Dr Allison Brager Highlights the Influence of Sleep on Cardiovascular Health

Circadian misalignment can lead to increased risk of cardiovascular disease, heart attack, stroke, and other heart-related conditions, says Allison Brager, PhD, neuroscientist, Walter Reed Army Institute of Research.

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Brager discussed the interaction between daily behaviors and the circadian system with cardiovascular health at the 2024 SLEEP: American Academy of Sleep Medicine and Sleep Research Society (APSS) Annual Meeting.

AJMC^®: How do circadian rhythms influence cardiovascular health, and what are the potential long-term impacts of circadian misalignment on the cardiovascular system?

Brager: Cardiovascular health is intimately tied to the circadian clock. We know, for example, that there is a daily robust rhythm in heart rate, and more particularly [in] heart rate variability. So, heart rate variability is a sign of overall health and fitness. The higher the heart rate variability, the healthier and the fitter the individual typically is. We know that heart rate variability is fairly lower during the waking day, because we're in a very high stress state, or fight or flight response. And then we know that heart rate variability actually rises during sleep, because this is giving an opportunity for the parasympathetic system or the restorative recovery arm of the nervous system to take over. And the problem with circadian misalignment is, if you were, say, working nights instead of working days, this preprogrammed rhythm to be in a parasympathetic state is essentially hijacked. So, you're not going to get the restoration and recovery response from the nervous system alone that drives the cardiovascular system, as [would] somebody doing day shift work. And that's really the impetus for why you see increased rates of cardiovascular disease, increased risk for heart attack, increased risk for stroke, or any other heart-related condition in night shift workers more so than day shift workers.

AJMC: What daily behaviors or lifestyle choices have the most significant impact on both cardiovascular health and circadian rhythms, and how can these be optimized for better heart health?

Brager: I'll focus a lot on exercise because that's what I do professionally. That's what I do personally, too. I used to be a professional athlete. In training the circadian clock, when it comes to optimizing, improving, and enhancing cardiovascular health, exercise is really the best thing you can do. And what's unique about some of the work my colleagues and I have done is that there actually are optimal times of the day to do select types of exercises. That's something I focused on in my talk, in fact.¹ For example, it's actually better to do heavy weight training in the evening when your cardiovascular system, and in particular, the norepinephrine and epinephrine portions of that system, are peaked and primed, vs somebody who is doing heavy weight training in the morning. Now, what's unique is you can get someone to their nighttime performance levels simply by giving them caffeine, because caffeine can prime the norepinephrine epinephrine system that allows somebody to lift heavy weight through the appropriate recruitment of muscle fibers and all the related athletic attributes of power and stamina that come with it.

Beyond that, any just cardiovascular fitness is going to ultimately improve your heart rate variability, which again is hugely important for long-term health. Trying to do as much as possible to [reach] a zone 2 state, so this idea of being at 60% to 70% of your maximum heart rate for 30 minutes to an hour at a time, at least 2 times a week. All those behaviors can help. And then ultimately, sleep. Even if you are a night shift worker, the best thing a night shift worker can do is to keep a consistent sleep schedule, because at least then the circadian clocks will adapt and adjust to the time this individual is going to bed, and they can somewhat protect themselves from the deleterious consequences of the shift work on the cardiovascular system.

AJMC: Can you explain the role of sleep quality and timing in maintaining optimal cardiovascular function and how disruptions in sleep patterns can affect heart health?

Brager: I think the most perfect clinical case study example of that is sleep apnea. So, sleep apnea is very dangerous, because it greatly increases risk for stroke, heart attack, high blood pressure, and everything else. It's mostly because when you're in a hypoxic state, your brain and your nervous system goes into fight or flight response. There's this immediate panic. So, you're constantly being disrupted from the most restorative stages of sleep that are important, not just for repair and recovery of all the bodily tissues, but also important for repair and recovery of the brain. And so, somebody with untreated sleep apnea, they're not just losing out on all the restorative sleep, which again, is going to favor and prioritize this high heart rate variability by prioritizing the parasympathetic nervous system. You're actually not being in a parasympathetic state. You're being in the sympathetic state because you're constantly trying to gasp for air to sustain life.

AJMC: How does physical exercise interact with circadian rhythms to influence cardiovascular health, and are there optimal times of day to exercise for maximizing heart health benefits?

Brager: When it comes to elite athletes, I can tell you it's not about health, it's about performance. We actually did this whole study where we controlled for when NFL teams are traveling, whether they're traveling East Coast or West Coast, and the amount of time zones they went to. We found equal distribution of flip-flopping between time zones between East Coast teams and West Coast teams, but one thing we found is that West Coast teams are actually more often playing games in their peak optimal zone for circadian alertness. So typically, when it comes to circadian alertness and athleticism, it starts to peak mid-morning through lunchtime. And so more West Coast teams are playing games during that time vs East Coast teams, which often play times in their biological afternoon, which is this period of the day where there's a natural circadian driven increase in sleepiness and fatigue. And as a result, we find if you track rate of injury in first-string players across the entire NFL, the East Coast teams are about 5 times more likely to get injured during the regular season compared with West Coast teams. And it's not just position-specific, it's across all positions. Whether you’re offensive line, defensive line, or sitting in as a quarterback, East Coast teams are far more likely to get injured. And I think this response is driven from the fatigue-related effects of playing in the biological afternoon.

AJMC: What are the potential benefits or challenges of using chronotherapy to manage cardiovascular diseases, and how might this approach be integrated into daily routines?

Brager: I would say there aren't any weaknesses. I would say they're only benefits at this. We were actually talking about this in a session I chaired yesterday.² Something you don't think about like drug toxicity, for example. There's this great presentation on how liver enzymes and the gut microbiome are primed during certain circadian phases. When it comes to shift workers, they are essentially operating during a time where nothing is primed to perform. So, if you think about drug toxicity, if you have somebody in the ER [emergency room], who needs and requires a medication and there’s serious or minor side effects of taking this medication, taking that medication at an optimal circadian time could push that person over into a state of toxicity, and then they'd be worse off than better off.

The same thing applies to cardiovascular health. I think the best example we have from public health is during that time in the spring when we set our clocks forward. So, essentially all of America except for Arizona loses an hour of sleep. The public health community has actually found increased risks for heart attack during that single day where we have a 1-hour shift in the time the sun rises in the morning, coupled with most people just having insufficient sleep. I think that's another example. Also, if we look at rates and prediction times of heart attacks and strokes across a 24-hour period, there are known circadian differences in the likelihoods during the day vs during the night.

Reference

1. Brager A, Brito L, Currie K. Cardiovascular health and performance: daily behaviors and their interaction with the circadian system. Session presented at: SLEEP 2024; June 1-5, 2024; Houston, TX.

2. Brager A, Davis C, Kombala C, et al. Sleep at the wrong time: mechanisms underlying internal desynchrony and long-term health risks in shift workers. Session presented at: SLEEP 2024; June 1-5, 2024; Houston, TX.