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Volume 08 No. 02
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Scientific Investigations

Incidence of Restless Legs Syndrome and Its Correlates

http://dx.doi.org/10.5664/jcsm.1756

Pooja Budhiraja, M.D1,2; Rohit Budhiraja, M.D1,2; James L. Goodwin, Ph.D2; 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

ABSTRACT

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 defined as the presence 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 obstructive lung disease (OR = 2.8, 95% CI: 1.37-5.83) were independent 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 significantly higher incidence of RLS. RLS, in turn, was associated with insomnia and increased sleepiness.

Citation:

Budhiraja P; Budhiraja R; Goodwin JL; Allen RP; Newman AB; Koo BB; Quan SF. Incidence of restless legs syndrome and its correlates. J Clin Sleep Med 2012;8(2):119-124.


Restless legs syndrome (RLS) is a common neurological sensorimotor disorder characterized by an urge to move 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 evening or nighttime.1

A commentary on this article appears in this issue on page 125.

The prevalence of RLS varies, depending on the selection criteria that are used to define RLS. The prevalence of RLS based on the above-mentioned IRLSSG criteria has been reported between 7% and 24%.27 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 affected the quality of life.5 Despite several studies evaluating prevalence, 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 significantly younger age (≤ 35 years), tend to have positive family history and have slower progression 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 deficiency.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.

BRIEF SUMMARY

Current Knowledge/Study Rationale: Restless legs syndrome is a common neurological disorder. Several studies have looked at the prevalence 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 incidence of RLS and its association with estrogen use and obstructive lung disease. An awareness of this relationship would facilitate early diagnosis and management of RLS in these patient groups, which may, in turn, lead to a decrease in insomnia and sleeping pill use.

The aim of the current study was to assess the incidence of RLS and its correlates in a community-based cohort. We were especially interested in whether estrogen use or presence of obstructive pulmonary disorders results in a higher incidence of RLS. We used the data from the Tucson cohort of the Sleep Heart Health Study.

METHODS

Study Sample

The Sleep Heart Health Study (SHHS) is a multicenter, prospective cohort study implemented by the National Heart, Lung, and Blood Institute, primarily aimed at elucidating the relationship between sleep disordered breathing and cardiovascular diseases in participants aged ≥ 40 years in the United States.9 In the second examination cycle of the SHHS (SHHS-2) in 2002, questionnaire data were obtained regarding RLS symptoms. Approximately 4 years later in the Tucson cohort of SHHS, participants self-completed their follow-up survey which included these same questions. There were 535 participants who answered questions regarding RLS on both the surveys, and these were included in the analysis. The SHHS protocol was approved by the institutional review boards of all participating centers.

Participants were asked specific questions to determine the presence and severity of RLS ( Table 1). We defined RLS as presence of all 4 IRLSSG criteria, with symptoms occurring ≥ 5 days/month and associated with at least moderate distress. These questions attempted to ensure that participants met IRLSSG criteria and had persistent and distressing symptoms. Participants whose responses suggested possible alternate diagnoses (discomfort from leg cramps/pain while exercising [claudication]) were excluded to decrease false positives.4 Participants who had RLS based on these criteria in 2006, but not on first survey on RLS in 2002, constituted the incident RLS group.

Questions used to diagnose and measure the severity of RLS symptoms

(1) In the past year, while SITTING OR LYING DOWN, have you had any of the following symptoms?
  • (1a) “An urge to move your legs?” (yes / no / do not know)

  • (1b) “Unpleasant or uncomfortable feelings in your legs?” (yes / no / do not know)

(2) “Are they worse when you are sitting or lying down than when you are moving around or walking?” (yes / no / do not know)
(3) “Do the symptoms improve if you get up and start walking?” (yes / no / do not know)
(4) “These symptoms are most likely to occur when you are? (resting, sitting or lying down / exercising or just stopped exercising / standing or walking / having a leg cramp or Charley horse / do not know)
(5) “What time of day do they occur?”(daytime only (before 6 PM) / bedtime only / evening or nighttime only / both day and night (after 6 PM)).
  • (5a) “If both day and night, do they get worse at night?” (yes / no / do not know)

(6) “How troublesome are the symptoms?” (hardly at all / a little / moderately / a lot / extremely).
(7) “How often do you get this symptom? (less than once a month / about once a month / 2-4 days a month / 5-15 days a month / most days (16-23 days a month) / daily (6 days a week or more))

[i] Subjects were instructed to check one best answer. In accordance with IRLSSG criteria, a yes response was required to the first 3 questions. The symptoms had to be present during resting, sitting, or lying down positions (question 4) and had to occur primarily during the evening, nighttime, or bedtime (question 5). If the participant's response was “both day and night” (question 5), then the symptoms had to be worse at night (question 5a). For the current study, RLS was defined as present if in addition to participants meeting the above criteria; the symptoms occurred at least 5 days a month (question 7) and were associated with at least moderate distress (question 6).

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Table 1

Questions used to diagnose and measure the severity of RLS symptoms

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Polysomnography

The participants also underwent overnight polysomnography in their homes, using a portable sleep-monitoring device that collected data on 12 channels, using electrodes attached to the head, face, and chest. Polysomnography was done during survey 1 (SHHS-2, 2002) only. Data obtained from polysomnography included: total sleep time, sleep onset latency, wake time after sleep onset, sleep efficiency, arousal index, and the apnea-hypopnea index. Sleep efficiency was defined as the percentage total time asleep divided by the total time in bed after lights off to the time of final awakening. The arousal index was defined as the total number of arousals in sleep divided by the total sleep time. Arousals were identified as abrupt shifts ≥ 3 sec in electroencephalogram frequency. Apneas were defined if airflow was absent or nearly absent for ≥ 10 sec; hypopneas were considered to be present if there was ≥ 30% reduction in airflow for ≥ 10 sec and were associated with ≥ 4% decrease in oxyhemoglobin saturation. The apnea-hypopnea index (AHI) was defined as the number of apneas plus hypopneas per hour of sleep.

Sleep Habits

Data regarding sleep habits was obtained during both surveys 1 (SHHS-2, 2002) and 2 (2006). For insomnia responses, the following 3 questions were used: Do you “Have trouble falling asleep,” “Wake up during the night, and have difficulty getting back to sleep,” and “Wake up too early in the morning and be unable to get back to sleep.” Response options were categorized into never, rarely (once a month or less), sometimes (2-4×/month), often (5-15×/month), and almost always (16-30×/month). Insomnia was defined as a present if the subjects answered “almost always” to any of these questions. In order to determine the daytime consequences of insomnia, subjects were asked if they “Feel unrested during the day no matter how many hours of sleep you had” or “Feel excessively (overly) sleepy during the day.” Adverse daytime consequences were considered to be present if they had any of the above symptoms ≥ 5-15 times a month. Insomnia disorder was defined as presence of any of the insomnia symptoms along with adverse daytime consequences.10 Use of sleeping pills was defined as present if the response to the question “Do you use sleeping pills” was “often (5-15×/month)” or “almost always (16-30×/month).” Finally, participants were asked “How often do you snore?” Responses were classified as “do not snore,” “rarely (less than one night a week),“ ”sometimes (1 or 2 nights a week),” “frequently (3 to 5 nights a week),” “always or almost always (6 or 7 nights a week),”and “don't know.” Participants were classified as frequent snorers if they snored ≥ 3 to 5 nights a week. The Epworth Sleepiness Scale (ESS), an 8-item self-report measure of sleepiness,11 was used to determine the level of daytime sleepiness. Scores range from 0 to 24, and values > 10 are generally considered to indicate excessive sleepiness.

Other Variables

Ethnicity, gender, education, and marital status were obtained from data already collected by the Tucson SHHS cohort. Data regarding medical history, medication use (including estrogen use), BMI, smoking, and alcohol consumption were also obtained from survey 1 done in 2002. Obstructive lung disease was defined as present if patient reported having asthma, chronic bronchitis, COPD, or emphysema.

Analysis

The primary outcomes were the incidence and correlates of RLS. We evaluated the participants with no RLS at baseline (i.e., on 2002 survey). Among these, the participants who developed RLS on 2006 survey (incident RLS) were compared with those with no RLS on the 2006 survey. We compared baseline (survey 1) demographic factors, tobacco use, alcohol and medication use, presence of medical comorbidities and polysomnographic variables between those with and those without incident RLS using Student's t -test or χ2 test. We then included the variables significant at level p < 0.1 to construct multivariate regression models to determine factors independently associated with incident RLS. We also investigated the relationship between incident RLS, insomnia, daytime consequences of insomnia, sleeping pill use, and daytime sleepiness (ESS score > 10). Statistical significance was defined as 2-tailed p-value < 0.05.

RESULTS

Population Characteristics

There were 535 participants who answered questions regarding RLS on both surveys. Mean age of the study sample on survey 1 was 59.8 ± 9.7 years; 52.6% of the participants were women. Mean age was 59.4 ± 10.0 for women and 60.1 ± 9.4 for men (p = 0.49). It was a predominantly Caucasian population (90.8%). Mean BMI was 28.7 ± 5.6 kg/m2.

Prevalence of RLS

Based on IRLSSG criteria alone, 71 participants (13.3%) had restless leg symptoms on survey 1 and 123 (23%) on survey 2. Prevalence of RLS (IRLSSG criteria, with symptoms occurring ≥ 5 days/month and associated with at least moderate distress) on survey 1 was 4.1% (22/535). Participants with RLS were older (65.09 ± 9.8 vs. 59.53 ± 9.7, p = 0.009), had higher prevalence of insomnia (22.7% vs. 5.7%, p = 0.009), higher sleep latency on PSG (49.47 ± 62.23 min vs. 27.34 ± 32.2 min, p = 0.014), and tendency towards poor sleep efficiency (77.08% ± 13.8% vs. 81.99% ± 10.14%, p = 0.056). Prevalence of RLS on survey 2 was 7.7% (41/535).

Incidence of RLS

The breakdown of incidence based on different frequency and severity criteria is shown in Figure 1. The annual incidence rate for RLS defined by IRLSSG criteria alone was 4.7%. In contrast, the annual incidence of RLS according to our definition which included occurrence ≥ 5 days/month and at least moderate distress was 1.7%. The comparison between the baseline characteristics of participants with and without incident RLS is shown in Table 2. All estrogen users were women. There was a higher prevalence of estrogen use and history of obstructive lung disease at baseline among those who developed RLS (Table 2). Conversely, estrogen users (n = 113) had higher incidence of RLS over 4 years than those who did not use estrogen (11.6% vs. 5.3%, p = 0.029). Similarly, patients with obstructive lung disease had higher incidence of RLS compared to those who did not have obstructive lung disease (12.5% vs. 5.0%, p = 0.009). Multivariable analyses confirmed significantly increased odds of developing RLS in estrogen users or those with a positive history of obstructive lung disorders (Table 3).

Baseline clinical, demographic, and polysomnographic characteristics (Survey 1, done in 2002) of subjects with incident RLS compared to subjects who did not develop RLS

Number of participants (Incident RLS/no RLS)Incident RLSNo RLSp-value
Age34/47960.4 ± 8.959.5 ± 9.70.597
Gender, Female34/47964.7 (%)51.4 (%)0.156
Hypertension32/46122 (%)25 (%)0.834
Cardiovascular disease33/47418 (%)9 (%)0.113
Diabetes mellitus30/4497 (%)3 (%)0.240
Body mass index34/47827.3 ± 5.2 (kg/m2)28.8 ± 5.6 (kg/m2)0.148
Current smoker34/47815 (%)8 (%)0.185
Antidepressants24/47724 (%)14 (%)0.126
Benzodiazepine34/4779 (%)4 (%)0.174
More than 7 drinks of alcohol a week34/47814.7 (%)14 (%)0.803
Estrogen34/47738.2 (%)20.8 (%)0.029*
Obstructive airway disease34/47941.2 (%)20.5 (%)0.009*
Sleep latency21/32229.1 ± 27.9 (min)27.2 ± 32.5 (min)0.792
Sleep efficiency24/34982.5 ± 9.3 (%)81.9 ± 10.2 (%)0.802
Apnea hypopnea index24/34512.1 ± 15.9/h13.0 ± 15.2/h0.767
Wake after sleep onset24/34556.8 ± 35.6 (min)60.9 ± 41.1 (min)0.640
Total sleep time24/349383.8 ± 71.6 (min)384.4 ± 66.1 (min)0.962
Arousal index24/34516.4 ± 9.2/h17.1 ± 10.0/h0.724
Sleepiness (Epworth Sleepiness Scale score ≥ 10)34/47823.5 (%)25.3 (%)NS
Epworth Sleepiness Scale score34/4787.1 ± 4.36.9 ± 4.00.8

* denotes statistically significant (p < 0.05).

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Table 2

Baseline clinical, demographic, and polysomnographic characteristics (Survey 1, done in 2002) of subjects with incident RLS compared to subjects who did not develop RLS

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Multiple logistic regression demonstrating odds for development of RLS

Odds ratio95% C.I.
p-value
LowerUpper
Estrogen2.4461.1725.1040.017*
Obstructive airway disease2.8201.3655.8280.005*
Age1.0070.9701.0460.725

* denotes statistically significant (p < 0.05).

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Table 3

Multiple logistic regression demonstrating odds for development of RLS

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Incidence of RLS as defined by different criteria

(A) Incidence for RLS according to frequency of symptoms. (B) Incidence of RLS according to severity of symptoms. Severe distress associated with RLS was defined to be present if subjects reported that symptoms were a lot or extremely troublesome and moderate distress if the symptoms were moderately troublesome.

jcsm.8.2.119.jpg

jcsm.8.2.119.jpg
Figure 1

Incidence of RLS as defined by different criteria

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Participants with incident RLS had higher prevalence of insomnia disorder (insomnia with daytime consequences) and higher use of sleeping pill in the second survey in 2006 (Table 4).

Prevalence of different sleep complaints and sleeping pill use in Survey 2 (done in 2006) in participants with and without incident RLS

Number of participants (Incident RLS/no RLS)Incident RLSNo RLSp-value
Prevalence of insomnia34/47626.5 (%)7.6 (%)0.001*
Prevalence of insomnia disorder (Insomnia with daytime consequences)33/47621.2 (%)4.4 (%)0.001*
Trouble falling asleep34/47620.6 (%)4.6 (%)0.002*
Wake up during the night and have difficulty getting back to sleep34/47511.8 (%)4.8 (%)0.097
Wake up too early in the morning and be unable to get back to sleep34/47517.6 (%)3.6 (%)0.003*
Use of sleeping pill34/45423.5 (%)9.7 (%)0.019*
Snore frequently34/47129.4 (%)30.6 (%)NS
Sleepiness (Epworth Sleepiness Scale score ≥ 10)34/46438.2 (%)22 (%)0.036*
Epworth Sleepiness Scale score34/4647.8 ± 3.26.6 ± 3.90.09

* denotes statistically significant (p < 0.05).

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Table 4

Prevalence of different sleep complaints and sleeping pill use in Survey 2 (done in 2006) in participants with and without incident RLS

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DISCUSSION

To our knowledge, this study is the first community-based study to look at the incidence of RLS and define its correlates. We found an annual incidence of RLS of 1.7%, while the incidence based upon IRLSSG criteria alone without severity measures was 4.7%. Factors associated with increased odds of developing RLS over a period of four years were estrogen use and a history of COPD, both of which conferred an almost three-fold risk of developing RLS. Estrogen use was associated with a significantly elevated risk of developing RLS in the current study. This supports previous literature suggesting an association between estrogen use and RLS. Further evidence of a role of estrogen is provided by the peak prevalence of RLS in pregnancy occurring in the third trimester, when estrogen levels are the highest.12 Dzaja et al. reported an association of elevated estrogen levels, but not other hormone or ferritin levels with RLS in pregnancy.13 Moreover, the prevalence of RLS is higher in parous women and increases with each additional pregnancy.3 While the mechanism of this association is still obscure, it has been postulated that estrogen, by acting directly at the D2 auto receptor or via increased turnover of brainstem noradrenaline, may interfere with dopaminergic transmission in the basal ganglia, thus contributing to RLS pathophysiology.12,14,15

Another novel and important finding of the current study was the higher incidence of RLS in participants with a history of obstructive lung disease. The association between these two disorders was first suggested in 1970 when a case series reported comorbid COPD in eight consecutive patients referred for neurological evaluation for severe RLS.16 Lococo et al. compared 87 COPD patients to 110 age and gender-matched controls, and found a three times higher prevalence of RLS in patients with COPD.17 The severity of RLS symptoms was also higher in COPD patients compared to controls with RLS.17 Another study reported that RLS was more frequent in subjects with COPD, especially those with late stages of COPD, and was associated with more severe airway obstruction, hypercapnia, and hypoxia.18 Furthermore, an increased prevalence of RLS has also been reported in patients with other pulmonary conditions such as sarcoidosis19 and pulmonary hypertension,20 as well as in lung transplant recipients.21

While the nature of the association between COPD and RLS is unclear, it may be hypothesized that hypoxemia is a contributing factor. Notably, recent literature demonstrates that hypoxic pathways may be activated in RLS. Hypoxic pathways may also be involved in the RLS pathophysiology associated with the well-documented brain iron deficiency state.22 The hypoxic pathways, particularly hypoxia inducible factor-1 (HIF-1), increase both tyrosine hydroxylase and the vascular endothelial growth factor (VEGF). Both of these changes have been documented in RLS. Connor et al. reported elevated tyrosine hydroxylase and phosphorylated tyrosine hydroxylase, the rate-limiting enzyme in the synthesis of dopamine, in nigro-stratial system in subjects with RLS.23 Another autopsy study demonstrated up-regulation of VEGF expression, as well as the HIF, in the brain microvasculature and substantia nigra neurons of RLS subjects.22 Hypoxic pathway is also activated in diverse cell types in subjects with RLS.22 Increased capillary network and VEGF have also been noted in tibialis anterior muscle of subjects with RLS.24 It is possible that hypoxia associated with COPD or other lung disorders could activate similar pathways and contribute to RLS.

In the current study, participants with incident RLS had a higher prevalence of insomnia ( Table 4). This is consistent with prior studies that demonstrate various sleep disturbances, including increased sleep latency, increased awakenings, difficulty in maintaining sleep, and lower sleep efficiency in RLS.25,26

Incident RLS was also associated with daytime sleepiness and sleeping pill use. Overall, neither the group with or that without incident RLS was sleepy (mean ESS < 10 for both, 7.8 ± 3.2 vs. 6.6 ± 3.9, respectively; p = 0.09). However, the proportion of sleepy people (ESS > 10) was higher in the RLS group (38.2%) than the other group (22%). These results are consistent with past studies, which demonstrate a weighted mean ESS score of 8.4 in RLS population, with 30% of RLS subjects having an ESS score > 10.27 The relatively modest degree of sleepiness is not, however, concordant with the profound sleep loss and insomnia reported by these patients. Sleepiness appears to increase in RLS, but unlike insomnia does not occur for most RLS patients. And when sleepiness occurs, it appears to be less than expected for the degree of sleep loss. We did not find a difference in sleeping pill use between sleepy (ESS > 10) or non-sleepy participants. As suggested by Fulda and Wetter, the factors predicting sleepiness in a subgroup of RLS subjects need to be elucidated.27

Further studies are also needed to understand the potential consequences such as decreased productivity and increased traffic accidents, and the resultant economic and social burden of RLS-related sleep abnormalities. Notably, a recent study showed a decrease in workplace productivity by 20% to 50% in RLS subjects.28

The study has several limitations. Firstly, the participants were predominantly Caucasian, and results may not be generalizable to non-Caucasian populations. Secondly, RLS was diagnosed by questionnaire and not confirmed by physicians. We tried to decrease false positives by excluding participants with symptoms suggestive of an RLS mimic (leg cramp symptoms or with symptoms associated with walking/exercising throughout the day). However, in view of the relatively low positive-predictive value of questionnaire utilizing self report of symptoms, it is likely that false positives were included in the RLS group. Thirdly, we did not have data regarding iron status, renal insufficiency, parity, and family history of RLS in our participants. Notably, altered iron metabolism is well-known correlate of RLS and it is possible that some or many of our findings could be explained by iron deficiency. However, in absence of these data, the contribution of altered iron homeostasis to the results is impossible to predict. Finally, all SHHS participants were older than 40 years of age, and the incidence and correlates of RLS in a younger population may be different.

In conclusion, to the best of our knowledge, this is the first community-based study looking at incidence of RLS. Estrogen use and obstructive lung disease were associated with higher likelihood of developing RLS, which in turn was associated with insomnia, increased daytime sleepiness, and higher use of sleeping pills. Considering the disease burden of RLS, these 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 socioeconomic burden associated with this condition.

DISCLOSURE STATEMENT

This was not an industry supported study. Dr. Allen serves as a consultant for Pfizer, GlaxoSmithKline, and UCB Pharma. He also has received research support from GlaxoSmithKline. The other authors have indicated no financial conflicts of interest.

Notes

[5] 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.

ACKNOWLEDGMENTS

This work was supported by National Heart, Lung and Blood Institute cooperative agreements U01HL53940 (University of Washington), U01HL53941 (Boston University), 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 Communities 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.

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