Restless Legs Syndrome Tied to Increased Mortality

The risk of death is nearly twice as great in relatively healthy men who have restless legs syndrome (RLS) as in those who do not, according to the results of a new prospective cohort study.

RLS, a neurological disorder characterized by unpleasant sensations in the legs and a distressing, irresistible urge to move them, may affect up to 10% of the U S population. The condition is more common in women; most patients who are affected severely are middle-aged or older.

RLS often is unrecognized or misdiagnosed, especially if the symptoms are intermittent or mild, according to Yanping Li, PhD, of The Channing Laboratory at the Harvard School of Public Health in Boston. “Primary care physicians need to pay more attention to this common medical disorder,” she said.

Dr Li and her colleagues conducted a survey of more than 18,000 US men free of diabetes mellitus, arthritis, and renal failure about symptoms of RLS and then monitored the men for 8 years. At baseline, 4% of the men had RLS, with symptoms at least 5 times monthly.

Overall, 15% of the men died during follow-up. After adjustment for confounders, including age and lifestyle risk factors, there was a 39% increased risk of death in the men with RLS. In a subgroup of men without major chronic conditions, such as cancer and cardiovascular disease, RLS increased the risk of death nearly 2-fold.

The increase in mortality primarily was attributed to deaths resulting from respiratory illnesses; blood diseases; and endocrine, metabolic, and immunity disorders. “RLS may co-occur with chronic obstructive pulmonary disease, iron deficiency anemia, and several autoimmune diseases, for example, Crohn disease and celiac disease,” said Dr Li.

The authors speculated that the nocturnal blood pressure variations associated with RLS could be among potential underlying mechanisms for the observed association between RLS and mortality. “RLS may lead to nocturnal hypertension through the influence of periodic limb movements of sleep, and nocturnal hypertension is a risk factor for cardiovascular diseases,” noted Dr Li.

Primary care physicians need to recommend that their patients with RLS maintain a healthy lifestyle, she said. “For example, in our previous study, we found that men with obesity are more likely to have RLS.”

Drug Therapy for RLS
A recent systematic review and meta-analysis looked at pharmacological therapy for RLS. Researchers from the Minneapolis Veteran’s Administration Health Care System in Minneapolis reviewed 29 randomized controlled trials that reported efficacy outcomes and harms of pharmacological treatments for patients with primary RLS of at least 4 weeks’ duration.

The researchers concluded that “on the basis of short-term RCTs that enrolled highly selected populations with long-term high-moderate to very severe symptoms, dopamine agonists and calcium channel alpha-2-delta ligands reduced RLS symptoms and improved sleep outcomes and disease-specific quality of life.”

They added that adverse effects and treatment withdrawals resulting from adverse effects were common. Adverse events associated with dopamine agonists included nausea, vomiting, and somnolence. Alpha-2-delta ligands adverse events included somnolence and unsteadiness or dizziness.

The Harvard researchers published their results online June 12, 2013 in Neurology.
The Minnesota researchers published their results online March 4, 2013 in JAMA Internal Medicine.