Associations of Incident Cardiovascular Events With Restless Legs Syndrome and Periodic Leg Movements of Sleep in Older Men, for the Outcomes of Sleep Disorders in Older Men Study (MrOS Sleep Study)

Study Objectives: Both restless legs syndrome (RLS) and periodic leg movements in sleep (PLMS) may be associated with incident cardiovascular disease (CVD). However, the individual contributions of these factors to adverse CVD outcomes are unknown. Methods: During the MrOS Sleep Study, 2823 men (mean age = 76.3 years) participated in a comprehensive sleep assessment from 2000 to 2002. RLS was identified by self-report of a physician diagnosis of RLS. A periodic limb movement of sleep index (PLMI) was derived from unattended in-home polysomnography. Incident cardiovascular events were centrally adjudicated during 8.7 ± 2.6 years of follow-up. The primary outcome was all-cause CVD; secondary outcomes included incident myocardial infarction (MI) and cerebrovascular disease. Cox proportional hazards regression models were adjusted for multiple covariates, including PLMI, to examine if there were independent associations of RLS and PLMI to the outcomes. Results: Physician-diagnosed RLS was reported by 2.2% and a PLMI ≥ 15 was found in 59.6% of men. RLS was not associated with the composite CVD outcome. RLS was significantly associated with incident MI (Hazard ratio [HR] = 2.02, 95% CI, 1.04-3.91) even after adjustment for multiple covariates. Results were only modestly attenuated when PLMI was added to the model. PLMI also was found to predict incident MI (per SD increase in PLMI, HR = 1.14, 95% CI, 1.00-1.30, p = .05), and was materially unchanged after addition of RLS. Conclusions: The independent risk that RLS confers for MI suggests a role for non-PLMS factors such as sleep disturbance, shared genetic factors, or PLM-independent sympathetic hyperactivity.