Key result
Non-linear mixed effects modeling of 24-hour blood pressure data revealed that 78% of healthy male subjects were 'dippers' with a nocturnal dip, while 22% were 'non-dippers'.
Why the study?
Characterizing the time course of baseline or pre-drug blood pressure is important to acquire unbiased estimates of antihypertensive drug effect.
Observational (n=23)
No
Non-linear mixed effects modeling successfully characterized circadian blood pressure patterns, identifying 22% of healthy male volunteers as non-dippers, which can serve as a reference for assessing antihypertensive drug effects.
May refine BP monitoring timing in trials; leaves open translation to hypertensive patients or drug-effect estimation.
Characterizing the time course of baseline or pre-drug blood pressure is important in acquiring unbiased estimates of antihypertensive drug effect. In this study, we recruited 23 healthy male volunteers and measured systolic (SBP) and diastolic blood pressure (DBP) over 24 hours on an hourly basis. Using a non-linear mixed effects model, circadian rhythm observed in blood pressure measurements was described by incorporating two cosine functions with periods 24 and 12 hours. A mixture model was applied to identify subgroups exhibiting qualitatively different circadian rhythms. Our results suggested that 78% of the study population, defined as 'dippers', demonstrated a typical circadian profile with a morning rise and a nocturnal dip. The remaining 22% of the subjects defined as 'non-dippers', however, were not adequately described using the typical profile and demonstrated an elevation of blood pressure during night-time. Covariate search identified weight as being positively correlated with mesor of SBP. Visual predictive checks using 1,000 simulated datasets were performed for model validation. Observations were in agreement with predicted values in 'dippers', but deviated slightly in 'non-dippers'. Our work is expected to serve as a useful reference in assessing systematic intra-day blood pressure fluctuations and antihypertensive effects as well as assessing drug safety of incrementally modified drugs.
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Chae et al. (2019) conducted an observational in Healthy volunteers (n=23). 24-hour blood pressure monitoring was evaluated on Proportion of subjects with 'dipper' versus 'non-dipper' circadian blood pressure patterns. Non-linear mixed effects modeling of 24-hour blood pressure data revealed that 78% of healthy male subjects were 'dippers' with a nocturnal dip, while 22% were 'non-dippers'.
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