relatively inaccessible arteries Transit time is measured as the time delay between the feet of the proximal and distal pulse waves (Fig 74.6) The foot of the pulse wave is used to locate the wavefront as it is relatively unaffected by wave reflections The most consistent method for determination of the foot of the pulse wave has been shown to be either the point at which its second derivative is maximum or the point formed by intersection of a line tangential to the initial systolic upstroke of the waveform and a horizontal line through the minimum point.204 FIG 74.6 Determination of pulse transit time The foot of the pulse wave is used to locate the wavefront, as it is relatively unaffected by wave reflections The time delay can be measured by simultaneously recording pulse waves at two sites of the arterial segment (left) Alternatively, the time intervals between the R wave of the electrocardiogram and the foot of the pulse wave at two sites may be recorded consecutively and the transit time calculated as the difference between the two (right) The distance is usually estimated by direct superficial measurement between the centers of the two pressure transducers or other devices The method of measuring distance, however, varies Some investigators use the total distance between the carotid and femoral sites of measurement, while others subtract the carotid-sternal notch distance from the total distance or subtract the carotidsternal notch distance from the femoral-sternal notch distance.153,205,206 A recent expert consensus document suggests using 80% of the directly measured carotidfemoral distance in adults.207 Although the carotid-femoral pulse-wave velocity is regarded as the gold standard measurement of arterial stiffness, pulse-wave velocities of the carotidbrachial, brachial-radial, and femoral–dorsalis pedis segments have also been measured.153 Simultaneous placement of oscillometric pressure cuffs at the brachia and ankles is also used to derive the brachial-ankle pulse-wave velocity that takes into account of both central and peripheral arterial stiffness.208 Despite the limitation of the need to estimate distance by superficial measurement, pulsewave velocity is probably the most widely used technique for the assessment of arterial stiffness Systemic Arterial Stiffness Pulse contour analysis is used to assess systemic or whole-body arterial stiffness noninvasively.209–211 One of the methods, based on the electrical analogue of a modified Windkessel model, concentrates on analysis of the diastolic pressure decay of the radial pulse contour Based on the diastolic portion of the pulse contour, the capacitative compliance of the proximal major arteries and the oscillatory compliance of the distal small arteries are estimated These parameters have been shown to change with aging and in diseases associated with increased cardiovascular events.209,210 The area method, based on a twoelement Windkessel model, has also been used to determine systemic arterial compliance using the formula compliance = Ad/[TVR × (Pes − Pd)], where Ad is area under the diastolic portion of the central arterial pressure waveform from end-systole to end-diastole, TVR is total vascular resistance, Pes is end-systolic pressure, and Pd is end-diastolic pressure.212,213 The biologic relevance of these parameters of arterial stiffness is, however, unclear Wave Reflection Indexes Arterial stiffening increases pulse-wave velocity and shortens the time for the pulse wave to return from the periphery Early arrival of the reflected waves augments systolic blood pressure in stiff arteries The effects of wave reflection can be quantified by determination of the augmentation index, which is defined as the ratio of difference between systolic peak and inflection point to pulse pressure (Fig 74.7).147,214 The inflection point corresponds to the time when peak blood flow occurs in the artery In adolescents and young adults with elastic arteries, the augmentation index is negative as late return of reflected waves during diastole causes the peak systolic pressure to precede an inflection point By contrast, in middle-aged and older individuals, the peak systolic pressure occurs in late systole after an inflection point, and the augmentation index becomes increasingly positive with age.140 Apart from arterial stiffness, the amplitude of the reflected wave, reflectance point, heart rate, and ventricular contractility are all important determinants of augmentation index As height is related to reflection sites, the augmentation index is inversely related to height.215 FIG 74.7 The augmentation index is calculated from pressure waveforms as the ratio of difference between the systolic peak pressure and the inflection point (Pi) to pulse pressure (ΔP/pulse pressure) ΔP is positive (A) when peak systolic pressure occurs after the inflection point and becomes negative (B) when peak systolic pressure precedes the inflection point The aortic augmentation index can be determined noninvasively from the central aortic waveform The latter is commonly estimated from the common carotid artery waveform obtained from applanation tonometry or sensors with multiple micro-piezoresistive transducers.196 Alternatively, the aortic waveform can be reconstructed using a transfer function from the radial waveform.187,188 The radial-to-aortic transfer function has nonetheless not been validated in children and, furthermore, its accuracy for derivation of aortic augmentation index has been debated.216–218 Contour analysis of the digital volume pulse waveform has also been used to derive wave reflection indexes.219–221 The first peak in the waveform is thought to correspond to a forward-traveling pressure wave from the heart to the finger, and the second peak or point of inflection to the backward-traveling reflected pressure (Fig 74.8).220,221 A reflection index, defined at the ratio of the