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SLEEP MEDICINE CLINICS
Sleep Med Clin 2 (2007) 593–601

Mortality in Obstructive Sleep Apnea
Jose M. Marin,
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MD

a,b,

*, Santiago J. Carrizo,
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MD

a,b

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Mortality as an outcome Markers of disease severity in obstructive sleep apnea Cohort versus randomized controlled trials Obesity and mortality Mortality studies in obstructive sleep apnea before 1995Mortality studies in obstructive sleep apnea after 1995

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The Zaragoza sleep cohort study Effect of continuous positive airway pressure on mortality in obstructive sleep apnea Summary References

Obstructive sleep apnea (OSA) is a frequent disease that affects 4% of middle-age men and 2% of middle-age women [1,2]. OSA is characterized by recurrent collapse of the pharyngeal airway during sleep.In those episodes, respiratory effort is present and arterial oxygen saturation decreases, terminated by an arousal from sleep. The two main clinical consequences of OSA are daytime sleepiness and cardiovascular sequelae, which are responsible for the potential increased morbidity and mortality associated with this condition (Fig. 1). Increased traffic accidents in untreated OSA patients comparedwith non-OSA patients have been demonstrated [3,4], but the cardiovascular consequences of OSA are still a subject of debate [5,6]. This article examines the growing evidence that links OSA with cardiovascular outcomes and specifically with an excess of mortality.

Mortality as an outcome
The term ‘‘outcome’’ is designed to evaluate the consequences of the disease as experienced by the patient,death being the main outcome of any medical entity. In OSA, outcomes include daytime sleepiness; snoring; morning hangover; poor health-related quality of life; increased health resource use; cardiovascular outcomes (systemic hypertension, myocardial infarction, stroke, congestive heart disease); and death (Box 1). Some clinical outcomes, such as drowsiness or snoring, are easily measured withinroutine practice and in the setting of a clinical trial and are very sensitive to medical intervention [7,8]. Others, such as cardiovascular outcomes or death, are subjected to comorbid conditions that make it more difficult to establish the specific role of OSA. As a consequence,

a ´ Respiratory Service, Hospital Universitario Miguel Servet, 1-3, Isabel la Catolica Avenue, 50009-Zaragoza, Spain bUniversity of Zaragoza, Zaragoza, Spain ´ * Corresponding author. Respiratory Service, Hospital Universitario Miguel Servet, 1-3, Isabel la Catolica Avenue, 50009-Zaragoza, Spain. E-mail address: jmmarint@unizar.es (J.M. Marin).

1556-407X/07/$ – see front matter ª 2007 Elsevier Inc. All rights reserved.

doi:10.1016/j.jsmc.2007.07.001

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Marin & Carrizo

OSASleep fragmentation Hypoxia / hypercapnia

Daytime sleepiness

Vascular dysfunction

Morbidity Mortality

Fig. 1. Clinical consequences of obstructive sleep apnea.

in OSA, studies designed to evaluate the effects of treatment directly on cardiovascular and mortality outcomes are impracticable and unethical, because these clinical outcomes may need to run for a long time in otherwisesymptomatic patients for whom an effective treatment is available [9]. Death is the strongest outcome in clinical trials. Some studies done in the cardiology field with antihypertensive drugs have shown that the active drug produced a modest reduction in blood pressure numbers and no modification in left ventricular ejection fraction [10]. Because the active drug also showed an increase in survival,however, these medications are included in the treatment guidelines of chronic heart failure.

AHI is used not only to define the OSA syndrome (AHI >5 plus daytime sleepiness) but also serves to stratify OSA severity: mild OSA (AHI between 5 and 15); moderate OSA (AHI between 16 and 30); and severe OSA (AHI >30) [11]. Some have argued that this classification is arbitrary, because there are...