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.