08:58am Monday 06 July 2020

Circadian Clock May Contribute to Daily Fluctuation in Risk of Heart Attack and Stroke

It has been generally assumed that this daily pattern of occurrence is caused (in vulnerable individuals) by the pattern of behaviors that change across the day. Researchers at Brigham and Women’s Hospital (BWH) have now demonstrated that the internal biological clock, or circadian system, regulates several components of the cardiovascular system, suggesting that the circadian system could also be involved in the daily pattern of occurrence of serious adverse events. These findings are published online in November in the Proceedings of the National Academy of Sciences (PNAS).

The master circadian clock in the brain, in concert with circadian clocks throughout the body, generates recurrent 24-hour rhythms. This circadian system controls much of our physiology, including temperature, the secretion of many hormones, and the timing of the sleep/wake cycle, presumably to optimize our physiological function to match our daily pattern of behaviors. The researchers performed an experiment over many days in volunteers where they carefully controlled all behaviors in order to study the internal circadian system and discovered that the circadian system regulates several components of the cardiovascular system, including hormones, heart rate, blood pressure, the autonomic nervous system, and blood clotting ability.

The lead author of the study, Frank Scheer, PhD, Associate Director of the Medical
Chronobiology Program at BWH, stated, “Much prior research has revealed clear effects of daily behaviors, like sleeping and exercise upon the cardiovascular function, and when considering that adverse cardiovascular events occur most often in the morning, many researchers have generally considered this a product of behaviors, not a result of the body’s internal circadian rhythm.” However, very little research prior to this study had been done to investigate the affect the circadian system on cardiovascular function to determine if this naturally occurring rhythm may also play a role in increasing likelihood for adverse cardiovascular events in the morning.

The study was conducted in the Center for Clinical Investigation at BWH, where research volunteers stay in an environment without any indicators of time-of-day, such as day-light exposure. In this study, twelve healthy adult volunteers were subjected to a recurring 20-hour schedule, rather than a 24-hour schedule, in order to separate the individuals’ circadian rhythms, which occurred naturally on a 24-hour cycle, from their behavioral cycle, which had been switched to a 20-hour cycle. Steven Shea, PhD, Director of the Sleep Disorders Research Program at BWH, and Principal Investigator of the study that was funded by the National Heart, Lung and Blood Institute at NIH, explained that “By the end of the two-week stay in the laboratory, because of this recurring 20-hour behavioral cycle, each participant experienced all of their scheduled behaviors, such as exercise, meals and sleep, across all phases of their internal circadian cycle. For example, they will have performed exercise during their biological clock’s morning, afternoon, evening and night. In this way, we could examine the effects of the circadian system on cardiovascular function while at rest, as well as the effect of the circadian system on the physiological reactions to a challenge, such as exercise”.

Throughout this separation of the circadian cycle from the behavioral cycle, researchers studied the participants cardiovascular risk markers. The researchers observed that, independent of changes to the participants’ environment or behavior, the circadian system causes an increase in risk markers epinephrine, cortisol, and blood clotting at a circadian time corresponding to the morning peak in adverse cardiovascular events. Remarkably, the researchers furthermore observed that the circadian system changed the size of the response of sympathovagal balance to standardized physical exercise dependent on the circadian timing of exercise, such that this risk marker was again largest at a circadian time corresponding to the ‘vulnerable’ morning hours.

Understanding the biologic mechanism behind the daily fluctuation in risk for adverse cardiovascular events has the potential to influence the development of novel treatments and the timing for administering current and future therapies. Dr. Scheer concludes, “More research involving individuals that are vulnerable to adverse cardiovascular events is needed to determine whether or not the circadian timing and circadian amplitude of cardiovascular risk markers at rest and in response to physiological stressors, such as exercise, is changed in those populations.”

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