Although high blood pressure has been undoubtedly shown to be a major risk factor for cardiovascular morbidity and mortality at all ages and in both sexes, the suitability and accuracy of traditional blood pressure measurements for cardiovascular risk staging is now a matter of lively debate . In this context, the possible additional contribution carried by central blood pressure values assessment and by pulse wave analysis has been underlined by a number of studies [2,3].
Indeed, the technique of pulse wave analysis, using noninvasive high fidelity arterial tonometers, has recently become increasingly popular [4,5]. This method can provide not only quantitative, although indirect, information concerning the levels of central blood pressure, but also qualitative data on the ascending aortic waveform. Analysis of such waveforms can, in fact, define the elastic properties of the arterial wall and can estimate the importance and the transmission speed of reflected waves [6,7].
In the last years, augmentation index (AIx) has been frequently used in the context of pulse waveform analysis and has been suggested to represent a parameter able to reliably reflect the level of arterial stiffness in the assessment of cardiovascular risk. Assessment of AIx provides an indication of the role played by reflected waves in determining pulse pressure. The contribution of the backward wave to pulse pressure is related to the timing of its superimposition onto the forward wave, as well as to its magnitude and shape. AIx is calculated as the ratio between the augmented central pressure, due to reflected waves, and pulse pressure. Conditions of markedly increased arterial stiffness are characterized by an early superimposition of backward waves onto the forward wave, causing an increase in central SBP. Assessment of AIx has, thus, been proposed as a simple approach to quantify the role of wave reflection in determining an elevation of central blood pressure values.
However, it has to be acknowledged that several other factors, apart from the viscoelastic properties of the aorta and of large arteries , may affect AIx, in particular: the magnitude and variability of reflected waves, mainly in relation to systemic vascular resistance; the length of the aorta (related to an individual's height), because at any given level of arterial distensibility, the nearer the reflection sites are to the ascending aorta, the shorter is the time needed for the reflected wave to reach it; the participant's heart rate, an increase in heart rate being accompanied by an increase in pulse wave velocity, but also by a decrease in augmented pressure , that is in AIx; the phenomenon of pressure waves attenuation while travelling along the arterial tree; and the role of gender, several studies having shown significantly higher values of AIx in female than in male individuals of comparable height (Fig. 1).
Thus, given the contribution of several factors to AIx magnitude, use of this parameter as a specific index of the viscoelastic properties of large arteries is incorrect and may lead to inaccurate estimates. In fact, in clinical practice it is not uncommon to find a marked discrepancy between pulse wave velocity (considered as the gold standard marker of arterial distensibility ) and AIx values, which may indeed be due to the multiple factors involved in determining the latter parameter.
The article by Cheng et al., published in this issue of the Journal of Hypertension, was aimed at exploring the potential contribution of cardiac motion and arterial properties, respectively, to arterial pressure waveform parameters, in particular to AIx.
The conclusion of this study is that AIx may not be predominantly determined by arterial properties, but, on the contrary, it largely depends on left ventricular systolic function. Thus, based on these data, the use of AIx as a surrogate index of arterial stiffness might need to be reconsidered .
These conclusions are based on data collected in 20 healthy male individuals (median age 22.3 years), without cardiovascular risk factors and free of chronic diseases. It has to be emphasized that although the selective inclusion in this study of a healthy young male cohort has carried the advantage of minimizing the possible confounding effects of vascular diseases and/or of aging, it might have also been responsible for some limitations. The most important one is that the results may be safely applied only to this specific population, which implies that they might not be easily extrapolated to individuals of different age and sex.
The conclusions by Cheng et al.  have to be considered in the light of the following considerations. First of all, according to current knowledge, the arterial pressure waveform is dynamically determined by the varying temporal relationship between the forward (centrifugal) and backward (centripetal) pressure waves, which is responsible for their variable degree of superimposition. Backward waves ‘travel’ centripetally from the periphery of the arterial system toward the heart. In individuals with preserved normal viscoelastic properties of large arteries wall, backward and forward waves meet in the ascending aorta at the end of systole, and the superimposition of these two waves occurs throughout the whole diastolic phase. Under normal physiological conditions, the peak central SBP is, therefore, not affected by reflected waves, and central SBP is only defined by the forward pulse wave magnitude, that is by the heart–aorta interaction. In these conditions, from a physiologic perspective, reflected waves play a positive role insofar as they maintain high blood pressure values during the diastolic phase, thus, favoring coronary blood flow, with no increase in left ventricular after-load. In young people, the inflection point in the aortic waveform, which corresponds to the point where backward and forward waves meet and where AIx is determined, occurs after the central peak systolic pressure. In these cases, the influence of backward waves on central SBP is insignificant and AIx values are negative or around zero. Moreover, in these young individuals the aortic pulse wave inflection point is sometimes not clearly evident, which makes the evaluation of the relationship between forward and backward pressure waves, and, thus, the assessment of AIx magnitude as well as the identification of its possible determinants, a difficult task.
The phenomenon of dumping pressure waves, that is the phenomenon of pressure waves attenuation while travelling along the arterial tree, represents another important, but widely underestimated, feature of large arterial vessels in young individuals [6,8]. The forward pressure wave, which is generated by the heart–aorta interaction, loses energy along its way from the heart to peripheral circulation . This energy dissipation is significant in conditions characterized by marked arterial distensibility, whereas it is negligible in individuals with increased arterial stiffness. In young healthy individuals, with elevated arterial distensibility, the pressure wave amplitude, thus, undergoes a significant attenuation on going from the ascending aorta to peripheral arteries, associated with weaker reflected waves travelling back toward central aorta. This process is easier to understand if we compare what occurs in the arterial system with what happens in an electrical circuit. In such a comparison, aortic distensibility can be considered as a capacitor inserted into the system. The higher is its capacity, the greater is the energy accumulated in the capacitor, and, hence, the greater is the difference in potential between the extremes of the electric circuit, which corresponds to the attenuation of pulse wave amplitude along the arterial tree in case of markedly distensible vessels. Actually, in clinical practice, the amplification phenomenon of blood pressure in central circulation is less than expected in very young individuals, who are characterized by a pronounced arterial elasticity. Indeed, also in these conditions it is possible to find a peripheral SBP lower than the central aortic systolic pressure, but this is due to a peripheral dumping of pulse waveforms rather than to their central amplification. A similar phenomenon can be observed also in rats. These small laboratory animals have been described to be characterized by marked arterial distensibility and by pulse wave velocity values around 4–5 m/s . In this animal model, when central and peripheral blood pressure values are simultaneously recorded with a dual sensor pressure sensing system (with one catheter in femoral artery and another one in ascending aorta), higher blood pressure values can be found in the aorta with respect to the peripheral vessel, in spite of compliant arterial vessel walls.
Therefore, the peculiar arterial properties, which characterize a healthy young cohort with pronounced arterial distensibility, do not allow a straightforward interpretation of whether an increased difference between central and peripheral pressures depends on cardiac or vascular factors, respectively. Thus, the selective inclusion of healthy young individuals with normal arterial distensibility in the study by Cheng et al., a choice made with the aim of minimizing the effect of vascular ageing, might have emphasized the contribution of pressure waves dumping to the difference between central and peripheral pressures, a contribution that may challenge the authors’ conclusion of a prevailing role exerted by changes in cardiac systolic function.
Notwithstanding some methodological limitations, the article by Cheng et al. underlines once more the complex and reciprocal interactions between heart and large arteries. If on one hand aortic stiffness affects afterload and favors the increase in left ventricular mass, on the other hand stroke volume can affect the amplitude of the pressure waveform and pulse wave velocity itself. The article by Cheng et al. provides further evidence that the latter effect is predominant in young individuals . The underlying hypothesis is that the relationship between left ventricular function and arterial function undergoes important changes during life time (Fig. 2), with left ventricular function affecting arterial function more markedly in youth, and, conversely, with arterial function affecting heart function more markedly in the elderly.
As a consequence of these age-specific cardiovascular changes, as correctly underlined also by the authors, the results of the study by Cheng et al. collected in young healthy male subjects cannot be generalized to individuals of different age and sex.
Further studies are, therefore, needed to assess whether the relationship between cardiac motion and features of the central pressure waveform remains unchanged over a broader age range and in patients with superimposed cardiovascular disease.
Conflicts of interest
P.S. is consultant for DiaTecne s.r.l., Milan, Italy. G.P has no conflicts of interest.
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