Age and Ageing Advance Access originally published online on December 15, 2006
Age and Ageing 2007 36(1):3-5; doi:10.1093/ageing/afl142
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Ageing and central aortic pulse wave analysis. Commentary on ‘Is Augmentation Index a Good Measure of Vascular Stiffness in the Elderly?’ by Fantin et al.
The function of the elastic central aorta is two-fold: to buffer the pulsatile cardiac output and to optimise conduit function, thereby distributing blood to working tissues without excess pressure load on small blood vessels. Age-related structural and functional changes in the aorta, predominantly associated with increased stiffness, result in measurable secondary changes in central and peripheral pressure wave morphology. In this issue of Age and Ageing, Fantin et al. [1] report on patterns of age-related changes in carotid and radial pressure pulse wave morphology determined by techniques of ‘pulse wave analysis’ (PWA).Assessment of vascular health, and potentially of the risk of future cardiovascular events, by non-invasive assessment of aortic stiffness or by techniques of PWA is increasingly proposed as a viable addition to the clinical armamentarium. Although the place for such techniques in clinical practice is a topic of debate and discussion, aspects of which remain controversial, the increasing availability of commercial devices for measuring aortic stiffness via pulse wave velocity (PWV) or for analysing the pressure pulse wave continues to fuel interest in the concept.
Deteriorating aortic mechanical function is now accepted as important in the pathophysiology of arterial diseases, with age being the greatest determinant for stiffening of elastic arteries in healthy individuals. In addition to age-related changes, functional aortic compliance and intrinsic stiffness have been shown to be deleteriously affected by the presence of classical cardiovascular risk factors and to be worsened by diseases such as diabetes and renal failure [2, 3]. Since the incidence of cardiovascular events also increases with age, age-related changes in aortic mechanical indices are candidate ‘biomarkers’ for determining vascular health. A similar logic could be used to justify the inclusion of aortic stiffness as a marker of target organ damage in risk assessment algorithms [4]. This concept is supported by recent community-based prospective studies of aortic stiffness (measured by PWV) and cardiovascular outcome [5, 6].
Blood pressure, the classical indicator of vascular health, is a consequence of the interaction of cardiac function (stroke volume) and arterial compliance, and the clinical condition of hypertension is associated with a mismatch in cardiac and arterial function. This is particularly true in the case of isolated systolic hypertension, the most prevalent form of hypertension in older age-groups, in which increased aortic stiffness is the predominant pathology [7, 8]. Although cardiac function is a reasonably understood entity with accepted assessment indices, aortic function is less well understood and currently its assessment must be considered to be in the formative phase. Increasingly, however, with the advent of improved non-invasive technology, central aortic blood pressure and various parameters descriptive of its morphology have been advanced to be potentially indicative of cardiovascular health and prognosis [9]. It is in this context that Fantin et al. [1] report differential effects of ageing on measured parameters of the blood pressure waveform.
It may be easily overlooked that the PWA parameters most commonly assessed are in fact the brachial systolic and diastolic pressure, and any additional pressure parameters must prove their worth in practice. In recent years, a number of other pressure parameters have been investigated, often utilising arterial transfer function techniques to estimate central blood pressure waveforms [10]. Identification of an ‘inflection point’ in the systolic portion of the pressure waveform allows assessment of three pulse wave morphological parameters—pressure at the inflection point (taken as representing forward pressure transmission and therefore cardiac function), absolute central pressure augmentation (AG mmHg, taken as the magnitude of the reflected pressure wave) and the time from start-systole to the inflection point (assumed to be dependent on distance to a reflection site and PWV). The dimensionless ratio augmentation index ([AI] = 100 x AG/pulse pressure (PP)) can also be calculated to indicate the relative contribution of the forward and reverse going waves to pulse pressure and left ventricular afterload.
Stiffening of elastic arteries decreases their buffering ability and increases the wave velocity of the propagating pressure pulse wave. Elastic artery dysfunction is therefore associated with inadequate aortic buffering, manifest as increased afterload and decreased coronary perfusion with deterioration of conduit function associated with the clinical manifestations of stroke, coronary artery disease, peripheral arterial disease and renovascular disease. Decreased buffering action is associated with increased PP, a surrogate of increased aortic stiffness, which has been shown to be a cardiovascular prognostic indicator [11]. Since ageing is by far the biggest influence on aortic mechanical behaviour, it is necessary to know the association of age with arterial indices if there is to be a place for routine assessment of arterial mechanical properties in the clinic or in population studies. The data of Fantin et al. [1] provide important observations on the effect of ageing on commonly used descriptive parameters of the central blood pressure waveform. They demonstrate that there is a dissociation in age-related changes in the two indices usually quoted in studies utilising central PWA. They found that the relative contribution of the reflected pressure wave to the central PP increases until around 55 years of age and then plateaus. The absolute contribution, the AG, on the other hand, continues to increase. Since AI is a ratio, it can increase either because of an increase in the numerator (AG) or a decrease in the denominator (PP). After 55 years of age, AG continues to increase whereas AI does not, implying that both the PP and AG increase proportionately. A similar study by Mitchell et al. [12] using data from the Framingham study showed an opposite effect of apparently normal ageing on AG after 50 years of age. In their cohort, the magnitude of the retrograde, reflected pressure wave (dependent on PWV and attenuation) was effectively unchanged (or possibly decreased). In the Framingham cohort, as in that of Fantin et al. [1], calculated AI was unchanged after the age of 55. It is notable that the age cutoff point (55 years) determined by Fantin et al. [1] and that suggested by Mitchell et al. [12] both approximate the age, as determined by Franklin et al. [13], at which PP becomes a better predictor of cardiovascular events than systolic or diastolic blood pressure and isolated systolic hypertension and deteriorating aortic stiffness become the predominant form and mechanism of elevated blood pressure. On the basis of the findings of Fantin et al. [1], AG may potentially be as good a candidate as pulse pressure, or even better, for prediction of risk in those older than 55 years, and it is likely to be more relevant than the AI ratio.
AI has gained popularity because commercial devices are available to measure it and because it is a dimensionless quantity, its assessment does not require dealing with the dilemma of non-invasive pressure scaling of (usually tonometrically) obtained waveforms. On the other hand, AG must be reported in units of pressure and therefore requires accurate scaling. Problems with scaling of non-invasively obtained waveforms to estimate central blood pressure have been repeatedly raised [14].
It is often implied (or worse, implicitly stated) that AI is a surrogate of stiffness; in fact, this is not the case because stiffness is only one contributor to the observed AI and a number of studies have now demonstrated divergence of AI and PWV (the current gold-standard assessment of stiffness) [15, 16]. Assessment of AG by PWA requires splitting the systolic component of the wave into two at the inflection point, the temporal point assumed to indicate the intersection of the forward going and the reflected pressure wave. This systolic time point will depend on the distance to the reflection sites and the transit time of wave propagation to and back from these reflection sites. It is clear therefore that the inflection point can be altered by changes in PWV as well as by relative movement of the principle reflection point in either a proximal or distal direction. The effect of ageing on the relative direction of movement of reflecting sites is not established and differences in individual groups may explain the differences between the results of Fantin et al. [1] and Mitchell et al. [12].
A number of other factors, besides PWV and aortic stiffness, are known to affect central aortic AI. It is confounded by height, as a surrogate for the distance to the principal distal reflecting site, and, therefore, gender (although female gender per se also appears to increase AI [17]). AI is inversely related to heart rate [18] (or more precisely ejection duration) and dependent on cardiac contractility. In their work, Fantin et al. [1] confirm these factors in their regression models. These dependencies would have been of less importance if both PWV and PWA had demonstrated independent relationships with outcome; however, this data is not available for PWA. Therefore, the question arises regarding the beneficial incremental information that might be provided by PWA and its role in assessing central blood pressure in general and AI and AG in particular.
Although there are currently no outcome studies justifying the utilisation of novel PWA indices in clinical use, they continue to be promoted as potentially useful prognostic indicators. There is also controversy regarding the appropriateness of generalised arterial transfer functions to derive estimates of central blood pressure [19] for wave analysis; however, Fantin et al. [1] have wisely avoided this issue by analysing only directly measured radial and carotid waveforms.
Since age is the strongest predictor of incident cardiovascular disease and also has the greatest contribution to progressive aortic stiffening, Fantin et al. [1] report a practical point that is important in any consideration of the use of PWA in community or epidemiological practice. They have shown that, unlike aortic stiffness, AI is not a surrogate of biological age in older age-groups and have suggested that AG may be a better index of arterial function and overall cardiovascular health than AI. From a practical perspective, it has been suggested that some of the differences in the outcome of blood pressure-lowering trials associated with different therapies may be due to drug-specific differential effects on central BP in the presence of similar changes in brachial blood pressure and that AI or AG may be useful in showing these effects. This has not been convincingly demonstrated, and in the recent CAFÉ sub-study of ASCOT [20] PWA parameters, although different in the two study arms, did not predict the primary outcome. Similar lack of predictive power was evident in elderly hypertensives enrolled in the ANBP2 study [21].
Potential users of any technique, including PWA, should ensure that the assessment parameter chosen is appropriate for the desired investigation. In particular, PWA parameters do not seem to be a surrogate for arterial stiffness, and the implication from the results of Fantin et al. [1] is that if PWA is to be successfully used, including in future epidemiological studies to rival PWV or even brachial blood pressure as an outcome predictor, more information and a better understanding of factors that influence components of arterial function are required. This would seem to be particularly applicable in older populations. The results of Fantin et al. [1] have added to the knowledge base concerning age-related changes in arterial function; however, further research is required before there is a place for pulse wave analytic techniques in clinical practice.
There are no conflicts of interest to declare.
Department of Vascular Sciences and Medicine, Dandenong Hospital and Biomedical Engineering Group, La Trobe University, Melbourne, Australia
Email: james.cameron{at}med.monash.edu.au
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