Impact of Circadian Disruption on Cardiovascular Function and Disease

Adverse CV events, including myocardial infarction, arrhythmias, and stroke, show time-of-day variations. Underlying factors may include circadian system control over a plethora of markers associated with CV function. Our modern lifestyle, which includes shiftwork, jet lag, and disturbed sleep, has been associated with increased CV risk. Misalignment of the endogenous circadian timing system and behavioral/environmental cycles can adversely impact on CV function in both animal models and human studies. These mechanistic insights may help to explain why some aspects of our modern lifestyle can increase CV risk. Circadian disruption may play a role in the onset and development of CV disease, and treatments aimed at mitigating circadian disruption may diminish CV risk. The circadian system, that is ubiquitous across species, generates ∼24 h rhythms in virtually all biological processes, and allows them to anticipate and adapt to the 24 h day/night cycle, thus ensuring optimal physiological function. Epidemiological studies show time-of-day variations in adverse cardiovascular (CV) events, and controlled laboratory studies demonstrate a circadian influence on key markers of CV function and risk. Furthermore, circadian misalignment, that is typically experienced by shift workers as well as by individuals who experience late eating, (social) jet lag, or circadian rhythm sleep–wake disturbances, increases CV risk factors. Therefore, understanding the mechanisms by which the circadian system regulates CV function, and which of these are affected by circadian disruption, may help to develop intervention strategies to mitigate CV risk. The circadian system, that is ubiquitous across species, generates ∼24 h rhythms in virtually all biological processes, and allows them to anticipate and adapt to the 24 h day/night cycle, thus ensuring optimal physiological function. Epidemiological studies show time-of-day variations in adverse cardiovascular (CV) events, and controlled laboratory studies demonstrate a circadian influence on key markers of CV function and risk. Furthermore, circadian misalignment, that is typically experienced by shift workers as well as by individuals who experience late eating, (social) jet lag, or circadian rhythm sleep–wake disturbances, increases CV risk factors. Therefore, understanding the mechanisms by which the circadian system regulates CV function, and which of these are affected by circadian disruption, may help to develop intervention strategies to mitigate CV risk. disruption of endogenous circadian rhythms. This can occur from the level of the molecular clock mutations to misalignment between the circadian system with behavioral and/or environmental cycles. misalignment between the endogenous circadian timing system and behavioral/environmental cycles (i.e., sleep/wake, light/dark, fasting/feeding), or between components of the circadian system. a biological process with an endogenous, entrainable oscillation of ∼24 h that persists under constant environmental and behavioral conditions. Circadian rhythms can be synchronized to the environmental cycle by the light/dark (LD) cycle. a rhythm in physiology or behavior over the 24 h LD cycle. When environmental and behavioral changes are present (e.g., LD cycle), it is virtually impossible to tease apart whether day/night rhythms are endogenously generated or whether they are a consequence of behavioral/environmental changes. the onset of melatonin secretion when individuals are exposed to dim light (typically <5 lux). DLMO is useful for determining whether an individual is entrained (synchronized) to a 24 h LD cycle, and for assessing the phase angle of entrainment (see definition below) in entrained individuals. a hormone, also known as adrenaline, that is secreted by the adrenal medulla upon stimulation by the central nervous system in response to stress, that is under strong circadian control, and acts to increase heart rate (HR), blood pressure (BP), cardiac output, and carbohydrate metabolism. the variation in the time interval between heartbeats. the ratio of low-frequency (LF) to high-frequency (HF) power, which allows an approximation of the ratio between sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) activity, although the validity of the measure depends on the conditions. a hormone, also known as noradrenaline, that is secreted by the adrenal medulla. Norepinephrine release is lowest during sleep, rises during wakefulness, with higher levels during situations of stress or danger. the relationship between the timing of two entrained oscillations. In chronobiology, this is often used to describe the relative time difference between the central circadian clock (often estimated in humans by DMLO) and the timing of an external time cue (e.g., light) or behavior (e.g., bedtime). the primary inhibitor of tissue plasminogen activator, and thereby an inhibitor of fibrinolysis (breakdown of blood clots). PAI-1 is associated with increased risk of developing occlusive thrombi (blood clots in the vascular system). the likelihood or ability of blood platelets to clump together as part of the sequence of events leading to the formation of a thrombus. a symptom or prodrome to the sudden and transient loss of consciousness owing to transient global cerebral hypoperfusion which is associated with hypotension and/or bradycardia. a work schedule that differs from the traditional 9:00 am–5:00 pm day. It can involve evening or night shifts, early morning shifts, or rotating shifts. reflects the autonomic state resulting from the sympathetic and parasympathetic influences.