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NEUROLOGY 2008;70:35-42
© 2008 American Academy of Neurology

Association of restless legs syndrome and cardiovascular disease in the Sleep Heart Health Study

John W. Winkelman, MD, PhD, Eyal Shahar, MD, MPH, Imran Sharief, MD and Daniel J. Gottlieb, MD, MPH

From the Division of Sleep Medicine (J.W.W.), Brigham & Women's Hospital, Harvard Medical School, Brighton, MA; Division of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health (E.S.), and Pulmonary and Critical Care Medicine Section, Department of Medicine, Arizona Respiratory and Sleep Disorders Centers (I.S.), University of Arizona, Tucson; and Boston University School of Medicine and the VA Boston Healthcare System (D.J.G.), MA.

Address correspondence and reprint requests to Dr. John W. Winkelman, Division of Sleep Medicine, Brigham & Women's Hospital, Harvard Medical School, 1505 Commonwealth Avenue, Brighton, MA 02135 JWinkelman{at}sleephealth.com

Objective: We evaluated the cross-sectional association between restless legs syndrome (RLS) and prevalent cardiovascular disease (CVD) in a large community-based sample of middle-aged and elderly subjects.

Methods: This is a cross-sectional observational study of 1,559 men and 1,874 women (mean age of 67.9 years) who were enrolled in the Sleep Heart Health Study, a community-based study of the cardiovascular consequences of sleep-disordered breathing. RLS was defined by positive responses on a self-administered questionnaire to the four diagnostic criteria, with symptoms occurring at least five times per month and associated with at least moderate distress. Coronary artery disease (CAD) was determined by self-report of doctor-diagnosed angina, myocardial infarction, or coronary revascularization procedure. Total CVD included CAD or history of physician-diagnosed stroke or heart failure. The relation of RLS to prevalent CAD and CVD was examined by multivariable logistic regression models

Results: RLS was present in 6.8% of women (n = 128) and 3.3% of men (n = 51). After adjustment for age, sex, race, body mass index, diabetes mellitus, systolic blood pressure, antihypertensive medication use, total:high-density lipoprotein cholesterol ratio, and smoking history, the ORs for CAD were 2.05 (95% CI 1.38 to 3.04) and for CVD were 2.07 (1.43 to 3.00) for subjects with RLS compared to those without RLS. The associations of RLS with CAD and CVD were stronger in those with RLS symptoms at least 16 times per month and were stronger in those with severe than in those with moderately bothersome symptoms.

Conclusions: Restless legs syndrome (RLS) is associated with prevalent coronary artery disease and cardiovascular disease. This association appears stronger in those with greater frequency or severity of RLS symptoms.

GLOSSARY: AHI = apnea-hypopnea index; CAD = coronary artery disease; CVD = cardiovascular disease; DBP = diastolic blood pressure; ESRD = end-stage renal disease; HDL = high-density lipoprotein; IQR = interquartile range; LDL = low-density lipoprotein; OSA = obstructive sleep apnea; OSAH = obstructive sleep apnea/hypopnea; PLMS = periodic leg movements of sleep; RLS = restless legs syndrome; SBP = systolic blood pressure; SHHS = Sleep Heart Health Study.

Received February 15, 2007. Accepted in final form June 15, 2007.

Supported by the National Heart, Lung and Blood Institute cooperative agreements U01 HL53940 (University of Washington), U01 HL53941 (Boston University), U01 HL53938 and Cooperative Agreement Supplement HL53938-07S1 (University of Arizona), U01 HL53916 (University of California, Davis), U01 HL53934 (University of Minnesota), U01 HL53931 (New York University), U01 HL53937 and U01 HL64360 (Johns Hopkins University), U01 HL63463 (Case Western Reserve University), and U01 HL63429 (Missouri Breaks Research), and research grant R01 HL71515 (Stanford University).

Disclosure: The authors report no conflicts of interest. Dr. Winkelman is a consult to and has conducted clinical trials research in restless legs syndrome sponsored by Boehringer Ingelheim, GlaxoSmithKline, and Schwarz Pharma.

The opinions expressed in the article are those of the authors and do not necessarily reflect the views of the Indian Health Service.






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