Increased RLS Severity Heightens Risk of Stroke

SEATTLE—Increased restless legs syndrome (RLS) severity is associated with increased risk of stroke, according to a study described at the 29th Annual Meeting of the Associated Professional Sleep Societies. The association between RLS severity and stroke risk is independent of traditional risk factors for stroke. The results suggest that RLS could be a novel risk factor for stroke. “For individuals with RLS, we may need to do more monitoring for stroke prevention,” said Xiang Gao, MD, PhD, Director of the Nutritional Epidemiology Laboratory at Pennsylvania State University in University Park.

In previous research, Dr. Gao and colleagues found a strong relationship between RLS and obesity, hyperlipidemia, and hypertension, which are risk factors for stroke. Because patients with RLS have autonomic and dopamine dysfunction, which play a key role in stroke etiology, they hypothesized that RLS was a risk factor for stroke.

The Nurses’ Health Study II
To test their hypothesis, Dr. Gao and colleagues decided to study middle-aged women. Although the prevalence of stroke doubled in the past decade for this group, previous trials did not include this population. In their prospective study, Dr. Gao’s group added a three-item questionnaire about RLS to the Nurses’ Health Study II. RLS was defined according to International RLS Study Group criteria. The researchers documented physician-diagnosed incident strokes during follow-up using questionnaires. They also used questionnaires to collect information about potential confounders (eg, obesity, smoking status, diet, and alcohol use).

Dr. Gao used Cox models to test the relationship between RLS and stroke risk. During data analysis, the researchers excluded participants with prevalent stroke as well as pregnant women. People with diabetes were excluded because diabetes is strongly correlated with peripheral neuropathy, a mimic of RLS.

A Clear Dose–Response Relationship
The study group included 72,916 female registered nurses between ages 41 and 58. Women with RLS tended to be older, be Caucasian, have high BMI, engage in a low amount of physical activity, and take iron supplements. The latter finding is consistent with the iron-deficiency hypothesis of RLS. Women with RLS also had a high prevalence of major chronic disease.

There were 161 cases of incident stroke during the six-year follow-up. The researchers found a clear dose–response relationship between the severity of RLS and future risk of stroke in the age-adjusted model and the multivariate-adjusted model. People with severe RLS had double the risk of stroke, after controlling for traditional stroke risk factors, compared with those without RLS. Various sensitivity analyses, including those that excluded patients with cancer or coronary heart disease, yielded similar positive dose–response trends.

In a meta-analysis, Dr. Gao’s group combined its results with those of two previous prospective studies of the relationship between RLS and stroke. These two studies included five cohorts. The results for five out of the six cohorts indicated a positive association between RLS and future risk of stroke. The meta-analysis suggested that RLS increases patients’ future risk of stroke by 30%.

—Erik Greb