Sleep-disordered breathing and stroke: is there a rationale for treatment?

The association between sleep-disordered breathing (SDB) and stroke cannot be attributed to chance. Indeed, if a link between SDB and cardiovascular disease were demonstrated [1–5], the absence of a relationship with stroke would be surprising. Although we still lack definitive and consistent data from large epidemiological surveys, multiple studies using a variety of methodologies have shown a high prevalence of SDB following stroke, especially obstructive sleep apnoea (OSA) [6–13]. This prevalence is greater than expected, bearing in mind the available epidemiological data [14, 15]. Nevertheless, these data must be interpreted with caution since stroke patients have a high mean age and the number of obstructive events increases with age, without clinical relevance [16, 17]. Moreover, case-control studies have also demonstrated a significantly higher prevalence of SDB in patients with stroke than in controls [8, 9, 11]. SDB may be regarded as a consequence (mainly central events) [18, 19] or as a cause (mainly obstructive events) [13] of stroke. Given the availability of an effective and safe treatment for OSA [20–24], nasal continuous positive airway pressure (nCPAP) could modify the incidence of stroke (if SDB is regarded as a risk factor) or the outcome of these patients (if SDB is considered as a prognostic factor). In this issue, WESSENDORF et al. [25] and SANDBERG et al. [26] have endeavoured to treat stroke and SDB patients with nCPAP. The resulting data are the first to show a beneficial effect of this treatment in these patients, thereby suggesting the feasibility of introducing nCPAP in such patients, in whom cognitive impairment and physical disability may constitute important drawbacks, and in whom excessive daytime sleepiness does not always justify treatment [27]. Despite concerns about some of the methods used, both papers are encouraging. In support of the idea that SDB is a risk factor for stroke, we have a number of case-control studies previously referred to [8, 9, 11], as well as a number of physiopathological mechanisms that could be involved. One such mechanism could be hypertension, known as the most prevalent and modifiable risk factor for stroke, and whose treatment substantially reduces the risk [28, 29]. Recently, PEPPARD et al. [3] not only demonstrated that SDB is an independent risk factor for hypertension, but also found a doseresponse association. Similar results were obtained using a cross-sectional analysis in the Sleep Health Heart Study [4]. As far as nCPAP seems to exert a positive influence on hypertension when OSA is present [30], a beneficial effect should also be expected in patients with stroke, hypertension and OSA. The paper by WESSENDORF et al. [25] is the first to show that, in patients with stroke, receiving optimal antihypertensive treatment nCPAP is associated with a decrease in nocturnal blood pressure, converting some patients from nondeeper to deeper, at least on a shortterm evaluation. Thus, nCPAP might have therapeutic and prognostic benefits, achieving a better optimization of secondary prophylaxis for stroke through a better control of hypertension. Moreover, in an earlier case report, WESSENDORF et al. [31] described a case of refractory hypertension in a patient with haemorrhagic stroke and OSA, in whom only nCPAP was able to control blood pressure. A second mechanism that could account for the link between SDB and stroke is based on biological mediators, such as fibrinogen plasma level. Fibrinogen has previously been implicated as a risk factor for myocardial infarction and stroke [32, 33]. WESSENDORF et al. [34] demonstrated the correlation between the severity of coexisting OSA and fibrinogen plasma level in patients with stroke, suggesting a possible physiopathological mechanism to explain an increased risk for stroke in patients with OSA. Furthermore, CHIN et al. [35] demonstrated a reduction in fibrinogen levels following nCPAP treatment. A third mechanism could be attributed to the haemodynamic changes in cerebral blood flow (reductions and fluctuations documented by transcranial doppler) occurring during obstructive apnoeas and favouring ischaemia [36, 37]. In addition, cerebrovascular reactivity to hypercapnia is diminished in patients with OSA, which can be corrected with nCPAP treatment, suggesting a reduction in cerebral vasodilator reserve and an increased susceptibility to cerebral ischaemia in patients with OSA [38]. From a prognostic point of view, the relationship between SDB and stroke can be addressed by analysing the outcome of patients in terms of neurological recovery, response to rehabilitation, quality of life, recurrence or mortality. Few reports with a small Sleep Unit, Pneumology, Hospital del Sagrat Cor., University of Barcelona, Barcelona, Spain.