Pulsatile and steady‐state 24‐hour hemodynamics in adolescents and young adults: The next steps ahead

Starting with the recording of pulse waves almost 150 years ago, non-invasive measurement of blood pressure (BP) at the upper arm in the doctor's office more than 100 years ago, and ambulatory recordings of brachial BP more than 50 years ago, our understanding of the physiology of the circulation has tremendously improved. Beyond BP, the focus of hemodynamics was on the relationship “mean arterial pressure = cardiac output × peripheral resistance.” These so-called steady-state hemodynamics did not take pulsatile phenomena (pulsatile pressure and flow, as determined by the pulsatile nature of the heart) into account, but led to the first successful and lifesaving clinical trials in hypertension 1967—notably targeting diastolic BP,1 which can be seen as somewhat closer to mean arterial BP. Steady-state hemodynamics dominated research for decades and convey important insights even in recent studies.2 Treatment targeted on systolic BP rather than diastolic BP was proven beneficial 20 years later (even in isolated systolic hypertension).3 The most recent decades have seen a rising interest in pulsatile aspects of the arterial circulation, comprising not only brachial systolic BP and pulse pressure, but extending to central pressures, measures of wave reflections and aortic stiffness. All sophisticated measurements beyond brachial BP, however, could be performed exclusively in the doctor's office. Assessment of 24-hour hemodynamics was restricted to invasive clinic measurement (focused on steady-state aspects of the circulation) or to ambulatory 24-hour monitoring of brachial BP and, not to forget, heart rate. Only in the last few years, technological progress made the development of automated brachial cuff-based sphygmomanometers for 24-hour assessment possible, which not only measure brachial BP and heart rate, but also—through recording and analysis of pulse waveforms—purport to measure or estimate pulsatile (central BP, wave reflections, arterial stiffness) and steady-state (cardiac output, peripheral resistance) hemodynamics.4-6 Against this background, as reported in the current issue of the Journal,7 Ntineri and colleagues from Athens, Greece, investigated 24-hour central ambulatory BP and 24-hour ambulatory pulsatile and steady-state hemodynamics in 136 adolescents and young adults (range 10-25 years), using an automated oscillometric upper-arm cuff device (Mobil-O-Graph 24h PWA, Stolberg, Germany). Twenty-five percent of participants were healthy volunteers, 34% had elevated 24-hour brachial BP, but all were free from antihypertensive medications. Central systolic BP was calculated by the device using two different calibration methods (C1SBP using brachial systolic and diastolic BP, and C2SBP using oscillometrically measured mean/diastolic BP). 24-hour brachial SBP was higher than C1SBP, with the difference (systolic BP amplification) being more pronounced during daytime than nighttime. Other determinants of SBP amplification were age, body height, and sex. Consequently, nighttime dipping of C1SBP was smaller, as compared to brachial SBP. In contrast, C2SBP increased (by 3.1 mm Hg) during nighttime sleep. The main focus of the analysis was on circadian changes of brachial and central systolic BP, taking two options of waveform calibration into account; however, the authors took advantage of the full set of hemodynamic variables provided by the device to describe the circadian variation in all parameters (Table 1). The authors have to be applauded for this endeavor for several reasons. Firstly, they provide new insights into circadian changes of central BPs in adolescents and young adults. These data may serve therefore as the first reported reference and comparator for healthy aging in young people, albeit acknowledging the relatively small sample. Potentially even more important, and going beyond BP, a full set of steady-state and pulsatile hemodynamics is provided in this young and relatively healthy group of participants. In future studies, the effects of healthy aging and of various diseases which disrupt hemodynamics, such as hypertension, diabetes, heart failure, and renal failure, could be compared with the Ntineri findings. The results of the study pose important questions: Has the time-honored sphygmomanometer evolved to a fully automated, non-invasive, easy-to-use, accurate and relatively cheap hemodynamic monitor, capable of 24-hour ambulatory recordings? Where are we in the process of technical and clinical validation of the devices purporting to measure central BP and hemodynamics4-6? and Is there room for improvement? For the reason of article length, we will focus here on the apparatus used in the study by Ntineri and colleagues. For other methods and devices, particularly those measuring pulsatile hemodynamics, we refer to the ongoing European COoperation in Science and Technology Action VascAgeNet,8 addressing many of these issues together with the ARTERY Society. Regarding accuracy, many studies have sought to determine the accuracy of the Mobil-O-Graph 24h PWA device for measuring brachial BP,9, 10 central BP,4, 11 wave reflections,12, 13 estimated aortic pulse wave velocity,14, 15 and stroke volume16, 17 in adults. Taken together, all studies showed at least a reasonable agreement with the reference standard. However, in children, two recent studies showed C1SBP to be overestimated compared with the invasive gold standard (by 2.0 mm Hg18 and 5.7 mm Hg19). Of note, whereas in adults the C2 calibration is more accurate than C1 calibration,4, 20 in children C2 calibration may lead to sizeable overestimation of central systolic BP (mean 19.1 mm Hg).19 Moreover, a contributory source of error in central systolic BP estimation is inaccuracies of the cuff brachial BP used for waveform calibration. Importantly, the magnitude of cuff brachial BP error is age-dependent21 and this is likely to be an influential factor on the central SBP differences observed by Ntineri et al between C1 and C2 calibrations. Our conclusion here is that we need more high-quality invasive validation studies to determine the accuracy of central BP devices across different age groups, but also more rigor in the validation of conventional oscillometric brachial BP devices used to calibrate central BP devices. Regarding clinical validation (eg, association of BP values with clinical outcomes), studies so far have focused on central systolic BP whereby C2 calibration is clearly superior to cuff brachial SBP and C1 calibration in terms of association with hypertension-associated organ damage22-25 and mortality outcomes.26 Also, in small studies the estimated aortic PWV shows some prognostic value.27, 28 Investigations on the potential input of more sophisticated steady-state or pulsatile hemodynamics are lacking so far. The study of Ntineri and colleagues provides interesting new data on non-invasive 24-hour ambulatory hemodynamics in children and adolescents. To stimulate further research in this field, the authors of this commentary invite colleagues around the world to join the academic international 24-hour aortic blood pressure consortium (www.i24abc.org). More than 30 centers from 6 continents currently contribute to the consortium. SW is one of the inventors (not holder) of a patent partly used in the ARCSolver Algorithms, which are used for waveform analysis in the Mobil-O-Graph 24h PWA device.