• Cardiovascular

    Science Saturday: Getting to the Heart of Sleep

Sleeping poorly can do more than make you tired. It can kill you.

Growing up in South Africa, Virend Somers and his two cousins would lie on a big bed with their grandfather as he told them stories. “We really enjoyed the stories. But what we also looked forward to — I say this with a bit of guilt now — is when he’d fall asleep. He would start snoring, and he’d stop breathing for these long periods. There’d be these incredible gasps when he’d breathe again. It was fascinating to us to study this from a child’s point of view. But we didn’t quite realize the implications,” he recalls.

Virend Somers, M.D., Ph.D.

That was his introduction to obstructive sleep apnea. Now, as a physician researcher, Virend Somers, M.D., Ph.D., directs the Mayo Clinic cardiovascular sleep research facilities. His team studies the role of the autonomic nervous system in cardiovascular regulation, especially during sleep. Yet that memory of his grandfather lives on in his medical research and practice.

“As it turned out, he died in his sleep,” he says. “It’s only now in later years that I’m beginning to understand what happened.”

Dr. Somers’ research in sleep was highlighted in a paper in the New England Journal of Medicine in the nineties, where his team described how normal sleep affects the heart, blood vessels and the sympathetic nervous system. His subsequent work shows that disturbed sleep, especially sleep apnea, has serious health effects. Those experiencing disturbed sleep are chronically drowsy and at higher cardiac risk. The periods of low oxygen when the poorest sleepers stop breathing can increase the risk of sudden cardiac death about 80 percent, he says.

OBSTRUCTIVE SLEEP APNEA

Obstructive sleep apnea is the most common of several types of apnea — the momentary cessation of breathing during sleep. It affects about 1 in 4 middle-aged men and 1 in 10 middle-aged women.

Sleep apnea occurs when the soft palate and tongue fall back into the throat either partially or entirely closing off the airway.

Breathing stops for as long as 20 seconds. The level of dissolved oxygen in the blood plummets. The loss of oxygen jolts the person awake, though he or she may soon fall back asleep and never remember the event. In severe sleep apnea, these episodes may repeat more than 30 times an hour, making continuous sleep nearly impossible.

“The patient struggles to breathe,” says Dr. Somers. “So — gack, gack. They suck in against a closed airway. They generate this huge negative pressure in the chest, trying to suck air in. Part of your heart is fairly thin-walled, and you’re putting it into this very strong vacuum — sucking on the outside. That changes the structure of the atria and, we think, may increase the likelihood of atrial fibrillation.”

“Your oxygen level falls, because you’re not breathing and your carbon dioxide goes up,” he says. That stimulates the chemo-reflexes that activate the sympathetic nervous system — the fight or flight response. The heart begins to pound, blood vessels tighten, blood pressure soars.

“The heart’s having to work hard, and it’s having to do this in a situation where there is not enough oxygen — and there’s a very high carbon dioxide level,” Dr. Somers says. “Acid from carbon dioxide, and adrenaline and similar hormones flood the bloodstream. So you have a perfect storm of cardiovascular misery.”

Dr. Somers and his co-authors published research findings in Circulation in 2003 and 2004 that show an association between sleep apnea and the loss of heart rhythm, called atrial fibrillation. Patients treated for atrial fibrillation had higher recurrences of that condition if they also had sleep apnea. In a 2005 paper in the New England Journal of Medicine, Dr. Somers and colleagues also showed that sudden death related to heart problems peak during sleeping hours for those with sleep apnea. Other people tend to have their heart attacks in the morning.

Obstructive sleep apnea, according to Dr. Somers’ research, is one of the strongest predictors of sudden cardiac death — much more so than blood pressure or high cholesterol. The most important measure seems to be how low a patient’s blood oxygen falls during episodes. A longitudinal study of 10,701 adults published in 2013 in the Journal of the American College of Cardiology showed that the magnitude of risk of sudden cardiac death was predicted by several measures of the severity of obstructive sleep apnea, particularly nighttime low blood oxygen.

A sleep study data readout. the yellow bar shows the time the patient's breathing was reduced; the red bar indicates the patient stopped breathing altogether.

 

Chronic sleepiness also is associated with sudden cardiac death, though it’s unclear if sleep deprivation is the cause or simply that sleepiness goes hand in hand with low oxygen during apnea episodes. “The more sleepy apneics seem to be at greater risk,” he says. “That’s something we definitely want to understand.”

Obstructive sleep apnea carries other risks as well, including coronary artery disease and stroke. And there’s more.

“There is a very strong but poorly understood relationship between sleep apnea and the development of dementia,” says Dr. Somers.

Even in children there’s evidence sleep apnea affects cognitive function. “If your child is breathing noisily at night or has even one apnea per hour, that’s considered abnormal and needs to be treated,” says Dr. Somers. “School performance among kids with sleep apnea is very poor. There’s evidence that fixing the apnea can allow them to more fully develop their intellectual skills.”

The usual cause of apnea in children is enlarged tonsils.

CURRENT TREATMENTS

Many people are chronically tired but don’t realize they have sleep apnea. Until recently, it wasn’t recognized as a problem. When Dr. Somers started practice, perhaps 85 percent went undiagnosed, he says. More are diagnosed now, but most people with sleep apnea still don’t know they have it.

Since patients often don’t remember their sleep disturbances, it is often spouses — usually wives — who suspect something is wrong. Spouses of sleep apneics are themselves often sleep-deprived.

Unfortunately, says Dr. Somers, “we don’t know whether treating the apnea will prevent future heart attacks.” But treating apnea does lower blood pressure and at the very least provides a better night’s sleep. And life changes can help. Losing weight is recommended, as is avoiding alcohol or other sedatives at bedtime.

“The reason you don’t stay apneic forever is because your brain wakes up, and you start breathing again,” says Dr. Somers. “But, when you take something that sedates the brain, like alcohol, it’s going to make the apnea last a little longer, because whatever mechanisms arouse the brain are less easily aroused.”

Another fix: a device to hold the lower jaw forward and prevent the tongue from falling back. But, Dr. Somers warns, it “has to be fitted by someone who truly knows what they are doing, so it doesn’t mess up your teeth and your bite.”

Finally, there are the continuous positive airway pressure or CPAP machines that gently force air into the airway through a mask. “CPAP is very effective. The problem is that it is not easily tolerated. Forty percent or more can’t continue using it. They can’t sleep,” says Dr. Somers. And the pump — the size of a toaster — isn’t convenient to travel with.

A TEAM APPROACH

As Dr. Somers took up the study of sleep apnea and cardiovascular disease in earnest, he found he didn’t have much company. Few medical schools taught sleep. “Can you imagine that?” he asks. “You spend a third of your life asleep. Yet, all the medical schools were focused only on daytime medicine.” He received a Sleep Academic Award from the National Institutes of Health to improve scientific understanding and public awareness of the cardiovascular consequences of disturbed sleep.

Francisco Lopez-Jimenez, M.D.; Virend Somers, M.D., Ph.D, the Alice Sheets Marriott Professor; and Michael Ackerman, M.D., Ph.D., the Windland Smith Rice Cardiovascular Genomics Research Professor

 

 

At Mayo, Dr. Somers often teams up with colleagues, such as Michael Ackerman M.D., Ph.D., who studies inheritable diseases that can cause sudden death. Drs. Somers and Ackerman have examined the relationship between sleep disorders and genetic heart rhythm syndromes, such as long QT syndrome, a disorder of the heart’s electrical recharge. It can cause sometimes fatal irregularities in heartbeat.

“We show that there’s kind of an interplay between sleep, sleep cycle and the heart’s recharging system in general,” says Dr. Ackerman. “That may provide a reason, or one of the potential reasons, why there’s increased risk of events during sleep in women with long QT, particularly during sudden arousal from sleep in the morning, like with the alarm clock going off or with the sound of their crying baby.”

Dr. Somers also collaborates with Francisco Lopez-Jimenez, M.D., a Mayo cardiologist who studies heart disease and obesity, which is often associated with sleep apnea. As he read Dr. Somers’ research, Dr. Lopez-Jimenez recognized related interests, including the effect of poor sleep on appetite and glucose metabolism.

Soon after Dr. Lopez-Jimenez joined Mayo Clinic 16 years ago, he asked Dr. Somers to be his mentor. “I approached him back then and said, I like the work you do, and I have some interest in obesity and cardiovascular disease — something he wasn’t doing. But, obviously, patients with sleep apnea, many of them have obesity. So I saw a lot of potential for collaboration there.”

“It has really been an exciting collaboration for me because Virend has an open mind,” says Dr. Lopez-Jimenez. “He has a scientist’s mind, and, therefore, no matter how crazy might be the idea that I propose, he will say that’s interesting. He has this gift of wonder or wondering why, or how can we explain this or that.”

The opportunities for sleep research will only get more important, according to Dr. Somers, because sleep deprivation is “getting worse and worse,” he says. “Compared to 20 years ago, we sleep less. Compared to 100 years ago, we sleep a lot less.”

The reason? Electric lights and, more recently, computer screens, the internet, smartphones and social media.

Says Dr. Somers, “If there are health implications of inadequate sleep, this could have enormous public health implications for the future, because of the vast numbers of young people who just aren’t sleeping enough.”

- Greg Breining, February 5, 2018

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