Method for and Evaluation of the Indirect Measurement of Arterial Stiffness Index

Department of Physiology, Kyorin University School of Health Sciences
Hideaki Shimazu

INDEX

We have developed a system that employs the principles of the oscillometric method (a highly accepted method for determining indirect blood measurement) which, in addition to measuring pulse pressure value and heart rate, also provides an index (ASI) for the degree of arterial stiffness. ASI possesses enormous significance for determining the efficacy of various diagnoses and treatments for hypertension. Since ASI is a new index, its measurement principles and clinical meaning are not yet fully understood. In order to clearly ascertain the meaning of ASI, we explain the fundamental principles of blood pressure measurement in this paper. Next, we indicate the method and way in which ASI is resolved, and explain ASI’s meaning. We also introduce fundamental ASI-related data.

1. Principles and Characteristics of Indirect Blood Pressure Measurement Based on the Oscillometric Method. 

When employing the oscillometric method to measure blood pressure, pressure is applied to a cuff wound around the arm of the patient. Blood pressure is then measured from very slight oscillations generated within the cuff when pressure is applied. As with auscultation, the arm is wound around the arm and pressure is raised above systolic pressure. Pressure is then reduced. As pressure is reduced, the pulsation of the artery varies, and very slight pressure changes occur in accordance with this arterial volume-pressure variation. The oscillometric method determines blood pressure based on these slight pressure variations.

When cuff pressure is raised above systolic pressure and then reduced, the pulse wave amplitude suddenly becomes wide near systolic pressure, and then gradually increases until it reaches its greatest width near mean pressure. The oscillometric method may be explained from studying the causes of this pulse wave amplitude variation.

1-1 Arterial Vascular Pressure-Volume Characteristics

The elastic fibers and collagen fibers of the arterial wall provide the arterial wall with its extensibility characteristics. Roach and Burton applied formic acid to the artery to selectively remove its collagen fibers and then investigated the extensibility characteristic of the inner membrane and tunica media, which are mainly composed of elastic fiber and smooth muscle. The result was that the layers of inner membrane and tunica media proved to be rich in extensible protein character fibers, and that since these were bundled together in a disorderly direction, it was clear that the elasticity coefficient was low and extensibility was high. Roach and Burton also applied trypsin to the arteries and blood vessels, removing the inner membrane and tunica media, and investigated the extensibility of the outer membrane’s collagen fibers. The result was that the collagen fibers proved high in dynamic strength compared to the elastic fibers, but their extensibility was strikingly low.

Using these results, we will consider the movement power (inner pressure) in the arteries and the extensibility of each of the arterial membranes.

Figure 1 displays the arterial structure and extensibility. As indicated in the figure, since the outer membrane is not stretched or extended in regions of relatively low pressure in an artery, arterial wall extensibility depends primarily on the properties of the inner membrane and tunica media. The layers of these membranes possess high extensibility, and the arterial wall indicates large elongation depending on variation of inner pressure. As a result, in high-pressure regions, the inner membrane and tunica media extend adequately and the outer membrane that covers the arterial exterior also extends. At this time, the extensibility of the whole vascular segment is decided based upon the properties of the outer membrane, which has the lowest extensibility. Thus, the arterial extensibility, corresponding to pressure variation, becomes strikingly low. Arterial inner pressure increases and volume variation, in particular differences between the tunica media and outer membrane's elastic modulus and manners of working, may be explained in terms of springs. We will describe the tunica media characteristic as a soft or limp spring and the outer membrane characteristic as a hard spring. Since force moves in the soft spring (tunica media) when the inner pressure is in a low state, elongation or stretching becomes larger with variations in inner pressure. When the inner pressure increases even further, arterial volume increases, and after elongation or stretching proceeds beyond a certain point, the hard spring (outer membrane) will respond and the arterial extensibility will decrease.

As displayed in Figure 2, the property of a normal artery manifests as the result of the synthesis between the properties of the tunica media and the outer membrane, and variation in vascular extensibility depends upon the rise and fall of inner pressure.

In this manner, since the three membranes composing the arterial wall all possess different extensibility properties, the arterial pressure volume property depends on the inner pressure (or on the volume) and is unique. In Figure 3, the relationship between the arterial pressure-volume property and the volume pulse wave is modeled. The vertical axis represents pressure, and the horizontal axis represents arterial vascular volume. As shown in the same figure, the arterial pressure-volume property indicates a strong non-linearity, and does not indicate volume variation, which is in proportion to pressure variation. Thus, even in the case that arterial pressure is equal, if the inner pressure acting within the blood vessel differs, a change in the size of the volume variation corresponding with that pressure will be generated in regards to the arterial pressure.

1-2 Principles of Blood Pressure Determination

Figure 4 represents the blood pressure added to the artery during blood pressure measurement. For measuring blood pressure, a cuff is wound around the arm and compressed with air. At this time, the artery is compressed as a result of cuff pressure. The pressure added from outside the artery by the cuff occurs in addition to the arterial inner pressure (the pressure produced by pulsation of the heart , i.e. the blood pressure inside the arterial wall).

In this situation, the "pressure" of the pressure-volume property vertical axis in Figure 5, which displays pulse wave variation produced during decompression, may be considered as the difference between the inner and outer arterial pressure (transmural pressure), in other words, the difference between blood pressure and cuff pressure. When the cuff pressure displayed in the figure is 0 during measurement, the only pressure active in the artery is the blood pressure, and the arterial volume variation produced by this pressure appears as 7 in the figure. When the cuff pressure is a larger value than systolic pressure (difference between arterial inner and outer pressure is negative), the volume variation appears as 1 in the figure. When gradually reducing cuff pressure from a pressure above systolic pressure, arterial volume varies with cuff decompression and the amplitude varies as reflected in 1 to 7. In other words, as pressure decreases, the artery expands and the amount of arterial pressure-volume variation corresponding with pulse pressure gradually becomes larger. When the mean arterial inner-outer pressure is equal, the volume variation corresponding with the pressure variation (pulse pressure) reaches its largest point as indicated in 2 in the figure. As a result, the cuff pressure where the pulse wave amplitude reaches its highest point is identical with mean pressure.

When cuff pressure reaches the mean blood pressure area, the inner and outer arterial pressure is on average 0. In this area, since the extensibilities of the inner media and tunica media are at their greatest point, the arterial pulsation, in other words, the volume variation, also reaches its greatest point at this time. Since elastic modulus increases simultaneously with swelling of the artery when cuff pressure is further reduced, the pulse wave amplitude decreases. When cuff pressure falls below diastolic pressure, the artery becomes even stiffer, and the pulse wave amplitude rapidly becomes small. This is due both to the fact that the outer membrane characteristic manifests in regards to arterial swelling and that the elastic modulus of the collagen fibers forming the main component of the outer membrane causes the artery to become stiff.

Since there are limits in the extent to which the cuff can effectively be compressed during actual measurement, the oscillometric method cannot correctly measure systolic pressure by depending upon the existence or non-existence of the pulse wave. There is also no sufficient explanation of a logical basis for determining diastolic pressure. In determining systolic and diastolic pressure, an analysis program has been prepared to improve concordance with blood pressure values derived from the auscultation method. The result is that that the blood pressure values of oscillometric and auscultation match relatively well on a statistical basis. With the CardioVision, cuff compression and decompression are conducted automatically, and in this process the pulse wave amplitude variation is analyzed and blood pressure is determined. Figure 6 displays the relationship between the cuff pressure and arterial amplitude that appear during the indirect measurement of blood pressure using the oscillometric method. In the oscillometric method, systolic pressure is determined as the pressure corresponding with the increased point of pulse wave amplitude, mean blood pressure as the largest point of amplitude, and diastolic as a sudden decrease in amplitude.

Thus, the computer becomes essential for measurement with the oscillometric method and for pattern analysis. Since the oscillometric method includes an automatic analysis program, it has the following merits.

1. Subjectivity of the measurer is not a factor in accuracy of measurement.

2. Unlike the auscultation method where a microphone is used, the operation of precise application to the upper arm position is unnecessary and is also effective against noise.

For these reasons, the oscillometric method is being increasingly used for infants and newborns and in households as well. In the clinical field, it is finding increasing use as an easy-to-use blood pressure monitor.

1-3 Why Is Arterial Volume Variation Acquired from Cuff Pressure Variation?

In blood pressure measurement using the oscillometric method, the arterial volume under cuff pressure is measured as slight variations in cuff inner pressure. In fundamental explanations of blood pressure measurement, the relationship between blood pressure and arterial volume variation is employed in the determination of blood pressure. For this reason, it is essential to precisely confirm to what degree cuff inner pressure variation corresponds with arterial volume variation.

We will now consider measurement of blood pressure on the upper arm. In the area underneath the cuff, we assume that an arterial volume (load) variation ��V is generated from one cardiac output (stroke volume). Since the tissue surrounding the artery may be considered to possess incompressible characteristics, the arm volume variation equals the arterial pressure variation. The cuff covering the circumference of the arm is inflated with air. Since the edges of the cuff are restricted with fabric that is not extendable, the arm volume variation is identical to the volume variation of the air in the cuff.

Now, when only ��V of the arm volume variation increases, the cuff indicates a −��V volume variation. During blood pressure measurement, V is the amount of air in the cuff and thus is the average pressure. In a constant temperature situation

P×V＝constant＝k

is established from a gas state equation.

Since −��V volume variation in regards to the cuff is provided by arterial volume variation generated from cardiac pulsation, volume variation ��P is generated in accordance with this volume variation. At this time, since the equation

（Ｐ＋�凾o）×（Ｖ−�凾u）＝ｋ

is established, if ��P��V is ignored because it is miniscule in comparison with other terms, the equation becomes

P×V＋V×��P−P×��V＝ｋ

and when P×V＝ｋis substituted, the equation becomes

V×��P−P×��V＝０

Thus, the volume variation ��V is expressed as

��V＝��P×V／P

After the cuff was applied experimentally and the relationship between the cuff inner pressure and the air volume was investigated, it proved that when pressure was reduced from systolic pressure to the diastolic pressure area, P／V increased gradually from systolic pressure value (the beginning value), but variation in this range remained within 20% and even if one considers this as a constant value, one may conclude that precision measurement of volume variation has no effect on blood pressure determination. Moreover, P／V value variation was under 5% for mean pressure area cuff pressure variation of approximately 20mmHg. The ASI standard value ranged from approximately 30 to 80, corresponding with cuff pressures of 3 to 8 mmHg. In this case, error was further reduced. When ASI is computed with this method, it is safe to assume that no significant problem arises in computing volume change from slight variations of cuff pressure.

2. Classification and Evaluation of Circulation Dynamics Using CardioVision

In general, since the pulse wave is determined from the relationship between the pulse pressure and the arterial pressure-volume characteristic, the pulse wave amplitude variation changes with the pulse pressure or the arterial elasticity property variation. The pulse pressure is determined from one stroke volume and the arterial elastic modulus.

On the other hand, since the arterial pressure-volume property is influenced by circulation dynamics during measurement, the pulse wave varies specifically according to various diseases. In the oscillometric method, since blood pressure is determined as the cuff is gradually decompressed, the pulse wave amplitude pattern manifests from the arterial volume variation (elastic modulus variation) causing variation in the difference in arterial inner and outer pressure (transmural pressure) and the pulse pressure. Since these parameters vary according to different types of circulatory disease and circulatory dynamics, the pulse wave pattern also varies. Until now, pattern variation was thought to be only an error factor (the causes of which were unknown) in precision blood pressure determination.

CardioVision analyzes the relationship between the pulse wave amplitude pattern appearing during blood pressure measurement employing the oscillometric method and circulatory dynamics, and then classifies the results into the 5 basic patterns A to E displayed in Figure 7.

A record obtained from a normal circulatory system displays as A (see Figure 8). When arterial stiffness is normal, the pulse wave during cuff decompression appears at the point at which cuff pressure approaches systolic pressure. It increases after this point, and after reaching its greatest amplitude, gradually decreases. The size of pulse wave amplitude is determined by arterial extensibility and the size of a single cardiac output. A pulse wave amplitude which extends to its greatest length after systolic pressure is reached and then subsequently decreases appears as a mountain shape with a single peak. This is classified as Pattern A.

Pattern B appears in case of low blood pressure, anemia, and shock. Arterial extensibility is normal, but since cardiac output is reduced, pulse pressure and pulse wave volume variation become small in accordance with falling blood pressure. This case is indicated with a mountain-shaped pattern of low amplitude.

Pattern C appears in the case of arterial stiffness, diabetes, obesity, old age, and high stress. These diseases are said in general to lower arterial elasticity. Pattern C appears because the mechanical properties of arteries in these cases differ from normal arteries. As indicated in Figure 9, when the arterial has undergone stiffening, this stiffening may be considered to have begun originally when damage occurs in part of the arterial inner membrane and tunica media containing smooth muscle and collagen fibers rich in extensibility. The impaired areas undergo thickening of the arterial wall and collagen formation (adhesion) and then subsequently become stiff. In comparison with normal or healthy arteries, the pressure-volume variation displays in particular a sharp linear line from the point at which the arterial inner and outer pressure difference is 0. When this is measured with CardioVision, the resulting arterial volume variation displays a wide flat pattern where the cuff pressure and mean pressure are either equal or near equal (see Figure 10). The extent of arterial volume variation becomes smaller in regards to constant pulse pressure due to lowered extensibility, but when the artery is stiff, or when strong stress is added to the circulatory system, since blood pressure rises and pulse pressure becomes large due to increasing vascular resistance, lowering of arterial extensibility does not necessarily cause the size of the pulse wave amplitude to fall. In CardioVision, with the goal of evaluating Pattern C, a numerical value is calculated to correspond with the width of the flat part of the pulse wave, which is the pattern's characteristic. Since this value increases with the stiffness of the artery, it is possible from this value to present the Arterial Stiffness Index (ASI) as numerical number information.

Pattern D is revealed in the case of arrhythmia. With arrhythmia, since the heart's diastole is not constant, one-time cardiac output becomes irregular. As a result, since the blood pressure value and pulse pressure from one stroke volume changes to a large degree, measurement of blood pressure becomes difficult. Moreover, since the arterial volume variation is not constant, both the pulse wave amplitude and the pattern displayed from the pulse wave width become irregular (see Figure 11).

Pattern E appears in cases of cardiac disease. In many types of cardiac disease, low cardiac output is maintained, and if this situation is prolonged, circulatory reflexes occur to maintain steady blood pressure. Among these, smooth muscle stress occurs in many arteries, and the conditions become different from those for a normal arterial pressure-volume characteristic (see Figure 12).

3-1 The Meaning of ASI

Figure 13 indicates a comparison of a normal artery pattern and a sclerotic artery pattern in regards to arterial pressure-volume characteristic. As the figure indicates, in the area where arterial inner pressure is low due to a stiffened tunica media, a steeply increasing linear slope indicates the pressure-volume relationship. As a result, the bent line for the whole arterial segment pressure-volume characteristic moves in an upward direction. The figure's vertical axis may be substituted for blood pressure-cuff pressure in arteries undergoing pressure added from the cuff. Thus, with the pulse pressure under a constant state, the pulse wave amplitude during cuff decompression manifests as this pattern. In the same figure, in the case of a tunica media with normal elasticity, the pulse wave pattern indicates the previous peaked mountain shape (a in Figure 13), but in a sclerotic artery, the pulse wave amplitude pattern shape becomes trapezoidal (b in same figure). The upper part of the trapezoid width is equivalent to the range or width when in the process of cuff decompression the difference between blood pressure and cuff pressure (transmural pressure) passes the pressure part corresponding with the linear part of the tunica media.

Since this range or width indicates time in pulse wave sequences obtained in actual measurement, the range seen in measured patterns varies with the speed of cuff decompression. If one, rather than considering the upper part of the trapezoid as time, considers the flat area as cuff pressure variation corresponding with this range or width, the flat region may be expressed as information truly independent of decompression velocity. This range or width is expressed in units of pressure and corresponds with the arterial pressure-volume characteristic that depends on the elasticity of the tunica media. Thus, if the tunica media is soft, the pressure range or width corresponding with the linear part becomes small, and in the reverse situation, if the tunica media is stiff, this range becomes wide. If we view the tunica media pressure-volume characteristic as a linear (straight line), the pressure range or width is in direct proportion with the elastic modulus.

When the cuff pressure variation part corresponding with the trapezoidal upper part, (which is recognized in pulse wave amplitude example patterns) is detected, the pressure range or width becomes a value in direct proportion to the elastic modulus of the arterial tunica media level. In this research, this pressure value was applied as an index from which arterial stiffness can be determined by designating the arterial stiffness index as

ASI=cuff pressure range (corresponds with pulse wave pattern trapezoidal part) X10

3-2 Fundamentals of ASI (Arterial Stiffness Index) Calculation

Figure 14 displays the relationship between ASI and the arterial pressure-volume characteristic. The upper part of the figure displays the arterial pressure-volume characteristic while the lower part displays the relationship between the cuff pressure during actual blood pressure measurement and the pulse wave pattern. From the figure, the ASI is understood to be in direct proportion with the tunica media elastic modulus, which falls within the arterial elastic modulus.

When actual measurements are conducted based on this method, the pulse wave sequences do not necessarily form a perfect trapezoidal shape but frequently exhibit a gentle curved shape. This is because the tunica media characteristic displayed here does not exhibit a linear line and also because of the manifestation of combined characteristics with the outer membrane. For this reason, in calculating the pulse wave trapezoidal part in this research, the pattern's highest value was confirmed as 100% and the area from that point to the point where the pulse wave amplitude falls to 80% as the flat part. Within this range, a detailed detection of the flat part is conducted. The areas between pulse waves are filled in with imaginary pulse wave sequences, and after applying noise correction smoothing using mobile addition averaging, the flat region is calculated as the area where the pulse wave height variation is within 5%.

One can also explain the meaning of ASI using a different expression. In Figure 15 the arterial pressure-volume characteristics of a normal artery and sclerotic artery are indicated on the left-hand side. A bent line with an incline indicates arterial compliance. Arterial compliance expresses arterial softness or extensibility. The right hand graph in the figure indicates the change of compliance in arterial inner pressure with regards to the two types of arteries displayed on the left-hand side of the figure. In this case, the compliance characteristic of a soft artery becomes suddenly and characteristically large near an inner pressure of 0. On the other hand, in the sclerotic artery, the compliance value remains high in comparison with the normal artery from 0 across a fairly high inner pressure range. However, the compliance value for the sclerotic artery does not become all that large nor does the compliance-pressure value vary that much in a high compliance value region, rather it becomes a flat-shaped graph. Figure 16 explains the dynamic meaning of the artery as indicated by ASI, measured using CardioVision.

4. Points of Difference Between ASI and Other Arterial Stiffness Indexes

4-1 Pulse Wave Velocity

The Pulse Wave Velocity indicates the velocity of the pulse wave transmitted through the artery. The arterial pulse wave velocity is expressed in the following manner.

PWV＝√（Ｅ・h／ρ・Ｄ）

　　　　　　　Ｅ＝arterial elastic modulus （Young's Modulus)

　　　　　　　ｈ＝arterial wall  thickness

　　　　　　　ρ＝blood density

　　　　　　　Ｄ＝arterial diameter

Here, a large E corresponds with a sclerotic artery. ρis blood density, but may be considered to be constant within the circulatory system. Moreover, in considering an analogous shape for the artery, since h/D becomes constant, differences in arterial thickness arising from differences in physique and other factors are unrelated to the PWV.

Thus, in the case of arterial stiffness, since E and h become simultaneously big, PWV also increases. The PWV is measured clinically from the distance and time between a heartbeat and arm and peripheral artery pulse wave emission (see Figure 17). Moreover, since PWV is expressed as the square root of variation in several factors, the rate of that variation becomes small in relation to the original values. The fact that PWV is related to age also suggests a relationship with arterial wall stiffness. In addition, it is said that PWV can detect hypertension and diabetes early stage angiopathy. 

However, when this index is applied clinically, sufficient care is necessary during blood pressure measurement. As explained previously, the dynamic characteristic of the artery is dependent on arterial inner pressure. Since arterial stiffness varies with the degree of arterial swelling, even if the blood pressure is at a normal level, the artery may swell to the point at which it causes the outer membrane to stretch or expand when a load of inner pressure is at work inside the artery. The artery's Young Modulus E becomes large in a non-linear fashion with the increase in arterial inner pressure, and thus, PWV varies with pressure. For these reasons, if the blood pressure varies when measuring the same person with the same artery, PWV will vary. In particular, since medications for reducing arterial stiffness and blood pressure are used in combination when treating arterial stiffness, it becomes essential to determine which of these medications causes a reduction in pulse wave velocity. Thus, PWV cannot be employed as an index to directly compare measurement values.

4-2 Compliance

Compliance (C) is the proportion (relationship) of arterial volume variation (△V) and pressure variation (ΔP) and thus is defined as  

Ｃ＝ΔＶ／ΔＰ

As explained previously, when the compliance value is large, the artery is soft. As is clear from the arterial pressure-volume characteristic, arterial compliance is large when blood pressure is low and low when blood pressure is high. The compliance value varies according to the extent to which the arterial wall is being stretched. In other words, compliance varies with arterial inner pressure (blood pressure). For this reason, when expressing arterial stiffness with compliance, it is impossible to determine which artery is stiffening by comparing compliance alone.

Moreover, since the size of the artery undergoing measurement influences compliance, an even greater arterial pressure-volume variation is indicated in a large artery of a large subject in response to the same pressure variation; consequently, the compliance measurement value increases with the thickness of the artery. Thus, comparing compliance in arms of different size in thickness becomes a problem.

It is not easy to directly measure compliance in actual measurement of living organisms. Instead, the pulse pressure may be employed as an easily measured index. The pulse pressure is an index related to circulatory system compliance. For instance, if one assumes that the blood volume ΔＶ transmitted through the circulatory system from one stroke volume is constant, the arterial inner pressure variation ΔＰ that appears as pulse pressure may be expressed as

ΔＰ＝ΔＶ／Ｃ

From this equation, it may be understood that ΔＰ is in indirect proportion to compliance, and in the same way that compliance is dependent on blood pressure at the time of blood pressure (mean blood pressure) measurement, the pulse pressure is also an index related to mean pressure during measurement.