a description will be given of the configuration of a blood flow index calculation system 101 including an apparatus for calculating a blood flow index of a test subject according to a second embodiment of the present invention. As shown in Fig. 3, the blood flow index calculation system 101 includes a blood flow measurement device 110 that measures the blood flow waveform of a peripheral artery of a subject, a blood pressure measurement device 20 that measures the arterial blood pressure of the subject, and a blood pressure index calculation device 130 that includes a computer or the like that stores and processes data received from the blood flow measurement device 110 and the blood pressure measurement device 120.

[0081] The blood flow index calculation device 130 includes a processing device 40 such as a CPU (Central Processing Unit), GPU (Graphics Processing Unit), ASIC (Application Specific Integrated Circuit), or FPGA (Field Programmable Gate Array) that performs calculations or judgments based on various data received from the blood flow measurement device 110 and the blood pressure measurement device 120 and / or data stored or generated internally, a storage device 150 such as a ROM, RAM, or hard disk that stores various data, and a display device 152 that displays the results of calculations performed by the processing device 140.

[0082] The blood flow measurement device 110 may be any device capable of measuring peripheral arterial blood flow, such as a known ultrasonic transducer. By using an ultrasonic transducer, it is possible to non-invasively collect aortic blood flow data, particularly waveform data of changes in blood flow velocity over time, from the surface of a subject's body.

[0083] The blood flow velocity or blood flow volume stored in the blood flow measurement device 110 for a certain period of time (for example, 5 to 30 seconds) The waveform data is transmitted to the blood flow index calculation device 130 and stored in the storage device 150. In a preferred embodiment, a user of the blood flow index calculation system 100 (hereinafter referred to as the user), who is a medical professional such as a doctor or a nurse, can select data from a time period (e.g., 10 seconds) that the user has determined to be stable from the stored blood flow velocity waveform data displayed on the time series axis on the display device 152, and select the data for subsequent calculation processing. In another preferred embodiment, the selection of blood flow velocity waveform data to be transmitted from the blood flow measurement device 110 to the blood flow index calculation device 130 is automatically performed by the blood flow index calculation device 130.

[0084] The blood pressure measuring device 120 may be any device capable of measuring the arterial blood pressure of a subject, such as a cuff-type oscillometer. Peripheral arteries that can be measured by the blood pressure measuring device 120 include, but are not limited to, the brachial artery, radial artery, and / or lower limb arteries. The arterial blood pressure measured by the blood pressure measuring device 120 includes the systolic blood pressure, diastolic blood pressure, mean blood pressure, and / or heart rate of the peripheral artery. Such blood pressure measurement methods are well known and can be performed by those skilled in the art with ordinary skill. The blood pressure data measured by the blood pressure measuring device 120 is transmitted to the blood flow index calculation device 130 and stored in the storage device 150 of the blood flow index calculation device 130. In a preferred embodiment, a user of the blood flow index calculation system 100 can select and / or average blood flow data determined by the user to be stable from the stored blood flow data displayed on the display device 152, and use the selected blood flow data for subsequent calculation processing. In another preferred embodiment, the selection of blood pressure data to be transmitted from the blood pressure measurement device 120 to the blood flow index calculation device 130 is automatically performed by the blood flow index calculation device 130.

[0085] The processing device 140 of the blood flow index calculation device 130 includes an average blood flow velocity waveform generation unit 141 that takes an ensemble average of blood flow velocity waveform data received from the blood flow measurement device 110 for a predetermined period and generates an averaged blood flow velocity waveform, and a blood flow velocity at the maximum positive peak of the systolic blood flow velocity waveform with respect to time change of the blood flow velocity waveform data of the peripheral artery to be examined generated by the averaged blood flow velocity waveform generation unit 141. FW , the blood flow velocity at the negative peak is V BW , and the blood flow velocity at the next positive peak in the diastolic phase is V FW2 In this case, the diastolic blood flow variability index (FFI) is calculated as follows: d ) is calculated.

[0086]

number

[0087] In the examples described below, an example is explained in which the diastolic blood flow variability index is calculated using blood flow velocity waveform data of the femoral artery. Fig. 5(c) is a graph of an averaged arterial blood flow velocity waveform obtained by taking the ensemble average of blood flow velocity waveform data of the subject's femoral artery measured by the blood flow measurement device 110.

[0088] The symbols in parentheses represent coordinates (x, y), T is time, and V is velocity. The waveforms in Figure 5(c) and Figure 5(b) have similar shapes in the diastolic part, but Figure 5(b) shows a time T R1 Figure 5(c) shows Time T BW is slightly faster.

[0089] Surprisingly, the diastolic flow variability index (FFI) calculated by Eq. (3) d has a strong correlation with pulse pressure amplification. Measurement of pulse pressure amplification requires measurements at two points, aortic blood pressure and peripheral blood pressure, which makes the measurement complicated. However, the diastolic blood pressure variability index (PFI) disclosed in the present invention can be used to measure pulse pressure amplification. d The diastolic blood flow variability index (FFI) of the present disclosure can be calculated simply by measuring one point on a peripheral artery. d By using this method, the cardiovascular system of a subject can be evaluated more easily and accurately.

[0090] In addition, the diastolic blood flow variability index FFI of the present disclosure d By using this, pulse pressure amplification and aortic blood pressure can be easily estimated without using a transfer function.

[0091] Furthermore, pulse wave velocity (PWV) is well known as an index of arteriosclerosis of blood vessels, but the diastolic blood flow variability index (FFI) of the present disclosure d The PWV ratio of the two peripheral arteries was also significantly correlated with the Therefore, the diastolic blood flow variability index (FFI) of the present disclosure can be easily calculated without measuring the pulse wave velocity. d can also be used to assess the degree of cure.

[0092] In addition, the diastolic flow variability index (FFI) d is the diastolic blood pressure variability index (PFI) d High correlation with (R=0.63 , P<0.001).

[0093] The processing device 140 of the blood flow index calculation device 130 calculates the diastolic blood flow variability index FFI. d The apparatus may further include a pulse pressure amplification estimation unit 144 that estimates the pulse pressure amplification based on the above.

[0094] Specifically, the diastolic flow variability index (FFI) d is peripheral arterial pulse pressure amplified PP peri Central aortic pulse pressure (PP) A Ratio of (PP peri / PP A ) has a strong correlation with pulse pressure amplification, and is therefore called the diastolic flow variability index (FFI). d From this, pulse pressure amplification can be estimated.

[0095] In one example, the storage device 150 stores a diastolic flow variability index (FFI). d and pulse pressure amplification PP peri / PP A The pulse pressure amplification estimation unit 144 calculates the pulse pressure amplification PP of a certain subject from the diastolic blood flow variability index of the subject, for example, by using this function. peri / PP A can be estimated.

[0096] Pulse pressure amplification PP peri / PP A = a×FFI d + b × age + c × heart rate + d × BMI (a, b, c, and d are constants that take unique values depending on the location of the peripheral artery.)

[0097] In another example, the storage device 150 stores a diastolic flow variability index (FFI). d The reference value and pulse pressure amplification PP peri / PP A and the reference value of the diastolic blood flow variability index FFI are stored.d If the pulse pressure amplification of the subject is higher than the reference value, the pulse pressure amplification PP peri / PP A It can be estimated that the diastolic blood flow variability index (FFI) is higher than the reference value. d Reference value and pulse pressure amplification PP peri / PP A The reference values for the diastolic blood flow variability index (FFI) for healthy individuals are d Average value and pulse pressure amplification PP peri / PP A or the diastolic blood flow variability index FFI of heart disease patients. d Average value and pulse pressure amplification PP peri / PP A It may be the average value of

[0098] In another example, the storage device 150 stores a diastolic flow variability index (FFI). d The reference value and pulse pressure amplification PP peri / PP A and the reference value of the diastolic blood flow variability index FFI are stored. d If the pulse pressure amplification of the subject is equal to or less than the reference value of PP peri / PP A It can be estimated that the diastolic blood flow variability index (FFI) is below the reference value. d Reference value and pulse pressure amplification PP peri / PP A The reference values for the diastolic blood flow variability index (FFI) for healthy individuals are d Average value and pulse pressure amplification PP peri / PP A or the diastolic blood flow variability index FFI of heart disease patients. d Average value and pulse pressure amplification PP peri / PP A It may be the average value of

[0099] In yet another example, the storage device 150 stores a diastolic flow variability index (FFI). d The reference value and pulse pressure amplification PP peri / PP AThe pulse pressure amplification estimation unit 144 stores the reference values of the diastolic blood flow variability index and the diastolic blood flow variability index FFI of a certain subject. d and the relationship with the reference value of pulse pressure amplification PP peri / PP A The estimated value of pulse pressure amplification for the subject can be calculated from the reference value of the diastolic blood flow variability index (FFI). d Reference value and pulse pressure amplification PP peri / PP A The reference values for the diastolic blood flow variability index (FFI) for healthy individuals are d Average value and pulse pressure amplification PP peri / PP A or the diastolic blood flow variability index FFI of heart disease patients. d Average value and pulse pressure amplification PP peri / PP A It may be the average value of

[0100] The processing device 140 of the blood flow index calculation device 130 calculates the diastolic blood flow variability index FFI. d The central aortic blood pressure estimation unit 145 may further include a central aortic blood pressure estimation unit 145 that estimates the central aortic blood pressure based on the above.

[0101] Specifically, the diastolic flow variability index (FFI) d is the peripheral arterial pulse pressure (PP) peri Central aortic pulse pressure (PP) A Ratio of (PP peri / PP A ) and therefore has a strong correlation with the diastolic flow variability index (FFI). d and peripheral arterial pulse pressure (PP) peri From the value of , the central aortic pulse pressure PP A Furthermore, peripheral arteries and central aorta can be calculated. Since the diastolic pressure of the central aortic pulse pressure PP A Central aortic systolic blood pressure Peripheral arterial pulse pressure (PP) can be estimated. peri can be measured by the blood pressure pulse wave measuring device 10 and transmitted to the blood flow index calculating device 130.

[0102] In one example, the storage device 150 stores a diastolic flow variability index (FFI). d , peripheral arterial pulse pressure PP peri , and central aortic pulse pressure PP A The central aortic blood pressure estimation unit 145 stores the function From the examiner's diastolic blood flow variability index and peripheral arterial pulse pressure, for example, using such a function, the central aortic pulse pressure PP A can be estimated.

[0103] Pulse pressure amplification PP peri / PP A = a×FFI d + b × age + c × heart rate + d × BMI (a, b, c, and d are constants that take unique values depending on the location of the peripheral artery.) Central aortic blood pressure = (PP peri ÷ pulse pressure amplification) + peripheral arterial diastolic blood pressure

[0104] In another example, the storage device 150 stores a diastolic flow variability index (FFI). d Reference values for peripheral arterial pulse pressure (PP) peri and the central aortic pulse pressure PP A The reference value of the central aortic blood pressure is stored in memory. The measurement unit 145 calculates the central aortic pulse pressure PP of a certain subject from the diastolic blood flow variability index and the peripheral arterial pulse pressure of the subject. A However, central aortic pulse pressure PP A It is possible to estimate whether the diastolic blood flow variability index (FFI) is higher than the reference value. d Reference values for peripheral arterial pulse pressure (PP) peri Reference values for PP and central aortic pulse pressure A The reference values for the diastolic blood flow variability index (FFI) for healthy individuals are d Average value of peripheral artery Pulse pressure (PP) peri and central aortic pulse pressure PP A It may be the average of the average values of The diastolic blood flow variability index (FFI) for patients with cardiovascular disease is d Average value of peripheral arterial pulse pressure (PP) periand central aortic pulse pressure PP A It may be the average value of

[0105] In yet another example, the storage device 150 stores a diastolic flow variability index (FFI). d Reference values for peripheral arterial pulse pressure (PP) peri Reference values for PP and central aortic pulse pressure A The reference value of the central aorta is stored. The blood pressure estimation unit 145 calculates the diastolic blood flow variability index (FFI) of a subject. d The relationship between the reference values of the subject's peripheral arterial pulse pressure and peripheral arterial pulse pressure PP peri and the relationship between the reference values of central aortic pulse pressure PP A From the reference value of the subject, the central aortic pulse pressure PP A The diastolic flow variability index (FFI) can be estimated. d Reference values for peripheral arterial pulse pressure (PP) peri Reference values for PP and central aortic pulse pressure A The reference values for the diastolic blood flow variability index (FFI) for healthy individuals are d The average value of Peripheral arterial pulse pressure (PP) peri and central aortic pulse pressure PP A It can be the average value of Diastolic flow variability index (FFI) in patients with cardiovascular disease d Average value of peripheral arterial pulse pressure (PP) peri and central aortic pulse pressure PP A It may be the average value of

[0106] The processing device 140 of the blood flow index calculation device 130 calculates the diastolic blood flow variability index FFI. d The apparatus may further include a vascular stiffness evaluation unit 146 that evaluates the stiffness of the blood vessel of the test subject based on the above.

[0107] In one example, the storage device 150 stores a diastolic flow variability index (FFI). d The vascular stiffness evaluation unit 146 stores the reference value of the diastolic blood flow variability index FFI of a certain subject. dIf the value is equal to or lower than the reference value, it can be estimated that there is a high possibility that the subject's blood vessels are suffering from advanced sclerosis. The high possibility can be displayed on the display device 52 in the form of a display, ranking, probability, etc. d The reference value of the diastolic flow variability index (FFI) in patients with arteriosclerosis is d It may be the average value of

[0108] In another example, the storage device 150 stores a diastolic flow variability index (FFI). d The vascular stiffness evaluation unit 146 stores the reference value of the diastolic blood flow variability index FFI of a certain subject. d If the FFI is equal to or higher than the reference value, it can be estimated that the possibility of the subject having advanced vascular sclerosis is low. The low possibility can be displayed on the display device 52 in the form of a display, ranking, probability, etc. d The reference value for the diastolic blood flow variability index (FFI) for healthy individuals is d It may be the average value of

[0109] 4 is a flowchart showing the main operations of the processing device 140 of the blood flow index calculation device 130 for calculating the blood flow index of the test subject. In step S101, the average blood flow velocity waveform generation unit 141 generates an average blood flow velocity waveform from the blood flow velocity waveform data of the peripheral artery of the subject. In step S102, the diastolic blood flow variability index calculation unit 143 calculates the blood flow velocity at the maximum positive peak of the average blood flow velocity waveform as V. FW , the blood flow velocity at the negative peak is V BW , and the blood flow velocity at the next positive peak in the diastolic phase is V FW2 In this case, the diastolic blood flow variability index (FFI) is calculated as follows: d ) is calculated.

[0110]

number

[0111] Optionally, in step S103, the pulse pressure amplification estimator 144 calculates a diastolic flow variability index FFI d Based on this, the pulse pressure amplification is estimated.

[0112] Optionally, in step S104, the central aortic blood pressure estimator 145 calculates a diastolic flow variability index FFI d Based on this, central aortic blood pressure is estimated.

[0113] Optionally, in step S105, the vascular stiffness assessment unit 146 calculates a diastolic flow variability index (FFI) d Based on this, the degree of hardening of the blood vessel of the test subject is evaluated.

[0114] According to the method for calculating a blood flow index of an examination subject of the second embodiment, the diastolic blood flow variability index, which is a blood flow index, can be calculated easily. Furthermore, using this diastolic blood flow variability index, the cardiovascular system of the subject, pulse pressure amplification, central aortic blood pressure, and vascular sclerosis of the examination subject can be evaluated easily and accurately.

[0115] In the above second embodiment, the blood flow index calculation device 130 of the test subject and the blood flow index calculation method have been described, but the present invention is not limited to this and also includes a program for causing a computer to function as the processing device 140 of the above blood flow index calculation device 130, and a computer-readable recording medium on which the program is recorded.

[0116] The second embodiment can be modified as follows. When measuring blood flow waveform data, the measurement time may be determined manually by the user, but it is also possible to preset a certain time period (for example, 5 to 30 seconds) and measure the blood flow waveform data within that time period. All steps may be automatically measured by the processing device 22 so that the measurement is started and finished automatically. Alternatively, the device may be configured so that the user can switch between manual and automatic operation. Instead of measuring blood pressure and blood flow separately, the blood pressure and blood flow of the subject may be measured simultaneously, and both sets of data may be synchronized and imported into a personal computer for automatic processing. In this case, more precise measurements are possible. In the second embodiment, the blood pressure pulse wave measuring device 10 and the blood pressure measuring device 20 are described as separate devices. However, the blood pressure pulse wave measuring device 10 and the blood pressure measuring device 20 may be the same device. That is, a single device may measure the blood pressure waveform from the subject's peripheral artery and the subject's arterial blood pressure. In the second embodiment, the mean blood flow waveform generating unit 141, the diastolic blood flow variability index calculating unit 143, the pulse pressure amplification estimating unit 144, the central aortic blood pressure estimating unit 145, and the vascular stiffness evaluating unit 146 of the processing device 140 are all present within the processing device 140. However, the units 141, 143, 144, 145, and 146 may be present in separate, physically separate processing devices. That is, the scope of the present invention includes not only cases where the units within the processing device 140 are present within the same hardware processor, but also cases where they are present in separate processing devices within different hardware. In the second embodiment, a storage device 150 and a display device 152 are provided in the blood flow index calculation device 130. However, the storage device 150 and / or the display device 152 may be provided separately from the processing device 140 outside the blood flow index calculation device 130 and connected via a LAN (Local Area Network), the Internet, etc. The storage device 150 may be configured to be communicatively connected to the processing device 140 via a communication line. In this case, for example, the storage device 150 can store data processed in each step of the processing device 40, including the steps shown in Fig. 4. The storage device 150 may also store data generated by the blood flow measurement device 110, the blood pressure measurement device 120, or both, and send such data to the processing device 140 for later processing in the processing device 140, including the steps shown in Fig. 4.

[0117] (Third embodiment) The blood pressure and blood flow index calculation system of the third embodiment of the present invention includes both a blood pressure index calculation system 1 including an apparatus for calculating a blood flow index of a test subject according to the first embodiment, and a blood flow index calculation system 101 including an apparatus for calculating a blood flow index of a test subject according to the second embodiment. The blood pressure and blood flow index calculation system of the third embodiment of the present invention includes a processing device that performs calculations or judgments based on various data received from the blood pressure pulse wave measuring device 10, the blood flow measuring device 110, and the blood pressure measuring devices 20 and 120 and / or data stored or generated internally, a storage device such as a ROM, RAM, or hard disk that stores various data, and a display device that displays the results of calculations performed by the processing device.

[0118] The processing device of the third embodiment of the present invention includes the processing device 40 of the first embodiment and the processing device 140 of the second embodiment, the storage device of the third embodiment is one or more storage devices that perform the functions of the storage device 50 of the first embodiment and the storage device 150 of the second embodiment, and the display device of the third embodiment is one or more display devices that perform the functions of the display device 52 of the first embodiment and the display device 152 of the second embodiment.

[0119] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples. [Example]

[0120] 1.Patient The patients in this study were 592 adult patients who were referred to the inventor's department at Tohoku University Hospital for clinical evaluation of hypertension and related cardiovascular risk. failure, valvular heart disease, stroke, end-stage renal disease, peripheral arterial disease (ankle-brachial index <0.9 or >1.4, or documented), aortic aneurysm, persistent atrial fibrillation, and acute cardiac arrest within the last 6 months Patients with vascular events were excluded. None of the patients had overt clinical symptoms in the extremities. The study protocol was approved by the Ethics Committee of Tohoku University, and all participants provided written informed consent.

[0121] 2. Measurement of arterial pressure and stiffness A series of noninvasive hemodynamic measurements were performed as detailed in Hashimoto J. et., Hypertension 2010; 56:926-933 and Hashimoto J. et., Hypertension 2011; 58:839-846. The study was performed in a quiet, temperature-controlled room. Briefly, after 20 minutes of rest in the supine position, the patient's arm blood pressure was measured twice using a cuff-oscillometric device (HEM-907; Omron Healthcare, Kyoto, Japan). Pressure waves were measured in the radial and common femoral arteries using an applanation tonometer sensor (SPT-301; Millar Instruments, Houston, TX, USA). The aortic waveform was estimated from the corresponding radial artery waveform using a generalized transfer function (SphygmoCor, AtCor Medical, West Ryde, Australia). The radial artery waveform was used to estimate the brachial systole. The mean arterial pressure (MAP) was calculated using the aortic and femoral artery pressures. The waveforms of the dorsalis pedis artery were also measured by averaging the MAP and diastolic pressure levels of the aortic and peripheral arterial signals. The calibration was performed by converting the data into the quantified data (Avolio AP et al., Hypertension 2009; 54:375-383. and Hashimoto J. et., Hypertension 2010; 56:926-933).

[0122] Aorto-femoral pulse wave amplification, aorto-dorsalis pedis pulse wave amplification, and aorto-radial pulse wave amplification (PP F / PP A , PP D / PP A and PP R / PP A ) is the aortic pulse pressure (PP A) was calculated as the ratio of each peripheral arterial pulse pressure to the PP (Hashimoto J. et., Hypertension 2010; 56:926-933). F , PP D and PP R represent the pulse pressures of the femoral artery, dorsalis pedis artery, and radial artery, respectively.

[0123] Pulse wave velocity (PWV) was measured using carotid-femoral and femoral-pedis pulses as previously described. pulse, and carotid-radial site (i.e., PWV CF , PWV FD and PWV CR ) was calculated (Hashimoto J. et al., Hypertension 2010; 56:926-933 and Hashimoto J. et al., Hypertension 2011; 58:839-846). CF reflects the stiffness of the aorta (elastic artery), and PWV FD and PWV CR The end Reflects the stiffness of peripheral arteries (muscular arteries) and PWV FD and PWV CR PWV CF the ratio to PWV FD / PWV CF and PWV CR / PWV CF ) ratio of aorta to peripheral arteries (i.e., elastic arteries to muscular arteries) This has long been considered to be the arterial stiffness gradient (London GM et al., Hypertension 2019; 74:1366-1372. and Hashimoto J. et al., Hypertension 2013; 62:542-549).

[0124] 3. Diastolic blood pressure waveform analysis The diastolic portion of the femoral artery pressure waveform was fitted to an exponential decay curve with a variable asymptote (Fig. 5(a)). First, the onset of diastole (i.e., end-systole, T ESThe time (time of ) was defined as the second inflection point of the pulse wave in the entire cardiac phase, which corresponds to the second positive peak of the second derivative wave (Balmer J et al., J Clin Monit Comput 2021; 35:79-88.). The end of diastole was determined as the end (foot) of the next cardiac cycle. Then, the first 95% of the diastolic period was defined as the diastolic period. The optimization window was extracted to avoid artifacts related to the pre-ejection period.

[0125] The curve fitting was performed according to the following equation (2) (Liu Z et al., Am J Physiol 1986;251(3 pt 2):H588-600. and Kottenberg-Assenmacher E et al., Anesthesiology 2009;110:370-379.) and optimized using the Levenberg-Marquardt algorithm (OriginPro 2018; Origin Lab, Northampton, Massachusetts, USA).

[0126]

number

[0127] where t is the time from end-systole, P(t) is the exponential pressure waveform at t, P0 is the estimated (optimized) pressure at end-systole, and P ∞ is the optimization asymptotic pressure, and τ (tau) is is the optimization time constant. In this example, τ is set to a finite value. The goodness of fit is expressed as the coefficient of determination (R 2 ) and root mean square error (RMSE; i.e., the average difference in instantaneous pressure between the measured and estimated curves).

[0128] The residual pressure waveform was then derived as the difference between the measured and estimated curves (Figure 5(b)). Typically, the residual pressure waveform contains three pressure peaks: the first negative peak (P R1 ), the second positive Peak (P R2 ), and the third negative peak (P R3 These peaks were automatically detected as local minima or maxima using peak analysis software (OriginPro). The time from the systolic onset of the original waveform to these peaks was also determined (T R1 , T R2 and T R3 ). Therefore, the amplitude of the residual waveform fluctuation (i.e., diastolic pressure fluctuation amplitude, PFA d )of, It was calculated according to the following formula (4):

[0129]

number

[0130] The diastolic blood pressure variability amplitude was then normalized to the total amplitude of the original pulse wave (i.e., femoral artery pulse pressure) to obtain the diastolic blood pressure variability index (PFI d ) was calculated according to the following formula (1): PP Peri is the femoral artery pulse pressure PP F It was decided.

[0131]

number

[0132] PFI d It should be noted that the calculation of is solely waveform-dependent and is not affected by any pressure calibration. Furthermore, following the algorithm of a previous report (Oppenheim MI et al., Comput Biomed Res 1995; 28:154-170.), the diploic notch was identified as a notch (trough) or downward bending (deflection) between the end-systolic and diploic waves (Fig. 5(a)). Specifically, a dipping notch (trough) was identified if there was a zero-crossing from negative to non-negative values in the corresponding first derivative wave. If a trough does not exist, the downward direction of the second derivative wave The zero crossing point was instead detected as the deflection notch. In this example, because a clear trough could not be detected in a considerable number of waveforms, the dipping notch and the deflection notch are collectively referred to as the diploic notch. Subsequently, the (hidden) peak of the diploic wave was defined as the positive shoulder after the diploic prominence (Fig. 5(a)), and the residual pressure after the first-order lead method (OriginPro) was calculated. Force was used to determine the onset time. The instantaneous pressure and time from the onset of systole were calculated as the dicrotic notch (P DN and T DN ) and overlapping wave peak (P DW and T DW ) was calculated.

[0133] 4.Blood velocity waveform analysis As previously described (Hashimoto J et al., Hypertension 2010; 56:926-933), Blood flow velocity in the common femoral artery was measured using a cardiotomy ultrasound (Vivid i, GE Healthcare, Tokyo, Japan). The pulse velocity waveforms for each beat were mathematically ensemble averaged over 10 consecutive pulses. The femoral artery pulse waveform was essentially triphasic, and the following parameters (Figure 5(c)) were determined: systolic forward flow peak velocity (V FW ), and peak retrograde velocity (V BW ), diastolic forward flow peak velocity (V FW2 ), end-diastolic velocity, and time-averaged velocity. Time from systolic onset was also calculated. Systolic forward flow (T FW ) peak, reflux (T BW ) peak and diastolic forward flow (T FW2 ) peak. Then, the diastolic flow variability index (FFI) d ) is the diastolic velocity fluctuation amplitude relative to the total velocity pulse amplitude (i.e., V FW2 -V BW ) as a relative ratio of the following formula (3 ) was calculated according to

[0134]

number

[0135] FFI d In the calculation of V, if the waveform is biphasic and there is no forward diastolic flow, FW2 was considered to be 0 (Hashimoto et al. Hypertension 2010; 56:926-933.).

[0136] 5. Statistical analysis Data are presented as mean ± standard deviation (if normal distribution is assumed), median [interquartile range] for continuous variables (if asymmetric), or percentage for categorical variables. Asymmetric data were log-transformed to a normal distribution for subsequent statistical analysis.

[0137] Univariate linear correlations were assessed using the Pearson coefficient (r). Paired t-tests or repeated measures Analysis of variance was used to compare paired data for individual pressure, velocity, and time parameters. Correspondence for time parameters was assessed using Bland-Altman plot analysis. Unpaired data were compared using Student's t-test. Multivariate linear regression analysis was used to compare the various Independent correlations of pressure and hardness gradient parameters were obtained using PFI d and FFI d Compared to PFI. d and FFI d The PFI was adjusted for covariates including age, sex, height, BMI, MAP, heart rate, fasting plasma glucose, LDL cholesterol, HDL cholesterol, eGFR, treatment with calcium channel blockers, renin-angiotensin system inhibitors, beta-blockers, alpha-blockers, diuretics, aldosterone receptor blockers, antidiabetic drugs, and antihyperlipidemic drugs. d and FFI d The independent determinants of PP D / PP A and PWV FD / PWV CF and the same covariates as above were used as candidates and evaluated in a stepwise manner.

[0138] Mediation analysis was performed based on the results of linear regression to examine the hypothesized associations between amplitude or stiffness gradient, diastolic blood flow variability, and diastolic blood pressure variability. More specifically, indirect effects, direct effects, and confidence intervals were estimated in a model minimally adjusted for age and sex by bootstrapping with 5,000 resamples using the PROCESS program. Mediation was considered established if the indirect effect was significantly different from zero. Mediation rates were assessed as the ratio of the indirect effect to the total effect.

[0139] All statistical analyses were performed using SPSS Statistics (version 25.0; IBM, Armonk, NY). A P value of less than 0.05 (two-tailed test) was considered statistically significant. .

[0140] 6.Results (1) Patient characteristics The clinical and hemodynamic characteristics of the 592 patients (mean age 55 ± 14 years) are shown in Table 1. The majority (91%) were treated with antihypertensive drugs, so their blood pressure was largely controlled (brachial blood pressure (131±18 / 74±12 mmHg)). Diabetes and hypercholesterolemia were observed in 24% and 43% of all patients, respectively. PWV CF The median PWV was 7.8 m / s. FD / PWV CF (Aorta-leg artery arteriosclerosis Gradient (degree gradient) ratio and mean PWV CR / PWV CF The aortic-brachial stiffness gradient (PP ) ratio was 1.2±0.3 and 1.0±0.2, respectively. The pulse pressure amplification ratio (PP ) between the aorta and dorsalis pedis artery was 1.2±0.3 and 1.0±0.2, respectively. D / PP A ) 1.8±0.3, aorta Between the ventricle and the radial artery (PP R / PP A ) was 1.3±0.2.

[0141] [Table 1]

[0142] (2) Femoral artery diastolic pressure waveform Time from the onset of systole to the second inflection point (T ES ) was 309 ± 3 ms (Fig. 5(a) and Table 1). A dipping dicrotic notch (i.e., trough) was present in only 92 patients, and convergence The dicrotic notch (T) occurred at 428 ± 50 ms after the onset of systole, but the time of onset was not different from the dicrotic notch in the remaining 500 patients (436 ± 4 ms, P = NS). DN ) 63 ± 4 ms after the Jorda (T DW ) was confirmed.

[0143] The diastolic waveforms of all patients were successfully fitted to a single exponential decay curve (Figure 5(a)), with a goodness of fit of R 2 The results were satisfactory in terms of τ (median, 0.99) and RMSE (0.9 mmHg). The median values for the near lines were estimated to be 0.7 [interquartile range: 0.4-1.7] and 50 [14-64] mmHg, respectively.

[0144] Despite the excellent model fit, the residuals showed finite oscillatory fluctuations (Figure 5(b)). Residual waves were either triphasic (n = 492, 83%) or biphasic (n = 100, 17%) in pattern, i.e., a first negative wave (R1) was always followed by a second positive wave (R2) and almost always by a third negative wave (R3) (Table 1). Absolute wave heights were higher in their apparent order (|P R1 |>|P R2 |>|P R3 |; P<0.001). d) was 4.9 [3.4-6.6]%. The R1 peak occurred slightly earlier than the dicrotic notch (difference: 49 ± 39 ms; P < 0.001), and the R2 peak occurred later than the dicrotic peak (difference: 86 ± 62 ms; P < 0.001), but they were closely correlated with each other (r = 0.58, r = 0.62; P < 0.001).

[0145] (3) Femoral artery diastolic blood flow waveform Velocity pulse waveforms were triphasic with backward flow and forward diastolic flow in 549 patients. However, in 43 patients (7%), the diastolic flow was biphasic with no forward flow (93% and Figure 5(c)). Mean diastolic flow variability index (FFI) d The Bland-Altma histopathology was 34±8% (Table 1). The time of the peak reverse velocity (T BW ) is the second inflection point of the original compression wave It was found that the results were in good agreement with the results obtained from the previous study (T ES、 Figure 6(a)). The mean and 2SD of the difference were -2 and 46 ms, respectively.

[0146] (4) Correlation between diastolic residual pressure and blood flow waveform FFI d and PFI d There was a close correlation between the time to peak diastolic velocity (T FW2 ) is the R2 peak time (T R2 , r=0.68, P<0.001), but the former preceded the latter by 71 ms on average (Figure 6(c)).

[0147] (5) Determinants of diastolic blood pressure and blood flow fluctuations Table 2 shows the multivariate-adjusted associations of individual stiffness and pressure measurements with diastolic blood flow and blood pressure fluctuations. Even when adjusted for numerous covariates (including age, sex, MAP, heart rate, anthropometric parameters, biochemical parameters, and various medical therapies), higher PWV was associated with CF and lower PWV FDor PWV CR but a smaller FFI d Therefore, PWV FD / PWV CF Ratio and PWV CR / PWV CF The ratio (i.e., the elastic-muscular pressure gradient) is d Similarly, a greater pulse pressure amplification ratio (i.e., P PD / P PA , P PF / P PA and P PR / P PA )teeth, Greater FFI d Among them, P PD / P PA FFI d was most closely correlated with FFI. d Similarly, PFI d had a significant independent association with measures of pulse wave amplitude and stiffness gradient. (Table 2) This result is in line with the PFI d is the absolute amplitude of the residual pressure wave (PFA d It was essentially the same even if it was replaced with

[0148] FFI d and PPIs d The independent determinants of PWV were assessed using a stepwise linear regression model. FD / PWV CF Ratio and P PD / P PA ratio and other potential covariates (Table 3). Even when considered simultaneously, P PD / P PA and PWV FD / PWV CF Both are FFI d has been found to be an independent determinant of The two combined accounted for 67% of the total explained variance. d Same as Dear PFI d In addition to age and gender, P PD / P PAand PWV FD / PWV CF was independently determined by

[0149] [Table 2]

[0150] [Table 3]

[0151] (6) Mediation analysis Mediation analysis was performed to examine whether diastolic blood flow variability explained the correlation between arterial stiffness gradient and diastolic blood pressure variability (Figure 7(a)(b)). Figure 7(a) shows that higher PWV FD / PWV CF ratio and greater PFI d This correlation indicates a greater FFI. d Through The direct and indirect outcomes were assessed separately in terms of their mediation through FFI. Mediation analysis revealed that the indirect outcome was highly significant (P<0.001). d is PFI d PWV for FD / PWV CF was estimated to mediate 54% (95% confidence interval: 30-100%) of the total observed effect of PD / P PA When the ratio was evaluated as a predictor variable (Fig. 7(b)), FFI d HA P PD / P PA Ratio and PFI d It was estimated that it mediated 57% (42-80%) of the correlation between [Explanation of symbols]

[0152] 30...blood pressure index calculation device, 42...residual pressure waveform generation unit, 43...diastolic blood pressure variability index calculation unit, 44, 144...pulse pressure amplification estimator, 45, 145...central aortic blood pressure estimator, 46, 146...vascular stiffness evaluation unit, 143...diastolic blood flow variability index calculation unit,

Claims

1. An apparatus for calculating a blood flow index of a test subject, The blood flow velocity at the maximum positive peak of the systolic blood flow velocity waveform with respect to time change of the peripheral artery of the test subject is V FW , the blood flow velocity at the negative peak is V BW , and the blood flow velocity at the next positive peak in the diastolic phase is V FW2 In this case, the diastolic blood flow variability index (FFI) is calculated as follows: d ) diastolic blood flow variability index calculation section [Equation 1] A blood flow index calculation device comprising:

2. The blood flow index calculation device according to claim 1 , further comprising a pulse pressure amplification estimation unit that estimates a pulse pressure amplification based on the diastolic blood flow variability index.

3. The blood flow index calculation device according to claim 1 , further comprising a central aortic blood pressure estimation unit that estimates central aortic blood pressure based on the diastolic blood flow variability index.

4. The blood flow index calculation device according to claim 1 , further comprising a vascular stiffness evaluation unit that evaluates a stiffness of the blood vessel of the test subject based on the diastolic blood flow variability index.

5. A method for calculating a blood flow index in a diastolic phase of a test subject, comprising: The blood flow velocity at the maximum positive peak of the systolic blood flow velocity waveform with respect to time change of the peripheral artery of the test subject is defined as V FW , the blood flow velocity at the negative peak is V BW , the blood flow velocity at the next positive peak in the diastolic phase is V FW2 In this case, the blood flow velocity variability index (FFI) is calculated as follows: d a blood flow velocity variability index calculation step of calculating the blood flow velocity variability index; [Equation 2] A blood flow calculation method comprising:

6. The blood flow index calculation method according to claim 5 , further comprising a pulse pressure amplification estimation step of estimating pulse pressure amplification based on the diastolic blood flow variability index.

7. The blood flow index calculation method according to claim 5 , further comprising a central aortic blood pressure estimation unit that estimates central aortic blood pressure based on the diastolic blood flow variability index.

8. A program for causing a computer to execute a process for calculating a blood flow index of a test subject, Computer, The blood flow velocity at the maximum positive peak of the systolic blood flow velocity waveform with respect to time change of the peripheral artery of the test subject is V FW , the blood flow velocity at the negative peak is V BW , and the blood flow velocity at the next positive peak in the diastolic phase is V FW2 In this case, the blood flow velocity variability index (FFI) is calculated as follows: d ) Blood flow velocity variation index calculation unit [Equation 3] A blood flow index calculation program that functions as a

9. A computer-readable recording medium on which the program according to claim 8 is recorded.

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