Circadian Rhythm of Blood Pressure of Dipper and Non-dipper Patients With Essential Hypertension: A Mathematical Modeling Approach

Abstract

Blood pressure in humans presents a circadian variation profile with a morning increase, a small postprandial valley, and a deeper descent during night-time rest. Under certain conditions, the nocturnal decline in blood pressure can be reduced or even reversed (non-dipper), which is related to a significantly worse prognosis than a normal fall pattern (dipper). Despite several advances in recent years, our understanding of blood pressure's temporal structure, its sources and mechanisms is far from complete. In this work, we developed an ordinary differential equation-based mathematical model capable of capturing the circadian rhythm of blood pressure in dipper and non-dipper patients with arterial hypertension. The model was calibrated by means of global optimization, using 24-h data of systolic and diastolic blood pressure, physical activity, heart rate, blood glucose and norepinephrine, obtained from the literature. After fitting the model, the mean of the normalized error for each data point was <0.2%, and confidence intervals indicate that all parameters were identifiable. Sensitivity analysis allowed identifying the most relevant parameters and therefore inferring the most important blood pressure regulatory mechanisms involved in the non-dipper status, namely, increase in sympathetic over parasympathetic nervous tone, lower influence of physical activity on heart rate and greater influence of physical activity and glucose on the systemic vascular resistance. In summary, this model allows explaining the circadian rhythm of blood pressure and deepening the understanding of the underlying mechanisms and interactions integrating the results of previous works.