Restless Legs Syndrome Linked to Cardiovascular Disease

By Crystal Phend
BOSTON, Jan. 2 -- Restless legs syndrome patients may be at twice the risk of stroke and heart disease as those without the movement disorder.The risk was greatest among those with the most severe and frequent symptoms, found John W. Winkelman, M.D., Ph.D., of Harvard and Brigham and Women's Hospital, and colleagues in a questionnaire-based study in the Jan. 1 issue of Neurology.However, Barbara Scherokman, M.D., a Fairfax, Va., neurologist and an American Academy of Neurology spokesperson, was skeptical. "This study should not cause patients to be overly fearful about heart attack or stroke because this is not definite proof of a connection," Dr. Scherokman said. "It is only suggestive."
The cross-sectional observational analysis included 1,559 men and 1,874 women (mean age 67.9) in the larger community-based Sleep Heart Health Study.
Overall, 5.2% of participants had restless legs syndrome -- defined by positive responses on a self-administered questionnaire to the four diagnostic criteria symptoms -- on at least five days per month that was associated with at least moderate distress.
Women were twice as likely to report restless legs syndrome as men (6.8% versus 3.3%).
Self-reported physician-diagnosed coronary artery disease was 2.05 times more common (95% confidence interval: 1.38 to 3.04) among patients with restless legs syndrome than those without it, after controlling for age, body mass index, diabetes, blood pressure, antihypertensive medication use, smoking, and other factors.
Likewise, physician-diagnosed cardiovascular disease was 2.07 times more common among those with restless legs syndrome (95% CI: 1.43 to 3.00).
After additional adjustment for apnea-hypopnea index, the associations were primarily among patients with at least 16 restless legs episodes per month.
Coronary artery disease was not significantly elevated in those with fewer episodes per month but was in those with 16 to 23 episodes (odds ratio: 3.18, 95% CI: 1.48 to 6.85) or more per month (OR: 2.71, 95% CI: 1.37 to 5.39).
Likewise, cardiovascular disease was more common only among those with episodes most days of the month (OR: 3.92, 95% CI: 1.92 to 8.03, and OR: 2.26, 95% CI: 1.17 to 4.37, respectively).
The associations strengthened with increasing bothersomeness of symptoms. Compared with patients without restless leg syndrome, the odds ratios were:
2.27 (95% CI: 1.26 to 4.09) for cardiovascular disease among those with moderately bothersome symptoms.
2.50 (95% CI: 1.38 to 4.54) for cardiovascular disease among those with "extremely" bothersome symptoms.
2.14 (95% CI: 1.13 to 4.03) for coronary artery disease among those with moderately bothersome symptoms.
2.32 (95% CI: 1.22 to 4.39) for coronary artery disease among those with "extremely" bothersome symptoms.
The authors pointed out that the Sleep Heart Health Study is a study of middle-age and older participants with a minimum age of 44. "Analyses stratified by age above or below 65 years suggest an effect modification by age, with the association of restless legs syndrome and cardiovascular disease seen only in the older age stratum."
Dr. Winkelman's group suggested that restless legs syndrome could cause cardiovascular disease and events through sleep deprivation or by spikes in nocturnal blood pressure during the repetitive arousals and limb movements commonly seen with restless leg syndrome.
However, they cautioned that the cross-sectional study design did not allow determination of causality or direction of causality. Also, diagnosis of restless leg syndrome was made by questionnaire rather than in a face-to-face interview.
"Although the questionnaire reflects currently accepted diagnostic criteria," they said, some patients with "clinical mimics" such as leg cramps, diabetic neuropathy, and arthritis were counted in the restless leg syndrome group, which could have inflated the association.
Furthermore, the results might not be generalizable to younger or non-white patients, they said.
The study was supported by the National Heart, Lung, and Blood Institute through cooperative agreements to several universities.
Dr. Winkelman reported being a consult to and conducting clinical trials research in restless legs syndrome sponsored by Boehringer Ingelheim, GlaxoSmithKline, and Schwarz Pharma.
Neither the other researchers nor Dr. Scherokman reported conflicts of interest.
Primary source: NeurologySource reference:Winkelman JW, et al "Association of restless legs syndrome and cardiovascular disease in the Sleep Heart Health Study" Neurology 2008; 70: 35-42.