Hi, my name is Helena Schotland from the University of Michigan. Today, we're going to talk about the impact of disordered sleep and breathing on cardiovascular health. So here you are with your loved one, you're baling the hay, you're in France, it's a beautiful day, you're exhausted after all your work, so you take a lovely nap. It's a bucolic setting, it couldn't be any better. This is what sleep should look like, but in reality, sleep may look like this. Your bed partner is snoring away, it's 10 minutes to 2:00 in the morning, you can't fall asleep, you're becoming unglued. So today, we're going to talk about obstructive sleep apnea, and obstructive sleep apnea is a disorder characterized by recurrent episodes of shallow breathing or breathing cessation during sleep. An apnea is the total cessation of breathing for ten seconds or more. A hypopnea is an episode of shallow breathing associated either with a drop in oxygen level or with an arousal where your brain wakes up from sleep for a split second. An apnea-hypopnea index of greater than 5 times an hour, which is the number of apneas, plus the number of hypopneas per hour, is abnormal. So this is an example of an obstructive apnea. This is a 30-second, what we call, epoch, E-P-O-C-H, of sleep. And the top three channels are EEG channels, or electroencephalogram, brain waves. The next two channels are right EOG, and left EOG for electrooculogram for eye channels. Than you have the EMG channel, which measures rlectromyogram or chin muscle tone. You have the RAT and the LAT, which are the right anterior tibialis, and left anterior tibialis or right leg and left leg. Than you have the EKG, you have the nasal airflow channel, oral airflow channel, and then you have belts that go around the chest and the abdomen. Initially on this tracing, you can see regular nasal airflow, it goes up and down very nicely, and then towards the middle of the tracing, you can see it flattens out. This is when this particular person stops breathing. And you can see that the chest and the abdomen continue to try and initiate a breath, so they're still trying to move, even against this obstructed airway. At the beginning of the tracing, the chest and the abdomen are in sync. However, in the middle during the period of obstruction, they are out of sync and this is called paradoxical respiration. At the end of this event, the person may wake up with a snort or a gasp, it may be a sound that sounds kind of like [SOUND]. And then they wake up, and then they resume their air flow, and the chest and the abdomen are now back in sync once again. And what you can see, is you can see a little increase in the EMG or the muscle tone channel, when I made that snorting sound at the end of the apnic event, you can see a little deflection there. You can also look at the EEG channels. At the beginning of the tracing, the person is asleep and then following this apnic event when they have woken up, you can see the EEG become a little bit faster. And they have actually woken up transiently before they go right back to sleep. This is the man who produced that tracing. You can see he is a big guy, asleep somewhere in a park. And this is a common way that patients present to us with obstructive sleep apnea. So this is a gentleman having an overnight sleep study. And he's sort of settling down right now. You can see, he's not moving his chest; he's not taking a breath. He is not doing anything at the moment. He is having an apnea. And now you can see his chest and his abdomen are trying to move, trying to open up that obstructed airway. So they're moving, he's still not breathing, but he's trying hard, and very soon, you'll see him take a nice deep breath, and he will wake up from sleep. So there he goes, he takes a deep breath, he wakes up from sleep transiently, he may not even realize that he's waking up from sleep. And then he goes right back to sleep and starts the process again. As you can see, he's not breathing at all. Now he's trying to make some effort with his chest and abdomen. And he'll do the same thing again. And he can do this up to hundreds of times in the night. So next, we're going to talk about clinical features of obstructive sleep apnea. The hallmark is habitual, loud snoring. Some patients describe it as sucking the paint off the walls. However, that being said, not everyone with sleep apnea snores loudly. Many patients have witnessed apnea, where you can see them stop breathing at night just like the man that we saw in the last clip. Some patients wake up with episodes of snorting,and gasping at night. Some patients wake up frequently at night, and they have no idea why. Some gentlemen, when they get older, they say, well, my prostate's getting enlarged. I must need to wake up, four or five times, but i'm sure, it's just to go to the bathroom. But it may not be the case that they actually need to urinate, it maybe their sleep apnea waking them up. As I mentioned, nocturia, that's needing to wake up to urinate at night. Many of these patients present with excessive daytime sleepiness, and these may be truck drivers who fall asleep at the wheel or school bus drivers. What's interesting is men often present with daytime sleepiness and that's taken very seriously. Women, however, with sleep apnea, may present with daytime fatigue. And if I go to my doctor I may say, I'm tired. Doc will say, yeah, I'm tired too, everyone's tired. That's not unusual. But a lot of times women aren't taken as seriously as a man who says, I'm falling asleep driving my tractor trailer. So we've talked about fatigue. The other thing that can happen is decreased libido, people just don't have the sex drive that they would like. And that is something people may be shy about talking to you and mentioning when they come to see you as a patient, but it's something that we very commonly see. Next, we're going to talk about risk factors for obstructive sleep apnea. I always like to say that the top three risk factors for sleep apnea are obesity, obesity, obesity. So, you think about the man that we saw the picture of a sitting on the bench or asleep on the bench. He is a very common patient that we see in the sleep clinic. There are some thin patients with obstructive sleep apnea syndrome, and a lot of times, that's related to their upper airway anatomy. So you can look in someone's mouth and get a sense of how crowded or open their airway is. When I used to work in the emergency room, many years ago, someone would be coming to see me for a sore throat, something completely unrelated. And I would see a big tongue when they opened their mouths. I would see a uvula that would hang down all the way to the back of the tongue. I would see a low-lying soft palate. I would see enormous tonsils. And I'd say, do you snore? And they'd say, yes. And I'd say, do you stop breathing at night? Yes. Do you have sleep apnea? Yes. I was diagnosed with sleep apnea ten years ago. So it's something that you can see very commonly just by looking in someone's mouth, and many skinny patients with obstructive sleep apnea have abnormalities of the upper airway. The other thing that you can see in terms of upper airway anatomy is not only the soft tissue structures, but the bony structures. So you can have a patient with a small jaw or a patient with what we call retrognathia. Normally, if you take the line and draw it from your forehead, your chin should actually meet that line. If the chin is behind that line, we call that retrognathia. Also, you can have what's called an overbite or an overjet. Normally, these are your top teeth, these are you bottom teeth, normally, your bite is like this. An overbite is when your top teeth overlap your bottom teeth significantly. An overjet is when your top teeth are way in the front of your bottom teeth. Those are very common anatomic abnormalities that we see in patients with sleep apnea. Another risk factor for obstructive sleep apnea is an endocrine abnormality, such as hypothyroidism. Menopausal status may certainly play a role, so the prevalence of obstructive sleep apnea is in postmenopausal women is definitely higher than that in premenopausal women. Also genetic factors play a role. How you look like your parents on the outside? Well, you can look like your parents on the inside as well. So if you have a mother, say with a large tongue, and an overbite, and an elongated uvula. Not only do you look like her on the outside, but you can look like her on the inside. And you can have that higher risk for sleep apnea that she has. Next, we'll talk about the pathogenesis of obstructive sleep apnea. When you look in someone's mouth, the way I did in the patient in the Emergency Room, you can see a narrowed airway even during wakefulness. Many years ago, when I first started doing sleep medicine, I've studied English Bulldogs. They're a natural animal model for obstructive sleep apnea. And our control dog was a Beagle. When you look into a Beagle's mouth, you can see a huge yawning chasm. When you look into a Bulldog's mouth, you see lots of soft tissue, and you see this tiny pinhole of an airway, and that's when they're awake. When we go to sleep, our muscles relax, including the muscles up here in the airway that help to keep our air passages open. We don't have any bony tissues between this level and about where the trachea begins. So, that's all dependent on musculature to keep that area open. So if you have narrowing in that area, and you go to sleep, and those muscles relax, it's not a big surprise to see that airway become more narrow during sleep than during wakefulness. And what's really interesting is when you get into REM sleep or dream sleep, you basically have muscular paralysis of everything except for the diaphragm. And when you think about these muscles not only being, Having less tone, but now being completely paralyzed, it's not a big surprise that the airway can narrow even more. So we often see sleep apnea being worse during REM sleep than during non-REM sleep. Another role in the pathogenesis of sleep apnea is when you breathe in, you basically have more negative pressure in the upper airway. So by the Bernoulli principles, the walls of the airway tend to get suck closed. And as I was mentioning, you have loss of airway tone during sleep, and this can be exaggerated by alcohol and also by sleep deprivation. So if you take, say, a football player, and normally he may not snore. If you give him a beer and he falls asleep, he may start snoring. If you give him a six pack and he falls asleep, he may not only snore but have episodes of apnea and hypopneas. So let's talk about how common sleep apnea syndrome is. This is an interesting study called the Wisconsin Sleep Cohort Study. This is the study done in Wisconsin state employee. And these employees were given an initial questionnaire that stratify them into a high risk group and a low risk group. And all the high risk subjects ended up getting a sleep study, and 25% of the low risk subjects had a sleep study. And what it showed is when we brought them into the sleep laboratory, we looked at what's called respiratory disturbance index, or the number of times you have episodes of apnea or hypopnea. And we are cutoff with the respiratory disturbance index of greater than 15 events per hour. And we found lab abnormalities in 9% of men and 4% of women. When you combine the lab abnormalities with people who also had daytime or nighttime symptoms, such as witness apneas, snoring, excessive daytime sleepiness, we found the prevalence to be 4% of men and 2% of women. This data was published. And ever since that time, every article in sleep medicine starts with obstructive sleep apnea has an estimated prevalence of 2 to 4%. Now you know where that data comes from. So, let's think about what our patients look like on the inside with obstructive sleep apnea syndrome. On the left is a patient without obstructive sleep apnea, on the right is a patient with obstructive sleep apnea. You can see the gentleman on the left. Black is air, and you can see he has a fair amount of air over his tongue and down his posterior pharynx. Contrast him to the gentlemen on the right, and you can see he has has a lot of soft tissue. You can see the folds of skin behind his neck. You can see extra skin and fat under his chin. You can see his chin is also kind of smaller than the gentleman on the left. And now take look at his airway. Look at that black column of air, it is much smaller. And in the gentleman on the right, and remember he's awake. When he goes to sleep, that column of air may become much more narrow. So why do we treat people with obstructive sleep apnea? Well, these are some of the consequences of untreated sleep apnea. You can have excessive daytime sleepiness, which can impair your quality of life, increase the risk of crashes, so people can crash their cars, their trucks, their boats. You can have cognitive dysfunction, so people often come to see me in clinic and tell me, I don't feel a sharp as I should. I'm also much more irritable, and much more short tempered with my kids and with my spouse. The other big thing that happens with untreated sleep apnea is there's an increase risk of hypertension, heart attack, stroke, diabetes, congestive heart failure, and arrhythmias, and we're going to talk about that. So, let's talk about obstructive sleep apnea and the pathogenesis of vascular disease. With obstructive sleep apnea, when someone stops or has shallow breathing, you can see a drop in oxygen levels. And so you get intermittent hypoxia, which leads to stimulation of carotid chemoreceptors, and leads to a big increase in sympathetic nerve activation and a surge in blood pressure. So your blood pressure can go up. Your intracerebral pressure can go up. Your pulmonary blood pressure can go up. You can also get endothelial dysfunction. Intermittent hypoxia can also lead to oxidative stress. And then you can get Inflammation. And the next slide is basically a schematic of this process. You can have intermittent hypoxia, which leads to reactive oxygen species. This can result in endothelial damage and can lead to hypertension. The reactive oxygen species can also result in an impaired baroreflex, which can also lead to hypertension. With the reactive oxygen species, you can get sympathetic nerve overactivity, also contributing to hypertension. Also can be associated with changes in renin, angiotensin II, and aldosterone levels, which can lead to hypertension. Coming around it the other way, you can have metabolic syndrome, which can be associated with endothelial damage, again, leading to hypertension. You can have metabolic syndrome with atherosclerosis, all leading to hypertension. So basically, all roads here, I want to say, lead to Rome, but in this case, lead to hypertension. So now we're going to look at sleep apnea prevalence in patients with cardiovascular disease. In patients who have drug-resistant hypertension, the prevalence of obstructive sleep apnea is 80%. That's absolutely enormous. In patients who have congestive heart failure, the prevalence of obstructive sleep apnea is 50%. Same thing for patents who have atrial fibrillation. Let's look at patients who have hypertension of all stripes. The prevalence of sleep apnea is 35%. For coronary artery disease and angina, the prevalence of sleep apnea is 30%. Remember, the estimated prevalence for the typical adult population was 2 to 4%. When you look at these special groups of patients, especially those with drug-resistant hypertension, congestive heart failure, and AFib, the prevalence is enormous. Next we're going to talk about, what are sleep apnea patients being treated for prior to a diagnosis of obstructive sleep apnea? And this is a study done in Canada with 773 patients. We'll start with an odds ratio of 1 as a reference point. So patients with obstructive sleep apnea are more commonly being treated for cardiovascular disease, the white circles are men, the black circles are women, also hypertension. Ischemic heart disease is diagnosed more often in men than in women prior to a diagnosis of obstructive sleep apnea. Look at the data for congestive heart failure. It is enormous. Many of these patients have already been treated for congestive heart failure, both in men and women, prior to a diagnosis of obstructive sleep apnea. In arrhythmia, there are many more men than women who've already been treated for arrhythmia prior to a diagnosis of sleep apnea. There is more COPD or chronic obstructive airway disease being treated in women than in men who are subsequently diagnosed with sleep apnea. The data is less strong, but still positive, for arthropathy and depression. Now we're going to talk about talk about sleep-disordered breathing and hypertension. And this was a large study called the Sleep Heart Health Study, and this was published in JAMA in 2000. And this looked at the respiratory disturbance index, or the number of apneas and hypopneas per hour, plus a few other sleep-disordered breathing events. And it stratified them into patients without sleep apnea, patients with mild, moderate, and severe sleep apnea. And the way we discuss severity of sleep apnea, you remember at the beginning of the talk, I said an apnea-hypopnea index or a respiratory disturbance index of greater than 5 is abnormal. So less than 5 is considered normal. 5 to 14.9 is mild sleep apnea. 15 to 29.9 events per hour is moderate sleep apnea. And greater than 30 events per hour is severe sleep apnea. And remember, our odds ratio of 1 is our reference point. So everyone would agree that if someone stops or has shallow breathing less than 1.5 times per hour, they're definitely normal. So you have an odds ratio of 1. Let's look at our patients who have mild sleep apnea, a respiratory disturbance index of 5 to 14.9. The yellow bar is the odds ratio adjusted for age, sex, and ethnicity. The blue bar is the odds ratio adjusted for age, sex, ethnicity, and body mass index. And you can see the odds ratio is definitely increased compared with those patients that everyone would agree are normal, those with a respiratory disturbance index of less than 1.5. Now let's look at our patients with moderate obstructive sleep apnea, those in the 15 to 29.9 group. Their odds ratio is even higher. And then look at the patients with severe sleep apnea, those with an respiratory disturbance index of 30 or more. So there is definitely a linear trend of higher your respiratory disturbance index, the greater chance you have of having hypertension. Now let's look at this interesting group, those patients who have a respiratory disturbance index of 1.5 to 4.9. Their odds ratio is a little bit elevated. And those are patients, remember we said that those patients with an AHI or an RDI of less than 5 are considered normal. Well, these patients, it's just a little bit increased. So that just puts some questions in your mind as to what actually is normal.
