Incident Cardiovascular Events and Death in Individuals With Restless Legs Syndrome or Periodic Limb Movements in Sleep: A Systematic Review

Study Objectives: To systematically review the current evidence examining restless legs syndrome (RLS) and periodic limb movements in sleep (PLMS) as prognostic factors for all-cause mortality and incident cardiovascular events (CVE) in longitudinal studies published in the adult population.

Methods: All English language studies (from 1947 to 2016) found through Medline and Embase, as well as bibliographies of identified articles, were considered eligible. Quality was evaluated using published guidelines.

Results: Among 18 cohorts (reported in 13 manuscripts), 15 evaluated the association between RLS and incident CVE and/or all-cause mortality and 3 between PLMS and CVE and mortality. The follow-up periods ranged from 2 to 20 years. A significant relationship between RLS and CVE was reported in four cohorts with a greater risk suggested for severe RLS with longer duration and secondary forms of RLS. Although a significant association between RLS and all-cause mortality was reported in three cohorts, a meta-analysis we conducted of the four studies of highest quality found no association (pooled hazard ratio = 1.09, 95% confidence interval: 0.80-1.78). A positive association between PLMS and CVE and/or mortality was demonstrated in all included studies with a greater risk attributed to PLMS with arousals.

Conclusions: The available evidence on RLS as a prognostic factor for incident CVE and all-cause mortality was limited and inconclusive; RLS duration, severity, and secondary manifestations may be important in understanding a possible relationship. Although very limited, the current evidence suggests that PLMS may be a prognostic factor for incident CVE and mortality.