Document Reviewers: Luis Alcocer (Mexico), Christina Antza (Greece), Mustafa Arici (Turkey), Eduardo Barbosa (Brazil), Adel Berbari (Lebanon), Luís Bronze (Portugal), John Chalmers (Australia), Tine De Backer (Belgium), Alejandro de la Sierra (Spain), Kyriakos Dimitriadis (Greece), Dorota Drozdz (Poland), Béatrice Duly-Bouhanick (France), Brent M. Egan (USA), Serap Erdine (Turkey), Claudio Ferri (Italy), Slavomira Filipova (Slovak Republic), Anthony Heagerty (UK), Michael Hecht Olsen (Denmark), Dagmara Hering (Poland), Sang Hyun Ihm (South Korea), Uday Jadhav (India), Manolis Kallistratos (Greece), Kazuomi Kario (Japan), Vasilios Kotsis (Greece), Adi Leiba (Israel), Patricio López-Jaramillo (Colombia), Hans-Peter Marti (Norway), Terry McCormack (UK), Paolo Mulatero (Italy), Dike B. Ojji (Nigeria), Sungha Park (South Korea), Priit Pauklin (Estonia), Sabine Perl (Austria), Arman Postadzhian (Bulgaria), Aleksander Prejbisz (Poland), Venkata Ram (India), Ramiro Sanchez (Argentina), Markus Schlaich (Australia), Alta Schutte (Australia), Cristina Sierra (Spain), Sekib Sokolovic (Bosnia and Herzegovina), Jonas Spaak (Sweden), Dimitrios Terentes-Printzios (Greece), Bruno Trimarco (Italy), Thomas Unger (The Netherlands), Bert-Jan van den Born (The Netherlands), Anna Vachulova (Slovak Republic), Agostino Virdis (Italy), Jiguang Wang (China), Ulrich Wenzel (Germany), Paul Whelton (USA), Jiri Widimsky (Czech Republic), Jacek Wolf (Poland), Grégoire Wuerzner (Switzerland), Eugene Yang (USA), Yuqing Zhang (China).

Our study demonstrates that the innate pressure-dependence of arterial stiffness may have implications for the clinical use of arterial stiffness measurements, both in risk assessment and in treatment monitoring of individual patients. We propose a number of clinically feasible approaches to account for the blood pressure effect on PWV measurements.

β and CAVI as currently implemented are inherently BP-dependent, potentially leading to erroneous conclusions in arterial stiffness trials. BP-independent forms are presented to readily overcome this problem.

Inflammation is a physiological response to aggression of pathogenic agents aimed at eliminating the aggressor agent and promoting healing. Excessive inflammation, however, may contribute to tissue damage and an alteration of arterial structure and function. Increased arterial stiffness is a well recognized cardiovascular risk factor independent of blood pressure levels and an intermediate endpoint for cardiovascular events. In the present review, we discuss immune-mediated mechanisms by which inflammation can influence arterial physiology and lead to vascular dysfunction such as atherosclerosis and arterial stiffening. We also show that acute inflammation predisposes the vasculature to arterial dysfunction and stiffening, and alteration of endothelial function and that chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease and psoriasis are accompanied by profound arterial dysfunction which is proportional to the severity of inflammation. Current findings suggest that treatment of inflammation by targeted drugs leads to regression of arterial dysfunction. There is hope that these treatments will improve outcomes for patients.

Cerebral blood flow regulation is based on a variety of different mechanisms, of which the relative regulatory role remains largely unknown. The cerebral regulatory system expresses two regulatory properties: cerebral autoregulation and neurovascular coupling. Since partly the same mechanisms play a role in cerebral autoregulation and neurovascular coupling, this study aimed to develop a physiologically based mathematical model of cerebral blood flow regulation combining these properties. A lumped parameter model of the P2 segment of the posterior cerebral artery and its distal vessels was constructed. Blood flow regulation is exerted at the arteriolar level by vascular smooth muscle and implements myogenic, shear stress based, neurogenic, and metabolic mechanisms. In eight healthy subjects, cerebral autoregulation and neurovascular coupling were challenged by squat-stand maneuvers and visual stimulation using a checkerboard pattern, respectively. Cerebral blood flow velocity was measured using transcranial Doppler, whereas blood pressure was measured by finger volume clamping. In seven subjects, the model proposed fits autoregulation and neurovascular coupling measurement data well. Myogenic regulation is found to dominate the autoregulatory response. Neurogenic regulation, although only implemented as a first-order mechanism, describes neurovascular coupling responses to a great extent. It is concluded that our single, integrated model of cerebral blood flow control may be used to identify the main mechanisms affecting cerebral blood flow regulation in individual subjects.

Tan et al Heart Rate Dependency of Large Artery Stiffness 237 Hemodynamic MeasurementsBrachial BP, central aortic BP, and cfPWV were determined by cuffbased pulse wave analysis (SphygmoCor XCEL, AtCor, Sydney, Australia). Brachial BP was obtained by oscillometric method with a brachial cuff positioned on the right arm, and central aortic waveform was derived from the brachial BP volume displacement waveform using a validated transfer function. 16 For measurement of cfPWV, the carotid and femoral pulse waveforms were obtained by tonometry on the skin above the right carotid artery and by a cuff placed on the right upper thigh, respectively. 17,18 Subtraction method for path length was used to calculate cfPWV, whereby the path length was calculated as the distance between the sternal notch and the carotid site subtracted from the distance between the sternal notch and top of the thigh cuff. 17 In a subset of the study's cohort (n=45), beat-to-beat stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were determined from the finger arterial pressure waveform using the Modelflow method (Finometer PRO, Finapres Medical Systems, Amsterdam, The Netherlands). 19 Study ProtocolSubjects were advised to refrain from caffeine and fatty meals 4 hours before their study appointment, but to continue with their prescribed medications. There were no current tobacco users in the cohort. After 10 minutes of seated rest, seated brachial BP was measured in duplicate (SphygmoCor XCEL). After a further 10 minutes of supine rest, finger arterial pressure waveform was measured from the left middle finger (Finometer PRO) to obtain SV, CO, and TPR. Brachial and central aortic BP and cfPWV were then obtained (SphygmoCor XCEL). Subjects were then paced in a randomized sequence at 60, 70, 80, 90, and 100 bpm using their prescribed pacemaker settings, with BP and cfPWV measurements repeated at each pacing step after 3 minutes of stabilization. ECG was also acquired continuously for the duration of the study for monitoring of HR (PowerLab acquisition system, LabChart software, ADInstruments, Dunedin, New Zealand), and SV, CO, and TPR from the Finometer PRO device were also recorded via PowerLab and LabChart. The average duration for study protocol completion was 60 minutes. Data AnalysisFor pulse wave analysis, brachial and central aortic BP waveforms were averaged >5 s, and cfPWV was averaged >10 s. Observations with measured HR differing from the paced rate by >5 bpm were excluded from the analysis, and the lowest pace rates of 60 and 70 bpm were not achievable in some subjects because of a higher unpaced resting HR. A linear mixed model with maximum likelihood was used to determine the effects of HR on each measured variable, with paced HR modeled as the fixed effect and the random effect modeled as the intercept for each individual (Equation 1).where Yij denotes the outcome measure at a particular paced HR for one individual, ε ij , the residual of variances, and u j , the random effect becase of individual subjec...

Aging has a profound influence on arterial wall structure and function. We have previously reported the relationship among pulse wave velocity, age, and blood pressure in hypertensive subjects. In the present study, we aimed for a quantitative interpretation of the observed changes in wall behavior with age using a constitutive modeling approach. We implemented a model of arterial wall biomechanics and fitted this to the group-averaged pressure-area (P-A) relationship of the "young" subgroup of our study population. Using this model as our take-off point, we assessed which parameters had to be changed to let the model describe the "old" subgroup's P-A relationship. We allowed elastin stiffness and collagen recruitment parameters to vary and adjusted residual stress parameters according to published age-related changes. We required wall stress to be homogeneously distributed over the arterial wall and assumed wall stress normalization with age by keeping average "old" wall stress at the "young" level. Additionally, we required axial force to remain constant over the cardiac cycle. Our simulations showed an age-related shift in pressure-load bearing from elastin to collagen, caused by a decrease in elastin stiffness and a considerable increase in collagen recruitment. Correspondingly, simulated diameter and wall thickness increased by about 20 and 17%, respectively. The latter compared well with a measured thickness increase of 21%. We conclude that the physiologically realistic changes in constitutive properties we found under physiological constraints with respect to wall stress could well explain the influence of aging in the stiffness-pressure-age pattern observed.

This paper aims to summarize and map contemporary views on some contentious aspects of arterial hemodynamics that have remained unresolved despite years of research. These were discussed during a workshop entitled Arterial hemodynamics: past, present and future held in London on June 14 and 15, 2016. To do this we formulated a list of potential consensus statements informed by discussion at the meeting in London and quantified the degree of agreement and invited comments from the participants of the workshop. Overall the responses and comments show a high measure of quantitative agreement with the various proposed 'consensus' statements. Taken together, these statements seem a useful basis for proceeding with a more detailed and comprehensive consensus document on the current understanding and approaches to analysis of the pulse waveform. Future efforts should be directed at identifying remaining areas of dispute and future topics for research.