Megan Brooks

June 15, 2015

SEATTLE — More severe restless legs syndrome (RLS) is associated with an increased risk for stroke, particularly ischemic stroke, a new analysis of data from the Nurses' Health Study II suggests.

"We were surprised at the importance of taking into account RLS severity — it was only severe RLS, not milder RLS, that was associated with increased risk of stroke," principal investigator Xiang Gao, MD, PhD, director, Nutritional Epidemiology Lab, Department of Nutritional Sciences, Pennsylvania State University in University Park, said in a statement.

He discussed the results in an oral presentation here at SLEEP 2015: the Annual Meeting of the Associated Professional Sleep Societies.

RLS is associated with several risk factors for stroke, such as obesity, hypertension, and autonomic dysfunction. Few prospective studies have examined whether individuals with RLS have higher risk for stroke, and none have been done in middle-aged women, Dr Gao explained.

He and his colleagues analyzed data on 72,916 women in the Nurses' Health Study II. At baseline in 2005, the women were aged 41 to 58 years and free of diabetes, stroke, and pregnancy.

Participants were considered to have RLS if they met four RLS diagnostic criteria recommended by the International Restless Legs Syndrome Study Group (RLSSG) and had restless legs five or more times per month.

The primary outcome was diagnosis of stroke (ischemic, hemorrhagic, or unknown cause).

Compared with women without RLS, those with RLS tended to be older, to be white, to have higher body mass index, to be less physically active, to be more likely to use iron supplements, and to have a higher prevalence of chronic disease, such as hypertension and hypercholesterolemia.

During 6 years of follow-up, 161 women sustained a stroke, including 139 with no RLS, 10 with RLS less than 15 times per month, and 12 with RLS 15 or more times per month.

In Cox proportional hazard models that adjusted for numerous potential confounders, increased RLS severity was associated with increased risk for stroke.

Table. Risk for Stroke According to RLS Severity

RLS Measure Adjusted Hazard Ratio (95% Confidence Interval)
RLS < 15 times/mo 1.37 (0.72 - 2.62)
RLS ≥ 15 times/mo 2.07 (1.13 - 3.77)


The association was particularly strong for ischemic stroke alone, with an adjusted hazard ratio of 3.52 (95% confidence interval, 1.46 - 8.49) in women with RLS 15 or more times per month, Dr Gao reported.

A similar association between RLS symptom severity and stroke was observed when women with cancer, myocardial infarction, arthritis, or those with stroke onset during the first 2 years of follow-up were excluded.

These prospective findings indicate that "appropriate management" of cardiovascular risk factors for primary prevention of stroke is particularly important in patients with RLS, Dr Gao said.

Reached for comment, Michael Thorpy, MD, director of the Sleep-Wake Disorders Center at Montefiore Medical Center in New York City, said, "We know that RLS is associated with some autonomic changes and cardiovascular changes. This new study on a large number of people does show that there is an association."

But, he adds, "It's just an association. It's not a cause and effect and there may be some other factors involved, but I think it's consistent with what we know about the autonomic disturbance that can be associated with restless legs syndrome."

The study was supported by the National Institutes of Health. The authors and Dr Thorpy have disclosed no relevant financial relationships.

SLEEP 2015: Annual Meeting of the Associated Professional Sleep Societies. Abstract 0710. Presented June 8, 2015.


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