Arterial stiffening plays an important role in the development of hypertension and cardiovascular diseases.

Arterial stiffening plays an important role in the development of hypertension and cardiovascular diseases. The intrinsically nonlinear (ie, pressure-dependent) elastic behavior of arteries may have serious consequences for the accuracy and interpretation of arterial stiffness measurements and, ultimately, for individual patient management. We determined aortic pressure and common carotid artery diameter waveforms in 21 patients undergoing cardiac catheterization. The individual pressure-area curves were described using a dual exponential analytic model facilitating noise-free calculation of incremental pulse wave velocity. In addition, compliance coefficients were calculated separately in the diastolic and systolic pressure ranges, only using diastolic, dicrotic notch, and systolic data points, which can be determined noninvasively. Pulse wave velocity at systolic pressure exhibited a much stronger positive correlation with pulse pressure (P<0.001) and age (P=0.012) than pulse wave velocity at diastolic pressure. Patients with an elevated systolic blood pressure (>140 mm Hg) had a 2.5-times lower compliance coefficient in the systolic pressure range than patients with systolic blood pressures <140 mm Hg (P=0.002). Most importantly, some individuals, with comparable age or pulse pressure, had similar diastolic but discriminately different systolic pulse wave velocities and compliance coefficients. We conclude that noninvasive assessment of arterial stiffness could and should discriminate between systolic and diastolic pressure ranges to more precisely characterize arterial function in individual patients. Key Words: arterial structure and compliance pulse wave velocity blood pressure measurement systolic hypertension carotid arteries Previous SectionNext Section Introduction Decreased elasticity of the arterial wall plays an important role in the development of hypertension and related cardiovascular complications, such as heart failure, stroke, and renal failure.1–4 Therefore, noninvasive assessment of arterial stiffness has recently entered the European Society of Hypertension/European Society of Cardiology guidelines for the management of hypertension.5 Basic studies have shown that the elastic behavior of the arterial system is nonlinear, that is, arterial stiffness is pressure dependent.6–11 This intrinsic property of the arterial system may have serious consequences for the quantitative assessment of arterial stiffness, and changes therein, in response to age,12,13 physiological stress,7 and possibly antihypertensive treatment.14,15 Currently, arterial stiffness is assessed noninvasively either at the diastolic pressure level (aortic or carotid-femoral pulse wave velocity [PWV]) or estimated as an average over the diastolic-systolic pressure range. In the latter case, distensibility and compliance coefficients are calculated as, respectively, the relative and absolute changes in the cross-sectional area normalized to pulse pressure from diastolic minimum to systolic peak,16 tacitly assuming a linear pressure-area relationship. In ex vivo human cranial and femoral arteries, Hayashi et al8 found that the relationship between transmural pressure and vessel radius can be described by a single exponential relation. Meta-analysis of studies on the relationship between pressure and cross-sectional vessel area by Powalowski and Pensko17 confirmed this finding. However, Wolinsky and Glagov11 (in rabbit aorta, ex vivo) and Armentano et al6 (in dog aorta, in vivo) observed a more marked change in elasticity as a function of distending pressure, which is related to the ultrastructural interaction of elastin and collagen fiber networks in the tunica media. Viscous behavior of the arterial wall, associated with smooth muscle cell function, is observed ex vivo, especially with prolonged dynamic distension of the vessel, but appears insignificant in vivo if the waveforms are properly acquired and processed.18,19 To the best of our knowledge, the degree of nonlinearity of arterial stiffness in individual cardiovascular patients has not been studied in detail yet. Invasive measurement of pressure-area curves in vivo permits such a comprehensive description of arterial stiffness as a function of pressure.10,19,20 However, the challenge is to derive the pressure-dependent relationship for data obtained noninvasively. The aim of the present study was to quantify the degree of nonlinearity of the arterial pressure-area relationship to evaluate its consequences for the (noninvasive) assessment of arterial elastic properties. We obtained carotid artery diameter and proximal aortic pressure recordings in patients undergoing cardiac catheterization. We used a dual exponential analytic model to derive incremental PWV for each individual, using all of the data points in the pressure-area range. To explore clinical applicability, we also calculated compliance and distensibility coefficients for the diastolic and systolic pressure ranges separately, on the basis of only diastolic, dicrotic notch, and systolic data points, which can be measured noninvasively with certain confidence. We discuss our findings with regard to the associations with pulse pressure, systolic blood pressure (SBP), and age within our study population and the potential for the application of noninvasive methods in clinical practice. Previous SectionNext Section Materials and Methods Study Population Patients referred for a diagnostic coronary angiographic procedure were recruited in the outpatient clinic.21 Included patients were either suspected of coronary artery disease (anginal complaints) or had had previous percutaneous transluminal coronary angioplasty or coronary artery bypass grafting. All 21 of the patients gave written informed consent before enrollment. The study was approved by the joint medical ethical committee of Maastricht University and Maastricht University Medical Centre. Protocol Patients were prepared for the invasive diagnostic procedure following a standard protocol: overnight fast, refrainment from smoking, and prophylactic anticoagulation (Clopidogrel). Diabetes medication (Metformin), if any, was discontinued on the day of the examination; other medications were taken as usual. Age, weight, and height of the patients were copied from their clinical files. During antiseptic preparations and application of ECG electrodes, patients were in the supine position on the catheterization table, allowing localization of the left common carotid artery by means of a 7.5-MHz linear array/high frame-rate ultrasound system (PICUS, Esaote Europe). All of the ultrasound recordings (see below) were obtained with the patients in this position. If the common carotid artery was located too deep for high frame-rate image acquisition (because of dermal fat), the patient was excluded from the study. After percutaneous access was established by the intervention cardiologist, an angiographic guiding catheter (6F or 7F Wiseguide, Boston Scientific) was advanced over a guide wire and placed with the tip in the ostium of the targeted coronary artery. After initial coronary angiograms were obtained, the catheter was flushed with saline to wash out radiopaque contrast fluid, and the connection to the contrast pump was blocked to achieve the highest possible bandwidth for, and minimal ringing in, the aortic pressure signal. Bench testing of the fluid-filled system showed a flat frequency response from 0 to 25 Hz. At least 3 and maximally 5 repeated echo recordings of the left common carotid artery were obtained simultaneously with a continuous registration of aortic root pressure. The recording session took <4 minutes. After the last ultrasound recording, the angiographic procedure was continued.