Aortic Ambulatory Blood Pressure Monitoring and Target Organ Damage: Are the Data Really Conflicting?

In the last decade, major advances in biomedical engineering have enabled the simultaneous measurement of aortic (a) and brachial (b) blood pressure (BP) in ambulatory conditions.1 Although there is still limited evidence on the clinical utility of 24-hour aortic ambulatory BP monitoring (aABPM), these methodologies have many potential advantages in the management of cardiovascular risk. The concept of implementing aABPM in research protocols, with the purpose of extending in clinical use, is based on 2 cardinal factors. First, due to anatomical and physiological reasons, aBP, the pressure “seen” by the heart, may be closer associated with hypertension-associated target organ damage (TOD).2 Second, the well-known superiority of 24-hour bBP over office bBP, in terms of circadian patterns recognition, BP variability assessment, TOD association, as well as its greater prognostic value.3 In other words, the currently available technology of ABPM may incorporate the advantages of both aortic and ambulatory BP measurement, while simultaneously providing clinical gold standard data by bABPM.1 In the current issue of the Journal, Blanch et al.4 present their work on the association and/or possible superiority of 24-hour aBP over 24-hour bBP with TOD, specifically left ventricular mass (LVM)/hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD). Based on a population of 208 hypertensive patients, they conclude that 24-hour aBP is not significantly better associated with hypertensive cardiac alterations (LVH or LVDD) compared to 24-hour bBP. In the previous years, a few more studies on the same subject have been published, some of them using exactly the same device and methodology as in the present study (Table 1).4–8 In our commentary, we will present briefly the underlying principles of aABPM and further discuss the rationale of aABPM implementation in clinical research. Then, we will compare the results obtained so far and suggest remaining issues that need to be addressed before aABPM can be implemented in the clinical management of arterial hypertension. Pearson’s correlation coefficients and AUC (derived from receiver operator characteristics analysis) for 24-hour brachial and aortic SBP, with LVMI (LVM indexed for body surface area) and LVH respectively, in the 4—so far—published studies using the same device (Mobil-O-Graph, IEM, Stolberg, Germany) and calibration methodology for aortic SBP measurement (i.e., MBP and DBP) Abbreviations: AUC, area under the curve; DBP, diastolic blood pressure; i24ABC, international 24-hour aortic blood pressure consortium; MBP, mean blood pressure; LVM, left ventricular mass; LVH, left ventricular hypertrophy; SAFAR, noninvaSive Aortic ambulatory blood pressure monitoring for the detection of tARrget organ damage; SBP, systolic blood pressure. *P <0.05 for comparison between 24-hour brachial and 24-hour aortic SBP. Pearson’s correlation coefficients and AUC (derived from receiver operator characteristics analysis) for 24-hour brachial and aortic SBP, with LVMI (LVM indexed for body surface area) and LVH respectively, in the 4—so far—published studies using the same device (Mobil-O-Graph, IEM, Stolberg, Germany) and calibration methodology for aortic SBP measurement (i.e., MBP and DBP) Abbreviations: AUC, area under the curve; DBP, diastolic blood pressure; i24ABC, international 24-hour aortic blood pressure consortium; MBP, mean blood pressure; LVM, left ventricular mass; LVH, left ventricular hypertrophy; SAFAR, noninvaSive Aortic ambulatory blood pressure monitoring for the detection of tARrget organ damage; SBP, systolic blood pressure. *P <0.05 for comparison between 24-hour brachial and 24-hour aortic SBP. There are mainly 2 different technologies available for 24-hour aABPM: (i) the brachial oscillometric and (ii) the radial tonometric. The brachial oscillometry is implemented in several devices, using various transfer function algorithms and calibration methods: Mobil-O-Graph PWA, (IEM, Stolberg, Germany), Arteriograph (TensioMed Kft, Budapest, Hungary), Oscar 2 with SphygmoCor inside (Sun Tech Medical, Morrisville, NC, and AtCor Medical, Sydney, Australia), and BPLab (Petr Telegin Ltd, Nizhny Novgorod, Russian Federation). As a working principle, most of the oscillometric devices—after a conventional bBP measurement—obtain pulse waves through a brachial cuff inflated at the diastolic or suprasystolic level and then generate aBP by means of different generalized transfer functions.1 On the other hand, the tonometric method (BPro, HealthStats, Singapore) uses a wristwatch-like device which obtains pressure waveforms through radial tonometry and derives aBP through an n-point moving average algorithm.1 All the aforementioned devices have validation studies9; the device used in the present study in particular has been extensively validated in terms of feasibility, accuracy, and reproducibility.10,11 The calibration methodology of the peripheral pressure waveform varies among the available devices, but it is now widely accepted that use of mean and diastolic BP (rather than systolic and diastolic BP) provides a more accurate estimate of the “true” aBP, as recently proposed by a consensus document.9,12 The implementation of 24-hour aABPM in clinical trials seems of great importance, since it is was originally shown that not only aBP but also the difference between aBP and bBP (i.e., the BP amplification), features significant intraindividual and interindividual variability throughout the day in static conditions.13 In other words, the “error” of bBP to assess left ventricular BP load is not constant, neither in time nor the same for all individuals, and therefore cannot be mathematically assessed, but only measured in real time. This was later confirmed by application of the aforementioned aABPM devices in the 24-hour ambulatory setting, emphasizing the various mechanisms contributing to the phenomenon of BP amplification, the different parameters affecting day–night variation and the different circadian pattern of aortic and brachial BP.5,14,15 Moreover, aortic BP variability has been shown to be superior to brachial BP variability in terms of association either with cardiac16 or carotid damage.17 A recent meta-analysis suggested that office, i.e., static aBP is more strongly related to preclinical TOD (LVM, carotid intima media thickness and pulse wave velocity) than bBP.18 Therefore, it seems reasonable to suggest that aABPM could provide a greater prognostic value than the currently available gold standard in clinical hypertension, that of bABPM. Four studies, including the just published one,4 have evaluated and compared the association of 24-hour aBP and 24-hour bBP with LVM/LVH, using the same device and methodology, since data obtained from studies using different methodologies, algorithms, and calibrations should not be considered interchangeable. The SAFAR study showed that 24-hour aBP is superior to 24-hour bBP for correlation with LVM and prediction of LVH,5 results that were later corroborated by a multicenter study with blinded echo readings, that included only untreated patients.6 In another publication of the SAFAR study, it was shown that 24-hour aBP is superior to 24-hour bBP in terms of association with LVDD.19 The findings regarding LVM and LVH were just recently confirmed by a preliminary analysis of an international consortium in a quite large sample (n = 1,299)8—Table 1. Comparing the previous studies with the data obtained by Blanch et al.,4 it is quite obvious that the trend in the correlations of all studies is similar, even for those that did not achieve statistical significance. One can safely conclude, also taking the current study into account, that 24-hour aSBP is closer associated with hypertensive cardiac alterations, namely (increased) LVM and LVH. The present study has some limitations; the most important one is sample size. It follows a study already published by the same group, using a composite TOD that included LVH, renal dysfunction, or aortic stiffness.7 In the present study, the authors confined the TOD definition on the selected population to cardiac dysfunction, i.e., LVH and LVDD. The initial sample size estimation was made for the composite TOD and not for each component. Consequently, the current study was probably underpowered to show any superiority (if existing) and to draw firm conclusions. Given that 24-hour aABPM is a novel technology, many important aspects such as validation, feasibility, and relationship with intermediate endpoints have been covered already. Studies investigating the effects of medical20 and interventional21 therapies on 24-hour aABPM are emerging, large outcome studies with clinical endpoints including mortality are still missing. Moreover, and not surprising given the novelty of the technology, the critical final step, a study showing the superiority of a 24-hour aABPM-based strategy for hypertension, as compared to a conventional strategy, remains to be performed. In order to provide more definitive answers on many outstanding issues, an international, academic research consortium on 24-hour hemodynamics has been initiated, already comprising more than 40 centers. All interested researchers are invited to participate (website: http://i24abc.org). Future, prospective studies focusing on hard endpoints, as well as studies with therapeutic interventions should be designed to provide evidence for a generalized utilization of 24-hour aBP assessment. ADP group has received unrestricted research grants and equipment from I.E.M GmbH, Stolberg, Germany. T.W. has received an unrestricted research grant for central echo readings in a multicenter study from I.E.M. GmbH, Stolberg, Germany.