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While You Were Sleeping
By following 1,500 subjects for 25 years, a landmark study at the University of Wisconsin helped reinvent sleep science and proved that sleep apnea causes more than snoring. Scientists now link the sleep disruption to health risks ranging from high blood pressure and stroke to cardiovascular disease and early death. Is your aging brain a risk too?


Photo by GKDRC/iStock

In today’s always-connected and endlessly monitored world, there is still nothing quite like getting wired up for a sleep study. Four sensors are glued to your head to record brainwaves. Two are attached near your temples to log telltale rapid eye movement (REM). A cannula measures breath from the nose, and a microphone on the neck records snoring. A blood oxygen monitor is taped to the index finger, and leads on the chest measure heart rate. Wires on each leg monitor any twitches.

The lines were uncomfortable, and the ambiance at the sleep lab nothing special – a curious cross of hospital and Hampton Inn decor – but the bed was fine, and the Rev. Debra Trakel drifted away for a good night’s sleep.

Or so she thought. A few weeks after her night in the Wisconsin Sleep Cohort lab, she got a call. They’d analyzed every minute of her night, and when Trakel had considered herself fast asleep, she’d actually stopped breathing, again and again. Her body would grow alarmed and awaken her, but only just enough that she could take another breath. This cycle of sleep-suffocate-wake had happened continuously – 29 times an hour.

Since her previous sleep test, Trakel, a pastor at St. Christopher’s Episcopal Church in River Hills, had developed severe obstructive sleep apnea. Left untreated, it put her at all kinds of risk: high blood pressure, stroke, cardiovascular disease and early death. It blurred her cognitive skills, and left her more prone to depression and car accidents. Perhaps one in 20 Americans suffer from sleep apnea, and it’s estimated that millions more go undiagnosed. It’s a major component of a societal sleep deprivation so severe that the Centers for Disease Control calls our collective lack of shut-eye an epidemic.

Sleep, so basic a human function, is actually quite difficult to study. But since 1988, 1,500 Wisconsin residents – the Wisconsin Sleep Cohort – have been quietly going to sleep under the scientific gaze of the University of Wisconsin-Madison Department of Population Health Sciences. This

painstaking study has helped reveal some of the most important insights about sleep and human health, elevating sleep science to a new level.

Sleep apnea was long considered an uncommon sleep disorder in older men who snored. It was suspected of causing high blood pressure, even death, but treatments were extreme – tracheotomy, for one. That changed in the 1980s with the introduction and refinement of the continuous positive airway pressure machine (CPAP), a sleep mask connected to a respirator. With treatment available, sleep apnea became a pressing research question.

UW doctors who wanted to study the condition tapped epidemiologist Terry Young, a medical detective who could help them understand the disease picture across an entire population. “As soon as I looked at [the research proposal], I knew this was just fantastic,” she says. “There was almost nothing known about the epidemiology, and it was potentially a significant disorder.” The study began after the National Institutes of Health awarded the group a grant in 1987.

With 1,500 subjects taking turns in a lab that could accommodate only eight visits a week, it took nearly four years just to get the full group through the initial round of research. But studying real sleep in real lives over decades would allow the Sleep Cohort to become a powerful testing ground for new ideas.

They had results within five years. In their middle-age study group, nearly a quarter of men and a tenth of women had some degree of sleep apnea. They estimated that 2 percent of women and 4 percent of men in the general population had apnea severe enough to be treated. That was more than expected, particularly for women. (More recent estimates put the prevalence of moderate-to-severe obstructive sleep apnea between 6.5 percent and 8.5 percent.) Those findings, published in 1993 in the New England Journal of Medicine, remain one of that prestigious journal’s most-cited papers of the last two decades.

Not only was sleep apnea common, Young’s group established an important pattern. “It’s not like a broken bone, where you have it or you don’t,” she explains. “There is a range of abnormality. Some people stop breathing five times an hour. Some people, 80 times an hour. This, of course, gave rise to the huge questions: What level is of clinical significance, and what should be treated?”

A typical healthy adult will enter a light sleep and fall deeper and deeper through slow wave sleep for about 90 to 120 minutes. Then the first REM cycle typically begins, lasting about 10 minutes. Finally, you pop out of REM and start over again, cycling through stages throughout the night.

While you’re in REM, you become partially paralyzed. “If you didn’t, you’d act out your dreams,” explains Paul Peppard, who now heads up the Sleep Cohort. But this paralysis can extend to the upper airway, which is what collapses or narrows during a sleep apnea event. The body tries to breathe harder and harder, but against that closed airway, it’s like sucking on a thick malt through a straw. “You’re actually sucking the upper airway more and more closed,” he says. The body must awaken partially to gain control over the upper airway muscles. A person experiencing sleep apnea might notice that they’re less rested, but they are unaware of what’s happening. “People don’t wake up and say, ‘I woke up 500 times last night,’” Peppard explains.

Peppard joined the study team as a young grad student in epidemiology. When he was diagnosed with high blood pressure himself, he decided to study hypertension. There was no question that, during a sleep apnea event, blood pressure spiked. That straw-sucking action creates a negative pressure in your chest around your heart, which then has to push harder.

Could the repeated stress of sleep apnea, night after night, cause blood pressure to rise over time? That was the speculation. Just the force of those pressure spikes could injure blood vessel walls. And each apnea event activates the fight-or-flight response, bathing the body in stress hormones. Could sleep apnea trigger a remodeling of the whole vascular system?

It was a reasonable deduction, but the things that cause sleep apnea also contribute to high blood pressure – like obesity, smoking or alcohol consumption. That severely complicates the story. So which came first, the sleep apnea or the hypertension?

After sorting through all the confounding factors, Peppard followed people who had no hypertension but a sleep apnea index of at least 15, meaning 15 breathing stoppages per hour, the level at which treatment is typically prescribed. His research indicated a clear link between sleep apnea and the development of high blood pressure: People with sleep apnea that merited treatment were nearly three times more likely to develop hypertension during the four-to-eight-year period of the study.

Hypertension. Cardiovascular disease. Another recent discovery even suggests sleep apnea could accelerate cancer. The diseases are complicated – you can rarely point to one cause – yet the Wisconsin Sleep Cohort has helped us understand how sleep, and sleep apnea, are connected to some of our biggest killers.

The annual estimated cost of diabetes in this country is $245 billion. Hypertension, $93.5 billion. Cancer, $124.6 billion. It’s impossible to sort out what portions of these

total costs are from sleep apnea. One reputable estimate from Harvard Medical School puts it between $65 and $165 billion.

Health care systems are beginning to realize the treatment benefits. Hospitals that pay attention to sleep apnea in their admissions significantly reduce the number of post-

operative complications. A recent study of 22,000 Union Pacific employees found that increasing awareness and treatment of sleep apnea decreased health care costs by nearly $5 million over just three years.

The economic equation could look even better after the next round of Sleep Cohort research, which hopes to examine whether sleep apnea has a role in the cognitive decline that happens as we age. As you get older, you’re more likely to be diagnosed with sleep apnea, and the number of borderline cases also goes up. With a burgeoning boomer population, Peppard says the question of how aggressive our treatment should be is a billion-dollar one. Sleep apnea treatment is annoying and costly. “But it would be well worth getting to 90 in great cognitive shape versus hitting 80 and just kind of deteriorating over the next 10 years and being institutionalized,” he says. That kind of intensive care dramatically accelerates health care costs. “How hard do you push someone who comes in with borderline symptoms?” asks Peppard. “What do you do to eke out an extra five years of cognitive health? We don’t know what to tell those people.”

With more than two decades spent untangling the cardiovascular elements of sleep apnea, refocusing on the cognitive side will take some effort. But the original study design was comprehensive and included several tests of brain function, so researchers have important baseline data. Using that, they’ve already been able to link sleep apnea with an Alzheimer’s gene. Subjects who have the gene and obstructive sleep apnea are particularly likely to experience verbal memory decline. The next phase of their research hopes to pair cutting-edge brain imagery with the deep medical history of the Wisconsin Sleep Cohort.

“It’s not important just for Wisconsin or North America,” says collaborator Mary Morrell, a respiratory physiologist from Imperial College London. “It’s important for the world. There is no other set of data like this. We have no other aging group of people who have been followed for such a long period of time for this disease.”

Debra Trakel, at least, is sleeping better. After the lab told her she had sleep apnea, she followed through with two more sleep tests to diagnose her and to fit a mask for her sleep machine. It’s uncomfortable, but she’s compliant. “I’ve done my research. I understand the risks,” she explains. “Because you’re stopping breathing so frequently, and every time you do, you’re putting enormous pressure on your cardiovascular system.”

She knows the sleep apnea probably did some damage before it was diagnosed, but she’s happy to have her sleep machine now. “My concentration level is higher,” she says. “I see it in precision of thought, precision of writing, ability to manage complex relationships. I hear more acutely. I listen better. Food tastes better.”

Trakel admits she’s a bit of a zealot when she hears about people not using the machine. She may even be addicted, she laughs. “Everything seems better,” she adds. “It has revolutionized my life.”
This article appears in the February 2014 issue of Milwaukee Magazine.
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