Toward Precision Medicine: Circadian Rhythm of Blood Pressure and Chronotherapy for Hypertension - 2021 NHLBI Workshop Report

Abstract

Healthy individuals exhibit blood pressure variation over a 24-hour period with higher blood pressure during wakefulness and lower blood pressure during sleep. Loss or disruption of the blood pressure circadian rhythm has been linked to adverse health outcomes, for example, cardiovascular disease, dementia, and chronic kidney disease. However, the current diagnostic and therapeutic approaches lack sufficient attention to the circadian rhythmicity of blood pressure. Sleep patterns, hormone release, eating habits, digestion, body temperature, renal and cardiovascular function, and other important host functions as well as gut microbiota exhibit circadian rhythms, and influence circadian rhythms of blood pressure. Potential benefits of nonpharmacologic interventions such as meal timing, and pharmacologic chronotherapeutic interventions, such as the bedtime administration of antihypertensive medications, have recently been suggested in some studies. However, the mechanisms underlying circadian rhythm-mediated blood pressure regulation and the efficacy of chronotherapy in hypertension remain unclear. This review summarizes the results of the National Heart, Lung, and Blood Institute workshop convened on October 27 to 29, 2021 to assess knowledge gaps and research opportunities in the study of circadian rhythm of blood pressure and chronotherapy for hypertension.

Keywords: circadian clock; kidney; microbiota; sleep; vasculature.

Figure 1.. Physiology and molecular structure of circadian rhythms.

The molecular circadian clock is present in nearly every cell and tissue type (tissues relevant to this review are pictured). Clock inputs include light and food. The clock controls various physiological outputs, such as blood pressure, body temperature, hormone release, sleep/wake patterns and metabolism. The molecular structure (cell inset) of the circadian clock in mammals is a transcriptional translational feedback loop that takes about 24 hours to complete and involves the core clock genes BMAL1, CLOCK, PER1/2, and CRY1/2.

Figure 2.. Components of nocturnal hypertension and determinants—night-time dipping status and surge in blood pressure.

BP indicates blood pressure; CHF, chronic heart failure; CKD, chronic kidney disease; OSA, obstructive sleep apnea; and REM, rapid-eye-movement. Figure from Kario, Hypertension 2018, open access. Intense physical activity during the day and job strain can increase daytime BP and the day-night BP difference. Sedentary lifestyle during the day and fragmented nighttime sleep (elderly) can reduce the day-night BP difference.