Characterization of circadian blood pressure patterns using non-linear mixed effects modeling

Area of Science:

• Pharmacokinetics and Pharmacodynamics
• Chronobiology
• Cardiovascular Physiology

Background:

• Accurate assessment of antihypertensive drug effects requires understanding baseline blood pressure variability.
• Circadian rhythms significantly influence blood pressure, impacting drug efficacy and safety evaluations.

Purpose of the Study:

• To characterize the 24-hour circadian rhythm of blood pressure in healthy males.
• To identify subgroups with different blood pressure circadian profiles.
• To evaluate the influence of covariates on blood pressure rhythms.

Main Methods:

• Hourly measurement of systolic (SBP) and diastolic blood pressure (DBP) over 24 hours in 23 healthy males.
• Non-linear mixed-effects modeling with two cosine functions (24- and 12-hour periods) to describe circadian rhythm.
• Mixture modeling to identify distinct subject subgroups based on blood pressure patterns.
• Covariate analysis and visual predictive checks for model validation.

Main Results:

• Two distinct circadian blood pressure profiles were identified: 'dippers' (78%) with a typical nocturnal dip, and 'non-dippers' (22%) with elevated nighttime blood pressure.
• Subject weight was positively correlated with the mean blood pressure (mesor) of SBP.
• The model accurately predicted blood pressure patterns in 'dippers' but showed slight deviations in 'non-dippers'.

Conclusions:

• Healthy males exhibit distinct blood pressure circadian rhythms, with a significant 'non-dipper' subgroup.
• Understanding these individual variations is crucial for unbiased antihypertensive drug effect estimation and safety assessment.
• This research provides a reference for analyzing intra-day blood pressure fluctuations and drug-induced changes.