Evaluation of arterial function

1.9.3.1 Measures of arterial remodelling

Currently, assessment of arterial pressure in routine clinical practice is confined to measurement of peak systolic and end diastolic pressure by sphygmomanometry at the brachial pulse. These measurements provide only a limited summary of the arterial pulse wave however, and furthermore may not be an accurate representation of the pressure within central arteries. Given the complexity of the arterial wave form, a more comprehensive analysis may allow for a better understanding of the cardiovascular sequelae of disturbances in arterial function.

As described in section 1.6, the arterial system has two closely related functions. Firstly, there is a conduit function, by which blood is delivered from the heart to peripheral tissues which is achieved largely due to the composition of peripheral arteries. Secondly, there is a cushioning or ‘Windkessel’ function, whereby the oscillatory flow produced by left ventricular contraction is converted to smooth flow delivered to peripheral vessels. This is largely achieved by the viscoelastic nature of the large, proximal arteries, whereby a fraction of the energy produced is systole is converted into potential energy within the elastic vessel walls, which recoil during diastole resulting in forward flow of blood reserved within the vessels. This has the effect of dampening peak systolic pressure and increasing end diastolic pressure, protecting tissue capillary systems from extremes of pressure.

The effectiveness of this second function is dependent on the elasticity and structure of the vasculature. This elasticity can be described by a number of intimately related physical parameters (Oliver and Webb, 2003). For example, compliance describes the change in volume which occurs given a certain change in pressure, whilst elasticity, or stiffness, is the inversion of this; meaning the change in pressure which occurs at a given change in volume. Distensibility is the degree of stretch which occurs at a given pressure, whilst the elastic modulus is the opposite; the amount of pressure required to stretch the vessel to double the resting diameter. Elasticity is non-linear, as at low pressure, tension is borne within elastin fibres in the vessel wall, whilst at higher distending pressures stiffer collagen fibres and smooth muscle tend to bear this energy. Knowledge of the distending pressure, meaning the mean arterial blood pressure, is therefore required for interpretation of these stiffness parameters.

Clinically, arterial stiffness is evaluated by measuring the velocity of the pressure wave through the arterial system, by analysis of the pressure wave, or by measurement of the diameter to pressure curve at a certain point of the vasculature. A number of systems are commercially available which facilitate non-invasive measurement of these parameters.

1.9.3.2 Pulse wave velocity

The pulse wave velocity (PWV) is the speed at which the arterial pulse wave is transmitted through the vasculature. In order to measure this, the pulse wave is analysed at two different places along the arterial tree, and the time delay between a particular moment of the pulse wave occurring at each of the two locations is measured, usually by timing against the R wave on an ECG. The carotid and femoral pulses are typically utilised, such that the technique measures the PWV along the aortic and aorto-iliac routes. The distance between the two points is measured as an estimate of the distance the pulse wave travels, and PWV is derived by the distance divided by the time. The Moens-Korteweg equation describes PWV as proportional to the square root of the elastic modulus such that a higher velocity equates to a higher degree of stiffness (Gosling and Budge, 2003). Given that this technique is in effect measuring aortic PWV, this provides information regarding the ability of the central arteries to distend with changes in pressure, such as those which occur during the cardiac cycle.

PWV is raised with ageing, and in association with a number of cardiovascular risk factors including hypertension, obesity, diabetes, and dyslipidaemia (Gottsater et al., 2015). In patients with hypertension, a 5 m/s rise in PWV is associated with a more than doubled likelihood of mortality, after adjustment of other risk factors. PWV is also higher in CKD, has also been shown to rise in proportion to the degree of renal impairment. Furthermore, the CRIC study showed that PWV was independently associated with a variety of vascular outcomes in CKD including heart failure, cognitive impairment, and progressive renal impairment. In a study of 241 patients with end stage renal disease receiving maintenance haemodialysis, PWV was a significant independent predictor of outcome, with patients with the highest third of PWV at 5.9 times risk of a cardiovascular event and 5.4 times risk of death.

1.9.3.3 Pulse wave analysis

In addition to PWV, analysis of the central arterial waveform also allows assessment of large arterial function and stiffness. The antegrade pressure wave generated during left ventricular

systole encounters many points of bifurcation as it travels along the arterial tree away from the heart. Wave reflections are generated at these points of impedance mismatch, where flow exceeds capacity, and are propagated in a retrograde direction back towards the heart. The shape of the arterial waveform therefore results from the summation of forward and backward flowing waves. Given that the effect exerted by the reflections will vary depending on their timing relative to the antegrade pressure wave, this summation will differ at different sites along the vasculature, and the arterial waveform accordingly varies at different sites from central to peripheral arteries. At sites of bifurcation in peripheral arteries where the reflections are generated, reflected waves are in phase with the antegrade pressure wave, resulting in augmentation of systolic pressure. Wave reflections reach central arteries during diastole, augmenting diastolic pressure with the physiologically desirable result of improving coronary blood flow, without increasing systolic pressure. This, together with the Windkessel effect, reduces pulse pressure whilst optimising afterload (Nichols et al., 2008).

Arterial stiffness influences the nature of the waveform by a number of mechanisms. Firstly, the amplitude of the pressure waveform is increased when the left ventricle ejects into stiff central arteries. Secondly, higher PWV results in earlier return of reflected waves to the central arteries, augmenting systolic rather than diastolic pressure. Additionally, the amplitude, as well as the timing of reflected waves, is also affected by the elasticity of small arteries. The degree to which peak systolic pressure is augmented by reflected waves is termed the augmentation index (Aix) and is used as a marker of arterial stiffness. In addition to the timing and amplitude of reflections, left ventricular ejection time will also affect the overlap of forward and backward waves, such that when ejection time is short, such as in tachycardia, reflected waves are more likely to return during diastole. Aix is often adjusted to a heart rate of 75 bpm for this reason (Safar et al., 2003).

Conventionally, applanation tonometry is used to non-invasively evaluate the arterial waveform at a readily accessible peripheral site, typically the radial artery, and a transfer function is used to derive the central arterial waveform from this. Whilst PWA has good reproducibility in both healthy and unhealthy populations, the use of a generalised transfer function may result in systematic error. One study compared invasively measured central waveforms and those derived from radial PWA, and found that individualised transfer functions were only marginally superior to the use of a generalised transfer function, although Aix tended to be underestimated by the use of radial PWA (Segers et al., 2000). Other studies have found that adjustment of the transfer function by parameters such as

gender and the presence of vascular disease provides more accurate analysis of central pulse pressures (Hope et al., 2002).