Next, we're going to talk about obstructive sleep apnea and coronary artery disease. Obstructive sleep apnea, as we've mentioned, can cause endothelial dysfunction, inflammation, and lipid dysfunction. And you can also have sympathetic activation associated with obstructive sleep apnea in association with the above pathologic factors, and this may lead to ischemic events or higher risk of ischemia and heart attack. We'll talk about again the Sleep Heart Health Study. What this study found is that obstructive sleep apnea is an independent risk factor for coronary artery disease, independent of hypertension, obesity, age, gender. So, sleep apnea all by itself is a risk factor for coronary artery disease, and that has really changed the way a lot of us have practiced. Now when we see patients who present to us with mild obstructive sleep apnea, but have a history of heart attack, we are very aggressive about treating those patients. Patients with coronary artery disease and obstructive sleep apnea actually have an increased risk of death over a five year period. This is 38 percent for the patients with obstructive sleep apnea versus nine percent for controls. Next, we're going to switch gears and talk about obstructive sleep apnea syndrome and arrhythmia. We're going to show you an epoch of sleep or a 30-second snippet, and remember, we've got the three EEG channels on top, left eye and right eye and EKG channel, chin muscle tone, leg EMG, airflow; nasal airflow, oral airflow, chest, abdomen, a snore channel, and saturation, oxygen saturation. And what you can see here at the beginning about two thirds of the way through the tracing, you can see there is no airflow. This person is having an apneic event. And actually, they're in REM sleep which is a stage of sleep, where you can have rapid eye movements and you can see the deflections in the LOC and ROC channels, the oculogram channels. It's not that their eye movements are more rapid than waking eye movements, but they look like wakeful eye movements compared to much of the rest of sleep where you have these slow rolling eye movements. The other thing that if you remember I told you about during REM sleep, is you essentially have postural muscle atonia, where you have paralysis of postural muscles. So, you can see this apneic event occurring, and now let's look at the EKG channel. The EKG is fairly regular at the beginning of the epoch, where you can see the heart rate starting to slow down a little bit, and then you get a huge pause and then the person may wake up with a snort or a gasp, start breathing again, and the EKG speeds right back up and the person probably goes on to do this again and again throughout the course of the night. So, this is an arrhythmia that we're seeing and this is one of many arrhythmias that we can see in the course of the night. Now, we're going to look at some more data from the Sleep Heart Health Study. This looks at the association of nocturnal arrhythmias with sleep-disordered breathing. This is data published from the American Journal of Respiratory and Critical Care Medicine in 2006. This looks at 228 subjects with sleep-disordered breathing. Those patients had a respiratory disturbance index of 30 or more, so they had severe sleep apnea, and it looked at 338 subjects without sleep-disordered breathing or a respiratory disturbance index of less than five events per hour. And what you can see, you can see data for atrial fibrillation or AF, complex ventricular ectopy, nonsustained ventricular tachycardia, bigeminy, and quadrigeminy. And you can see in those patients who have sleep-disordered breathing, those are the dark bars and the patients without sleep-disordered breathing are the light bars. You can see the percentage of patients with atrial fibrillation is higher, complex ventricular ectopy is higher, nonsustained ventricular tachycardia is higher as is bigeminy and quadrigeminy. And the conclusion from the study is that subjects with severe sleep-disordered breathing are patients who stop or have shallow breathing greater than 30 times an hour have a 2-4 fold higher odds of complex arrhythmias than those without sleep-disordered breathing, even when you adjust for age, sex, and body mass index as well as prevalence of heart disease. Now, we're going to talk about sleep apnea and congestive heart failure. Again, we're looking at data from the Sleep Heart Health Study. We're looking at 2058 participants. Compared to those with an apnea-hypopnea index of less than five participants with an apnea-hypopnea index of 30 or more had an adjusted odds ratio of 1.78 for left ventricular hypertrophy. Higher apnea-hypopnea index and higher hypoxemia index were associated with larger left ventricular diastolic dimension and lower left ventricular ejection fraction. So, you can see how this contributes to congestive heart failure. We're going to look at survival in congestive heart failure and coronary heart disease. This is a study taken from the sleep heart health data, and this looks at 1927 men and 2495 women who were free of coronary heart disease and congestive heart failure at baseline, and they followed these patients for a median of 8.7 years. And let's look at the boxes on the left. This is coronary heart disease free survival in men and congestive heart failure for survival in men. So, we can break up the apnea-hypopnea index into categories. The red is for 5-15, green is for 15-30, and yellow is for greater than 30. If we look at the coronary heart disease free survival by AHI in men, you can see patients with no sleep apnea, mild or moderate sleep apnea are not significantly different. But men who have severe sleep apnea have a marked decrease in their survival compared to the other groups. And if we look at the data on congestive heart failure, we can see a similar pattern for congestive heart failure being much worse in patients with severe sleep apnea than in patients with no sleep apnea. But you can see that there is a difference between patients with mild sleep apnea and patients with moderate sleep apnea compared to survival in patients without sleep apnea, which is the blue line. If we look at the data in women, we don't see a significant effect in terms of survival either for coronary heart disease or for congestive heart failure. Next, we're going to look at obstructive sleep apnea syndrome and incidence stroke. This is a study published in the American Journal of Respiratory and Critical Care Medicine in 2010. This is taken from data from the Sleep Heart Health Study looking at 5422 participants without stroke at baseline and who are untreated for sleep apnea. These patients were followed for a median of 8.7 years. During this time, 193 ischemic strokes occurred. So if we look at the top box, this is adjusted survivorship data in men on the Y axis and follow-up in years on the X axis. We have the data broken up by quartiles. Q1 is patients without sleep apnea, Q2 is patients with mild sleep apnea, Q3 is patients with moderate sleep apnea, and Q4 is patients with severe sleep apnea. You can see the survivorship decreases as the follow-up in years goes on, and this is most prominent for men with severe sleep apnea. If we look at the data in women as the follow-up in years goes on, you can see survivorship decrease. So, let's talk about treatment of sleep apnea and treatment outcomes. First things first, we'll talk about CPAP, which is continuous positive airway pressure. It is really the mainstay of therapy. I like CPAP because it's simple, it's noninvasive, and can work very well. But some patients aren't completely sold on CPAP therapies, so we have some other options that we can talk about, upper airway surgery and the type of surgery really depends on what you look like on the inside. So, you may have nasal polyps or a deviated septum or a large tongue or an elongated uvula or a small jaw. So, the type of surgery really depends on what type of anatomic findings are present. Another thing that can sometimes work very nicely for sleep apnea and is good for you regardless is weight loss. I've had patients who've lost a significant amount of weight and their sleep apnea has gone away. I've had others who've lost a significant amount of weight and their sleep apnea is better. It may not be gone, but they may require lower CPAP pressure settings and it may make the CPAP easier for them to tolerate. Position therapy, some people are much worse lying on their back versus lying on their side. So, a lot of spouses say when my husband is on his back, he snores like a bear, so I kind of nudge him, he rolls to his side and he stops snoring, we see that with sleep apnea. An oral appliance is something that you can wear on your teeth. The purpose is to pull your lower jaw forward. By doing that, you pull the base of the tongue forward, and you're trying to make more airspace in the posterior pharynx, so your airway is less likely to collapse. Another option is something called Provent. Provent is a one-way nasal valve. It looks sort of like a little cloth Band-Aid with a one-way valve in the middle. You put one over this nostril and one over that nostril. What it does, it allows the air to go in through your nose but resists the air coming out through your nose. By doing that, it keeps the air passages open and keeps you breathing. Let's talk a little bit more about CPAP therapy. CPAP treats obstructive sleep apnea by providing a pneumatic splint to keep the upper airway open. Basically, it pushes air in through the nose or the nose and mouth and puts pressure in the upper airway to keep that area open and not allow it to collapse, the nice thing is that most of the time prevents people from snoring as well, so it's a positive thing. CPAP therapy doesn't have to look like this anymore, and it doesn't have to look like this anymore. I've been studying sleep medicine for 20 years, and things have changed dramatically over that period of time. So now, we have little CPAP interfaces. You don't have to have a big mask on your face, although some people like what we call the full-face mask that goes over nose and mouth or a nasal mask that just goes over the nose. But we have things called nasal pillows, which just go in the nostrils and you can see the headgear is super light and a lot of people love this type of interface. So, there usually is something for everyone. The other thing is that CPAP machines have gotten a lot smaller, a lot lighter, the designs are better. Now, they have integrated humidifiers, even with heated tubing. And as you can see in the CPAP machine on the bottom right, it has a data card in there. In the old days, we used to give patients a CPAP therapy, and they would come back for a visit and we'd say, "Are you using your CPAP?" and they'd say," Oh, yes." And the next time, we'd say,"Well, bring your CPAP machine next time you come into clinic", and they'd bring the CPAP machine and a true Philadelphia Story [inaudible] out of the CPAP unit, so you knew they weren't using it, but that evolved to the point where they started putting our meters on the bottom of the CPAP machine. So, at least you knew when the CPAP was turned on and when CPAP machine was turned off. Now, we have algorithms built into the machine, where we can see not only how much the patient is using the machine, but also how well it works for them and if the mask leaks, and that has really changed the way we practice. In this slide, this is some of the data that can be downloaded from a CPAP machine. The top graph shows you the pressure delivered by the CPAP machine, the middle graph shows you leakage from the CPAP mask, and then the bottom graph shows you residual apnea-hypopnea index and apnea index. For example, if you see a patient who has a large leak and an elevated apnea-hypopnea index, you know that you need to go back and you need to fix the leak. So, this kind of data has really changed the way that we practice and troubleshoot our patients with sleep apnea. Next, we're going to talk about some of the outcomes of CPAP therapy.
