Restless legs syndrome, periodic limb movements during sleep and cardiovascular risk

Multiple mechanisms may modulate an association between restless legs syndrome/Willis-Ekbom disease (RLS/WED) and cardiovascular disease (CVD), including chronic sleep deprivation, intermittent, periodic limb movements in sleep (PLMS)-related autonomic fluctuations and possible autonomic dysfunction intrinsically associated with RLS per se. The purpose of this paper is to review the existing RLS/WED literature focusing on the pathophysiologic evidence for possible associations between RLS/WED and PLMS with CVD and events (CVE). Specific intrinsic dysautonomic aspects of the disease, which may contribute to generating CVD, are separately discussed. The association between RLS/WED and both CV risk factors and CVD still remains elusive. Although several shared pathophysiological causes could explain these possible relationships, the emerging body of literature focusing on these disorders remains controversial. Not only longitudinal population-based studies and meta-analyses, but also more animal models and therapeutic interventions are needed in order to build a sufficiently robust body of evidence on this topic.