Drs. Alan D. Steljes and Lee A. Surkin share their insights on the connections between cardiovascular disease and OSA.
Welcoming All Cardiologists to Collaborate
by Alan D. Steljes, MD, FACC, FRCP, and Lee A. Surkin MD, FACC, FCCP, FASNC
Readers of this magazine are passionate about obstructive sleep apnea (OSA). They recognize that treatment of OSA leads to better sleep and better daytime functioning. Results are often life-changing.
But why are cardiologists, specifically, so interested in sleep apnea? Because so many of their patients have it. OSA prevalence is as high as 40% to 80% in patients with the entire spectrum of cardiovascular disease (CVD.) This includes such diverse disorders as elevated blood pressure, congestive heart failure, coronary artery disease, pulmonary hypertension, atrial fibrillation and stroke.
Severe sleep apnea is associated with substantially higher risk of cardiovascular death.
Why this association between OSA and CVD? Is it coincidental? Possibly. After all, the risk factors for sleep apnea are male gender, advancing age, and added body weight – the same as risk factors for CVD. Furthermore, sleep apnea is commonly associated with diabetes mellitus – another risk factor for CVD.
But could sleep apnea be the cause of CVD? Proving a cause and effect relationship requires several conditions. First, we would have to have a physiological explanation as to how sleep apnea could stress the heart. We would then have to have objective data confirming such an effect. Finally, we need proof that treatment of sleep apnea, favorably affects the course of the CVD.
There is no doubt that untreated OSA is very stressful to the heart and CV system. OSA is characterized by repeated obstruction of the upper airway. The patient struggles to breathe against the closed airway. This effort generates negative pressure within the chest. Additional blood is drawn into the chest at the same time as outflow of blood from the chest is impaired. These mechanical effects of low barometric pressures stress the right ventricle (RV) and left ventricle (LV), respectively.
The concept of transmural or transmyocardial pressure is worthy of understanding given its role in the pathophysiology of this association. As stated above, airway obstruction results in a tremendous increase in negative intrathoracic pressure. Keeping in mind that the heart is basically in the center of the thoracic cavity, it is subjected to a pressure gradient simply calculated as the intra-cardiac pressure minus the extra-cardiac pressure. A real-world example to better elucidate this is to imagine that a typical left ventricular systolic pressure is 120 mmHg (intra-cardiac) and when the airway is obstructed and the person is sucking against a closed airway, the negative pressure can rise to as high as 200 mmHg (extra-cardiac). So simple addition and subtraction to determine the transmural or transmyocardial pressure is 120-(-200) which is 320 mmHg. Now, imagine this happening repeatedly during the night and the negative impact this has on cardiac hemodynamics and myocardial stress during a time that the heart is normally subjected to the lowest pressure of the 24 hour period.
The marked increase in transmural or transmyocardial pressure will lead to a shift in the interventricular septum from the right ventricle to the left ventricle which reduces left ventricular filling and thereby cardiac output. There is then a reflex vasoconstriction in the periphery. Coupled with this is usually hypoxia which results in vasoconstriction of the pulmonary arteries further straining the right ventricle. So, a cascade of events occur that are all deleterious to the heart.
Considering other metabolic effects, without airflow to the lungs, the carbon dioxide levels begin to rise, making the blood more acidic. The heart is now bathed in a low oxygen, high acid milieu, further impairing heart function and contributing to heart rhythm problems.
These events sound the alarm. The body reacts by activating the sympathetic nervous system – the so-called fight or flight mechanism. Adrenaline pores into the blood stream. Heart rate accelerates. Blood pressure rises. Heart rhythm becomes irritable.
And this is just one cycle. This process can be repeated 100’s of times per night, night after night, month after month and year after year.
The sum of these mechanical, chemical and hormonal responses are measurable. We see elevated markers of inflammation, oxidative stress, endothelial dysfunction and hypercoagulability – all well known pathways to cardiovascular disease
These processes are not limited to nighttime. The adverse effects persist into daytime. For example, blood samples show persistent activation of the sympathetic nervous system (SNS). Ultrasounds of the heart may show impairment in heart function, both in chamber filling and emptying. Pressures in the pulmonary artery are elevated to dangerous levels.
In short, everything that happens during sleep apnea is bad for the heart and the cardiovascular system. This understanding of these events, presents a plausible mechanism of how untreated sleep apnea may exacerbate pre-existing cardiovascular disease. It is also a plausible explanation on how sleep apnea may also be one cause of CV disease.
What is the impact of treatment? Treatment which is effective to eliminate OSA, will lower the SNS activation. It will improve cardiac function and elevated PA pressures. It will reduce heart rhythm irregularities. We see these benefits almost daily in our clinical practice.
Furthermore, there is evidence that treatment improves clinical outcomes. Reduced recurrence of atrial fibrillation post ablation. Reduced health care utilization due to less frequent hospitalization…
But does treatment of sleep apnea save lives? This, to date, has been much harder to prove. In observational studies that examined several modalities of PAP, a significant mortality reduction was observed with PAP, with greater risk reduction observed among patients with CHF.
The most definitive proof of a survival benefit requires a prospective randomized trial involving thousands of patients. The outcomes of patients on therapy would be compared with outcomes of patients not on therapy, followed over several years. In cardiology, this typically would involve a comparison group on a placebo or sham therapy – not possible with CPAP or oral appliance.
“Despite its high prevalence in patients with heart disease and the vulnerability of cardiac patients to OSA-related stressors and adverse cardiovascular outcomes, OSA is often underrecognized and undertreated in cardiovascular practice.”
– American Heart Association, October 2021
Prospective, randomized controlled trials have been hampered by a lack of consensus as to what constitutes an ideal comparator group. Studies have involved small numbers of patients followed for short periods of time and have yielded inconsistent results. The largest impediment, especially with CPAP, has been adherence with therapy. In one recent trial, treated patients used their CPAP an average of 3.3 hours a night – not enough to fully correct apnea.1 Not surprisingly, there was no apparent benefit on mortality.
Would the results have been better with better adherence to therapy? Or with an alternative therapy such as an implanted hypoglossal nerve stimulator? Or oral appliance? Quite possibly, but this hypothesis needs to be tested in future studies. Randomized controlled trials with longer follow-up and focus on high-risk patients with severe OSA are needed to clarify the clinical benefits.
Future directions for research include innovative and effective options for therapy that are better tolerated and cost-effective. Better identification of which patients with OSA should be treated with the goal of preventing or mitigating CVD.
However, the evidence of the heart-sleep connection is so compelling that the American Heart Association, in October 2021, published their scientific statement on sleep apnea. The paper states that, “Despite its high prevalence in patients with heart disease and the vulnerability of cardiac patients to OSA-related stressors and adverse cardiovascular outcomes, OSA is often underrecognized and undertreated in cardiovascular practice.”
This was a call to action to cardiologists to recognize sleep apnea within their patient population and to consider therapy. This appeal was echoed by the American Academy of Sleep Medicine which is encouraging cooperation between cardiologists and sleep providers.
Cardiologists are encouraged to pre-screen their patients with commonly used screening questionnaires such as STOP-BANG (Snoring, Tiredness, Observed Apnea, Blood Pressure, Body Mass Index, Age, Neck Circumference, and Gender). Scores of 3 or greater correlate with a high risk of moderate to severe sleep apnea.
High Risk patients are then followed up with home sleep apnea testing or other remote monitoring technologies.
Cardiologists will need to seek out practitioners with the expertise to treat their sleep apnea patients. This is likely to be a panel of sleep medicine experts including dentists, ENT physicians, and sleep medicine specialists.
Now the reason we treat patients, is not only so they feel better, but hopefully, also so their overall health is improved/optimized and perhaps their cardiovascular mortality is improved.
Cardiovascular disease and OSA may share risk factors, but there are many other considerations when screening for sleep disorders as well. Read “Objective Sleep Disorder Screening” at https://dentalsleeppractice.com/objective-sleep-disorder-screening/.
- McEvoy RD, Antic NA, Heeley E, et al. CPAP for prevention of cardiovascular events in obstructive sleep apnea N Engl J Med2016;375: