Calculation of trough: peak ratio of antihypertensive treatment from ambulatory blood pressure: methodological aspects : Journal of Hypertension

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Calculation of trough: peak ratio of antihypertensive treatment from ambulatory blood pressure: methodological aspects

Omboni, Stefano; Parati, Gianfranco*; Zanchetti, Alberto; Mancia, Giuseppe

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Journal of Hypertension 13(10):p 1105-1112, October 1995.



To address several methodological questions related to calculation of trough:peak ratio from 24 h ambulatory blood pressure (BP) recordings.


Data from patients with mild essential hypertension who were included in parallel group (n=280) or cross-over studies (n=39) were pooled. 24 h ambulatory BP recordings were available after 2- to 4-week washout from treatment and at the end of a 4- to 8-week period of treatment with calcium antagonists (n=143), angiotensin converting enzyme inhibitors (n=103) or placebo (73 patients from parallel group studies and 39 from a cross-over study). Each recording started between 0900 and 1000h, immediately after the drug or placebo intake during the treatment phase. BP was measured at 15 min intervals during the day and at 15-20 min intervals during the night. Peak changes were calculated from systolic BP and diastolic BP 2-8 h after drug intake, and trough changes from readings taken during the last 4 h of the 24 h.


Peak changes induced by drug treatment were progressively reduced when data were averaged over 1, 2, 4 and 6h. BP reproducibility showed a concomitant increase and the best compromise between correct estimate of peak changes and reproducibility was the average of the adjacent 2h with the maximal BP fall. Peak and trough (average of last 2h) changes showed a normal distribution, whereas trough:peak ratios showed non-normal distributions, large scatters and many individual values with no pharmacodynamic significance (namely, much above unity and below zero). Selecting responders to treatment reduced the dispersion and made the trough: peak ratio distribution normal. There was no correlation between trough: peak ratios and changes in BP variability (standard deviation of 24 h mean) induced by treatment. Placebo administration caused no trough but a modest peak fall. Peak changes during placebo also showed a wide scatter and a non-normal distribution, which makes correction with respect to average peak placebo data inappropriate in parallel-group studies. However, placebo correction may be performed for each subject in cross-over studies, leading to a reduction in peak changes and an increase in trough:peak ratio values.


When the trough:peak ratio is assessed from ambulatory BP, peak and trough changes should preferably be computed over a 2h time window. To remove values with no pharmacodynamic significance, the analysis should preferably be conducted only in responders to treatment at peak. Although placebo is accompanied by some peak effect, placebo correction might be appropriate only for individual subjects in cross-over studies.

© Lippincott-Raven Publishers.

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