FIG 74.3 Aortic input impedance spectra obtained in normal adults (From Nichols WW, Conti CR, Walker WE, Milnor WR Input impedance of the systemic circulation in man Circ Res 1977;40:451–458.) The impedance at zero frequency is equivalent to resistance in the steady-flow state Characteristic impedance is the ratio of pulsatile pressure to pulsatile flow at a site where pressure and flow waves are not influenced by wave reflection The concept of characteristic impedance is important as it is related directly to stiffness of the major arteries distal to the site of measurement Hence it represents the pulsatile component of the hydraulic workload presented to the left ventricle when measured at the ascending aorta As wave reflection is always present, characteristic impedance cannot be measured directly It is usually estimated by averaging impedance moduli over a frequency range where fluctuations due to wave reflection above characteristic impedance are expected to cancel out those below.143 Hence characteristic impedance has been estimated as the average value of moduli between 2 and 12 Hz,144 above 2 Hz,145 or above the frequency of the first minimum.140 Wave Reflection As the velocities of pressure and flow waves transmitted in the arteries are in the order of meters per second, it is obvious that the waves have sufficient time to travel to the periphery and be reflected back before the next cardiac cycle The terminations at where low-resistance conduit arteries terminate in high-resistance arterioles are usually regarded as the principal sites for reflection Possible reflecting sites include branching points in major arteries,146,147 areas of alterations in arterial stiffness,148 and high-resistance arterioles.140 The pressure and flow waves measured at any site in the arterial system can be envisaged as a summation of a forward or incident wave and a reflected wave Wave reflection exerts opposite effects on pressure and flow Reflected pressure wave increases the amplitude of the incident pressure wave, whereas a reflected flow wave decreases the amplitude of the incident flow wave In most experimental animals and in young human subjects who have elastic arteries, wave reflection returns to the ascending aorta from the periphery after ventricular ejection.140 Such timing is desirable, as the reflected pressure wave augments early diastolic blood pressure and contributes to aortic valve closure, thereby boosting the perfusion pressure of the coronary arteries without increasing left ventricular afterload Stiffening of the systemic arteries due to aging or disease processes, however, increases pulse-wave velocity and causes an earlier return of the reflected wave to augment aortic blood pressure in late systole rather than in diastole The implications of this pressure augmentation are discussed in the section on ventriculoarterial interaction further on Measurement of Arterial Function Arterial Stiffness Arterial stiffness describes the rigidity of the arterial wall It is primarily determined by the structural components of the arterial wall, elastin and collagen in particular, vascular smooth muscle tone, and transmural distending pressure.149 The endothelium also plays a role in the regulation of arterial stiffness through the release of vasoactive substances to alter the smooth muscle tone.150–152 The significance of arterial stiffness stems from its direct relationship to characteristic impedance, hence the pulsatile component of the arterial afterload, and its effect on the timing of return of the reflected waves from peripheral sites In adults, the role of arterial stiffening in the development of cardiovascular disease is recognized Associations between increased arterial stiffness and various pathophysiologic conditions, which are themselves also associated with increased cardiovascular risk, in adults has been extensively reviewed.153–156 Importantly, stiffness of central arteries, as assessed by aortic pulse-wave velocity and carotid distensibility, has been shown to have independent predictive value for cardiovascular events in the general adult population,157,158 in the elderly159 and adults with hypertension,160–162 end-stage renal disease,163–166 and impaired glucose tolerance.167 Although stiffness of the central arteries has been the focus of adult studies, the contribution of stiffness of the smaller peripheral arteries to total vascular impedance cannot be ignored Structural remodeling occurs also in smaller arteries and branching points, and changes in the mechanical properties of conduit and resistive arteries influence wave reflections and contribute to augmentation of late systolic blood pressure in the aortic root.168 Associations between increased small artery stiffness, as assessed by pulse contour analysis, and aging, hypertension, smoking, diabetes, and cardiovascular events have also been reported.169,170 Indeed, the mapping of arterial stiffness at multiple sites may provide a holistic approach to the prediction of cardiovascular events.171,172 The increasing application of noninvasive methods to determine systemic arterial stiffness in the clinical and research arenas has significantly increased the understanding of its pathophysiologic significance With adoption of these