Affiliations: New Orleans, LA
Dr. Ventura is Professor of Medicine, Tulane University; Dr. Mehra is Professor of Medicine, Louisiana State University; and Dr. Potluri is a Cardiology Fellow, Ochsner Clinic Foundation.
Correspondence to: Hector O. Ventura, MD, Ochsner Clinic Foundation, 1514 Jefferson Hwy, New Orleans, LA 70121; e-mail: firstname.lastname@example.org
Many years ago Hippocrates stated, “In whatever disease sleep is laborious, it is a deadly symptom; but if sleep does good, it is not deadly.” Today, a potential role for sleep disorders in the pathogenesis and complications of cardiovascular disorders is a concept that has gained support.1–2
Specifically, several studies3–4
have been performed in order to analyze the underlying mechanisms and the clinical importance, as well as the effects and consequences of sleep apnea in patients with heart failure. In this issue of CHEST (see page 1536), the article by Sin et al from Toronto reports on the relationship of systolic BP to obstructive sleep apnea in patients with heart failure. Before discussing their findings in detail, we briefly summarize our knowledge regarding the association of sleep apnea, heart failure, and hypertension.
Observations from epidemiologic studies point toward an association between obstructive sleep apnea and heart failure. Thus, the Sleep Heart Health Study2–
demonstrated that the presence of obstructive sleep apnea was associated with relative odds of 2.38 for heart failure independent of other known risk factors. This risk exceeded that for all other cardiovascular diseases examined, including hypertension, coronary artery disease, and stroke. Two series3–4
have evaluated the presence of sleep breathing disorders in patients with heart failure with systolic dysfunction. In one of the studies,3–
51% of men with heart failure experienced sleep breathing disorders, 40% had central sleep apnea, and 11% had obstructive sleep apnea. In addition, the other study by the Toronto group4
demonstrated that the prevalence of obstructive sleep apnea was even higher (ie, up to 37%) in the 450 patients with heart failure who were studied. This work also demonstrated that an increase in body mass index in men and increasing age in women were risk factors for the development of sleep apnea in patients with heart failure.
The association of sleep apnea and hypertension has also been the focus of epidemiologic studies.5–7
Because of the importance of hypertension as a risk factor for the development of heart failure,8
and because of the prevalence of sleep apnea in both, one could ask, does obstructive sleep apnea contribute to the development of heart failure or is it a consequence of heart failure?
First, patients with heart failure and obstructive sleep apnea are predisposed to underlying periodic breathing disorders. Tidal volumes measured during hyperpneas often have a waxing-waning appearance, which is typical Cheyne-Stokes respiration, compared to patients with obstructive sleep apnea and normal cardiac function who have abrupt rises and rapid falls in tidal volume.1
Second, the accumulation of edema in the soft tissues of the neck and pharynx on reclining could narrow the upper airway and make it more collapsible, therefore causing obstructive sleep apnea.1
Regardless the underlying cause in patients with heart failure and obstructive sleep apnea, the application of continuous positive airway pressure reverses the airway collapse.
The most obvious mechanism and the link to the development of heart failure in patients with obstructive sleep apnea would be hypertension.8
Other risk factors, such as ischemia, decreased left ventricular contractility secondary to hypoxia and cardiac myocyte injury, which are related to catecholamine stimulation, and also can contribute to the development of heart failure in patients with sleep apnea.1–2
Some experimental studies have demonstrated that obstructive sleep apnea per se can lead to the development of pulmonary edema and to the development of left ventricular hypertrophy and left ventricular dysfunction. Fletcher et al9–
demonstrated in dogs the development of subtle degrees of pulmonary edema after 8 h of exposure to recurrent obstructive apneas. Parker et al10–
have shown that dogs who were exposed to obstructive apneas during sleep for several weeks to months showed an increase in left ventricular mass and a reduction in left ventricular ejection fraction in association with the development of hypertension. The association of obstructive sleep apnea and the development of left ventricular hypertrophy in humans has shown disparate results. One study11–
reported that left ventricular wall thickness was increased in normotensive patients with obstructive sleep apnea compared to normotensive control subjects. Another study12
did not find this association.
Although the association between obstructive sleep apnea and the development and progression of heart failure is not completely clear, one can conclude that the presence of obstructive sleep apnea and the deleterious effects of increasing daytime and nocturnal BP play a role in the development and progression of heart failure. Patients with established heart failure and sleep apnea may be susceptible to the adverse effects of increased BP and afterload.13–
It also has been shown that obstructive sleep apnea raises nocturnal BP in patients with heart failure despite treatment with antihypertensive agents.14
The presence of obstructive sleep apnea in patients with heart failure might have prognostic implications. It has been shown that the higher the degree of stimulation of the sympathetic nervous system, the higher the mortality rate among patients with heart failure.13
Then the presence of obstructive sleep apnea and its association with an increase in sympathetic activity would be detrimental in patients with heart failure.1
What is not known, however, is whether obstructive sleep apnea is associated with daytime hypertension in patients with heart failure who are treated medically.
The interesting study by Sin et al analyzes the association of daytime BP and obstructive sleep apnea in stable patients with heart failure. The authors demonstrate that obstructive sleep apnea (ie, an apnea-hypopnea index of >10 events per hour of sleep, of which ≥ 50% had to be obstructive) was present in 121 patients, and that those patients had a significantly higher systolic BP that patients without obstructive sleep apnea. More importantly, patients with obstructive sleep apnea were 2.89 times (95% confidence interval, 1.25 to 6.73) more likely to have systolic hypertension than were those patients without obstructive sleep apnea, after controlling for other risk factors such as obesity. Interestingly, patients who have central sleep apnea and heart failure did not show any elevation in BP during the day or night. The authors conclude that obstructive sleep apnea in patients with heart failure should be considered as a contributing factor not only for increasing BP but also as a possible therapeutic target in patients who remain symptomatic despite medical therapy.
From these findings, one can speculate that BP control may be more difficult to achieve in patients with obstructive sleep apnea and heart failure. There are some data that support the latter concept. As an example, it has been shown15
that drug-resistant hypertension is more common in patients with obstructive sleep apnea. In addition, another study14
in patients with heart failure and obstructive sleep apnea demonstrated that patients experience recurrent apnea-related surges in systolic BP, despite being treated with several combinations of agents that have antihypertensive effects. The elimination of obstructive sleep apnea by continuous airway pressure abolished these apnea surges in BP.14
Observational studies like this one will allow the design of prospective trials in order to assess the impact of the treatment of obstructive sleep apnea in patients with heart failure. The next step is to prove that the treatment of obstructive sleep apnea will not only improve the daytime elevation of BP, but also symptoms and left ventricular function in patients with heart failure.
Since the collection of the data was done before the use of beta-blocker medications became the standard of care in patients with heart failure, few patients were treated with these drugs. Thus, we do not know how this therapy will affect daytime BP as well as obstructive sleep apnea. Despite the fact that the relationship between daytime BP and obstructive sleep apnea held up statistically, the number of patients was too small to make any final conclusions. It would be very interesting to analyze the same data in a majority of patients with heart failure who had been treated with beta-blockers. One intriguing finding of the study that will provoke further investigations into this topic is the lack of relationship between BP elevation and central sleep apnea in patients with heart failure.
The understanding of the underlying mechanisms and clinical observations is paramount in achieving success in the treatment of sleep breathing disorders in patients with heart failure. This excellent contribution by Sin et al adds to the previous knowledge of sleep disorders in patients with heart failure and signals that the treatment of sleep apnea could become the next target for the treatment of heart failure. However, easier methods of diagnosis and less cumbersome forms of treatment of sleep apnea should be developed to impact the quantity and quality of life of patients with this disorder and heart failure.
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