We conducted a population-based cross-sectional study to assess prevalence of cardiovascular risk factors in subjects with and without restless legs syndrome (RLS). Adults attending their annual checkup completed the International RLS Study Group questionnaire and underwent an interview by a neurologist. Data from the annual checkup were compared between subjects with and without RLS. The prevalence of RLS was 6.7% (95% CI 5.45-7.95) among 1,537 responders. RLS subjects' blood tests showed significantly higher fasting blood glucose level (P = 0.029), higher prevalence of hypercholesterolemia (P = 0.029) and reduced renal function (P = 0.013), and increased prevalence of low hematocrit (P = 0.008). RLS subjects weighed more (P = 0.029), had a higher BMI (P = 0.033), larger hip circumference (P = 0.033), and were less fit (P = 0.010). To control for interactions among statistical predictors, we also employed multivariate logistic regression models adjusted for age, gender, smoking, BMI, hemoglobin, glucose, HDL/LDL cholesterol, triglycerides, and creatinine. We found that female gender (OR 2.16; 95% CI 1.11-4.17), smoking (OR 1.82; 95% CI, 1.10-3.00), and HDL/LDL cholesterol (OR 0.18; 95% CI 0.034-0.90) were significantly associated with RLS compared with subjects without RLS. RLS was associated with cardiovascular risk factors.
"Although the role of Apolipoprotein A1 in the CNS is not completely understood, it is thought to be important for transport of lipids into the brain . To date, no association has been reported between Apo-A1 and RLS/WED, however, recent studies [40,41] have described a higher prevalence of hypercholesterolemia in RLS/WED subjects. Decreased serum Apo-A1 levels have been linked to increased incidence of cardiovascular disease  which, if the decrease in Apo-A1 that was observed in RLS/WED CSF was reflective of a global Apo-A1 level, this could be related to the increased risk for cardiovascular disease in RLS/WED [4-7]. "
[Show abstract][Hide abstract] ABSTRACT: Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) is a sensorimotor disorder that causes patients to experience overwhelming and distressing sensations in the legs compelling the patient to move their legs to provide relief. The purpose of this study was to determine if biomarkers in the cerebrospinal fluid can distinguish RLS/WED patients from neurological controls.
We obtained CSF samples by lumbar puncture from 5 early-onset RLS/WED patients and 5 controls. We performed 2-dimensional difference in-gel electrophoresis (2D-DIGE). Proteins that were significantly altered were identified by Student's t-test. Protein spots that were differentially expressed (p ≤ 0.05, Av. Ratio ≥ 2.0) between RLS/WED and control CSF samples were identified using MALDI-TOF-MS. Statistical analyses of the validation immunoblot assays were performed using Student's t-test.
In this discovery study we identified 6 candidate CSF protein markers for early-onset RLS/WED. Four proteins (Cystatin C, Lipocalin-type Prostaglandin D2 Synthase, Vitamin D binding Protein, and β-Hemoglobin) were increased and 2 proteins (Apolipoprotein A1 and α-1-acid Glycoprotein) were decreased in RLS/WED patients.
Our results reveal a protein profile in the RLS/WED CSF that is consistent with clinical findings of disruptive sleep, cardiovascular dysfunction and painful symptoms. Moreover, protein profiles are consistent with neuropathological findings of activation of hypoxia inducible factor (HIF) pathways and alterations in dopaminergic systems. These data indicate the CSF of RLS/WED patients may provide information relevant to biological basis for RLS/WED, treatment strategies and potential new treatment targets.
Fluids and Barriers of the CNS 06/2013; 10(1):20. DOI:10.1186/2045-8118-10-20
"As a result, assessing the causal nature between the two is difficult. A majority of studies, however, do show a small yet significant relationship between RLS and obesity.106–113 This relationship has been demonstrated through a significantly greater BMI in those with RLS versus those without,107,113 an increased prevalence of RLS in obese versus nonobese individuals,109,110,112 or an increased prevalence of obesity in RLS versus non-RLS.106,111 "
[Show abstract][Hide abstract] ABSTRACT: Decreased sleep duration and quality is associated with an increase in body weight and adiposity. Insomnia, obstructive sleep apnea, and restless legs syndrome are three of the most prevalent types of sleep disorder that lead to an increased risk for numerous chronic health conditions. Various studies have examined the impact of these sleep disorders on obesity, and are an important link in understanding the relationship between sleep disorders and chronic disease. Physical activity and exercise are important prognostic tools in obesity and chronic disease, and numerous studies have explored the relationship between obesity, sleep disorders, and exercise. As such, this review will examine the relationship between sleep disorders and obesity. In addition, how sleep disorders may impact the exercise response and how exercise may impact patient outcomes with regard to sleep disorders will also be reviewed.
Nature and Science of Sleep 03/2013; 5:27-35. DOI:10.2147/NSS.S34838
"The association, if present, would improve the standard of care for IBS and RLS, and suggest a role of the gastrointestinal disorders in the development of RLS. We also explored the effect of RLS on sleep and mood, and a possible association between RLS and cardiovascular risk or diseases that has been reported by recent studies (Schlesinger et al., 2009; Winkelman et al., 2008). "
[Show abstract][Hide abstract] ABSTRACT: This study aimed to explore the association between restless legs syndrome and irritable bowel syndrome in an epidemiological cohort. We included 3365 adults, of whom 1602 were female (age 52.5 ± 7.5 years), who had participated in the Korean Genome and Epidemiology Study (2005-2006). The diagnosis of restless legs syndrome was based on the criteria proposed by the International Restless Legs Syndrome Study Group, and irritable bowel syndrome was defined according to the Rome II criteria. The prevalence of each condition was determined and their association was tested by logistic regression analysis. Age, sex, haemoglobin concentration, renal insufficiency, use of medications and depressive mood were all adjusted for. The prevalence of restless legs syndrome and irritable bowel syndrome was 4.5 and 11.1%, respectively. Irritable bowel syndrome was more prevalent in the group with restless legs syndrome (24.0 versus 10.5%, P < 0.001). Subjects with restless legs syndrome were older (54.2 ± 8.4 versus 52.4 ± 7.4, P = 0.006) and more depressive (26.7 versus 12.5%, P < 0.001), and were predominantly female (57.3 versus 47.2%, P = 0.015), had more frequent insomnia symptoms (44.0 versus 28.2%, P < 0.001), had lower haemoglobin concentration (13.7 ± 1.5 versus 14.1 ± 1.6 g dL(-1) P = 0.004) and higher highly sensitive C-reactive protein (1.8 ± 5.1 versus 1.4 ± 2.9 mg dL(-1) , P = 0.08). The adjusted odds ratio of restless legs syndrome in relation to irritable bowel syndrome was 2.59 (1.74-3.85, P < 0.001). Irritable bowel syndrome appeared to be associated with restless legs syndrome independently from other major risk factors for restless legs syndrome. Searching for the mechanisms underlying this association is indicated.
Journal of Sleep Research 03/2012; 21(5):569-576. DOI:10.1111/j.1365-2869.2012.01011.x · 3.35 Impact Factor
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