Reply.

W e thank Maniar et al. [1] for their warm comments on our publication comparing three different methods of blood pressure (BP) measurement techniques in an epidemiological setting [2]. However, the authors also raised some concerns, to which we would like to respond to point by point. Firstly, Maniar et al. conclude that the BP differences across the three modalities are not significant in the Bland–Altman plot. This may be because of the confusion about the confidence intervals (CI) – there are CIs of the BP difference and CIs of agreement (or limits of agreement), as suggested by Bland–Altman. For the BP difference CI, standard error is used for calculation, whereas for the agreement CI, standard deviation is used. For example, the 95% CI for the SBP difference between auscultatory BP and AOBP is 10.3–11 mmHg, which is significantly different from 0 (P < 10), whereas the 95% CI of agreement, depicted in the Bland–Altman plot (and also reported in the results section), ranges from 6.9 to 28.2 mmHg. Thus, Bland–Altman plot CI cannot be used to make any statistical inferences about the magnitude of the difference [3]. However, the Bland–Altman plot suggests a significant difference as most data points are above 0. The opponents have correctly noticed large intra-individual BP variability in our study. Several previous studies, including the studies using intra-arterial BP measurement, have shown large short-termphysiologicalBPvariability,even under standardized conditions, that was within the range of 20mmHg for SBP [4]. Despite this large physiological BP variability, the systematic bias between attended and unattended BP values was highly significant in our study. Maniar et al. have concluded that BP variability should be the same under different conditions, including the presence of a physician. However, in our study, auscultatory and attended oscillometric mean BP values did not differ; on the other hand, there was a significant difference if a physician had left the room. This suggests that BP variability increases in the physicians’ presence, with pulse pressure (a surrogate of arterial stiffness) being associated with an increased BP variability (the difference between attended and unattended BP). Secondly, as described in the Methods section, BP measurement was performed under standardized conditions by trained physicians. The participants did not change their position and posture between BP measurements, the same arm was used, and the BP measurements were taken in a defined consecutive order. Therefore, no major changes in the other mentioned factors (emotional state, bladder fullness, recent exercise, recent caffeine intake, antihypertensive medication use and type, comorbidities, diet) may have had an effect on the recorded BP. Thus, the only major change in the stable conditions was the presence or absence of a physician. Thirdly, we agree with the opponents that shifting the AOBP values to lower cut-offs may have increased the proportion of patients with white-coat hypertension. However, our aim was to harmonize these BP measurement techniques to yield a similar proportion of patients with hypertension, which may be helpful to compare the results from epidemiological studies using different BP measurement techniques. Nonetheless, the information on BP response to stressors, such as the presence of a physician, may be also found of interest. In a recent metaanalysis of patients with isolated elevated office BP, cardiovascular risk was increased only in untreated white-coat hypertension, but not in treated white-coat hypertension [5]. Thus, further research is needed to determine the appropriate approach to patients with isolated office BP elevation.