Feasibility and Reproducibility of Noninvasive 24-h Ambulatory Aortic Blood Pressure Monitoring With a Brachial Cuff-Based Oscillometric Device

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1 nature publishing group Feasibility and Reproducibility of Noninvasive 24-h Ambulatory Aortic Blood Pressure Monitoring With a Brachial Cuff-Based Oscillometric Device Athanase D. Protogerou 1, Antonis Argyris 1, Efthymia Nasothimiou 3, Dimitris Vrachatis 2, Theodoros G. Papaioannou 2, Dimitris Tzamouranis 3, Jacques Blacher 4, Michel E. Safar 4, Petros Sfikakis 1 and George S. Stergiou 3 Background Accumulating evidence suggests the potential superiority of office aortic blood pressure (BP) over brachial in the management of arterial hypertension. The noninvasive aortic 24-h ambulatory brachial BP monitoring (ABPM) is potentially the optimal method for assessing BP profile. The objective of the present study was to investigate the feasibility and reproducibility to perform noninvasively 24-h aortic ABPM with a novel validated brachial cuff-based automatic oscillometric device (Mobilo-O-Graph) which records brachial BP and waveforms and assesses aortic BP via mathematical transformation. METHODS Thirty consecutive subjects (mean age: 53.6 ± 11.6 years, 17 men) had a test retest ABPM with at least 1-week interval. No modification of vasoactive drug treatment during the interval was allowed while similar 24-h activity during both recording days was recommended. Results The average number of valid readings for brachial vs. aortic BP were 69.9 ± 1.4 vs. 58. ± 13.3 in the initial 24-h assessment (P <.1) and 68.3 ± 1.8 vs ± 13.6 in the repeat assessment (P <.1). No differences in average 24 h aortic BP values were observed between the two assessments (systolic blood pressure (SBP) ± 7.7 vs ± 6. mm Hg, respectively, P =.48, and diastolic 79.7 ± 7.4 vs ± 8.7, P =.54). Reproducibility indices of aortic pressure including, intraclass coefficient of variation (SBP:.8 (95% confidence interval.58.9); diastolic:.92 (.83.96)) and s.d. of differences (SBP/diastolic: 6./4.5 mm Hg) indicated acceptable reproducibility. The Bland Altman plots indicated no evidence of systemic bias. Conclusions In conclusion, these data suggest that noninvasive 24-h ABPM is feasible and provides reproducible values. Future studies should validate the prognostic ability of 24-h aortic hemodynamics. Keywords: 24 ambulatory blood pressure monitoring; aortic blood pressure; blood pressure; central blood pressure; feasibility; hypertension; reproducibility American Journal of Hypertension, advance online publication 7 June 212. doi:1.138/ajh The noninvasive assessment of central (aortic or carotid) blood pressure (BP) is now feasible with various commercially available devices, 1 but remains a challenge to the clinical investigation of arterial hypertension. The reasons why to assess central BP have been extensively addressed in recent experts opinions and reviews. 2,3 In brief, central systolic (SBP) and pulse pressure (PP) are lower than peripheral SBP and PP (i.e., from 1 to 3 mm Hg). This PP disparity, defined as PP amplification, 2 is an undisputable physiological 1 Hypertension Center and Cardiovascular Research Laboratory, 1st Department of Propaedeutic Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece; 2 Biomedical Engineering Unit, 1st Department of Cardiology, Hippokration Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 3 Hypertension Center, 3rd University Department of Medicine, Sotiria Hospital, Athens, Greece; 4 HTA Unit, Diagnosis and Therapeutic Center, Paris Descartes University, Paris 5, Hôtel-Dieu, AP-HP, Paris, France. Correspondence: Athanase D. Protogerou (aprotog@med.uoa.gr) Received 2 January 212; first decision 24 March 212; accepted 6 April American Journal of Hypertension, Ltd. phenomenon and depends on the individual s arterial age 4,5 and its pathophysiological characteristics. 4 The superior physiological relevance of central PP over brachial PP in respect to cardiovascular (CV) disease/events is supported by published data. 3,6 Nonpharmacological 7 and pharmacological interventions 8 seem to have clinically important effects on PP amplification, i.e., on central PP independently from brachial PP and potentially on CV outcomes. 2,3,6 The 24-h ambulatory BP monitoring (ABPM) at the brachial artery is superior to office brachial BP in order to diagnose the BP-related CV risk. 9 This superiority is derived from the fact that the average 24 h BP is more closely related to the usual BP than the office BP and that 24 h ABPM recognizes specific BP phenotypes (e.g., white coat hypertension, masked hypertension, morning surge, and dipping status). The latter 24 h ABPM parameters may alter CV risk and cannot be identified by office BP readings alone. 9 Recently, evidence was presented regarding the fact that office central PP may predict all-cause 876 august 212 VOLUME 25 NUMBER AMERICAN JOURNAL OF HYPERTENSION

2 Noninvasive Ambulatory Aortic Pressure Monitoring original contributions mortality better than brachial 24-h average SBP or PP. 1 By taking all together the aforementioned evidence is likely that the noninvasive 24-h aortic ABPM will further improve the models of CV risk assessment which are currently based solely on brachial BP. So far all the epidemiological data on aortic BP have been derived from studies conducted in laboratories or office settings because the assessment of out of office aortic BP was not technically feasible. Recently, Weber et al. introduced a novel noninvasive brachial cuff-based automated oscillometric device recording (Mobilo-O-Graph NG; IEM, Stolberg, Germany) that records brachial waveforms and mathematically transform them to aortic waveform and BP, allowing thereby 24-h aortic ABPM. Both the noninvasive and invasive validation of this device provided acceptable results regarding the ability to assess aortic BP in laboratory conditions The major limiting step seems to be, as previously also shown, 14 the error introduced from the inaccurate, yet clinically accepted, brachial BP recording with the oscillometric technique There are major methodological differences in the measurement/assessment of brachial and aortic BPs with the aforementioned device. The estimation of the latter requires two additional steps: the brachial pressure waveform recording and its mathematical processing. Thus, technically, aortic BP estimation seems more demanding and perhaps more sensitive to measurements/recording errors. Previous studies have focused on the ability of the device to determine precisely the aortic BP The objective of the present study was to focus on and investigate the feasibility and short-term reproducibility of 24-h aortic ABPM performed using this novel device. Methods Study design and population. From January to June 211, consecutive subjects referred to hypertension clinics of two University Departments at Laiko and Sotiria hospitals in Athens, Greece were invited to participate in a prospective observational study. Inclusion criteria were: age >18 years, stable CV medication for at least 2 months as well as willingness and ability to provide written informed consent. Exclusion criterion was the presence of sustained atrial fibrillation and modification of vasoactive drug treatment during the study period. All subjects underwent two consecutive 24-h aortic ABPM recordings (day 1: test and day 2: retest with at least 1-week interval) with the Mobilo-O-Graph NG device (IEM). All subjects were instructed to keep as similar as possible their 24-h activity during both recording days in terms of exercise, working hours, diet, sleep patterns and were advised to take their vasoactive medication (if any) the same hour of the day. In order to enhance the compliance to this advise each participant filled-in a predesigned log-book during day 1 (test) of ABPM recording and was advised to follow it at day 2 (retest). In order to detect with 8% power and level of significance <.5 the clinically meaningful difference of 5 mm Hg in the average 24-h brachial SBP ABPM between the test retest recordings (considering an anticipated pooled s.d. for the average 24 h SBP of 8 mm Hg), a sample size of 21 subjects was estimated. We aimed at recruiting 3 consecutive subjects. The study protocol was approved by the scientific committees of the participating hospitals and all patients provided written informed consent before entering the study. ABPM with the Mobil-O-Graph NG. The Mobil-O-Graph NG is a new commercially available brachial cuff-based oscillometric 24-h ABPM device with FDA and CE approval. Its BP detection unit is validated according to the British Hypertension Society (BHS) protocol and European Society of Hypertension (ESH) International Protocol BP, i.e., the underlying working principle of the oscillometric method defined as the lowest cuff pressure at which the oscillations are maximal is also displayed by the device. The device was set to function under the manufacturer s inbuilt protocol number 11, i.e.,: 4 BP recordings per hour from 8: to 23:59 and 2 recordings per hour from : to 7:59. In this mode of function the device performs both brachial BP and brachial pressure waveform recordings simultaneously; aortic BP is assessed by software analysis (with the application of generalized transfer functions) when the data are downloaded to the manufacturer s software (HMS version 4.5). The exact mode of action has been previously described in detail. 11,13 In brief, following the conventional oscillometric BP measurement, the brachial pulse waves are recorded by keeping the brachial cuff inflated at the diastolic BP (DBP) level for roughly 1 seconds. The brachial waveform is calibrated with the SBP and diastolic brachial BP. Thereafter, an aortic pulse wave is generated by the means of a generalized transfer function. Analysis of ABPM data. The analysis of each subject s dataset that was obtained by the device software was performed in steps as following. The actual patient reported nighttime sleep period was introduced in the software. The raw data set was exported as Excel data file (Microsoft, Redmond, WA) and the brachial BP readings were evaluated and searched/annotated for the following errors/conditions: (i) erroneous brachial BP recordings defined as: SBP <6 mm Hg or >25 mm Hg and DBP <3 mm Hg or >15 mm Hg; (ii) duplicate readings, defined as consecutive identical SBP and DBP readings; (iii) asleep (siesta and night) or awake readings (defined on the basis of the subject s logbook). Then the raw BP readings were evaluated and annotated as following: (i) erroneous on the basis of brachial DBP higher than aortic DBP or brachial SBP lower than aortic SBP; (ii) invalid, on the basis of at least 5% acceptable brachial pressure waveforms per recording (i.e., same amplitude and shape) after visual inspection of 1 by 1 all the brachial pressure waveforms; accordingly we tested the quality of the obtained signal as well as the observer s agreement with the automatically derived quality message. The calculation of the brachial and aortic BP average values of 24 h, awake, asleep was performed for all valid brachial and all valid aortic readings. Statistics. Statistical analysis was performed using SPSS 18. (SPSS, Chicago, Illinois) and significance was defined as P <.5. All continuous variables were checked for normal distribution AMERICAN JOURNAL OF HYPERTENSION VOLUME 25 NUMBER 8 august

3 Noninvasive Ambulatory Aortic Pressure Monitoring with the one-sample Shapiro Wilk test. Continuous variables were expressed as mean ± s.d. and noncontinuous as absolute frequency and percentage. The differences between the test retest parameters were performed with the paired t-test or the Wilcoxon test as appropriate. The reproducibility of the SBP, DBP, mean BP, PP between the test retest was quantified by means of: (i) their mean difference; (ii) the s.d. of their mean difference (SDMD); (iii) coefficient of variation; (iv) intraclass correlation coefficient (ICC) between test/retest data, as well as (v) by Bland Altman plots. ICC values can be interpreted as follows:.2 indicates poor agreement:.3.4 indicates fair agreement;.5.6 indicates moderate agreement;.7.8 indicates strong agreement; and >.8 indicates almost perfect agreement. 2 Although the correlation coefficients are not reliable measures of reproducibility, these are presented since they are commonly reported and can be used for comparison with previous data from brachial ABPM studies. The reproducibility analysis was performed for all valid brachial and all valid aortic readings (24 h, awake, asleep). A separate reproducibility analysis for those valid brachial BP readings with corresponding valid aortic BP readings was also performed. For both the brachial and aortic 24 average SBP and DBP values, the number of subjects required for a crossover trial comparing the antihypertensive efficacy of two different drugs to detect clinically important BP differences of 1 mm Hg for SBP and 5 mm Hg for DBP with a power of.8 and two-sided significance level of.5 on the basis of the observed SDMD in the present reproducibility study, was calculated. Results The demographic characteristics of the study population are presented in Table 1; intervals between day 1 and 2 ranged from 1 to 6 weeks. Feasibility In order to obtain 3 subjects with successful test retest pairs of 24 h ABPM recordings 35 subjects were recruited. Three subjects were excluded because they discontinued the 24-h ABPM recording during the initial assessment; in 1 subject the device was set to function during the day 1 under wrong protocol number and did not perform brachial waveform recordings; 1 subject refused to repeat ABPM. Thus, 3 subjects were finally included in the present feasibility and reproducibility statistical analysis. The mean number of valid brachial BP readings per subject between the test and retest day were comparable (24-h period: 69.9 ± 1.4 vs ± 1.8, P =.32; awake period: 53.5 ± 1.7 vs ± 1.1, P =.52; asleep period: 16.4 ± 4. vs. 16. ± 3.5, P =.62). No erroneous or duplicate brachial readings were detected. The mean number of valid aortic BP readings per subject, between the test and retest, were also comparable (24-h period: 58. ± 13.3 vs ± 13.6, P =.41; awake period: 43.5 ± 13.5 vs ± 12.4, P =.58; asleep period: 14.4 ± 4. vs. 14. ± 3.2, P =.54). The above number of valid aortic readings was consistently and significantly less than the corresponding number of valid brachial readings (P <.1 for all brachial vs. aortic pairs i.e., 24 h, awake and asleep Table 1 Demographic characteristics of the study participants (n = 3) Age, (years) 53.6 ± 11.6 Female gender, n (%) 13 (43.3) Body mass index, kg/m (4.4) Cardiovascular disease, n (%) 6 (2) Hypertension, n (%) 16 (53.3) Treated for hypertension, n (%) 12 (4) Diabetes mellitus, n (%) 3 (1) Renal disease, n (%) 2 (6.7) Smoking, n (%) 19 (6.7) period). During the 24 h ABPM ~12 aortic readings per subject (17%) were not feasible or invalid. On average, 1 out of those 12 were due to the inability of the brachial cuff to record reliably (or at all) the brachial pressure waveforms and as a result the device automatically discarded the readings; 1 out of 12 readings was discarded manually after visual inspection of all the brachial waveforms and 1 due to erroneous aortic BP result (as defined in the Methods section). Reproducibility for all valid brachial and aortic BP readings The observed mean values ± s.d. of the average 24 h SBP, DBP, mean BP, and PP between the test retest, as well as their mean difference and the SDMD are reported in Table 2. No significant differences were observed in any BP (brachial or aortic) parameter. Similar results were observed for the awake and asleep average brachial and aortic BP parameters (Table 2). The mean differences as well as the SDMD of aortic BP data were similar to the mean and the SDMD of the respective brachial BP data. The indices of test retest reproducibility of the 24 h, awake and asleep average values of brachial and aortic BP between the test retest are presented in Table 3. Bland Altman plots for 24-h average brachial and aortic SBP, DBP, and PP are presented in Figures 1 3. More than 93% of the paired measurements had a difference of any measured BP parameter that ranged within 2 s.d. of mean difference for the specific BP index. Bland Altman analysis indicated no evidence of systemic bias and no trend for the reproducibility of measurements to vary with their underlying mean value. Similar results were observed for the corresponding awake and asleep BP data (Table 3, the corresponding Bland Altman plots are not shown). The distribution (number and %) of the 3 test retest pairs of 24-h ABPM according to the level of absolute difference of the 24-h average SBP of both the brachial and aortic BP readings are reported in Table 4. Reproducibility of brachial readings with a corresponding valid pair of aortic BP (i.e., valid n = ~57/24 h, see above) The ICC of the 24-brachial BPs were for SBP:.861 (95% confidence interval ); for DBP:.924 (95% confidence interval ); for PP:.95 (95% confidence interval 878 august 212 VOLUME 25 NUMBER 8 AMERICAN JOURNAL OF HYPERTENSION

4 Noninvasive Ambulatory Aortic Pressure Monitoring original contributions Table 2 Twenty-four hour, awake and asleep average values of all valid brachial and all valid aortic ambulatory blood pressure assessed by the Mobil-O-Graph device at day 1 (test) and day 2 (retest), as well as their differences and the s.d. of the mean differences Day 1 Day 2 difference P 24 h average bsbp ± ± 9..6 ± bdbp 79. ± ± ± bpp 45. ± ± ± MBP ± ± ± asbp ± ± ± adbp ± ± ± app 36.2 ± ± 74.2 ± Awake average bsbp ± ± ± bdbp 82.6 ± ± ± bpp 45.2 ± ± ± MBP 13.3 ± ± ± asbp ± ± ± adbp 84. ± ± ± app 35.4 ± ± ± Asleep average bsbp ± ± ± bdbp 69.9 ± ± ± bpp 44.6 ± ± ± MBP 9.3 ± ± ± asbp 18.9 ± ± ± adbp 7.7 ± ± ± app 38.2 ± ± ± All variables are expressed in mm Hg as mean ± s.d. a, aortic; b, brachial; DBP, diastolic blood pressure; MBP, mean blood pressure; PP, pulse pressure; SBP, systolic blood pressure ). These data show slightly higher values compared to those presented above regarding all the valid brachial BP readings. Similar results were found for the awake, asleep data throughout the entire reproducibility analysis (data not shown). Number of subjects required for crossover trials assessing drug effects on 24 aortic BP Based on the SDMD (between the test retest) the number of subjects required for a crossover comparative trial of two antihypertensive drugs aiming to detect a 1 mm Hg difference in 24 average SBP and 5 mm Hg DBP with a power of.8 and two-sided significance level of.5, was n = 6 for both brachial and aortic SBP and n = 9 for both brachial and aortic DBP. Discussion To our knowledge this is the first feasibility and reproducibility study regarding the noninvasive assessment of 24-h aortic Table 3 Test retest reproducibility assessed by correlation coefficients (r), coefficients of variation (CV), intraclass coefficient of variation (ICC), s.d. of mean (s.d.), percentage of number of observations within 2 s.d. in Bland Altman (B A%) of the 24 h, awake and asleep average values of all valid brachial and all valid aortic blood pressure values 24 h average r* CV ± s.d. ICC (95% confidence interval) B A% bsbp ± 2.2 ( ).83 ( ) 96.7 bdbp ± 2.7 ( ).92 ( ) 93.3 bpp ± 3.3 ( ).95 ( ) 1. MAP ± 2.3 ( ).86 ( ) 96.7 asbp ± 2.4 ( ).85 ( ) 93.3 adbp ± 2.5 ( ).92 ( ) 96.7 app ± 3.5 ( ).95 ( ) 1. Awake average bsbp ± 2.3 ( ).8 (.58.9) 96.7 bdbp ± 3. ( ).92 ( ) 1. bpp ± 3.7 ( ).93 ( ) 1. MAP ± 2.3 ( ).86 (.75.93) 96.7 asbp ± 2.4 (.4 8.9).82 ( ) 93.3 adbp ± 2.6 ( ).92 ( ) 96.7 app ± 4.5 ( ).94 ( ) 1. Asleep average bsbp ± 2.8 ( ).88 ( ) 96.7 bdbp ± 3.8 ( ).86 (.78.93) 93.3 bpp ± 3. ( ).95 (.89.97) 96.7 MAP ± 3. ( ).85 ( ) 96.7 asbp ± 3.3 ( ).87 ( ) 93.3 adbp ± 4.1 ( ).84 ( ) 93.3 app ± 4. ( ).93 ( ) 93.3 a, aortic; b, brachial; DBP, diastolic blood pressure; MAP, mean arterial pressure; PP, pulse pressure; SBP, systolic blood pressure. * P <.1. ABPM. ABPM was performed with a validated novel device the first brachial cuff-based for the noninvasive assessment of 24-h aortic BP. Feasibility In the present study the device was set to perform 8 BP readings/24 h which is a relatively high frequency of readings. Valid brachial BP readings were feasible at a satisfactory frequency (almost 9%). The frequency of valid aortic BP readings was significantly less (~74%), leading to a significantly less (yet still acceptable) 24 h average number of aortic readings. It should be noted that, as it is usually the case with most ABPM devices, the Mobilo-O-Graph NG performs a second BP reading (after ~2 min) in case that the 1st brachial BP reading fails (e.g., due to movements artifacts) but that it does not perform a 2nd sequential reading on the basis of invalid AMERICAN JOURNAL OF HYPERTENSION VOLUME 25 NUMBER 8 august

5 Noninvasive Ambulatory Aortic Pressure Monitoring a b Bland Altman plot/sbp 24 h brachial of two measures (mm Hg) Bland Altman plot/sbp 24 h aortic + 2s.d. 2s.d. + 2s.d. 15 2s.d of two measures (mm Hg) Figure 1 Bland Altman plots for 24 h brachial and aortic blood pressure. (a) Bland Altman plot for 24 h brachial systolic blood pressure. (b) Bland Altman plot for 24 h aortic systolic blood pressure (SBP). brachial pressure waveform recording. Approximately 2 inappropriate readings per subject, not detected automatically by the device, were detected manually suggesting that the visual inspection of the raw data is most likely not needed since this will not change substantially the final result. Reproducibility The aortic BP reproducibility analysis should be critically judged on the basis that it can be influenced by two major factors: (i) the reproducibility of the brachial BP readings and (ii) the ability to provide reproducible brachial waveform recordings. Therefore, the analysis was performed by taking into account (i) all the valid brachial and BP aortic readings and (ii) brachial BP readings with a pair of valid aortic readings. By analyzing the total number of valid brachial readings we provide clinically oriented data. The analysis based on paired measurements eliminates the impact of the different number of readings between the brachial artery and the aorta. In all cases the reproducibility was acceptable and rather similar for both the brachial and aortic data. Of note it was shown that the reproducibility of the brachial data was slightly improved when the data without a pair of valid aortic reading were discarded, i.e., despite the smaller number of readings. This is a Difference of two measures (mmhg) b Bland Altman plot/dbp 24 h brachial 7 8 of two measures (mm Hg) Bland Altman plot/dbp 24 h aortic + 2s.d. 2s.d of two measures (mm Hg) most likely explained by the fact that the discarded readings represent less valid readings or extreme conditions in the daily life activities. In general, the statistical methods used for the assessment of the reproducibility of biomarkers should be carefully interpreted in terms of clinical application. The present study shows that in about 1% of the subjects the test retest BP difference was >1 mm Hg and in more than the 25% >5 mm Hg, for both aortic and brachial ABP. Similar analysis of previous data in the literature are lacking. Moreover, in order to interpret correctly the data presented in Table 4 one must take into consideration two parameters: (i) the fact that 5 mm Hg reduction of DBP represents higher reduction of CV risk than a similar SBP reduction 9 and (ii) the possibility that the same might be true for brachial and aortic BP i.e., a 5 mm Hg reduction in aortic BP may represent higher CV risk reduction than a similar brachial BP reduction. Data regarding the latter hypothesis are not available, but this is the case when brachial 24-h ABPM data are compared to brachial office BP data. 21 Finally, based on data from previous published studies 9 + 2s.d. 2s.d. Figure 2 Bland Altman plots for 24 h brachial and aortic blood pressure. (a) Bland Altman plot for 24-h brachial diastolic blood pressure. (b) Bland Altman plot for 24-h aortic diastolic blood pressure (DBP). 88 august 212 VOLUME 25 NUMBER 8 AMERICAN JOURNAL OF HYPERTENSION

6 Noninvasive Ambulatory Aortic Pressure Monitoring original contributions a Bland Altman plot/pp 24 h brachial s.d s.d of two measures (mm Hg) b Bland Altman plot/pp 24 h aortic + 2s.d. 2s.d of two measures (mm Hg) Figure 3 Bland Altman plots for 24 h brachial and aortic blood pressure. (a) Blant Altman plot for 24 h brachial pulse pressure (PP). (b) Blant Altman plot for 24-h aortic pulse pressure. Table 4 Distribution of subjects (number with % in parentheses) according to the level ( 5; 5.1 1; >1 in mm Hg) of the absolute differences between test retest 24-h ambulatory monitoring Absolute difference between test retest 5 mm Hg mm Hg >1 mm Hg bsbp 17 (56.7) 1 (33.3) 3 (1) bdbp 22 (73.3) 7 (23.3) 1 (3.3) asbp 19 (63.3) 8 (26.7) 3 (1) adbp 25 (83.3) 4 (13.3) 1 (3.3) Average values were calculated for all the valid brachial and aortic BP readings. a, aortic; b, brachial; BP, blood pressure; DBP, diastolic blood pressure; SBP, systolic blood pressure. (obtained by a Medline search performed with the key words reproducibility and ABPM as well as after evaluation of the reference list from the detected manuscripts) regarding the brachial ABPM reproducibility the present results suggest that the reproducibility of aortic BP (with the Mobil-O-Graph device) is, if not better, at least well within the expected limits (Table 5) Table 5 Indices describing the reproducibility of 24-h average blood pressure in previously published studies, which investigated the reproducibility of brachial ambulatory blood pressure monitoring, as well as in the present study Test s.d. (mm Hg) Retest s.d. (mm Hg) SDMD (mm Hg) R ICC SBP/ DBP Author James 9/7 (NT) 8/7 (NT).93/.87 et al. (ref. 22) 11/1 (HTN) 12/1 (HTN) Reeves et al. (ref. 23) 15.3/ / /8..86/.67.86/.66 Palatini 11./8. 11./8..71/.68 et al. (ref. 24) Musso 11.4/ /1.4 et al. (ref. 25) Stergiou 13.3/ /5.6.8/.84 et al. (ref. 26) Eguchi 16.1/ / /6.7.77/.84 et al. (ref. 27) Current study Brachial 7.8/7.2 9./ /4.5.73/.86.83/.92 ABPM Aortic ABPM 7.7/ / /4.9.62/.86.85/.92 ( ): data not provided; ABPM, ambulatory blood pressure monitoring; DBP, diastolic blood pressure; HTN, hypertensive; ICC, intraclass coefficient of variation; NT, normotensive; R, correlation coefficient; SBP, systolic blood pressure; SDMD, s.d. of the mean differences. Perspectives In the present study, we provided data solely on the reproducibility of brachial and aortic BP; further analysis regarding useful and promising vascular biomarkers derived from the pulse wave analysis (i.e., amplification, pulse wave velocity, augmentation index) is underway in order to test further the feasibility and reproducibility of noninvasive assessment of 24-h central hemodynamics. To conclude, given the described results the noninvasive 24-aortic ABPM with this new device appears to be feasible and reproducible. The reproducibility results were similar for both the brachial and aortic ABPM. The accuracy of this device to assess aortic BP was beyond the scope of the present study. It must be noted that although previous studies have addressed this issue, these studies were conducted in laboratory and not ambulatory conditions and thus cannot be extrapolated. The reproducibility of aortic BP estimation by this automated device requires also further investigation in different populations. Most importantly, future studies should validate whether the assessment of noninvasive 24 h aortic BP can provide further information regarding CV risk stratification and target organ damage beyond the 24 h brachial ABPM. Acknowledgment: The Mobil-O-Graph NG devices were provided by the IEM, Stolberg, Germany. Disclosure: The authors declared no conflict of interest. 1. Ding FH, Fan WX, Zhang RY, Zhang Q, Li Y, Wang JG. Validation of the noninvasive assessment of central blood pressure by the SphygmoCor and Omron devices against the invasive catheter measurement. Am J Hypertens 211; 24: Avolio AP, Van Bortel LM, Boutouyrie P, Cockcroft JR, McEniery CM, Protogerou AD, Roman MJ, Safar ME, Segers P, Smulyan H. Role of pulse pressure amplification in AMERICAN JOURNAL OF HYPERTENSION VOLUME 25 NUMBER 8 august

7 Noninvasive Ambulatory Aortic Pressure Monitoring arterial hypertension: experts opinion and review of the data. Hypertension 29; 54: Protogerou AD, Papaioannou TG, Blacher J, Papamichael CM, Lekakis JP, Safar ME. Central blood pressures: do we need them in the management of cardiovascular disease? Is it a feasible therapeutic target? J Hypertens 27; 25: McEniery CM, Yasmin, McDonnell B, Munnery M, Wallace SM, Rowe CV, Cockcroft JR, Wilkinson IB; Anglo-Cardiff Collaborative Trial Investigators. Central pressure: variability and impact of cardiovascular risk factors: the Anglo-Cardiff Collaborative Trial II. Hypertension 28; 51: Segers P, Mahieu D, Kips J, Rietzschel E, De Buyzere M, De Bacquer D, Bekaert S, De Backer G, Gillebert T, Verdonck P, Van Bortel L; Asklepios investigators. Amplification of the pressure pulse in the upper limb in healthy, middle-aged men and women. Hypertension 29; 54: Vlachopoulos C, Aznaouridis K, O Rourke MF, Safar ME, Baou K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis. Eur Heart J 21; 31: Karatzi K, Papaioannou TG, Papamichael C, Lekakis J, Stefanadis C, Zampelas A. Red wine, arterial stiffness and central hemodynamics. Curr Pharm Des 29; 15: Protogerou AD, Stergiou GS, Vlachopoulos C, Blacher J, Achimastos A. The effect of antihypertensive drugs on central blood pressure beyond peripheral blood pressure. Part II: Evidence for specific class-effects of antihypertensive drugs on pressure amplification. Curr Pharm Des 29; 15: Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 27; 25: Huang CM, Wang KL, Cheng HM, Chuang SY, Sung SH, Yu WC, Ting CT, Lakatta EG, Yin FC, Chou P, Chen CH. 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