Evidence continues to mount on the relationship of restless legs syndrome/ periodic limb movements in sleep to hypertension, cardiovascular disease, and stroke.

SINCE THE PUBLICATION OF OUR RECENT REVIEW IN SLEEP,1 WE HAVE BECOME AWARE OF A FEW LARGER STUDIES THAT WE EITHER DID NOT COVER IN OUR review2,3 or have come to publication recently.4–6 We are sorry that we missed the older study by Ferri et al. published in 2007, where he and coauthors show in 16 patients with restless legs syndrome (RLS) that the pulse rate elevations seen with isolated leg movements are even higher than those seen with periodic limb movements in sleep (PLMS).2 This is in contrast to the study by Guggisberg et al. quoted in our review, where 24 patients with PLMS but not RLS have pulse rate elevations with PLMS that are higher than those with isolated leg movements.6 In both studies pulse rate elevations accompanying PLMS are significant, however, and could conceivably convey additional cardiovascular risk as blood pressure elevations would be expected to follow.1 We are also sorry that we missed the study previously published by Elwood et al., where 1986 men aged 55-69 years completed a questionnaire regarding RLS and other sleep disorders. During the following 10 years, 107 men experienced an ischemic stroke and 213 had an ischemic heart event. Compared with men who reported no symptoms of sleep disturbance of any kind, the relative odds of an ischemic stroke was 1.67 (1.07-2.60) P = 0.024 in patients who responded positively to a question on RLS.3 A new study by Lee et al. evaluates 137 patients immediately after ischemic stroke and documents the new onset of RLS symptoms directly after the stroke in 12.4%. The vast majority of these are in subcortical regions, suggesting that these regions are pertinent to the pathogenesis of RLS symptoms.4 A new study by Minai and colleagues documents RLS symptoms in 43.6% of 55 patients with pulmonary hypertension.5 The authors conclude that patients with pulmonary hypertension should be screened for RLS because good treatment options are available. These larger studies add to the growing body of knowledge regarding the relationship of RLS/PLMS to hypertension, heart disease, and stroke. We plan new studies to look for the presence of silent stroke in patients with RLS versus controls. A study of isoprostanes which are markers of inflammation would be interesting as well.