The Hidden Risks of Obstructive Sleep Apnea

Sree Roy: Hello and welcome. I’m Sree Roy with Sleep Review, and I’m thrilled to be here with sleep specialist Indira Gurubhagavatula, MD, MPH. She served as chair of the Count on Sleep Tool Development and Surveillance Workgroup for a national indicator report for obstructive sleep apnea. The Obstructive Sleep Apnea Indicator Report provides an in-depth analysis of the symptoms, risk factors, prevalence, and burden of obstructive sleep apnea, and serves as a resource for both the public and the healthcare communities on the importance of diagnosis and long-term treatment.

We are chatting about the hidden risks of obstructive sleep apnea.

What is obstructive sleep apnea, also known as OSA for short?

Dr. Indira Gurubhagavatula:

Thank you for having me, Sree. OSA, or obstructive sleep apnea, is a medical disorder that occurs when a person is asleep. It does not happen when they’re awake.

And what happens when they’re asleep is that the upper airway closes intermittently during sleep. The airway muscles relax to the point where there’s actual mechanical obstruction of the throat, and that results in a transient reduction in airflow, which is called a hypopnea, or a complete stoppage in airflow, which is called an apnea. Within a few seconds of partial or complete airway closure, the oxygen level in the bloodstream drops, and the brain responds to this intermittent hypoxia with a surge of adrenaline, which causes the person to arouse briefly from sleep. And then, during the arousal, the airway muscles then reactivate, the airway opens up, the oxygen level gets restored, they take a few deep breaths, and then they can go back to sleep again.

But once they do, the muscles relax and collapse, and the whole process starts again. And for some people, this can happen hundreds of times a night. And what sleep studies do is measure how often this is happening, and we characterize the frequency of this airway closure and intermittent hypoxia, and sometimes actual arousal from sleep if EEG waves are being measured, and up to five times per hour is actually considered a normal range for adults, five to 15 is considered in the mild range, 15 to 30 times per hour is moderate, and 30 or more is considered in the severe range.

And this is an extremely common problem. We believe 29 million adults in the US, which is roughly 12% of the overall population, have OSA, and yet only about six million are diagnosed.

Sree Roy:

What do you think is the most troubling risk of not treating obstructive sleep apnea?

Dr. Indira Gurubhagavatula:

Well, I think that you’ll get a different answer depending on who you ask. But there are so many troubling risks, it’s hard to pick just one.

But since you’re asking someone with a special interest in road safety and traffic safety, I would say one of the most troubling risks is fall-asleep crashes.

When you think about the risk of not treating sleep apnea, there are a lot of potential adverse consequences in the short term and in the long term. The recurrent drops in oxygen affect the entire body, every tissue, and fragmented sleep can affect every tissue. So the impact is broad if we leave it untreated. And what you get is not only intermittent hypoxia, but also surges in adrenaline. And these are stressful for the heart and for the brain, and the sleep fragmentation and daytime sleepiness can then impair performance. So cardiovascular disease and downstream effects of sleepiness are the two big categories of risks that need to be considered.

Daytime sleepiness can have very sudden and serious effects on a person’s function. And obviously, the most dangerous thing is the risk of injury or death if you’re doing safety-sensitive work like driving or operating heavy machinery.

Sleepy people, though, can also experience consequences that are very important to them. For example, in the workplace, being late or being absent because they’re tired or they’re sleepy or they feel sick. We also see something called presenteeism, where the person shows up for work but they’re not engaged, or they’re making mistakes, doing things wrong, missing things, serious errors that can affect their livelihood. So that’s a very important outcome, reduced overall quality of life.

And then when we look at the other side, the intermittent hypoxia, we see an association with that higher levels of inflammatory cytokines, which can be damaging to blood vessels. And this, along with high sympathetic activity that’s seen in OSA patients over years, can lead to cardiovascular disease. So hypertension, heart attacks, arrhythmia, stroke. And not just the heart and the brain, but other organs are also vulnerable to these effects. So insulin resistance and metabolic syndrome, weight gain, obesity over time, impaired immunity, which can make it harder for our bodies to mount a good immune response to either viruses or vaccine challenges. Certain eye disorders, including glaucoma, which can be vision-threatening. I see patients reporting acid reflux that improves when they get their apnea treated, sexual dysfunction. So the bottom line is that, that we need oxygen and we need sleep, and our entire body needs oxygen and needs sleep, and this is a treatable disorder.

So the fact that 80% of people are undiagnosed means that there is a huge burden of preventable illness that can be attributed to sleep apnea, and it is costing us billions annually. In our healthcare system alone, we’re paying for these downstream effects after they’ve already happened, and this can become costly, and instead of preventing them in the first place, we are spending close to $150 billion a year on undiagnosed sleep apnea and its consequences, and the prevalence of obesity is high, and it’s another indicator of how big the problem is because obesity is a major risk factor for sleep apnea.

Sree Roy:

Let’s dive into some of the aspects that you just touched on, some of the morbidity linked to obstructive sleep apnea. So treatment-resistant hypertension is a frustration for patients and clinicians. How has treatment-resistant hypertension been linked to OSA?

Dr. Indira Gurubhagavatula:

So let’s just define treatment-resistant hypertension. It means that in spite of using three or more medications, the person’s blood pressure continues to be high.

We believe that the recurrent burst of adrenaline contribute to the hypertension that’s seen with OSA. There’s probably overlapping effect as well from obesity, which is a major comorbidity with OSA.

Now we have evidence from longitudinal studies as well as randomized trials of people with hypertension who’ve received either CPAP therapy or a placebo. And we know that CPAP is effective in lowering blood pressure. There are several meta-analyses that have been published. So the good thing about this is that treating sleep apnea effectively reduces the levels of adrenaline-type chemicals in the blood and lowers blood pressure.

So what that means for people who are sufferers of hypertension is that they may end up needing lower doses of blood pressure medication, or eventually, under the supervision of their healthcare provider, they find that they no longer need blood pressure-lowering medication once they’re on effective therapy. So the amount of money spent on such medications and possible side effects of these medications can then be avoided.

So anyone with treatment-resistant hypertension, the estimates of prevalence suggest that 80% of those people have untreated sleep apnea. So if you see somebody who’s on multiple meds for blood pressure lowering, it’s a really good idea to screen those people for sleep apnea and get them treated.

Sree Roy:

What about impaired brain function? How can the impaired brain function linked to OSA manifest in patients?

Dr. Indira Gurubhagavatula:

That’s a really important question. We rely on our brains for most of our waking activities, and our brain function can get impaired in a number of ways.

So people with sleep apnea, because of the recurrent sleep fragmentation that happens, the constant arousals to reestablish airflow, means that they’re not getting the restful sleep they need. And their brains are now being subjected to not only low oxygen levels off and on throughout their sleep period, but also the constant interruptions in sleep. Without restful sleep, daytime sleepiness becomes a concern. So people may experience actual falling asleep inappropriately in the daytime when they are trying to do things like attending meetings at work or while sitting or trying to be in a conversation or in front of a TV show or at a movie theater, or importantly, while driving, which can be really dangerous and life-threatening for the person and also poses a risk to others on the road.

So a number of functions though also get impaired, whether the person feels sleepy or not: our ability to remember things, to focus, concentrate, make decisions, exercise good judgment, take in lots of information, and figure out what’s important and what’s not, motor functioning like coordination, reaction time, speed. All of these functions require a well-rested brain.

And what we also know is that some regions of the brain are particularly vulnerable to sleep deprivation. So the frontal lobe, for example, and that’s the lobe that’s responsible for executive function. So judgment, decision-making, parsing information, what’s called working memory. So these are all really, really important attributes of brain function that we rely on to navigate our days. And these problems can occur in the short term. If somebody is on treatment and they stop treatment, they can notice these symptoms, and also in the long term can continue to impair people.

And a lot of people just sort of adapt their lives around their impairment, so they’re not even aware how much they are impaired until someone, a healthcare provider, asks the questions and offers the intervention.

Now, the longer-term consequences of brain function, some of these are really worrisome, including an increased risk of stroke, which can leave someone debilitated permanently. And even dementia has been linked with this. And in addition to our cognitive abilities, there’s also the mood aspects of brain functioning. So impaired brain function can mean that some people with untreated sleep apnea are more likely to experience mood disorders like depression and anxiety, and they don’t have to, right? This is preventable. So if we can get their apnea identified and treated, they can notice an improvement in their mood.

Sree Roy:

Wow. Yeah, that’s some compelling data. What evidence is out there that erectile dysfunction and female sexual dysfunction can be tied to OSA?

Dr. Indira Gurubhagavatula:

So let’s talk about these terms. Sexual dysfunction means a failure to achieve and maintain an erection or sexual satisfaction.

Most of the evidence comes from observational studies instead of randomized trials. But there is a meta-analysis of nine observational studies with over 1,000 people, and the pooled data suggests that sleep apnea doubles the risk of erectile dysfunction, men and female sexual dysfunction for women. So this is something that a lot of people don’t necessarily admit to their doctors or want to talk about. It is a sensitive subject. So for healthcare providers who are treating these disorders, it’s a really great idea to ask about sleep apnea in these subgroups.

So as to why that might be happening, I mean, if you ask new parents, for example, who have newborns that are keeping them up all night, the exhaustion alone can be a reason.

So it’s possible that people are exhausted from sleep deprivation, that it results with untreated sleep apnea, or they may have depression as a result of untreated apnea, or that the sleep deprivation is actually altering sex hormones levels, or it could be coexisting obesity or diabetes or some other comorbidity that’s occurring with sleep apnea. We don’t know the degree to which OSA may cause cell damage from the recurrent intermittent hypoxia and the abnormal sympathetic activity, and the inflammation that there could be endothelial dysfunction and damage to small blood vessels and reproductive organs. So this is an area where we really need a lot more study to help us understand this.

Sree Roy:

In my view, the worst link is that obstructive sleep apnea has been linked to an earlier death. Why is that?

Dr. Indira Gurubhagavatula:

So there are a number of observational studies that seem to suggest a dose-response relationship. The more frequently someone experiences apnea, the higher their risk.

So people in the severe group with apnea-hypopnea frequencies that exceed 30 times per hour, 20 times per hour seem to have double the risk of mortality. So what the AHI (or the apnea-hypopnea index) is, is it’s a measure of intermittent hypoxia and how often it’s happening, and sympathetic load. And from Framingham, the Framingham heart data, we know that a hyperactive sympathetic state is associated with higher mortality.

See, healthy sleep is the opposite. It’s a state where parasympathetic drive predominates. We have lower heart rate, lower blood pressure, and in people with sleep apnea, this state is compromised. So some of this cardiovascular mortality and some of these increased moralities all-cause mortality, and it could be linked to this higher sympathetic state.

We also know that driving accident risk is almost five times higher in people with untreated sleep apnea, especially if sleep apnea is in that moderate to severe range. And these accidents are horrific because if you think about when you’re driving and you think an accident is about to happen, you will take countermeasures to prevent it from happening. So those avoidance maneuvers like steering away or hitting the brakes, people who are sleepy or impaired because of insufficient sleep, even if they’re not feeling sleepy, they can be impaired. They’re not going to respond in the same way, which means these accidents tend to be very high impact. They’re much more likely to result in severe injury or in death.

Sree Roy: How has OSA been linked to diabetes?

Dr. Indira Gurubhagavatula:

That’s a great question. So OSA has been linked to the development of incident type 2 diabetes, which is very compelling information, but it’s also been associated with gestational diabetes. And even in type 1 diabetes, and again, it all comes back to the pathophysiology. You have intermittent hypoxia, you have sleep fragmentation, and you have more inflammation. But we believe that all of this adrenaline results in dysregulation and glucose metabolism. And that is what’s seen if you bring in healthy people and do studies in the lab, and subject them to intermittent hypoxia or sleep fragmentation, we see glucose dysregulation.

So it’s possible that there’s microvascular injury going on or direct damage to pancreatic beta cells that then results in an inability to regulate insulin. But it could also be an indirect effect. When we’re sleep-deprived, we see abnormalities in hormones that regulate appetite, hunger, and satiety, leptin and ghrelin, and the ratios of those hormones actually invert in some people.

So they end up eating a lot more, and they choose foods that are obesogenic. So the fried foods, the sweet foods that are tasty but we know we shouldn’t be eating. So it’s possible that some of the effect is through that, through alterations in hormones.

But we also know that there’s a lot of overlap between sleep apnea and obesity. So sleep apnea is often occurring together with obesity, which is another big driver for diabetes. But the interesting thing about sleep apnea is that there are actually enough evidence now that we know that there is a relationship.

As far as the impact of treatment on glucose metabolism, the effects are a little bit more mixed. We know that CPAP restores insulin sensitivity, but as far as reversing type 2 diabetes, the way we see with hypertension, that has not been shown yet.

Sree Roy:

That actually segues nicely into my next question, which is, treatment of sleep apnea typically involves a device such as a CPAP machine or an oral appliance, though surgery can be an option for some patients. Is there any evidence that treating OSA can alleviate some of the sleep apnea morbidities or mortality?

Dr. Indira Gurubhagavatula:

So this is a really exciting question because there is good news. We have a very large body of evidence that sleep apnea is treatable, and treatment reduces the risk of many of these serious downstream consequences.

Some of the strongest evidence is for sleepiness, which we measure using a subjective scale called the Epworth Sleepiness Scale. But we also have randomized trial data looking at high blood pressure and driving accidents. There are meta-analyses published on these that show that CPAP improves blood pressure and lowers the risk of driving accidents and crashes. We also know that some cardiovascular outcomes have been improved in people, and the data seems to be strongest for those who actually use their machines.

Adherence to CPAP is a major predictor of outcome and of mortality, and the evidence for this is so strong that CPAP has been and still continues to be first-line therapy for the treatment of sleep apnea.

Sree Roy:

Excellent. With all of this evidence in mind, what should healthcare providers do to help identify patients who are likely to have obstructive sleep apnea?

Dr. Indira Gurubhagavatula:

Healthcare providers are a major line of defense. Again, some of the really serious downstream consequences we talked about.

Early intervention can help patients with getting on effective therapy as soon as possible. So what healthcare providers can do is ask their patients about habitual loud snoring or daytime sleepiness, especially if they’re still feeling sleepy even after a full night’s sleep, or if they have insomnia or nocturia or morning headaches, mood changes, difficulty with memory or concentration.

The symptom experience, though, can be very different from one person to the next. Some have just a couple of symptoms, some have all the symptoms, and the majority of people will not report anything. A lot of people think that snoring is just normal and natural and just something that happens as you get older, and they just take it as a normal part of aging. Some people equate sleepiness with laziness. They don’t want to admit it.

So it is important to ask, and it’s also important to look for other clues in asymptomatic people that they may still be at risk. So number one, look, are they overweight or obese? Are they falling asleep in your waiting room or as you’re talking to them, or are they a middle-aged man or a post-menopausal woman with central obesity? Are they coming from particularly vulnerable racial subgroups? So Black, Hispanic, and Asian subgroups seem to be at higher risk than Caucasians, and they should be asked about symptoms. And your index of suspicion should also be really high if they’ve already had comorbidities like cardiovascular disease, hypertension, especially resistant hypertension, or if they’re obese with type 2 diabetes.

And then people in safety-sensitive occupations. So if you have a truck driver in front of you or law enforcement officer, somebody who operates heavy machinery, they in particular should be asked about common symptoms of sleep apnea, like snoring and daytime sleepiness. And if you want to use a quick screening tool, the STOP-Bang is available. It’s easy to use. And another quick rule of thumb is a neck size of 17 inches or larger in men, and that’s a surrogate for central obesity. And it could be another simple screening tool when figuring out who should be sent for sleep testing.

Sree Roy:

What should patients listening to this podcast do if they think they have symptoms of obstructive sleep apnea?

Dr. Indira Gurubhagavatula:

The first thing they have to do is put their sleep and sleep health first. We live in a society that undervalues sleep and sleep health, and we think it’s normal to snore, get tired in the daytime, so don’t ignore symptoms. Sleep apnea is easy to diagnose and treat, and treatment will help you feel better.

So call your doctor, ask for a sleep evaluation. And the nice thing is nowadays sleep studies can often be done directly in your home, and a lot of sleep practices have incorporated telemedicine, so you can get an evaluation and get treated, and hopefully start feeling better very soon without too much inconvenience.

Sree Roy:

Fantastic. Are there any other resources online that you’d like to share, perhaps websites or social media handles for anybody listening to this episode?

Dr. Indira Gurubhagavatula:

I would direct everyone to the National Indicator Report. It contains a great deal of detail, much more than we can cover in this brief podcast, but that might be of particular interest to anyone who wants to learn more about sleep apnea.

Sree Roy:

Fantastic, and we will link to that.

Dr. Indira Gurubhagavatula:

Yeah, and sleepeducation.org, also, in general has a lot of resources.

Sree Roy:

Fantastic. We will link to that report. It is the Obstructive Sleep Apnea Indicator report in the show notes, which are available on sleepreviewmag.com.

Thank you so much for chatting with us about the hidden risks of OSA.

You can find Sleep Review at sleepreviewmag.com; go to sleepreviewmag.com/podcasts for the show notes; and on LinkedIn, Facebook, Twitter, and YouTube. Thank you so much for tuning in to this episode.