title: The relationship among restless legs syndrome (Willis-Ekbom Disease), hypertension, cardiovascular disease, and cerebrovascular disease.
abstract: Untreated sleep disorders may contribute to secondary causes of uncontrolled hypertension, cardiovascular disease (CVD), and stroke. Restless legs syndrome, or Willis-Ekbom Disease (RLS/WED), is a common sensorimotor disorder with a circadian rhythmicity defined by an uncontrollable urge to move the legs that worsens during periods of inactivity or at rest in the evening, often resulting in sleep disruptions. Sleep disorders such as insomnia and obstructive sleep apnea (OSA) are established risk factors for increased risk of hypertension and vascular diseases. This literature review outlines the lessons learned from studies demonstrating insomnia and OSA as risk factors for hypertension and vascular diseases to support the epidemiologic and physiologic evidence suggesting a similar increase in hypertension and vascular disease risk due to RLS. Understanding the relationships between RLS and hypertension, CVD, and stroke has important implications for reducing the risks associated with these diseases.
authors: Sleep Disorders Center, Vita-Salute San Raffaele University, Milan, Italy, ferinistrambi.luigi@hsr.it.
authors: Luigi
authors: L
authors: Ferini-Strambi
authors: Arthur S
authors: AS
authors: Walters
authors: Domenic
authors: D
authors: Sica
mesh_terms: D002318:Cardiovascular Diseases / Q000150:complications*; D002561:Cerebrovascular Disorders / Q000150:complications*; D006801:Humans; D006973:Hypertension / Q000150:complications*; D012148:Restless Legs Syndrome / Q000150:complications*
references: Mov Disord. 2009 Jan 15;24(1):77-84
references: 18816657
references: J Clin Hypertens (Greenwich). 2006 Feb;8(2):93-8
references: 16470077
references: Sleep Med Rev. 2012 Apr;16(2):151-66
references: 21641838
references: Acta Neurol Scand. 2010 Jul;122(1):63-9
references: 19951275
references: Sleep. 2009 Jun;32(6):760-6
references: 19544752
references: Arch Intern Med. 2004 Jan 26;164(2):196-202
references: 14744844
references: Brain. 2009 Sep;132(Pt 9):2403-12
references: 19467991
references: Mov Disord. 2005 Feb;20(2):260-1
references: 15573387
references: Hypertens Res. 2010 Aug;33(8):767-71
references: 20613761
references: Open Neurol J. 2010 Jun 15;4:73-7
references: 20721325
references: Sleep Med. 2006 Oct;7(7):545-52
references: 16740407
references: Neurology. 2009 Apr 7;72(14):1255-61
references: 19349606
references: Sleep Med. 2010 Feb;11(2):161-6
references: 20022805
references: Sleep. 2001 Sep 15;24(6):721-5
references: 11560187
references: Dig Dis Sci. 2010 Jun;55(6):1667-73
references: 19731029
references: Sleep. 1999 Aug 1;22(5):575-80
references: 10450592
references: Psychosom Med. 2004 Nov-Dec;66(6):925-31
references: 15564359
references: Eur Neurol. 2012;67(6):321-5
references: 22555556
references: J Psychosom Res. 2004 May;56(5):497-502
references: 15172205
references: Eur J Neurol. 2011 Nov;18(11):1329-35
references: 21985026
references: Sleep Breath. 2012 Mar;16(1):117-22
references: 21221825
references: Circulation. 2008 Jun 24;117(25):e510-26
references: 18574054
references: Am J Kidney Dis. 2003 Apr;41(4):833-9
references: 12666070
references: Sleep. 2010 Jun;33(6):759-65
references: 20550016
references: J Psychosom Res. 2002 Jul;53(1):547-54
references: 12127170
references: Sleep. 2005 Jan;28(1):147-8
references: 15700730
references: Sleep. 1999 Nov 1;22(7):901-12
references: 10566908
references: Sleep. 2007 Jul;30(7):861-5
references: 17682656
references: Acta Neurol Scand. 2012 May;125(5):319-25
references: 21718253
references: Mov Disord. 1999 Jan;14(1):102-10
references: 9918351
references: Clin Cardiol. 1998 Apr;21(4):271-6
references: 9562937
references: Sleep Med. 2003 Mar;4(2):101-19
references: 14592341
references: Parkinsonism Relat Disord. 2004 Oct;10(7):429-31
references: 15465401
references: Hypertension. 2007 Jan;49(1):69-75
references: 17159087
references: J Hypertens. 2003 Nov;21(11):1983-92
references: 14597836
references: Sleep. 1991 Apr;14(2):163-5
references: 1866530
references: J Clin Sleep Med. 2012 Oct 15;8(5):597-619
references: 23066376
references: Arch Intern Med. 2005 Jun 13;165(11):1286-92
references: 15956009
references: J Am Board Fam Med. 2007 Jul-Aug;20(4):365-74
references: 17615417
references: J Heart Lung Transplant. 2008 Mar;27(3):335-40
references: 18342758
references: PLoS One. 2009;4(2):e4589
references: 19240794
references: Med Hypotheses. 2013 Jan;80(1):39-42
references: 23111202
references: Sleep Med. 2013 Jun;14(6):555-61
references: 23643655
references: Sleep Med Rev. 2012 Aug;16(4):309-39
references: 21733722
references: Neurology. 2005 Jun 14;64(11):1920-4
references: 15955944
references: Circulation. 2007 Jul 3;116(1):32-8
references: 17576871
references: Haematologica. 2010 Feb;95(2):199-205
references: 19815838
references: Chest. 1996 Jun;109(6):1497-502
references: 8769500
references: PLoS Med. 2009 Aug;6(8):e1000132
references: 19688045
references: Psychiatry Clin Neurosci. 2008 Aug;62(4):457-63
references: 18778444
references: J Clin Sleep Med. 2010 Oct 15;6(5):428-30
references: 20957841
references: J Am Coll Cardiol. 2009 Apr 14;53(15):1309-17
references: 19358946
references: Blood Press Monit. 2012 Dec;17(6):231-4
references: 23111555
references: Hypertension. 2011 Nov;58(5):791-6
references: 21986505
references: Nat Genet. 2007 Aug;39(8):1000-6
references: 17637780
references: Neurol Clin. 2012 Nov;30(4):1137-66
references: 23099132
references: Climacteric. 2008 Oct;11(5):422-8
references: 18781488
references: Acta Neurol Belg. 2012 Mar;112(1):27-32
references: 22427286
references: Parkinsonism Relat Disord. 2008;14(2):157-60
references: 17442610
references: Sleep Med. 2010 Oct;11(9):807-15
references: 20817595
references: J Am Coll Cardiol. 2007 Feb 6;49(5):565-71
references: 17276180
references: N Engl J Med. 2000 May 11;342(19):1378-84
references: 10805822
references: Sleep Med. 2010 Dec;11(10):1043-8
references: 20961808
references: Sleep Med. 2011 Jan;12(1):47-55
references: 20851046
references: Sleep Med Rev. 2012 Aug;16(4):341-54
references: 22258033
references: Acta Neurol Belg. 2010 Sep;110(3):284-6
references: 21114142
references: Hypertension. 2003 Dec;42(6):1206-52
references: 14656957
references: Neurology. 2000 Mar 14;54(5):1064-8
references: 10720275
references: J Sleep Res. 2012 Jun;21(3):297-307
references: 21917047
references: Inflamm Bowel Dis. 2005 Aug;11(8):707-12
references: 16043984
references: Mov Disord. 2008 Feb 15;23(3):350-8
references: 18058820
references: J Clin Sleep Med. 2013 Feb 01;9(2):147-53
references: 23372468
references: Sleep. 2006 Sep;29(9):1183-7
references: 17040005
references: Circulation. 2011 Sep 13;124(11):1223-31
references: 21859975
references: BMJ. 2000 Feb 19;320(7233):479-82
references: 10678860
references: Chest. 2008 Mar;133(3):793-804
references: 18321908
references: J Clin Endocrinol Metab. 2004 May;89(5):2119-26
references: 15126529
references: Hypertension. 2007 Nov;50(5):869-76
references: 17893376
references: Sleep. 2008 Sep;31(9):1221-7
references: 18788647
references: Eur J Neurol. 2011 Jan;18(1):144-9
references: 20528909
references: J Epidemiol Community Health. 2006 Jan;60(1):69-73
references: 16361457
references: Neurology. 2007 Apr 10;68(15):1213-8
references: 17420405
references: Circulation. 2011 Aug 30;124(9):1046-58
references: 21824920
references: Arch Intern Med. 2001 Jun 25;161(12):1501-8
references: 11427097
references: Stroke. 2005 Mar;36(3):578-82
references: 15677579
references: Nephrol Dial Transplant. 2002 May;17(5):852-6
references: 11981073
references: Am J Hypertens. 2013 Jan;26(1):83-94
references: 23382331
references: Am J Med. 2013 Mar;126(3):228-35, 235.e1-2
references: 23410563
references: J Sleep Res. 2013 Aug;22(4):434-42
references: 23374090
references: Psychiatry Clin Neurosci. 1997 Jun;51(3):103-7
references: 9225372
references: J Epidemiol. 2013;23(3):158-62
references: 23604062
references: J Am Soc Echocardiogr. 2013 Jul;26(7):783-90
references: 23622883
references: Eur Heart J. 2004 Feb;25(3):260-6
references: 14972428
references: Biochem J. 2007 Jul 1;405(1):1-9
references: 17555402
references: Neurology. 2008 Jan 1;70(1):35-42
references: 18166705
references: Sleep Med. 2011 Jun;12(6):614-9
references: 21570342
references: BMJ. 2010 Jul 26;341:c3666
references: 20660506
references: Am J Respir Crit Care Med. 1998 Jan;157(1):111-5
references: 9445287
references: Neurology. 2006 Jul 11;67(1):125-30
references: 16832090
references: Mov Disord. 2001 Nov;16(6):1159-63
references: 11748753
references: Chronobiol Int. 2013 Mar;30(1-2):31-42
references: 23072288
references: Curr Atheroscler Rep. 2013 Jul;15(7):334
references: 23666861
references: Sleep. 2009 May;32(5):589-97
references: 19480225
references: Indian J Med Res. 2010 Feb;131:126-40
references: 20308738
references: Sleep. 2007 Sep;30(9):1145-52
references: 17910386
references: Tex Heart Inst J. 2011;38(6):643-52
references: 22199424
references: Clin Exp Hypertens. 2009 Nov;31(8):705-12
references: 20001463
references: BMJ Open. 2012 Nov 05;2(6):
references: 23129573
references: PLoS Genet. 2011 Jul;7(7):e1002171
references: 21779176
references: Brain Behav Immun. 2012 Nov;26(8):1239-43
references: 22750520
references: BMJ Open. 2012 Mar 23;2(2):e000866
references: 22447047
references: Am J Med. 2013 Mar;126(3):220-7, 227.e1-2
references: 23410562
references: Chest. 2006 Jan;129(1):76-80
references: 16424415
references: Hypertension. 2006 May;47(5):833-9
references: 16585410
references: Inflamm Bowel Dis. 2004 Sep;10(5):661-5
references: 15472532
references: J Physiol. 2006 Dec 1;577(Pt 2):705-16
references: 16973705
references: Mov Disord. 2003 Nov;18(11):1403-5
references: 14639696
references: Sleep Med. 2011 Jun;12(6):610-3
references: 21570907
references: Sleep. 2011 Nov 01;34(11):1487-92
references: 22043119
references: Sleep Breath. 2009 Mar;13(1):43-7
references: 18592284
references: Handb Clin Neurol. 2011;99:913-48
references: 21056236
references: Hypertension. 2011 Jun;57(6):1076-80
references: 21502568
references: Chest. 2010 Aug;138(2):434-43
references: 20682533
references: J Clin Invest. 1995 Oct;96(4):1897-904
references: 7560081
references: Mov Disord. 2006 Nov;21(11):2027-8
references: 16991156
references: Circulation. 2012 Oct 2;126(14):1689-94
references: 22967852
references: Stroke. 2005 Sep;36(9):1859-63
references: 16081866
references: Int J Hypertens. 2011;2011:605359
references: 22121474
references: Int J Cardiol. 2006 Jan 4;106(1):21-8
references: 16321661
references: Circulation. 2008 Sep 2;118(10):1080-111
references: 18725495
references: Clin Neurophysiol. 2007 Sep;118(9):1923-30
references: 17588809
references: J Appl Physiol (1985). 2009 Oct;107(4):1328-38
references: 19679741
references: Mov Disord. 2011 Jan;26(1):114-20
references: 21322022
references: Sleep. 1992 Dec;15(6):489-92
references: 1475562
references: Neurology. 2013 Jul 2;81(1):52-9
references: 23761622
references: J Clin Sleep Med. 2006 Jul 15;2(3):281-7
references: 17561540
references: Br J Pharmacol. 1998 Jan;123(1):136-42
references: 9484864
references: Sleep Med. 2006 Dec;7(8):642-5
references: 17023211
references: Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20541-6
references: 21059915
references: Inflamm Bowel Dis. 2010 Feb;16(2):275-9
references: 19575360