Is polysomnography screening effective for stroke prevention?

Stroke ranks as the second most common cause of death worldwide and the leading cause of adult disability [1]. Thus, identification and treatment of modifiable risk factors represent the most effective approach to diminish stroke-related burden. A recent meta-analysis supports existing evidence that obstructive sleep apnea (OSA) represents an independent stroke predictor, showing that cerebrovascular risk increases with OSA severity [2]. Another meta-analysis revealed a high prevalence of sleep-disordered breathing (SDB) in patients with stroke or transient ischemic attack (TIA) (63% of patients with an apnea– hypopnea index more than 10/h); SDB was primarily obstructive in nature (OSA), with only 7% of patients having primarily central apneas [3]. Moreover, SDB seems to be similarly prevalent in stroke and TIA patients, indicating that SDB probably represents a preexisting condition. OSA has been also associated with poor outcomes among patients with stroke, including higher mortality and recurrent vascular events, worse functional status, and longer hospitalization duration [4]. Thus, screening and intervention in OSA patients represent a relevant issue not only for prevention of stroke recurrence but, probably, to facilitate poststroke recovery as well. The mechanisms underlying the relationship between OSA and stroke are not fully established. Recurrent OSA events lead to different acute adverse consequences: brain arousal, intrathoracic pressure changes, and intermittent episodes of hypoxemia. These events activate pathways such as oxidative stress, sympathetic activation, inflammation, hypercoagulability, endothelial dysfunction, and metabolic dysregulation that, in turn, predispose OSA patients to other main risk factors for stroke: hypertension, atherosclerosis, and atrial fibrillation (AF) [5]. In particular, OSA represents the most common condition associated with resistant hypertension [6]. Moreover, current literature reports a strong association between OSA and AF, with a prevalence of AF in patients with OSA of approximately 5%, which is higher than the prevalence of AF in the general population (1–2%). Conversely, the prevalence of OSA among AF patients ranges between 21% and just over 80% [7]. A retrospective study showed that in a group of AF patients, the occurrence of first-time stroke was more common in patients with OSA compared with patients without; this association remained significant after accounting for cardiovascular risk factors [8]. Besides these long-standing mechanisms, sleep apnea could act as a precipitating, acute factor, favoring a cardioembolic cerebrovascular ischemic event in patients with patent foramen ovale (PFO). Indeed, a study conducted in 335 patients with mild stroke or TIA found that the association of sleep apnea events with right to left shunt increases the risk of wake-up stroke, suggesting that OSA might provoke paradoxical embolism [9]. Even though studies analyzing the prevalence of SDB in different stroke etiologies obtained discordant results, a recent work revealed a strong association between OSA and cardioembolic stroke [10]. Interestingly, Lipford et al. [10] found that the association between OSA and cardioembolic stroke remains even after adjustment for the presence of known AF. This finding may be explained by a high rate of occult paroxysmal AF in this population but, alternatively, OSA may lead to stroke through mechanisms independent of cardiac arrhythmias. One of this could be represented by a PFO-mediated paradoxic embolism. Although OSA affects 24% of middle-aged men and 9% of women [11], as many as 70–80% of them are neither diagnosed nor treated [12]. Considering the high prevalence of OSA and its role as an independent risk factor for stroke, the American Heart Association/American Stroke Association (AHA/ASA) recently included recommendations on diagnosis and treatment of SDB for the primary prevention of Stroke (Class IIb; Level of Evidence C) [13]. Recently, a low level of accuracy for the diagnosis of OSA of different clinical prediction algorithms against PSG has been highlighted [14]. For instance, the high number of potential false-negative results using different questionnaires compared to PSG limits their use as instruments to diagnose individual patients with OSA (for the AHI ≥5 cutoff: Berlin Questionnaire sensitivity was 0.76 and specificity was 0.45; Epworth Sleepiness Scale sensitivity was 0.27–0.72 and specificity was 0.50–0.76; STOP-BANG questionnaire sensitivity was 0.93 and specificity was 0.36). For these reasons, the recent guidelines of the American Academy of Sleep Medicine recommend that clinical tools, questionnaires, and prediction algorithms not be used to diagnose OSA in adults, in the absence of polysomnography (PSG) or home sleep apnea testing [14]. Thus, an integration of hypnological anamnesis together with a physical examination