Cardiovascular comorbidity in patients with restless legs syndrome: current perspectives

Abstract

Introduction:

Restless legs syndrome (RLS) is a sensorimotor neurological disorder associated with poor quality of life. Growing evidence links RLS and periodic limb movement in sleep (PLMS) with increased risk of cardiovascular and cerebrovascular disease. This article reviews the association of RLS and PLMS with cardiovascular disease (CVD).

Methods:

PubMed and Medline database (1990 to July 2016) were searched for the terms “restless legs,” “restless legs syndrome,” “periodic limb movements,” “periodic limb movements in sleep” cross-referenced with “cardiovascular disease,” “heart disease,” “coronary artery disease,” “coronary heart disease,” “heart arrhythmia,” “heart failure,” “congestive heart failure,” “echocardiogram,” “echocardiographic,” “hypertension,” “high blood pressure,” “cerebrovascular disease,” “stroke,” “autonomic nervous system,” “heart rate,” “heart rate variability,” “hypoxia,” “microcirculation,” “oxidative stress,” “inflammation,” “chronic kidney disease,” “end-stage renal disease,” “renal disease,” “hemodialysis,” “multiple sclerosis,” “Parkinson,” “Parkinson’s,” “iron deficiency anemia,” and “mortality.” Other relevant articles from the reference list of the above-matched manuscripts were also reviewed. Studies that did not specify the diagnostic criteria for RLS or manuscripts in languages other than English were excluded. Articles with emphasis in RLS secondary to pregnancy were not included in this manuscript.

Results:

Eighty-six original articles were included in this review. Although mixed results were found regarding the association of RLS and PLMS with CVD, hypertension, stroke and mortality, an informal review of the literature does suggest that the bulk of the evidence favors such an association.

Conclusion:

The current evidence in general supports the association between RLS/PLMS and CVD. The variability of results likely represent differences in study designs, RLS criteria used, RLS severity, duration of disease, and time of follow-up between the studies. As the association between RLS/PLMS and CVD is not definitive at this time, further suggested studies are outlined.

Keywords::

• restless legs syndrome
• periodic limb movements in sleep
• cardiovascular disease
• heart disease
• hypertension
• stroke
• chronic kidney disease

Disclosure

This was not an industry-sponsored study. Dr Vargas-Pérez has indicated no financial conflicts of interest. Dr Bagai has received grant money from Xenoport and UCB Pharma for studies on RLS. Dr Walters has received grant money from Xenoport, UCB Pharma, and MundiPharma for studies on RLS, and has served on the RLS medical advisory board for Xenoport and UCB Pharma. The authors report no other conflicts of interest in this work.