Periodic Limb Movements in Sleep and Cardiovascular Disease: Time to Act

PLMS and CardiovaSCuLar riSk We recently reported that uremic RLS patients with severe PLMS experienced further detrimental alterations in cardiac structure in comparison to PLMS-free uremic RLS patients. These alterations included an increased left ventricular internal diameter in diastole, which lead to a significantly increased left ventricular mass compared to their PLMS-free counterparts (5). In addition, systolic blood pressure during sleep correlated with left ventricular mass, indicating therefore an association of PLMS and raised nocturnal blood pressure levels (non-dipping effect), with the later to be associated with left ventricular hypertrophy (LVH) (7). Still, an increase in nocturnal blood pressure levels induced by PLMS has been reported in idiopathic RLS patients (3) and very recently in healthy RLS-free individuals (8) as well. Of course in our study the compounding effect of renal disease per se could not be totally disregarded. However, in a recent study, Mirza and colleagues reported that frequent PLMS was independently associated with severe LVH in idiopathic RLS patients, and thus concluded that PLMS could be considered as a risk factor for increased CV morbidity and mortality (6). Interestingly, in the same study, PLMS was found to be stronger independent predictor of LVH, compared to introduCtion Periodic limb movements in sleep (PLMS) is a common sleep disorder in both the general population and in patients with chronic diseases such as patients receiving hemodialysis therapy. PLMS can be assessed during an overnight polysomnographic examination and are described as repetitive, stereotypical, and unconscious leg movements that occur during sleep. It is noteworthy, that PLMS are present in up to 80% of patients with a condition occurring during wakefulness, called restless legs syndrome (RLS). Indeed, the presence of PLMS is considered to be one of the supportive criteria for the diagnosis of the later condition (1). PLMS may also occur in patients with sleep apnea, narcolepsy, and rapid eye movement behavior disorder or even can be present in patients without any sleep or medical-related pathological condition, and especially in the elderly (2). PLMS could cause significant sleep disturbance and result in non-restorative sleep via its associated arousals and motor restlessness. It is logical then to assume that as PLMS interferes with the expected sleep associated dipping of blood pressure (3), it may constitute a risk factor for cardiac disease and mortality. Notably, a role of PLMS as a predictor of mortality has been proposed in small survival study by Benz et al. (4) in which PLMS was strongly and independently associated with mortality in renal patients. Recently direct observations on cardiac structure added strong support on the association between the severity of apnea-hypopnea index. These new results come to further support our earlier observations on the association of PLMS with cardiac structure alterations in secondary RLS patients and more specifically in patients with uremic RLS. Research findings highlighting an association between RLS disorder and an increased risk for CV disease has been slowly accumulating during the last years alerting the health care providers (especially the cardiologists) of the potential harmful impact of both idiopathic (9) and uremic (10) – forms of those conditions on CV morbidity and mortality. As mentioned earlier however PLMS coexists with RLS in ∼80% of RLS cases. It is still unclear whether it is the severity of RLS or the severity of PLMS that may provoke the increased CV risk. According to our findings, the severity of RLS symptoms, as assessed by the gold standard method, the International RLS Study Group questionnaire, did not seem to affect cardiac structure indices (5). However, in our study, it was the severity of PLMS that was associated with LVH in uremic RLS patients. In addition, PLMS severity was associated with increased CV risk in uremic patients independently of the presence of obstructive sleep apnea (11). Taking into account our data in uremic patients (5) and the data of Mirza et al. (6) in idiopathic RLS patients it appears that the major contributor to cardiac structure abnormalities in RLS patients (either idiopathic or uremic) is the severity of PLMS and not the severity of RLS. Periodic limb movements in sleep and cardiovascular disease: time to act