Existence of an endogenous circadian blood pressure rhythm in humans that peaks in the evening

Abstract

Rationale: Blood pressure (BP) usually decreases during nocturnal sleep and increases during daytime activities. Whether the endogenous circadian control system contributes to this daily BP variation has not been determined under appropriately controlled conditions.

Objective: To determine whether there exists an endogenous circadian rhythm of BP in humans.

Methods and results: In 28 normotensive adults (16 men), we assessed BP across 3 complementary, multiday, in-laboratory protocols performed in dim light, throughout which behavioral and environmental influences were controlled and/or uniformly distributed across the circadian cycle via: (1) a 38-hour "constant routine," including continuous wakefulness; (2) a 196-hour "forced desynchrony" with 7 recurring 28-hour sleep/wake cycles; and (3) a 240-hour forced desynchrony with 12 recurring 20-hour sleep/wake cycles. Circadian phases were derived from core body temperature. Each protocol revealed significant circadian rhythms in systolic and diastolic BP, with almost identical rhythm profiles among protocols. The peak-to-trough amplitudes were 3 to 6 mm Hg for systolic BP and 2 to 3 mm Hg for diastolic BP (always P<0.05). All 6 peaks (systolic and diastolic BP in 3 protocols) occurred at a circadian phase corresponding to ≈9:00 pm (ie, the biological evening). Based on substantial phase differences among circadian rhythms of BP and other variables, the rhythm in BP appeared to be unrelated to circadian rhythms in cortisol, catecholamines, cardiac vagal modulation, heart rate, or urine flow.

Conclusions: There exists a robust endogenous circadian rhythm in BP. The highest BP occurred at the circadian time corresponding to ≈9:00 pm, suggesting that the endogenous BP rhythm is unlikely to underlie the well-documented morning peak in adverse cardiovascular events.

Figure 1. Three complementary protocols used to examine underlying circadian rhythmicity of blood pressure

Three protocols designed to keep behaviors constant across the circadian cycle (top panel, 2 baseline days followed by 38-h ‘constant routine’ while semi-recumbent and awake) or to evenly distribute behaviors across all circadian phases (middle panel, 7 recurring 28-h behavioral cycles [28-h ‘forced-desynchrony’]; bottom panel, 12 recurring 20-h behavioral cycles [20-h forced desynchrony]). In each panel, subsequent days are ‘double-plotted’ to the right and below prior days to visually aid protocol continuity. X-axes: clock times for an example subject having an habitual wake time of 8 AM. Black boxes, scheduled sleep episodes in darkness; gray/hatched bars, scheduled wakefulness in dim light conditions (<4 lux) to avoid circadian rhythm resetting.

Figure 2. Similar endogenous circadian variations in blood pressure across two complementary forced desynchrony protocols

Shown are (mean ± SEM) systolic BP (SBP), diastolic BP (DBP) and heart rate (HR) expressed in absolute units (left axes) and as percentages of individual averages (right axes). Data are aligned according to circadian phase (X-axis) and plotted in 60° bins (equivalent to ~4 h). Corresponding approximate clock time is shown on top X-axis. 0° represents core body temperature minimum (~5 AM in these subjects). Thin gray shaded bars are shown at the top of each panel to indicate the average equivalent clock time when subjects would normally sleep when at home (although all data were collected during wakefulness in the laboratory). Solid lines represent the Cosinor model fit and the p values indicate significance of circadian rhythmicity. The phases of the peak SBP are shown by dashed vertical lines in each protocol and occurred close to 240° (equivalent to ~9 PM), which was similar to the timing of the peaks in DBP, but quite distinct from the timing of the circadian peaks in HR.

Figure 3. Endogenous circadian variation in blood pressure during the constant routine protocol is out of phase with circadian variations in other measured variables

Shown are data from the constant routine protocol. lnHF is a marker of cardiac vagal tone (see legend to Figure 2 for other abbreviations and explanations). The phase of peak SBP is shown in each panel by a dashed vertical line close to 251° which was similar to the timing of the circadian peak in DBP, but quite distinct from the circadian peaks or troughs in other relevant physiological variables shown above in the other panels. Very similar circadian rhythms occurred in the two forced desynchrony protocols (Figure 2; Supplemental Material Online Figure I and Online Table I).