ORIGINAL ARTICLE

The Clinical Respiratory Journal

Survey of restless legs syndrome in a pulmonary hypertension population Kamonpun Ussavarungsi, Joseph Kaplan, Charles Burger and Vichaya Arunthari Division of Pulmonary Medicine, Mayo Clinic, Jacksonville, FL, USA

Abstract Introduction: The prevalence of restless legs syndrome (RLS) varies from 5% to 24% in the general population and is associated with a variety of medical disorders. However, the association between RLS and pulmonary hypertension (PH) is unknown. Objectives: To determine the prevalence of RLS in PH patients. Methods: A cross-sectional questionnaire was given to patients with PH who attended the Pulmonary Hypertension Association conference. We used the RLS Diagnostic Index questionnaire. Demographic data included age, gender, height, weight, body mass index (BMI), medication list, PH World Health Organization (WHO) diagnosis group and current WHO functional class. Results: The study included 128 PH patients. Most were females (86.8%) with a mean age of 49.68 years [standard deviation (SD) 14.24]. The mean BMI was 31.3 (SD 20.46). One hundred and twenty-one patients (93.75%) were classified as WHO group 1 (pulmonary arterial hypertension). Three patients were identified in WHO group 3 (hypoxemic states), four patients in group 4 (chronic thromboemboli) and one patient in group 5 (2.3%, 3.1% and 0.8%, respectively). Definite RLS was found in 16 of 128 patients with PH resulting in a prevalence of 12.5%, possible RLS in 39 of 128 patients (30.46%) and no RLS in 73 (57.03%) patients. Conclusion: The prevalence of RLS is not increased in PH. There is a high prevalence of possible RLS in our study. The overall prevalence of combined definite and possible RLS is significant. Future research is needed to assess more patients with PH and the association or correlation with RLS. Please cite this paper as: Ussavarungsi K, Kaplan J, Burger C and Arunthari V. Survey of restless legs syndrome in a pulmonary hypertension population. Clin Respir J 2015; 9: 98–103.

Key words epidemiology – hypertension – prevalence – pulmonary/complications – pulmonary hypertension – restless leg syndrome Correspondence Kamonpun Ussavarungsi, MD, Pulmonary Medicine, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL 32224, USA. Tel: 904 943 2282 Fax: 904 953 2082 email: [email protected] Received: 15 May 2013 Revision requested: 12 December 2013 Accepted: 21 January 2014 DOI:10.1111/crj.12114 Authorship and contributorship KU analyzed data and wrote the paper. JK and CB made critical revisions. VA designed and performed the study, collected the data and wrote the paper. All authors made significant contributions and approved the final manuscript. Ethics The study has been approved by the Mayo Clinic Institutional Review Board (IRB). All patients gave written informed consent prior to participation in the study. Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article.

Introduction Restless legs syndrome (RLS) is a common movement disorder characterized by dysesthesias in the lower extremities, which are associated with an urge to move (1). These symptoms typically occur at rest or during periods of inactivity, are relieved by movement, and follow a circadian rhythm with onset in the evening and at night (2).

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In most cases, RLS is a primary idiopathic disorder but may be associated with a variety of underlying medical disorders, including end-stage renal disease, iron deficiency or pregnancy. Several neurological conditions, such as spinal cerebellar atrophy, Charcot–Marie tooth disease type 2, spinal stenosis, lumbar sacral radiculopathy and Parkinson disease may coexist with RLS or be RLS mimics (3).

The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd

Ussavarungsi et al.

The prevalence of RLS varies depending upon the population surveyed and the severity of symptoms required for inclusion, with estimates ranging from 5% to 24% in the general population (4–8). The first large-scale, multinational population-based study using standard diagnostic criteria (Appendix S1) (9) reported on the evaluation of 15 391 adult subjects from the United States and five European countries. The study identified RLS symptoms of any frequency in 7.2% (10). The RLS symptom complex was reported to be twice as high in women compared with men, and the prevalence increased with age (10). The prevalence of RLS in individuals with iron deficiency states, pregnancy and end-stage renal disease is estimated to be 25%–30% (11). Pulmonary hypertension (PH) is a serious and often progressive disorder that results in right ventricular dysfunction, exercise intolerance and, if untreated, usually leads to right-heart failure and death (12). Diagnosis is often delayed with a mean interval from onset of symptoms to diagnosis of 2 years with a subsequent median survival of 2.8 years (13, 14). Symptoms and signs of PH are typically nonspecific and are often confounded by comorbidities that contribute to this delay in diagnosis (15). Whether an association between RLS and PH exists is unknown. A study by Minai et al. suggests that there may be a relationship. To our knowledge, this is the only epidemiological study on RLS among patients with PH. Patients with PH can develop peripheral neuropathies from medications and electrolyte abnormalities, as well as renal insufficiency, which may precipitate RLS. In their cross-sectional study, RLS was present in 24 of 55 patients with PH (43.6%), and more than half (54%) of these patients had moderateto-severe RLS (16). The prevalence did not correlate with measures of PH severity. Our study was performed to evaluate the prevalence of RLS in a population known to have PH utilizing the RLS Diagnostic Index (RLS-DI).

Materials and methods A cross-sectional questionnaire survey study was performed at the International Pulmonary Hypertension Association conference and scientific sessions June 22–24, 2012 at the Renaissance Orlando at Sea World, Orlando, Florida after we received Institutional Review Board approval. We used a convenience sample of patients with PH who attended this conference. Patients who refused to participate in the questionnaire were excluded from the study. We assigned one

The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd

RLS in pulmonary hypertension patients

board certified sleep physician (VA) to perform a oneon-one, face-to-face interview for all participants with questions based on the RLS-DI questionnaire. The physician further clarified associated and supportive criteria for the RLS diagnosis. Given that this was an interview and no chart review was available, objective findings from a polysomnography, actigraphy or suggested immobilization were scored as not assessable or not done. The RLS-DI questionnaire utilized consists of 10 items divided into two parts (Appendix S2). The essential criteria are questioned in items 1–5 (part A) and the nonessential diagnostic information is in items 6–10 (part B). The cutoff point of equal to or greater than 11 points on a scale ranging from −22 (no RLS) to 20 (definite RLS) is used for the diagnosis of RLS based on the diagnostic criteria published by the International RLS Study Group (IRLSSG). The RLS-DI is a questionnaire validated by Benes and Kohnen (17) for diagnosing patients with persistent or major RLS and for excluding patients with sleep disturbances due to other causes that mimic the essential diagnostic criteria of RLS. Using the cut point of 11, the RLS-DI was found to be highly sensitive at 93% and specific at 98.9% for distinguishing between the presence and absence of RLS by comparing the RLS-DI total score to the diagnosis of two independent sleep experts (17). Demographic data that was available for collection included age, gender, height, weight, body mass index (BMI), medication list, PH World Health Organization (WHO) diagnosis group and current WHO functional class.

Statistical analysis Continuous variables are reported in means and in standard deviations (SDs). The categorical variables are reported in percentages of total subjects. The Pearson chi-squared and Fisher’s exact test were used to determine the relationship between the results of RLS-DI and other categorical variables, and the Student’s t-test was used on continuous variables. A P value

Survey of restless legs syndrome in a pulmonary hypertension population.

The prevalence of restless legs syndrome (RLS) varies from 5% to 24% in the general population and is associated with a variety of medical disorders. ...
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