Restless legs syndrome and conditions associated with metabolic dysregulation, sympathoadrenal dysfunction, and cardiovascular disease risk: A systematic review

Kim E. Innesa, b, , , Terry Kit Selfea, b, c, , Parul Agarwala, d, a Department of Community Medicine, West Virginia University School of Medicine, PO Box 9190, Morgantown, WV 26506-9190, USAb Center for the Study of Complementary and Alternative Therapies, University of Virginia Health System, PO Box 800782, McLeod Hall, Charlottesville, VA 22908-0782, USAReceived 1 February 2011. Revised 7 April 2011. Accepted 11 April 2011. Available online 5 July 2011.View full text Restless legs syndrome (RLS) is a distressing sleep and sensorimotor disorder that affects a large percentage of adults in the western industrialized world and is associated with profound reductions in quality of life. However, the etiology of RLS remains incompletely understood. Enhanced understanding regarding both the antecedents and sequelae of RLS could shed new light on the pathogenesis of RLS. Evidence from an emerging body of literature suggests associations between RLS and diabetes, hypertension, obesity, and related conditions linked to sympathetic activation and metabolic dysregulation, raising the possibility that these factors may likewise play a significant role in the development and progression of RLS, and could help explain the recently documented associations between RLS and subsequent cardiovascular disease. However, the relation between RLS and these chronic conditions has received relatively little attention to date, although potential implications for the pathogenesis and treatment of RLS could be considerable. In this paper, we systematically review the recently published literature regarding the association of RLS to cardiovascular disease and related risk factors characterized by sympathoadrenal and metabolic dysregulation, discuss potential underlying mechanisms, and outline some possible directions for future research.

prs.rt("abs_end");Restless legs syndrome; RLS; Ekbom disease; Cardiovascular disease; Hypertension; Diabetes; Impaired glucose tolerance; Obesity; Weight gain; Dyslipidemia; Autonomic dysfunction; HPA axis dysfunction

Figures and tables from this article:

Table 1. Summary table of study characteristics. N = 30 studies (1995-2010).

Abbreviations: CVD = cardiovascular disease; DM = diabetes; DM2 = type 2 diabetes; dx = diagnosis; IGT = impaired glucose tolerance: IRLSSG = international restless legs syndrome study group; Min freq/sev = minimum frequency and/or severity; pts = patients; pts = patients; VA = veterans administration; w/ = with.

View Within ArticleTable 2. Relation of RLS to cardiovascular disease. Summary of study characteristics and findings (N = 15 studies published between 1995 and 2010).

Abbreviations: appt = appointment; ARIC = atherosclerosis risk in communities; BOLD = the burden of obstructive lung diseases study; BP = blood pressure; btwn = between; CAD = Coronary artery disease; CHF = congestive heart failure; CHS = cardiovascular health study; condn = condition; CVD = cardiovascular disease; DM = diabetes mellitus; DM2 = type 2 diabetes; dx = diagnosis; ECA = epidemiologic catchment area; F=female; FBG = fasting blood glucose; FHS = framingham heart study; Freq = frequency; Hgb = hemoglobin; HPFS = health professionals follow-up study; HTN = hypertension; hx = history; ICD = International Classification of Diseases; ICSD = international classification of sleep disorders; IRLS = international RLS study group rating scale; IRLSSG = international restless legs syndrome study group; M = male; MEMO = the memory and morbidity in augsburg elderly study; MI = myocardial infraction; MONICA = monitoring trends and determinants in CVD survey-Augsburg; n’s = numbers; NC-FP-RN = north carolina family practice research network; NHS II = nurses health study II; NSF = national sleep foundation poll; NY cohorts = new york hypertension cohorts; OR = odds ratio (95% Confidence Interval); pt = patient; RLS = restless legs syndrome; SDB = sleep disordered breathing; SHHS = sleep heart health study; SHS = strong heart study; SPAR = the official database covering the total population of Sweden; Sx = symptoms; TG = triglycerides; Tucson cohorts = tucson epidemiologic study of airways obstructive diseases and the health and environment study; tx = treatment; VA = veterans administration; w/ = with; w/o = without.*Calculated from data provided in paper.

View Within ArticleTable 3. Relation of RLS to hypertension: Summary of study characteristics and findings (N = 17 studies published between 1995 and 2010).

Abbreviations: appt = appointment; ARIC = atherosclerosis risk in communities; BOLD = the burden of obstructive lung diseases study; BP = blood pressure; btwn = between; CHF = congestive heart failure; CHS = cardiovascular health study; condn = condition; CVD = cardiovascular disease; DBP = diastolic blood pressure; DM = diabetes mellitus; DM2 = type 2 diabetes; DM1 = type 1 diabetes; dx = diagnosis; ECA = epidemiologic catchment area; F=female; FBG = fasting blood glucose; FHS = framingham heart study; Freq = frequency; Hgb = hemoglobin; HPFS = health professionals follow-up study; HTN = hypertension; hx = history; ICD9CM = international classification of diseases, 9th revision, clinical modification; ICSD = international classification of sleep disorders; IRLS = international RLS study group rating scale; IRLSSG = international restless legs syndrome study group; M = male; MEMO = the memory and morbidity in augsburg elderly study; MI = myocardial infarction; MONICA = monitoring trends and determinants in CVD survey-Augsburg; n’s = numbers; NC-FP-RN = north carolina family practice research network; NHS II = nurses health study II; NSF = national sleep foundation poll; NY cohorts = new york hypertension cohorts; OR = odds ratio (95% Confidence Interval); Pt = patient; RLS = restless legs syndrome; SBP = systolic blood pressure; SDB = Sleep disordered breathing; SHHS = sleep heart health study; SHS = strong heart study; SPAR = the official database covering the total population of Sweden; Sx = symptoms; TG = triglycerides; Tucson cohorts = tucson epidemiologic study of airways obstructive diseases and the health and environment study; tx = treatment; VA = veterans administration; w/ = with; w/in = within; w/o = without.* Calculated from data provided in paper.

View Within ArticleTable 4. Relation of RLS to diabetes and impaired glucose tolerance: Summary of study characteristics and findings (N=26 studies (1995-2010)).

Abbreviations: appt = appointment; ARIC = atherosclerosis risk in communities; BG = blood glucose; BMI = body mass index; BOLD = the burden of obstructive lung diseases study; BP = blood pressure; btwn = between; CHF = congestive heart failure; CHS = cardiovascular health study; condn = condition; CVD = cardiovascular disease; DM = diabetes mellitus; DM1 = type 1 diabetes; DM2 = type 2 diabetes; dx = diagnosis; ECA = epidemiologic catchment area; F=female; FBG = fasting blood glucose; FHS = framingham heart study; Freq = frequency; Hgb = hemoglobin; HOMA = homeostasis model assessment; HPFS = health professionals follow-up study; HTN = hypertension; hx = history; ICD9CM = international classification of diseases, 9th revision, clinical modification; IGT = impaired glucose tolerance; ICSD = international classification of sleep disorders; IGR = impaired glucose regulation; IGT = impaired glucose tolerance; IRLS = international RLS study group rating scale; IRLSSG = international restless legs syndrome study group; M = male; MEMO = the memory and morbidity in augsburg elderly study; MONICA = monitoring trends and determinants in CVD survey-Augsburg; NC-FP-RN = north carolina family practice research network; NHS II = nurses health study II; NSF = national sleep foundation poll; NY cohorts = new york hypertension cohorts; OGTT = oral glucose tolerance test; OR = odds ratio (95% Confidence Interval); pts = patients; RLS = restless legs syndrome; SDB = sleep disordered breathing; SHHS = sleep heart health study; SHS = Strong heart study; SPAR = the official database covering the total population of Sweden; Sx = symptoms; TG = triglycerides; Tucson cohorts = tucson epidemiologic study of airways obstructive diseases and the health and environment study; tx = treatment; VA = veterans administration; w/ = with; w/in = within; w/o = without.*Calculated from data provided in table.

View Within ArticleTable 5. Relation of RLS to obesity, weight gain, and dyslipidemia: Summary of study characteristics and findings (N=18 studies with data on the association of RLS to obesity/weight gain, 7 studies with data on the association of RLS to lipid profiles).

Abbreviations: appt = appointment; ARIC = atherosclerosis risk in communities; BMI = body mass index; BOLD = the burden of obstructive lung diseases study; BP = blood pressure; btwn = between; CHF = congestive heart failure; CHS = cardiovascular health study; condn = condition; CVD = cardiovascular disease; DM = diabetes mellitus; DM1 = type 1 diabetes; DM2 = type 2 diabetes; dx = diagnosis; ECA = epidemiologic catchment area; F=female; FBG = fasting blood glucose; FHS = framingham heart study; Freq = frequency; Hgb = hemoglobin; HPFS = health professionals follow-up study; HTN = hypertension; hx = history; ICSD = international classification of sleep disorders; IRLS = intl RLS study group rating scale; IRLSSG = international restless legs syndrome study group; M = male; MEMO = the memory and morbidity in augsburg elderly study; MI = myocardial infarction; MONICA = Monitoring trends and determinants in CVD survey-Augsburg; NC-FP-RN = north carolina family practice research network; NHS II = nurses health study II; NSF = national sleep foundation poll; NY cohorts = new york hypertension cohorts; OGTT = oral glucose tolerance test; OR = odds ratio (95% confidence interval); RLS = restless legs syndrome; SDB = sleep disordered breathing; SHHS = sleep heart health study; SHS = strong heart study; SPAR = the official database covering the total population of Sweden; Sx = symptoms; TG = triglycerides; Tucson cohorts = tucson epidemiologic study of airways obstructive diseases and the health and environment study; tx = treatment; VA = veterans administration; w/ = with; w/o = without.*Calculated from data provided in paper.

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