The tolerance-hyperbaric test: a chronobiologic approach for improved diagnosis of hypertension

Blood pressure (BP) displays predictable large-amplitude circadian variability. Thus, the identification and the proper definition of hypertension are highly ambiguous when based on single time-unspecified measurements. One way to deal with such variability in the diagnosis of hypertension is to replace the commonly used constant limits of BP by a time-specified reference interval based on the normal circadian BP rhythm assessed by ambulatory BP monitoring (ABPM). A proper reference limit can be constructed, for instance, as a tolerance interval computed for every specific time interval throughout the 24 h. Once such a threshold (given by the upper limit of the tolerance interval) is constructed, a hyperbaric index (HBI) can be computed by numerical integration of the total area of any given patient's BP profile above threshold. The HBI plus the duration of excess within the 24h day serves as nonparametric endpoints for assessing hypertension. Both retrospective and prospective evaluation of this tolerance-hyperbaric test validate its high sensitivity and specificity in the diagnosis of hypertension. We describe the theory of the HBI as well as a newly created dedicated software program that automatically derives the tolerance intervals from a reference database of normotensive subjects and calculates the HBI and other potentially valuable parameters based on data obtained by ABPM. The establishment of time-qualified tolerance limits and the assessment of the extent and timing of BP elevation represents a valuable tool for the more accurate diagnosis of hypertension as well as means of gauging response to treatment.