Sleep Apnea and Cardiovascular Disease

Jay Widmer, MD, PhD: Howdy, I'm Jay Widmer, cardiology fellow here at Mayo Clinic Rochester. During today's recording, we'll be discussing sleep apnea, its impact on the cardiovascular system, and treatment options. I'm joined by my friend and colleague, Dr Virend Somers, who is an expert both in cardiovascular diseases and sleep apnea. Welcome, Dr Somers.

Virend Somers, MD, PhD: Thanks, Jay. Thanks for inviting me.

Dr Widmer: Absolutely, so we'll get started. Briefly tell us a little bit about sleep apnea: What is it, and why does this occur?

Obstructive vs Central Sleep Apnea

Dr Somers: When you think of sleep apnea, there are two essential types. There's obstructive apnea and central apnea. Obstructive apnea is the kind of apnea that's noisy, socially disruptive, and associated with snoring. The patient is often obese. [Obstructive apnea] affects males and females at a 2:1 ratio. The apnea occurs because when people fall asleep, they lose their postural muscle tone. Because the upper airway has striated muscle, it loses tone as well. Particularly during rapid eye movement (REM) or dream sleep, you want to have low muscle tone so you don't act out your dreams. With inspiration, the airway collapses and causes an obstruction. The resolution of the obstruction occurs when the patient's brain wakes up. The patient doesn't know he or she is waking up, but the brain wakes up, the muscle tone is restored, and they start breathing again.

Central apnea is the quieter kind of apnea that [tends to] occur with heart failure. You'll also see it in your kids or spouse when you travel to [high] altitude. The low carbon dioxide that is generated by being at altitude causes the central apnea, which we also know as Cheyne-Stokes breathing. It's a nonobstructive apnea that occurs because of the lack of the central drive to breathe. We see that mainly in heart failure. We see it in normal people at altitude. Premature infants also often have a high likelihood of central apnea.

Central apnea also occurs mainly in males and particularly with severe heart failure. But central apnea in heart failure tends to be more prominent in people with low body weight, low muscle mass, who are more cardiac cachectic; they will often have central apnea.

Association With CVD

Dr Widmer: You mentioned heart failure and central sleep apnea. With regard to those two types of sleep apnea, [is either of them] particularly associated with cardiovascular disease or do they cause cardiovascular disease?

Dr Somers: Good question. Let's talk about obstructive first. Obstructive is associated with a breadth of cardiovascular diseases—hypertension, atrial fibrillation, myocardial ischemia, particularly ischemia that occurs at night. If someone has a heart attack or chest pain at night, look for obstructive sleep apnea; there is a high likelihood that he or she has it. There also seems to be an increased risk of sudden death in people with obstructive apnea, and there is an increased risk of sudden death and defibrillator firing that occurs at night. So if patient has an [implantable cardioverter defibrillator] ICD and it triggers at night and wakes them from sleep, then look for sleep apnea.

Dr Widmer: Sleep apnea, with both ischemic and nonischemic causes?

Dr Somers: Yes, absolutely. The other important question you asked is, does sleep apnea cause heart disease? We don't know for sure. There's good evidence suggesting it does—and sleep apnea certainly makes it worse—but we haven't got the definitive answer to that yet. Sleep apnea probably causes high blood pressure, but [as for] the rest, the jury is still out.

Now let's talk about central apnea. Its relationship with heart failure is less clear. In patients with central apnea and heart failure, the central apnea seems to accompany the heart failure. Whether the central apnea is causing the heart failure to become worse, we don't know—probably not based on recent evidence that we will talk about.

Dr Widmer: We talked a little bit about ischemic heart disease and heart failure. Are there any other cardiovascular conditions that would be associated with sleep apnea, or would we need to think about sleep apnea?

Dr Somers: In those cardiovascular conditions that we mentioned, if the patient has intractable hypertension or recurrent atrial fibrillation, or heart failure that's not responsive to standard therapy, then you must look for sleep apnea. Because treating the apnea can sometimes make the underlying cardiovascular condition more amenable to standard therapy.

Now, I haven't mentioned that aneurysmal dilatation of the aorta has been linked to obstructive sleep apnea. Patients with pulmonary emboli seem to have a higher prevalence of sleep apnea than we would expect. Certainly, patients with [deep vein thrombosis] DVT have a high prevalence of sleep apnea. Research that came from us at Mayo showed^[1] that if you have a [patent foramen ovale] PFO and you have a left-to-right shunt, generally, during the obstructive apnea, during the Müller's maneuver, you can actually get reversal of the shunt, so you get a right-to-left shunt. If you think if you have a DVT that's embolized up to the right atrium and suddenly you get a change due to the obstructive apnea from left-to-right to right-to-left shunting, you can get a paradoxical embolus. These are the more esoteric links to sleep apnea.

Treatment Options for Sleep Apnea

Dr Widmer: It's certainly something we all need to think about in the clinical realm.

What are treatment options for sleep apnea, and what are their impacts on cardiovascular disease? You mentioned treating hypertension earlier, but what are some of the ways that we can treat it, and then how will that help our patients?

Dr Somers: We'll start with treatment options for obstructive apnea. If the patient is overweight, you want them to lose weight. If they have sleep apnea that is worse on their backs, it's a gravitational [issue]. With loss of muscle tone in the upper airway, the tongue can fall backward into the airway; that is worse when they are sleeping on their backs. This is why patients with apnea often improve if they sleep on their sides. A T-shirt with tennis balls sewn in will cause discomfort when patients sleep on their backs, so they sleep over on their sides. That can help relieve apnea to some extent.

There are several other approaches we could talk about, but the gold standard of sleep apnea therapy is CPAP, or continuous positive airway pressure. What that does is splints the airway open during inspiration, so it makes it easier for the subject to breathe.

There are new investigational therapies on the horizon. For example, for obstructive sleep apnea, there is a stimulator for the nerves that control the upper airway so that when you have an apnea, the stimulator activates and maintains airway tone. Again, that's fairly experimental, and there have been some papers suggestive of reasonable results, but we have to wait and see.^[2]

The optimal way to treat central apnea is what we call "adaptive servoventilation." It's a CPAP-like device that, in a simplistic way, learns your breathing when you're awake and breathing normally and tries to simulate that breathing pattern when you're asleep to stabilize your breathing. If you think CPAP—continuous positive airway pressure—is a pressure-driven breathing aid, then ASV, or adaptive servoventilation, seeks to maintain the volume of airflow. When you stop breathing, it's not a question of the airway collapsing, it's just that you're not breathing. So, ASV tries to generate the breathing for you.

Effects of Therapy

Now you did ask—what are the effects of therapy? I'm going to talk about obstructive apnea first. We know that treating obstructive apnea in hypertensive patients, particularly those with severe sleep apnea and with severe hypertension who are sleepy, will lower blood pressure.

How does treating sleep apnea do in terms of increasing lifespan? We've had a fairly large study—the SAVE study^[3]—come out in the New England Journal [of Medicine] a few months ago, and those results were a little disappointing. When [researchers] treated people with established cardiovascular disease—some randomized to CPAP treatment and others to usual care without CPAP—those receiving CPAP did not show any striking improvement in outcome.

There are many possible explanations for this. One is that [the study included] only nonsleepy patients, and what we have learned over the years is that sleepy obstructive apneics seem to be at greatest risk. So there's something about having obstructive apnea and being sleepy that actually confers risk. Whether the cause of the sleepiness is also the cause of the cardiovascular problem, we don't know, but it certainly is interesting to think about. This study, unfortunately, did not include sleepy patients. What the [researchers] did find, though, was that those people who use their CPAP diligently for a significant part of the night [tended to have] better outcomes. Although the randomization to CPAP didn't work on an intention-to-treat basis, perhaps using CPAP more diligently with better adherence may give a better outcome. We don't know that for sure.

Dr Widmer: Interesting.

Dr Somers: Let's talk about central apnea because those results are clearer, and this is a study that I was involved in. It was called SERVE-HF.^[4,5] We had about 1300 patients with predominant central apnea and low ejection fraction (EF) heart failure—EFs were less than 45%. We randomized them to either ASV, which is good for treating central apnea, or no ASV. Our expectation was that ASV would improve outcomes. Well, it turned out it actually did not improve outcomes in heart-failure patients with low EF who also have central sleep apnea. In fact, we found an increase in cardiovascular mortality in the treated group. What does that tell us? It tells us that maybe we shouldn't be treating central sleep apnea in low-EF heart failure with ASV. Whether treating it with other methods makes a difference, we don't know. But to clarify, this does not apply to patients with normal-ejection heart failure. If you have a normal ejection fraction and you have heart failure, we still have to figure out if ASV is [appropriate] or not.

Dr Widmer: Good to know. There are a lot of treatment options and certainly [many considerations] in terms of diagnosis, risk stratification, comorbidities, and choosing the best option for patients.

Dr Somers: Absolutely.

Dr Widmer: This has been very instructive. Thank you for giving us these insights.

Thank you for joining us today on theheart.org on Medscape.

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