Journal of Clinical Sleep Medicine, Vol. 8, No. 2, 2012
Background: Restless legs syndrome (RLS) is a common
sensorimotor disorder whose incidence is not known. The aim
of the study was to determine the incidence and correlates of
RLS in a population-based sample.
Methods: We obtained data from the Tucson Cohort of the
Sleep Heart Health Study, a prospective multicenter study.
This cohort included 535 participants aged ≥ 40 years, who
answered questions regarding RLS on the 2002 and 2006
sleep surveys. For this study, RLS was defi ned as the pres-
ence of all 4 International RLS Study Group criteria, with
symptoms occurring ≥ 5 days/month and associated with at
least moderate distress.
Results: Mean age of the predominantly Caucasian (90.8%)
participants on the 2002 survey was 59.8 ± 9.7 years; 52.2%
were women. RLS prevalence was 4.1% in 2002 and 7.7%
in 2006. The yearly incidence of RLS was 1.7% (6.6% over
4 years). Multivariate analyses demonstrated that estrogen
use (OR = 2.5, 95% CI: 1.17-5.10) and self-reported obstruc-
tive lung disease (OR = 2.8, 95% CI: 1.37-5.83) were inde-
pendent risk factors predicting incident RLS. Incident RLS
was associated with higher prevalence of insomnia (26.5%
vs. 7.6%, p = 0.001), increased sleepiness (38.2% vs. 22%,
p = 0.036); and higher sleeping pill use in 2006 (23.5% vs.
9.7%, p = 0.019).
Conclusion: The incidence of RLS in this population sample
was 1.7% per year. Use of estrogen and history of obstructive
lung disease were associated with a signifi cantly higher inci-
dence of RLS. RLS, in turn, was associated with insomnia and
keywords: Restless Legs Syndrome, incidence, estrogen,
obstructive airway disease, COPD
Citation: Budhiraja P; Budhiraja R; Goodwin JL; Allen RP;
Newman AB; Koo BB; Quan SF. Incidence of restless legs syn-
drome and its correlates. J Clin Sleep Med 2012;8(2):119-124.
Incidence of Restless Legs Syndrome and Its Correlates
Pooja Budhiraja, M.D.1,2; Rohit Budhiraja, M.D.1,2; James L. Goodwin, Ph.D.2; Richard P. Allen, Ph.D.3; Anne B. Newman, M.D.4;
Brian B. Koo, M.D.5; Stuart F. Quan, M.D.2,6
1Department of Medicine, Southern Arizona Veterans Affairs Health Care System, Tucson, AZ; 2Department of Medicine, University
of Arizona College of Medicine, Tucson, AZ; 3Division of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD;
4Division of Epidemiology, University of Pittsburgh, Pittsburgh, PA; 5Division of Neurology, Case Western Reserve University School
of Medicine, Cleveland, OH; 6Division of Sleep Medicine, Harvard Medical School, Boston, MA
S C IE n T IF IC In V E S T IgAT IOn S
the legs during periods of rest or inactivity. The International
Restless Legs Syndrome Study Group (IRLSSG) has described
4 mandatory clinical features to establish the diagnosis of RLS,
namely: (i) an urge to move the legs, usually accompanied or
caused by uncomfortable and unpleasant sensations in the legs;
(ii) these symptoms begin or worsen during periods of rest or
inactivity such as lying or sitting; (iii) are partially or totally
relieved by movement; and (iv) symptoms are worse in the eve-
ning or nighttime.1
estless legs syndrome (RLS) is a common neurological
sensorimotor disorder characterized by an urge to move
The prevalence of RLS varies, depending on the selection cri-
teria that are used to defi ne RLS. The prevalence of RLS based
on the above-mentioned IRLSSG criteria has been reported be-
tween 7% and 24%.2-7 The RLS epidemiology, symptoms, and
treatment (REST) study reported a prevalence rate of 11.1% for
RLS, with 9.6% reporting at least weekly symptoms, and 2.4%
having symptoms that occurred at least twice weekly and affect-
ed the quality of life.5 Despite several studies evaluating preva-
lence, the incidence of this disorder is yet to be ascertained.
RLS can either be primary (idiopathic) or associated with
other factors (secondary RLS). Persons with idiopathic RLS
develop symptoms at a signifi cantly younger age (≤ 35 years),
tend to have positive family history and have slower progres-
sion of symptoms. Those with secondary RLS have later onset
and faster progression.8 RLS has been associated with diverse
conditions such as pregnancy, end-stage renal disease, and
iron defi ciency.1 Another factor potentially associated with
RLS is estrogen. While estrogen has been hypothesized to be
the etiology of pregnancy-related RLS, whether estrogen use
is associated with a higher incidence of RLS is not known.
Similarly, some studies have suggested an association between
pulmonary disorders such as COPD, pulmonary hypertension,
and sarcoidosis; whether the presence of these disorders bodes
a higher incidence of RLS is yet to be elucidated.
Current knowledge/Study Rationale: Restless legs syndrome is a
common neurological disorder. Several studies have looked at the prev-
alence of RLS but the incidence and correlates of RLS still need to be
elucidated. The aim of the current study was to assess the incidence of
RLS and its correlates in a prospective community-based cohort.
Study Impact: The study demonstrates a relatively high annual inci-
dence of RLS and its association with estrogen use and obstructive lung
disease. An awareness of this relationship would facilitate early diagno-
sis and management of RLS in these patient groups, which may, in turn,
lead to a decrease in insomnia and sleeping pill use.
A commentary on this article appears in this issue on page 125.
Journal of Clinical Sleep Medicine, Vol. 8, No. 2, 2012
P Budhiraja, R Budhiraja, JL Goodwin et al
results have important clinical and public health implications.
Further studies need to be designed looking at incidence of RLS
in diverse populations, assessing the effect of parity, iron status,
family history, and renal function on incident RLS and the so-
cioeconomic burden associated with this condition.
22. Patton SM, Ponnuru P, Snyder AM, Podskalny GD, Connor JR. Hypoxia-induc-
ible factor pathway activation in restless legs syndrome patients. Eur J Neurol
23. Connor JR, Wang XS, Allen RP, et al. Altered dopaminergic profile in the puta-
men and substantia nigra in restless leg syndrome. Brain 2009;132:2403-12.
24. Wahlin-Larsson B, Ulfberg J, Aulin KP, Kadi F. The expression of vascular endo-
thelial growth factor in skeletal muscle of patients with sleep disorders. Muscle
25. Hornyak M, Feige B, Voderholzer U, Philipsen A, Riemann D. Polysomnography
findings in patients with restless legs syndrome and in healthy controls: a com-
parative observational study. Sleep 2007;30:861-5.
26. Winkelman JW, Redline S, Baldwin CM, Resnick HE, Newman AB, Gottlieb DJ.
Polysomnographic and health-related quality of life correlates of restless legs
syndrome in the Sleep Heart Health Study. Sleep 2009;32:772-8.
27. Fulda S, Wetter TC. Is daytime sleepiness a neglected problem in patients with
restless legs syndrome? Mov Disord 2007;22 Suppl 18:S409-13.
28. Allen RP, Bharmal M, Calloway M. Prevalence and disease burden of primary
restless legs syndrome: results of a general population survey in the United
States. Mov Disord 2011;26:114-20.
After acceptance of this manuscript, the authors note the following recently published
papers: Szentkiralyi A, Fendrich K, Hoffmann W, Happe S, Berger K. Incidence of
restless legs syndrome in two population-based cohort studies in Germany. Sleep
Med 2011;12:815-20 and Kagimura T, Nomura T, Kusumi M, Nakashima K, Inoue Y.
Prospective survey on the natural course of restless legs syndrome over two years in
a closed cohort. Sleep Med 2011;12: 821-26.
This work was supported by National Heart, Lung and Blood Institute cooperative
agreements U01HL53940 (University of Washington), U01HL53941 (Boston Univer-
sity), U01HL53938 (University of Arizona), U01HL53916 (University of California,
Davis), U01HL53934 (University of Minnesota), U01HL53931 (New York University),
U01HL53937 and U01HL64360 (Johns Hopkins University), U01HL63463 (Case
Western Reserve University), and U01HL63429 (Missouri Breaks Research).
Sleep Heart Health Study (SHHS) acknowledges the Atherosclerosis Risk in Com-
munities Study (ARIC), the Cardiovascular Health Study (CHS), the Framingham
Heart Study (FHS), the Cornell/Mt. Sinai Worksite and Hypertension Studies, the
Tucson Epidemiologic Study of Airways Obstructive Diseases (TES) and the Tucson
Health and Environment Study (H&E) for allowing their cohort members to be part of
the SHHS and for permitting data acquired by them to be used in the study. SHHS
is particularly grateful to the members of these cohorts who agreed to participate in
SHHS as well. SHHS further recognizes all of the investigators and staff who have
contributed to its success. A list of SHHS investigators, staff and their participating
institutions is available on the SHHS website, http://www.jhucct.com/shhs.
SUBMISSIOn & CORRESPOnDEnCE InFORMATIOn
Submitted for publication June, 2011
Submitted in final revised form October, 2011
Accepted for publication november, 2011
Address correspondence to: Pooja Budhiraja, MD, Southern Arizona VA HealthCare
System, 3601 S 6th Ave, Tucson, Arizona 85723; Tel: (520) 990-5179; Fax: (520)
629-1764; E-mail: email@example.com
This was not an industry supported study. Dr. Allen serves as a consultant for Pfiz-
er, GlaxoSmithKline, and UCB Pharma. He also has received research support from
GlaxoSmithKline. The other authors have indicated no financial conflicts of interest.
1. Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J.
Restless legs syndrome: diagnostic criteria, special considerations, and epide-
miology. A report from the restless legs syndrome diagnosis and epidemiology
workshop at the National Institutes of Health. Sleep Med 2003;4:101-19.
2. Allen RP, Walters AS, Montplaisir J, et al. Restless legs syndrome prevalence
and impact: REST general population study. Arch Intern Med 2005;165:1286-92.
3. Berger K, Luedemann J, Trenkwalder C, John U, Kessler C. Sex and the
risk of restless legs syndrome in the general population. Arch Intern Med
4. Winkelman JW, Shahar E, Sharief I, Gottlieb DJ. Association of restless legs
syndrome and cardiovascular disease in the Sleep Heart Health Study. Neurol-
5. Hening W, Walters AS, Allen RP, Montplaisir J, Myers A, Ferini-Strambi L. Im-
pact, diagnosis and treatment of restless legs syndrome (RLS) in a primary care
population: the REST (RLS epidemiology, symptoms, and treatment) primary
care study. Sleep Med 2004;5:237-46.
6. Hogl B, Kiechl S, Willeit J, et al. Restless legs syndrome: a community-based
study of prevalence, severity, and risk factors. Neurology 2005;64:1920-4.
7. Nichols DA, Allen RP, Grauke JH, et al. Restless legs syndrome symptoms in
primary care: a prevalence study. Arch Intern Med 2003;163:2323-9.
8. Winkelmann J, Wetter TC, Collado-Seidel V, et al. Clinical characteristics and
frequency of the hereditary restless legs syndrome in a population of 300 pa-
tients. Sleep 2000;23:597-602.
9. Quan SF, Howard BV, Iber C, et al. The Sleep Heart Health Study: design, ratio-
nale, and methods. Sleep 1997;20:1077-85.
10. Edinger JD, Bonnet MH, Bootzin RR, et al. Derivation of research diagnostic
criteria for insomnia: report of an American Academy of Sleep Medicine Work
Group. Sleep 2004;2:1567-96.
11. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleep-
iness scale. Sleep 1991;14:540-5.
12. Manconi M, Govoni V, De Vito A, et al. Pregnancy as a risk factor for restless
legs syndrome. Sleep Med 2004;5:305-8.
13. Dzaja A, Wehrle R, Lancel M, Pollmacher T. Elevated estradiol plasma levels in
women with restless legs during pregnancy. Sleep 2009;32:169-74.
14. Thompson TL, Certain ME. Estrogen mediated inhibition of dopamine transport
in the striatum: regulation by G alpha i/o. Eur J Pharmacol 2005;511:121-6.
15. Trenkwalder C, Hundemer HP, Lledo A, et al. Efficacy of pergolide in treatment of
restless legs syndrome: the PEARLS Study. Neurology 2004;62:1391-7.
16. Spillane JD. Restless legs syndrome in chronic pulmonary disease. Br Med J
17. Lo Coco D, Mattaliano A, Lo Coco A, Randisi B. Increased frequency of restless
legs syndrome in chronic obstructive pulmonary disease patients. Sleep Med
18. Kaplan Y, Inonu H, Yilmaz A, Ocal S. Restless legs syndrome in patients with
chronic obstructive pulmonary disease. Can J Neurol Sci 2008;35:352-7.
19. Verbraecken J, Hoitsma E, van der Grinten CP, Cobben NA, Wouters EF, Drent
M. Sleep disturbances associated with periodic leg movements in chronic sar-
coidosis. Sarcoidosis Vasc Diffuse Lung Dis 2004;21:137-46.
20. Minai OA, Malik N, Foldvary N, Bair N, Golish JA. Prevalence and characteristics
of restless legs syndrome in patients with pulmonary hypertension. J Heart Lung
21. Minai OA, Golish JA, Yataco JC, Budev MM, Blazey H, Giannini C. Restless legs
syndrome in lung transplant recipients. J Heart Lung Transplant 2007;26:24-9.