Does circadian rhythm affect the heart?

Researchers supported by British Heart Foundation have found that being a ‘night owl’ – someone who prefers going to bed and waking up later than an ‘early bird’ – could be linked to differences in the structure of the heart. They analysed the heart scans of around 1,300 UK Biobank volunteers (people who have provided their genetic and health information to be used in research).

They found that, in comparison with people who considered themselves to be ‘definitely a morning person’, people who considered themselves to be ‘definitely an evening person’ tended to have a smaller volume of blood in their heart chambers over the course of a heartbeat. This happened both when the heart was filling up with blood, and when it was fully contracted.

• Find out how your heart works

What controls our circadian rhythms?

But what determines when we prefer to sleep, and how is this linked to our heart and blood vessel system? Scientists refer to a person’s natural tendency to sleep and wake at a particular time of day as their chronotype. It varies from person to person, and across our lives – we tend to wake early and sleep early as children, shift later as teenagers, and become more of a morning person again as we age.

 

Sleep is one of many body processes that follow a roughly 24-hour cycle, or ‘circadian rhythm’. Our circadian rhythms are largely controlled by a part of our brain called the suprachiasmatic nucleus (SCN), which works as a sort of master clock for processes in the body. It responds to signals from our environment, including light detected by our eyes, to help keep our body processes in sync with what is going on around us.

In the case of sleep, when it gets dark at night, the brain produces a hormone called melatonin to help us drift off. When it gets light in the morning, the brain triggers the release of other hormones, including cortisol, that help us wake up. In people with an evening chronotype, these hormonal triggers tend to become activated later in the day than in people with a morning chronotype – helping to explain why many teenagers struggle to wake up for school.

However, the impacts of our circadian rhythms go far beyond sleep. For example, the hormonal changes that help us sleep and wake also influence our blood pressure, which naturally tends to fall during the night and peak around the middle of each day.

Our metabolism (how our body breaks down ‘fuel’ from food into energy) also has a circadian rhythm, as our body anticipates how our activity and food intake will vary over the course of a day. The heart needs a lot of energy to keep beating and can switch between using fat or glucose for fuel. Research has found that rat hearts are more able to take up and use glucose as fuel during the night – matching when they are most active.

What makes our cells ‘tick’?

As well as the ‘master clock’ found in the brain, most cells in the body also have their own internal ‘clock’ molecules. Levels of these molecules rhythmically rise and fall, helping to keep our body processes in sync. Take the cells which line all our blood vessels (endothelial cells). Scientists have found that even if you take these cells out of the body and grow them in the lab, you can see levels of their clock molecules rising and falling on a roughly 24-hour cycle.

A disruption to our circadian rhythms may make us feel tired and could affect our heart health too

In turn, this leads to cyclical changes in other molecules involved in the way blood vessels work, such as those which help to regulate blood clotting. For example, one study found that levels of a pro-clotting molecule called PAI-1 in the blood peak at around 6:30am each day. This may help explain why the risk of a heart attack (usually caused by a blood clot blocking the flow of blood to the heart muscle) is also highest in the morning.

So overall, a disruption to our circadian rhythms may make us feel tired and could affect our heart health too. This may also explain why people who have an irregular sleep pattern (such as people who work night shifts) are at a higher risk of developing cardiovascular diseases. It highlights the need for us to better understand how circadian rhythms affect the way our heart and blood vessels work, and BHF-funded researchers are working to do just that.

Why are episodes of atrial fibrillation more common at night?

Atrial fibrillation (AF) is a common form of abnormal heart rhythm, where the top two chambers of the heart (the atria) beat irregularly. It happens when the electrical impulses controlling the beating of the atria, which should be steady and regular, fire chaotically, causing the atria to quiver or twitch.

When AF comes and goes, it is known as ‘paroxysmal’. It’s long been known that episodes of paroxysmal AF tend to be more likely to happen at night, but exactly how this happens is not clear.

With the help of BHF funding, researchers based at the University of Bristol want to find out whether clock molecules in the heart could be behind this. Supervised by Dr Andrew James, Dr Laura Pannell is investigating whether clock molecules exist in heart muscle cells surrounding the pulmonary vein (the blood vessel that carries blood that has been oxygenated in the lungs back to the heart). This area is where the abnormal electrical signals that cause AF often ‘start’. Sometimes, AF is treated with an ablation procedure to ‘scar’ this area, blocking the abnormal electrical signals.

• Find out more about treatments for AF

Their research project looks at how the electrical activity of pulmonary vein heart muscle cells from rats varies over the course of a day, to see if this can be linked to levels of clock genes called Bmal1 and Per2. The researchers will also look at whether levels of molecules involved in how the heart beats rise and fall in these cells. In this way, the researchers aim to find out whether these cells have a circadian rhythm and whether this could be targeted with new treatments to help reduce AF episodes that happen at night.

Circadian rhythms and heart regeneration

During a heart attack, a blood vessel feeding the heart muscle becomes blocked and the heart muscle in that area can’t get the supply of blood it needs. This causes areas of the heart muscle to become damaged or die, and over time be replaced by scar tissue. This can affect the heart’s ability to beat effectively and can lead to heart failure. Once this happens, the heart muscle can never ‘regrow’ the way it was. Well, unless you are a zebrafish!

Zebrafish are small, freshwater fish native to South Asia. They are one of very few animals known to ‘regenerate’ their heart. While human heart muscle cells die if they become damaged, zebrafish heart muscle cells respond to an injury by dividing and growing until the area is replaced by brand new heart muscle.

Professor Mathilda Mommersteeg, based at the University of Oxford, leads a group of researchers who want to better understand heart development and regeneration. In previous work funded by BHF, the team discovered that a gene called lrrc10 is involved in the zebrafish’s ability to regenerate its heart.

BHF-funded researchers want to learn whether there are circadian pathways that could be switched on in the human heart

 

Now, with further BHF funding, they want to find out whether differences in zebrafish circadian rhythms could underlie this. While human circadian rhythms are regulated by our brain responding to light signals picked up by our eyes, every single cell in a zebrafish body (which is almost entirely transparent) can pick up and respond to light. The researchers believe that a zebrafish heart being able to directly detect light may be linked to its ability to divide and grow in response to injury.

In this project, they will compare how zebrafish and human heart muscle cells change over the course of 24 hours and look at whether these changes are linked to the zebrafish cell’s ability to directly pick up light. Overall, they want to learn whether there are circadian pathways that could be ‘switched on’ in the human heart to help it behave more like a zebrafish heart after an injury. Knowing this could in the future hold the key to preventing heart failure after a heart attack. 

What to read next...