Prognostic Value Of Arterial Elasticity Cardiovascular Disease Biology Essay

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It is generally known that the stiffening or loss of elasticity of the arteries by a process known as arteriosclerosis can result with many cardiovascular disorders2. Arteries of people with this disease will be hardened and blocked by fatty deposits.

An important problem being faced by the medical community for a long period of time has been the diagosis of asymptomatic people who are likely to result with cardiovascular disease3.

Firstly, I will mention the definition for arterial elasticity will be mentioned. Secondly, I will describe the link between arterial elasticity and common CV diseases, with associated evidence to prove my statements. Thirdly, I will show the reliability of certain devices which measure arterial elasticity to see its potential as a prognostic indicator.

Arterial Elasticity

Arterial elasticity is defined as the increment in volume per unit transmural pressure that stretches the artery so basically the physical property of a material when it deforms under stress (e.g. external forces), but returns to its original shape when the stress is removed4. It can also be described as arterial compliance.

The higher a substances elasticity, the greater the tendency for it to return to its original shape despite increasing deformation.

The arterial wall has 3 layers which consists of the intima(and endothelium), the media, and the adventitia. These layers have their own roles within the systemic circulation. The vascular tone, haemostasis and vascular permeability are maintained by the vascular endothelium, the media is the major determinant of arterial elasticity, which regulates the conduit function (delivery of blood to tissues) and cushioning effect (for generation of continuous blood flow). Failure of these functions can result in organ/vascular damage. 

The amounts of collagen and elastin(mainly within the tunica media) and their ratio are important determinants of wall stiffness. Experimental studies in hypertensive animals have shown increased extracellular matrix materials have some influence with elasticity5. Differences in these passive components could account for the variation in stiffness between people. In addition, neural, hormonal, and physical stimuli can activate smooth muscle cells which can lead to a reduced lumen diameter.

These substances give the blood vessel the ability to stretch in response to each pulse. Elasticity also gives rise to the Windkessel effect. This helps maintain a relatively constant pressure in the arteries regardless of the pulsating nature of the blood flow. Elastic arteries include the largest arteries in the body, those closest to the heart(conduit arteries). They also give rise to medium-sized vessels known as distributing arteries (or muscular arteries).

Other factors associated with elasticity are the non-linear stress strain relationship (which is seen as an increase in stiffness as a blood vessel is distended or stretched longitudinally), anisotropy(directionally dependent), visco-elasticity(exhibit both viscous and elastic characteristics when undergoing deformation) and the presence of residual stresses. This last property refers to the forces that remain within the vessel wall when all external loads have been removed. They are revealed by the tendency of a ring-shaped vessel segment to spring open into a horseshoe shape when cut along a line parallel to its long axis, and are thought to have evolved to minimize the stress gradients that inevitably arise across the wall of a pressurised tube6.

An important role in the atherosclerotic process involves arterial endothelial dysfunction and endothelial damage which can reduce arterial elasticity or increase the arterial stiffness, which can especially occur within the smaller arteries. The endothelium has a number of functions. An intact endothelium can maintain vasomotor tone and compliance, there is also an association between alterations in flow and changes in vessel diameter and synthetic activity which leads to alignment of the endothelial cells with the predominant direction of flow and remodelling of the entire vessel due to increased synthetic activity of the vascular smooth muscle cells(VSMC).

The functional stiffness of a blood vessel, that is a measure of the relative change in its diameter in response to a known change in pressure, defined by Mackenzie et al. as the 'elastic modulus' (although more often known in the literature as 'elastance', 'pressure-strain' or 'Peterson' modulus) is of more concern to the clinician for two reasons. Firstly, it is easier to measure, because it does not require knowledge of vessel wall thickness; secondly, it is an important determinant of the reservoir function of the large arteries (see below). Functional stiffness (Ep) is related to structural stiffness (Y) by the approximation as shown below:

Ep≈ Y x h/r 6

h= thickness of vessel wall, r= midwall radius

A high value of Ep indicates that for a given pulse pressure, the proportional change in lumen diameter would be relatively small. The Ep measurements are given in kilopascals (kPa) (1 kPa = 7.6 mm Hg).

Cardiovascular diseases can cause increased morbidity and mortality due to being related primarily to structural and functional alterations of the arterial wall. Changes in the arterial wall can lead to increased arterial stiffness, which has been shown to influence cardiovascular prognosis adversely. Therefore, the ideal situation would be to discover it early, before symptoms are detected or irreversible damage has occurred. Measuring arterial stiffness or elasticity has been recommended in the preventative management of cardiovascular disease.

Relationship between elasticity and cardiovascular diseases


Studies have been used to determine arterial elasticity in normotensive and hypertensive individuals. An evaluation of large artery and small artery elasticity in 212 normotensives (with and without a family history of hypertension) and hypertensives (treated and controlled or untreated and uncontrolled) demonstrated that both large artery and small artery elasticity indices were significantly higher (P<0.0001) in normotensives without a family history compared with untreated and uncontrolled hypertensives. After controlling for age and BSA, there was a significant linear trend (P=0.0001) across the four groups in these elasticity indices. As hypertension status worsened, large and small artery elasticity decreased, suggesting a potential for the diagnostic use of arterial elasticity determinations8.

In addition, ecologic comparisons of aortic pulse wave velocities in China showed an increased mean pulse wave velocity in a population with a high prevalence of hypertension15.

Myocardial Infarction and Diabetes Mellitus

There have been various studies linking cardiovascular disease to increased elasticity. Studies have shown that myocardial Infarction(Ml) and diabetes Mellitus (DM) are related to increased Ep9. In addition, black people have been shown to have a higher Ep. Speculatively, since blacks have greater cerebro-vascular disease mortality rates than do whites independent of blood pressure levels, the pathogenesis of cerebro-vascular disease may be related to factors associated with increased arterial wall stiffness7.

Increases in Ep of 7 to 9 kPa observed in children with reported parental histories of Ml and DM. These percentage increases in Ep, representing over one-half of its overall standard deviation, are greater than the previously observed increases in children and adolescents of levels of serum lipids, lipoproteins, and blood pressure associated with parental disease12. Others have shown that familial clustering of risk factors cannot entirely account for the familial aggregation of clinical disease, and the results of the current study suggest that the heritability of differences in arterial wall stiffness may be important in the aggregation of CVD.

Figure 1


Atherosclerosis has two components of vascular changes, namely morphological thickening (atherosis) and functional stiffening (sclerosis) of arterial wall10. Arterial wall thickness is non-invasively measured by ultrasonography11 and carotid artery intima-media thickness (CA-IMT) is the standard index of arterial wall thickening.

Animal studies indicate that elevated Ep levels are associated with the development of early atherosclerotic lesions in the carotid arteries. In previous work with male cynomolgus macaques (M. fasdcularis), mean Ep in animals fed a high cholesterol diet for 18 months was 109 kPa higher than in animals given standard monkey chow. The corresponding mean percentage stenoses in the carotid arteries were 30% and 0%, respectively13. Similarly, other work has demonstrated increased aortic pulse-wave velocities associated with increased Ep levels In cynomolgus monkeys fed an atherogenic diet and decreased pulse- wave velocities in rfesus monkeys undergoing regression of atherosclerosis14. More shall be mentioned about the relation between pule wave velocities and stiffness later. In addition, an abstract report on the use of M-mode ultrasound to determine aortic wall movement found increased Ep values in men with both angina and a positive stress test (as compared to age-matched controls) and in cholesterol-fed rabbits.

Several possibilities for the association between arterial stiffness and atherosclerosis can be hypothesized. First, the presence of atherosclerosis could lead to stiffening of the arteries. Second, increased arterial stiffness could lead to vessel wall damage and atherosclerosis. Third, both mechanisms could apply, and atherosclerosis not only would be a consequence of arterial stiffness but may by itself in advanced stages also increase arterial stiffness.


Evidence has also been found to show a correlation between age and decrease in arterial elasticity as can be seen below in figure 3. This has considered due to the lack of productivity of elastin after birth, and it therefore being used up. Also, trials have been undertaken on animals such as pigs. Trials have shown that the number of cycles to failure of pig aortic elastin rings increases as the maximum extension of the ring during each stretch cycle is reduced16 ­ as shown in figure 2. In other words, the greater the stretch, the sooner the failure. Such behaviour is characteristic of elastomeric fatigue fracture.

As suggested by researchers, fatigue failure is the result of fragmentation of arterial elastin which is said to cause this thinning of elastin.

Figure 2: Fatigue failure

Figure 3: Related changes in blood vessel due to age

In summary, ageing is associated with fragmentation of elastic lamellae increased aortic collagen synthesis and consequent increases in elastic modulus. The response of other vessels may differ from that of the aorta.

Ultrasound may be an important technique to detect early atherosclerotic lesions in epidemiologic studies and could further elucidate the role of risk factors in the development of CVD. Atherosclerosis in the carotid arteries is moderately associated (r = 0.4 to 0.5) with lesions in the coronary arteries. In addition, since the associations between Ep and parental histories of Ml and DM are independent

of TC and blood pressure, the elastic modulus may be important as an additional marker for future clinical disease.

In addition, experiments have shown an increase in CA-IMT in high-risk populations including elderly people17, patients with ischemic heart disease17, hypertension17, type 2 diabetes mellitus18, and chronic kidney disease19. Arterial wall stiffness has been non-invasively evaluated by measuring pulse wave velocity (PWV) of the aorta20 and other arteries21 and 22. Also, there are other indices for arterial stiffness including arterial compliance, distensibility, elastic modulus, incremental modulus of elasticity, and stiffness parameter β 23. Stiffness of carotid artery24 and the aorta25-29 has been shown as an independent predictor for death from CVD in high-risk populations.

Measuring elasticity

Arterial elasticity can be measured by several techniques, many of which are invasive or clinically inappropriate. Direct methods include magnetic resonance imaging and ultrasound. Indirect methods are pulse wave analysis which includes pulse wave velocity and augmentation index. These are useful in rapid assessment of arterial compliance by the bedside. At this time, there is no gold standard for its measurement.

In recent years, non-invasive imaging techniques have been playing an increasingly important role in detecting the development of cardiovascular disease. Several methods focus on the measurement of pulse wave velocity, the velocity at which the pressure wave propagates, because it is directly related to arterial elasticity/stiffness.

Pulse wave velocity (PWV)

The recent expert consensus document on arterial stiffness describes carotid-femoral PWV as the 'gold standard'measurement of arterial stiffness30. PWV is a simple measure of the time taken by the pressure wave to travel over a specific distance. This is generally undertaken by finding two blood flow waveforms using an ultrasound probe at two different locations of an artery. The delay in time of the two points divided by the distance gives us the pulse wave velocity. During each heart beat a pulse wave travels from the heart down the arterial wall in advance of blood flow31. The more rigid the wall of the artery, the faster the wave moves.

These changes can have significant clinical implications in terms of coronary artery blood flow and can contribute to an increase in systolic blood pressure.

When the left ventricle contracts, it generates a pulse wave which travels along the great arteries at a velocity proportional to the square root of Ep. This 'pulse wave velocity' (PWV) therefore depends on the combined effect of material stiffness and relative wall thickness as shown by the equation above6. It is worth emphasizing that the pulse wave velocity differs from the velocity of the blood in much the same way that the speed of a breaker approaching a beach differs from that of the much slower moving tide.

It is generally thought that many cardiovascular disorders are associated with increasingly rigid arterial walls from arteriosclerosis. The relationship between the pulse wave velocity and the elasticity of a thin-walled elastic tube filled with an incompressible fluid is expressed by the Moens-Korteweg Equation.


pDPWV=√ 6

As shown, PWV is related to the square root of Young's modulus of elasticity (E), so the higher the PWV the more stiffer an artery would be. Blood density-p , Density-D, h-Wall thickness

There are multiple trials that show that increased aortic PWV is associated with poor cardiovascular outcome. Increased aortic stiffness, as evidenced by measurement of aortic PWV, is associated with mortality in patients with end-stage renal disease32, essential hypertension34 and Type 2 diabetes mellitus33. Meaume et al.

35 studied rehabilitation patients in a Paris hospital and showed that, between the ages of 70 and 100 years, PWV could predict cardiovascular death. These findings were extended by the demonstration that, even among healthy older adults in their eighth decade, PWV was associated with cardiovascular mortality35. In a multivariate analysis with adjustment for pulse pressure and other variables, PWV remained associated with all end points, except congestive heart failure.

In addition to its predictive value for mortality, PWV can also predict primary cardiovascular events. Boutouyrie et al. 36 studied over 1000 subjects with

hypertension, and showed that a 1 S.D. rise in PWV was independently associated with a relative risk of a coronary event or cardiovascular event of 1.42 and 1.41


It should also be remembered that aortic PWV is solely a measure of large artery segments and offers no insight into the status of smaller blood vessels.

Pulse wave analysis(PWA)

PWA involves analysing the shape of the pulse wave to provide information about arterial elasticity and wave reflection distal to the measurement site, along with pulse pressure. It can also give us information about pulse pressure. It can help define the arterial system as a whole but has been said to rely more upon 'empirical foundations6.

It is currently impossible to use such technologies for the direct study of small vessels. Small blood vessels constitute a considerable part of the vascular network and are preferential targets in diseases such as diabetes mellitus and hypertension. Assessment of smaller arteries may allow much earlier identification of disease.

Stiffening of small arteries alters the magnitude and timing of reflected waves that

can often be identified visually in late systole or more reliably by computer analysis of the diastolic pressure decay part of the pressure waveform.

Unfortunately, since it is not currently possible to directly measure the mechanical properties of small vessels in vivo, results obtained by model-based analysis of arterial waveforms remain inconclusiveand more long-term data about the prognostic capabilities of such techniques are eagerly awaited. Pulse waveform analysis permits the identification of changes in waveforms and attempts to interpret that change in relation to a change in the mechanical properties of arteries. However, it must be remembered that this technique does not provide any direct assessment of the mechanical properties of blood vessels.

Augmentation Index(AI)

To calculate the augmentation index, we first need to find the augmentation pressure (AG) which is the measure of contribution that the wave reflection makes to the systolic arterial pressure or pulse wave, and it is obtained by measuring the reflected wave coming from the periphery to the centre as in from arterial bifurcation points, principally that of the distal aorta itself or the renal and femoral arteries, these waves are reflected back so that they reverse direction and travel back to their point of origin, becoming what are called wave reflections. A perfectly elastic aorta absorbs all the pulse wave generated by ventricular  contraction, whereas a completely rigid tube reflects a large proportion of the wave. Reduced compliance of the elastic arteries causes an earlier return of the 'reflected wave', which arrives in systole rather than in diastole, causing a disproportionate rise in systolic pressure and an increase in pulse pressure (PP), with a consequent increase in left ventricular afterload and a decrease in diastolic blood pressure (BP) and impaired coronary perfusion.

The augmentation index is therefore defined as the proportion of central pulse pressure due to the late systolic peak, which is in turn attributed to the reflected pulse wave. It is an indirect measure of arterial stiffness and increases with age, and it is calculated as AG(augmentation pressure) divided by PP x100 to give a percentage. With an increase in stiffness there is a faster propagation of the forward pulse wave as well as a more rapid reflected wave.

Studies have supported an association between augmentation index and the risk of cardiovascular and total mortality. Although it cannot be concluded that augmentation index predicts cardiovascular risk, results have shown the use of augmentation index in clinical studies in which arterial stiffness is assessed.

However, many studies have shown augmentation index to be somewhat unreliable. In additions, there have been clinical studies to see if augmentation index (AI) and pulse wave velocity (PWV) are closely correlated. They are not identical, having (like many of the other measures mentioned above) different units of measurement. 

A study investigating vascular function in Type 1 diabetes mellitus revealed an increased augmentation index in tandem with elevated PWV [119], although this finding has not always been duplicated[120]. The augmentation index was found to be elevated in subjects with hypercholesterolaemia [121].

Since the augmentation index can be affected by,multiple factors (LV ejection, PWV, timing of reflection, arterial tone, structure at peripheral reflecting sites, BP,

age, gender, height and heart rate) and the concern over the accuracy and validity of central augmentation index derivation from pulse waveform analysis, it is difficult

to see how it can provide clinically useful data in the assessment of intervals with hypertension or cardiovascular comorbidity [129].


As shown in this write-up, cardiovascular disease is associated with an increase in arterial elasticity, which therefore has a significant impact on the prognosis. This is a proven fact. However, to find an appropriate measure for arterial elasticity is debatable. No measure currently represents a complete description

of wall properties and all techniques have theoretical, technical and practical limitations [1]. However, it has been shown that increased CA-IMT is a significant predictor of death from cardiovascular disease (CVD) independent of other classical risk factors. Pulse wave analysis has had difficulties with detecting those with atherosclerosis and heart failure. Pulse wave velocity has been shown to be the gold standard test for arterial elasticity so there in some promise regards to that, therefore the possibility remains that this can be a suitable method for assessing cardiovascular risk. However until a suitable method of measuring arterial elasticity has been found which can relate to cardiovascular risk, it remains to be seen whether we can truly measure the prognosis of arterial elasticity on cardiovascular risk.

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