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CHEST Postgraduate Education Corner CONTEMPORARY REVIEWS IN SLEEP MEDICINE

Sleep and Hypertension

David A. Calhoun, MD; and Susan M. Harding, MD, FCCP

Ambulator !" studies indicate that e#en small increases in !"$ particularl nighttime !" le#els$

are associated with signi%icant increases in cardio#ascular morbidit and mortalit. Accordingl$

sleep&related diseases that induce increases in !" would be anticipated to substantiall a%%ect

cardio#ascular ris'. !oth sleep depri#ation and insomnia ha#e been lin'ed to increases in inci&

dence and pre#alence o% hpertension. (i'ewise$ sleep disruption attributable to restless legs

sndrome increases the li'elihood o% ha#ing hpertension. )bser#ational studies demonstrate

a strong correlation between the se#erit o% obstructi#e sleep apnea *)SA+ and the ris' and

se#erit o% hpertension$ whereas prospecti#e studies o% patients with )SA demonstrate a positi#e

relationship between )SA and ris' o% incident hpertension. ,nter#ention trials with continuous

positi#e airwa pressure *-"A"+ indicate a modest$ but inconsistent e%%ect on !" in patients withse#ere )SA and a greater li'elihood o% bene%it in patients with most -"A" adherence. Additional

prospecti#e studies are needed to reconcile obser#ational studies suggesting that )SA is a strong

ris' %actor %or hpertension with the modest antihpertensi#e e%%ects o% -"A" obser#ed in inter&

#ention studies. CHEST 2010; 138(2 ):434 – 443

Abbre#iations: AHI 5 anea!"#onea inde$% CPAP 5 continuous ositi&e air'a# ressure% OR 5 odds

ratio% OSA 5 o(structi&e s)ee anea% PLMS 5 eriodic )i*( *o&e*ents in s)ee% RLS 5 rest)ess )egs s#ndro*e

)ee a)ters autono*ic ner&ous s#ste* +unction andot"er "#sio)ogic e&ents t"at in+)uence ,P- .ur !

t"er*ore/ s)ee disorders a)ter t"e ,P resonse andincrease "#ertension ris0- Recent data on t"e e++ect

o+ s)ee and s)ee disorders on ,P and "#ertension'i)) (e e$)ored-

S)ee and Nocturna) ,P

During nor*a) s)ee/ t"ere is a decrease in ,P

re)ati&e to 'a0e+u)ness- T"is decrease is re+erred to

as 1nocturna) diing2 and art)# is attri(uta()e to

decreases in s#*at"etic outut- A)t"oug" ar(itrar#/a decrease o+ 34 to 64 in *ean nocturna) ,P

7(ot" s#sto)ic and diasto)ic8 co*ared 'it" *eanda#ti*e ,P is considered nor*a)- Con&erse)#/ ana(sence o+

Manuscrit recei&ed Dece*(er 34/ 6449% re&ision acceted.e(ruar# 39/ 6434-A%%iliations: .ro* t"e Vascu)ar ,io)og# and H#ertension Pro!gra* 7Dr Ca)"oun8/ Di&ision o+ Cardio&ascu)ar Diseases/ andS)ee Wa0e Disorders Center 7Dr Harding8/ Di&ision o+ Pu)*o!nar#/ A))erg# and Critica) Care Medicine/ :ni&ersit# o+ A)a(a*aat ,ir*ing"a*/ ,ir*ing"a*/ AL-Funding Support: T"is stud# 'as +unded (# t"e Nationa) Insti!tutes o+ Hea)t"/ Nationa) Heart/ Lung/ and ,)ood Institute ;5?3@!5/ 1Etio)og# o+ S)ee Anea!Re)ated H#er !a)dosteronis*/2 Da&id A- Ca)"oun/ Princia) In&estigator/ and

Susan M- Harding/ Co!in&estigator-

nocturna) diing/ or nondiing/ is designated as a/ 34 decrease in nocturna) ,P-

Lac0 or di*inis"ed nocturna) diing o+ ,P is astrong/ indeendent redictor o+ cardio&ascu)ar ris0-T"e O"asa*a stud# noted t"at on a&erage/ eac" 5

de+icienc# in t"e nor*a) dec)ine in nocturna) ,P 'asassociated 'it" an aro$i*ate)# 64 greater ris0 in

cardio&ascu)ar *orta)it#-3 Ot"er studies "a&e con!

+ir*ed t"is +inding-6!@ Man# diseases are associated

'it" di*inis"ed or a(sence o+ nocturna) diing/

inc)uding *ost secondar# causes o+ "#ertension/c"ronic 0idne# disease/ dia(etes/ o)der age/ resistant"#ertension/ and o(structi&e s)ee anea 7OSA8-

Large rosecti&e studies "a&e de*onstrated t"at

nocturna) ,P is a (etter redictor o+ cardio&ascu)ar ris0 t"an is da#ti*e ,P- In t"e Du()in Outco*eStud#/5/696 untreated atients 'it" "#ertension re+erredto a sing)e "#ertension c)inic 'ere rosecti&e)#

-orrespondence to: Da&id A- Ca)"oun/ MD/ Di&ision o+ Cardio&ascu)ar Diseases/ :ni&ersit# o+ A)a(a*a at ,ir*ing"a*/35B4 Brd A&e S/ ,ir*ing"a*/ AL B569@!3354% e!*ai) dca)"ounua(-edu 2010 American -ollege o% -hest "hsicians. Reroductiono+ t"is artic)e is ro"i(ited 'it"out 'ritten er*ission +ro* t"eA*erican Co))ege o+ C"est P"#sicians 7''' -c"estu(s-orgsite*iscrerints-$"t*)8-D),: 10.1/chest.0&234

434 Postgraduate Education Corner

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+o))o'ed +or cardio&ascu)ar e&ents-5 During a *edian

+o))o'!u eriod o+ F-@ #ears/ a*(u)ator# ,P *ea!sure*ents 'ere suerior to c)inic ,P *easure*entsin redicting cardio&ascu)ar *orta)it#/ and nig"tti*e,P 'as o&era)) t"e strongest redictor o+ outco*e- Int"is stud#/ a 34!** Hg increase in *ean nig"tti*es#sto)ic ,P 'as associated 'it" a 63 increase in car !dio&ascu)ar *orta)it#- Ot"er studies )i0e'ise "a&e

con+ir*ed t"e sueriorit# o+ nocturna) ,P in redict!ing cardio&ascu)ar outco*es-?/> O(ser&ationa) studiesindicate t"at 'it" aging/ t"e cardio&ascu)ar ris0 attri(uta()e to o++ice s#sto)ic ,P increases/ '"ereas t"eris0 attri(uta()e to diasto)ic ,P decreases- To '"at

e$tent t"is interaction 'it" aging is true o+ nocturna)"#ertension "as not #et (een +u))# e)ucidated-

Poor)# contro))ed "#ertension re*ains a strong

cause o+ cardio&ascu)ar *or(idit# and *orta)it#

'or)d'ide- E&en s*a)) c"anges in *ean ,P trans)ate

into otentia))# )arge decreases in cardio&ascu)ar co*)ications- .or e$a*)e/ data +ro* o(ser&ationa)

studies and rando*iGed tria)s suggest t"at a 6!** Hgreduction in diasto)ic ,P on a ou)ation (asis resu)tsin a 3> decrease in "#ertension re&a)ence/ a? reduction in coronar# "eart disease ris0/ and a

35 reduction in t"e ris0 o+ stro0e and transientisc"e*ic attac0-F A *etaana)#sis o+ rando*iGed tria)s

o+ anti"#ertensi&e *edications s"o'ed t"at a34!** Hg reduction in s#sto)ic ,P or a 5!** Hgreduction in diasto)ic ,P reduces ris0 o+ coronar#"eart disease e&ents (# 66 and stro0e (# @3-9

Ta0en toget"er/ t"ese resu)ts de*onstrate t"ate&en s*a)) c"anges in ,P/ esecia))# nocturna) ,P/

can a)ter cardio&ascu)ar ris0 signi+icant)#-According)#/ disease rocesses re)ated to s)ee t"at*a# a++ect ,P "a&e t"e otentia) to a)ter cardio&ascu)ar *or(idit# and *orta)it# su(stantia))#-

S)ee Duration and H#ertension

Ha(itua) s)ee duration o&er t"e ast 54 #ears "as

decreased (# 3-5 to 6 " da#/ and - B4 o+ A*ericans reort s)eeing )ess t"an ? " nig"t-34 In

t"e S)ee Heart Hea)t" Stud#/ su(ects s)eeing5 " nig"t "ad a "ig"er +reuenc# o+ re&a)ent

"#ertension 7adusted odds ratio ;OR/ 3-??% 95CI/ 3-B5!6-4@8/ a+ter adusting +or *u)ti)econ+ounders-33 T"e W"ite"a)) II Stud# e$a*inedcross!sectiona) and rosecti&e associations o+ s)ee duration 'it" re&! a)ent and incident"#ertension in a co"ort o+ 34/B4F ,ritis" ci&i) ser&ants aged B5 to 55 #ears-36

At (ase)ine/ no association 'as noted in *en%"o'e&er / 'o*en 7n 5 3/5?>8 s)eeing 5 " nig"t"ad a "ig"er ris0 o+ "#ertension co*ared 'it"t"ose s)eeing

> " nig"t 7OR/ 3->6% 95 CI/ 3-4>!6->@% P 5 -4B>8/

inde! endent o+ con+ounders- In t"e rosecti&eana)#sis/ t"e incident "#ertension ris0 'asattenuated a+ter

con+ounding +or cardio&ascu)ar 7OR/ 3-@6% 95 CI/4-9@!6-358 and s#c"iatric 7OR/ 3-B3% 95 CI/ 4-?5!6-?B8 co*or(idities/ e*"asiGing t"e i*ortance o+ e$ten! si&e e&a)uation o+ con+ounders inassessing t"is association-

In t"e +irst Nationa) Hea)t" and Nutrition E$a*i!nation Sur&e# o+ @/F34 *idd)e!aged 7B6!59 #ears8A*ericans in +u))# adusted *ode)s/ s"ort s)ee dura!

tion 7 5 " nig"t8 'as associated 'it" a ?4 "ig"er ris0 o+ se)+!reorted incident "#ertension o&er anF! to 34!#ear +o))o'!u eriod 7"aGard ratio/ 6-34%

95 CI/ 3-5F!6->98-3B No association 'as +ound in

indi&idua)s aged ?4 #ears-S)ee duration and "#ertension *a# not (e

associated in ersons aged - 5F #ears-3@ Int"e5/45F articiants o+ t"e ou)ation!(ased Rotterda*stud#/3@ and a Sanis" rosecti&e co"ort stud# o+ B/?F? ersons/35 no association 'as +ound in re&a!

)ent or incident "#ertension- Note t"at *ost o+ t"ese

cross!sectiona) ou)ation studies use su(ecti&ereorts o+ s)ee duration and not o(ecti&e data/ suc"as t"at o(tained +ro* ro)onged actigra"# *oni!

toring- Su(ecti&e reorts o+ s)ee duration *a# not (e accurate-

T"e association (et'een s"ort s)ee duration and"#ertension aears to (e *ost signi+icant during

*idd)e age- T"e Coronar# Arter# Ris0 De&e)o*entin Young Adu)ts co"ort e$a*ined o(ecti&e s)eeduration (# *easuring B!da# 'rist actigra"# t'ice

(et'een 644B and 6445/ s)ee ua)it#/ 5!#ear inci!dence o+ "#ertension/ and c"anges in s#sto)ic and

diasto)ic ressure in 5>F A*ericans aged BB to@5 #ears at (ase)ine-3? S"ort s)ee duration redictedincreased odds o+ incident "#ertension 7OR/ 3-B>%95 CI/ 3-45!3->F8- Eac" "our o+ reduced s)ee 'asassociated 'it" a B> increase in t"e odds o+ incident "#ertension-

In a sa*)e o+ 6BF ado)escents 'it"out s)ee aneaor se&ere co*or(idities +ro* t"e C)e&e)and C"i)!drenJs S)ee and Heart Stud#/ c"i)dren 'it" s"ort

s)ee duration 7 ?-5 " nig"t8 "ad an adusted OR o+ re"#ertension o+ 6-5@ 795 CI/ 4-9B!?-948-3> .ur !t"er*ore/ oor s)ee e++icienc# 7/ F58 on o&ernig"t

o)#so*nogra"# 'as associated 'it" an a&erageadusted increase in s#sto)ic ,P o+ @ ** Hg/ and t"eodds o+ re"#ertension increased B-5!+o)d 795 CI/3-5!F-48- T"e researc"ers de+ined re"#ertension ass#sto)ic or diasto)ic ,P 94t" ercenti)e +or age/se$/ and "eig"t as noted (# t"e Nationa) Hig" ,)ood

Pressure Education Progra* Wor0ing to F "-33

.ried*an et a)3F assessed t"e re)ations"i (et'eense)+!reorted

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s)ee duration and 6@!" a*(u)ator# ,P *onitoring

in 34F su(ects 'it" nor*a) ,P and @3> su(ects

'it" "#ertension- Assessing (ot" nondiing statusand e)e&ated *orning ,P surge/ a 3!" decrease in s)eeduration 'as associated 'it" nondiing 7nocturna),P +a))/ / 34% OR/ 3-36% P 5 -4@8 'it"out ane)e&ated *orning ,P surge- Ho'e&er/ )ong s)ee

duration 'as associated 'it" a *orning ,P surge

and )ess nondiing-

Inso*nia and H#ertension

Acti&ation o+ t"e "#ot"a)*ic!ituitar#!adrena) a$isand t"e s#*at"etic ner&ous s#ste* as seen in inso*!

nia *a# redisose to "#ertension de&e)o*ent-39

P"i))is and Mannino64 e$a*ined t"e F/>5> artici!

ants in t"e At"erosc)erosis Ris0 in Co**unitiesstud# o&er ? #ears to deter*ine '"et"er t"e#reorted inso*nia at (ase)ine- T"e co*(ination o+ di++icu)t# +a))ing as)ee/ sta#ing as)ee/ and "a&ing

nonrestor ! ati&e s)ee 'as not associated 'it" anincreased ris0 o+ "#ertension% "o'e&er/ articiantsreorting di+! +icu)t# +a))ing as)ee or s)ee continuit#

ro()e*s "ad a s)ig"t)# increased ris0 o+ "#ertension at +o))o'!u 7OR/ 3-6% 95 CI/ 3-4B!3-B8/ e&en a+ter contro)! )ing +or con+ounders/ so/

t"e e++ects are so*e'"at inconsistent-

I+ inso*nia is associated 'it" an increased ris0 o+ "#ertension/ it does not aear to (e t"e case in

o)der adu)ts- In t"e Cardio&ascu)ar Hea)t" Stud#/ a rosecti&e co"ort stud# o+ 3/@39 o)der ersons aged>B #ears at (ase)ine 'it" a ?!#ear +o))o'!u/ inso*nia

co*)aints did not redict incident "#ertension-63Lan+ranc"i et a)66 e$a*ined 3B su(ects 'it"

nor*a) ,P (ut 'it" c"ronic ri*ar# inso*nia

7 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria8 and 3B se$! andage!*atc"ed good s)eeers using 6@!" (eat!to!(eat,P a)ong 'it" e)ectroence"a)ogra"# sectra)ana)#sis- T"e su(! ects 'it" inso*nia "ad "ig"er nig"tti*e s#sto)ic ,P and a decrease in t"e da#!to!nig"t s#sto)ic ,P di! ing co*ared 'it" t"e goods)eeers 7(ot" P 5 -438- Da#ti*e diasto)ic ,P 7 P 5 -468 and nig"tti*e diasto)ic ,P 7 P 5 -438 'ere "ig"er

in t"e su(ects 'it" inso*! nia/ '"ereas t"e da#!to!nig"t diasto)ic ,P diing did not di++er (et'eent"e grous- A (order)ine asso! ciation 7r 5 4-BF% P 5-4F8 'as noted (et'een nig"t! ti*e s#sto)ic ,P ande)ectroence"a)ogra"# acti&it# in t"e ( +reuenc#-

Anot"er con+ounder '"en e$a*ining t"e associa!tion (et'een inso*nia and "#ertension ris0 is t"atinso*nia can )ead to s"ort s)ee duration/ and s"ort

s)ee duration a++ects "#ertension ris0- VgontGaset a)6B e$a*ined t"e oint e++ect o+ inso*nia ando(ecti&e s"ort s)ee duration on "#ertension in across!sectiona)/ ou)ation!(ased sa*)e o+ 3/>@3

rando*)# se)ected adu)ts +ro* Penns#)&ania- Inso*!

nia 'as associated 'it" a signi+icant)# "ig"er ris0 +or

"#ertension and '"en con+ounding &aria()es 'ereadusted +or 7OR/ 6-@3% 95 CI/ 3-?!B->% P / -458- A s)ee duration o+ 5 " increased"#ertension ris0 7OR/ 3-5?% 95 CI/ 3-3!6-3% P / -458 co*ared 'it" t"e grou s)eeing K ? "-:sing )ogistic regression ana)#sis/ t"e# e$a*ined

t"e oint e++ect o+ inso*nia and o(ecti&e s)eeduration on "#ertension- T"e resence o+ (ot"inso*nia and an o(ecti&e s)ee duration o+ 5" increased "#ertension ris0 7OR/ 5-36% 95CI/ 6-6!33-F8 co*ared 'it" s)eeing- ? "- On t"e (asis o+ t"ese +indings/aro$i*ate)#

54 o+ ersons 'it" c"ronic inso*nia run asigni+icant ris0 +or "#ertension- Additiona))#/contro))ing +or t"e resence o+ deression did notdi*inis" t"e associa! tion- T"ese data need to (eta0en serious)# (ecause t"e# are +ro* t"e +irst )arge

ou)ation!(ased stud# e$a*ining o)#so*nogra"ic&aria()es )in0ing inso*! nia 'it" s"ort s)ee

duration and "#ertension-39

Note t"at articiants 'it" inso*nia '"o s)et - ? "did not s"o' an increased ris0 +or "#ertension co*!

ared 'it" contro) su(ects-

Rest)ess Legs S#ndro*e and Periodic Li*(Mo&e*ents in S)ee and H#ertension

Eide*io)ogic studies "a&e suggested t"at a re)a!tions"i *a# e$ist (et'een se)+!reorted rest)ess )egs

s#ndro*e 7RLS8 and "#ertension-6@ O"a#on andRot"65 e$a*ined RLS re&a)ence in a cross!sectiona)

ou)ation stud# o+ 3F/9F4 su(ects aged 35 #earsin +i&e Euroean countries t"roug" a te)e"one inter !&ie'- H#ertension 7treated or untreated8 'assigni+! icant)# associated 'it" RLS 7 P / -4438and *ade an indeendent signi+icant contri(utionto RLS 7OR/ 3-B?% 95 CI/ 3-3@!3-?3% P / -4438

(ut not to eriodic )i*( *o&e*ents in s)ee7PLMS8-65 O+ note/ t"e diagnosis o+ PLMS 'as not*ade (# o)#so*nog! ra"# (ut (# t"e &a)idatedS)ee!EVAL s#ste* ues! tionnaire/ '"ic" "as a 0

+or diagnosing PLMS o+ 4-F@-65 Li0e'ise/ P"i))is et a)6? e$a*ined RLS re&a!

)ence and corre)ates as art o+ t"e 6445 Nationa)

S)ee .oundation Po))/ a te)e"one inter&ie' o+ 3/54?

rando*)# se)ected adu)ts in t"e :nited States-

H#ertension 'as associated 'it" RLS 7 P / -458- :)+(erg et a)6> e$a*ined (# uestionnaire arando* ou)ation sa*)e o+ @/444 *en )i&ing incentra) S'eden/ +inding t"at su(ects 'it"reorted RLS s#*to*s *ore +reuent)# reorted"#ertension 7OR/ 3-35% 95 CI/ 4-9!6-@8- E$a*iningt"e B/@BB *en and 'o*en enro))ed in t"e S)eeHeart Hea)t" Stud#/ Win0e)*an et a)6F a)sonoted on)# a 'ea0 association o+ RLS 'it""#ertension 7OR/ 3-B4%

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CI/ 4-96!3-F68 after adusting +or age/ se$/ race/ and ,MI-


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Ho'e&er/ con+)icting data co*e +ro* t"ree ou)ation! (ased studies t"at assessed (ot" re&a)ence o+ and ris0 +actors +or RLS one in ane)der)# ou)ation o+ >B3 su(ects in nort"ern Ita)#/ anot"er o+ >43 su(ects

+ro* t"e genera) co**unit# in Austria/ and a t"irdo+ 6/F63 su(ects +ro* t"e Wisconsin S)ee Co"ortStud#-69!B3 T"ese studies did not +ind an association

(et'een RLS and "#ertension- Potentia))#/ t"e ageo+ t"e stud# articiants enro))ed in t"ese co"orts*a# (e an i*ortant con+ounding +actor- T"is os!

si()e association needs +urt"er care+u) stud# (e+orede+initi&e conc)usions can (e *ade-

PLMS a)so *a# (e associated 'it" "#ertension/'it" *o&e*ents te*ora))# associated 'it" s#*!

at"etic acti&ation-6@ Pennestri et a)B6 e$a*ined t"ete*ora) association (et'een PLMS and (eat!to!

(eat ,P *onitoring in 34 atients 'it" RLS under !going o)#so*nogra"#- :sing a 65!(eat te*ora)

'indo' co*rising 34 (eats (e+ore and 35 (eats

a+ter onset o+ eac" *o&e*ent/ s#sto)ic ,P increased66 ** Hg and diasto)ic ,P increased 33 ** Hg in

association 'it" PLMS- .urt"er*ore/ t"e ,Presonse +or PLMS associated 'it" *icroarousa)s

'ere greater t"an PLMS not associated 'it"arousa)s 7 P / -458- T"is ,P resonse a)so 'asgreater 'it" increasing age 7s#sto)ic r 5 4->?% P 5 -468 and duration o+ RLS s#*to*s 7s#sto)ic r 54->?% P 5 -468- Anot"er in&esti! gation using a si*i)ar stud# design con+ir*ed t"ese +indings in eig"tsu(ects 'it" RLS-BB PLMS during 'a0e+u)ness 'asassociated 'it" a s#sto)ic ,P e)e&a! tion o+ 33-> ?

>-? ** Hg- PLMS associated 'it" *icroarousa)sduring s)ee 'ere associated 'it" a s#sto)ic ,Pe)e&ation o+ 3?-> ? 9-@ ** Hg/ and in PLMS notassociated 'it" an arousa)/ t"e s#sto)ic ,P increased33-6 ? F-> ** Hg- .a0e PLMS during'a0e+u)ness ser&ed as anot"er contro) and 'as associ!ated 'it" a *ean s#sto)ic ,P increase o+ B-6 ? B-3** Hg- T"ese resu)ts con+ir* t"at indi&idua)*o&e*ents are associated 'it" signi+icant e)e&ations

o+ s#sto)ic and diasto)ic ,P/ and t"ese e)e&ationsare greater i+ t"e PLMS is associated 'it" a cortica)arousa)-

Data are e*erging t"at )oo0 at PLMS and "#er !tension- A recent stud# a(stract reorted t"at in anIce)andic co"ort o+ F?3 su(ects enric"ed +or RLS

and o(ecti&e)# *onitored +or PLMS/ "#erten!sion )i0e)i"ood increased 'it" PLMS se&erit#-B@ .or instance/ "#ertension ris0 'as t'ice as "ig" +or aPLMS inde$ - B4 7OR/ 6-6?% 95 CI/ 3-6F!B-998/e&en a+ter contro))ing +or con+ounders-

OSA and Pre&a)ence o+ H#ertension

OSA and "#ertension co**on)# coe$ist- Aro$!

i*ate)# 54 o+ atients 'it" OSA are "#ertensi&e/and an esti*ated B4 to @4 o+ atients 'it" "#er !

tension "a&e OSA-B5!BF Cross!sectiona) studies "a&e (een

consistent in de*onstrating t"at *oderate!se&ereOSA 7anea!"#onea inde$ ;AHI - 35 e&ents "8

is signi+icant)# associated 'it" ris0 o+ "a&ing arteria)"#ertension-B> In genera)/ t"ere is a )inear re)ation!s"i (et'een AHI and re&a)ence and se&erit# o+ "#ertension/ t"at is/ t"e *ore se&ere t"e OSA/t"e "ig"er t"e ris0 o+ "#ertension o+ increasingse&erit#-

In t'o studies/ 4 #ears and 'it" an AHI 35 "ad an OR +or "#er !tension ris0 o+ 6-6F 795 CI/ 4-96!5-??8/ a+ter adust!

ing +or con+ounders suc" as ,MI/ nec0 circu*+er !ence/ and a)co"o) use-@5 In t"is ana)#sis/ an increase int"e AHI o+ 5 e&ents " increased t"e ris0 o+ "a&ing

"#ertension (# 3-65- In t"e S)ee Heart Hea)t"Stud#/ '"ic" inc)uded ?/36B su(ects aged - @4#ears/ an AHI B4 co*ared 'it" / 3-5 'as

associated 'it" an OR +or re&a)ent"#ertension o+ 3-B> 795 CI/ 3-4B!3-FB8-@? T"esedata de*onstrate t"at t"e resence o+ *oderate!se&ere OSA is ositi&e)# re)ated to (ot" t"e

re&a)ence and t"e se&erit# o+ "#ertension-

OSA and Ris of !ncident H"#ertension

T'o )arge o(ser&ationa) )ongitudina) studies

assessed t"e re)ations"i (et'een OSA se&erit# andsu(seuent ris0 o+ incident "#ertension in nor*o!tensi&e co"orts at (ase)ine- In t"e Wisconsin S)ee

Co"ort Stud#/ Peard et a)@>/@F +o))o'ed >49 su(ects

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'it" nor*a) ,P +or @ #ears a+ter e&a)uation (# o&er !nig"t o)#so*nogra"#- Su(ects 'it" *oderate!se&ere OSA 7AHI 35 e&ents "8 "ad a B-6!+o)dincreased odds o+ de&e)oing "#ertension re)ati&e

to su(ects 'it"out OSA- In contrast/ resu)ts +ro*

t"e recent S)ee Heart Hea)t" Stud# ana)#sis o+ 6/@>4 su(ects 'it" nor*a) ,P at 5!#ear +o))o'!unoted no increased ris0 o+ incident "#ertension/ e&en

in atients 'it" se&ere OSA 7AHI 358/ a+ter adust!ing +or ,MI-@9 T"ese disarate resu)ts *a# (e re)atedto *et"odo)ogica) di++erences/ inc)uding di++erencesin t"e co"ort siGe and di&ersit#-54 .or e$a*)e/ artic!iants in t"e S)ee Heart Hea)t" Stud# 'ere/ ona&erage/ considera()# o)der t"an articiants in t"eWisconsin S)ee Co"ort Stud# 7?4 #ears &s @> #ears/resecti&e)#8 and/ t"ere+ore/ er"as not as sensiti&e

to "#ertensi&e e++ects o+ untreated OSA- In addition/

t"e o(ser&ed ris0 *a# "a&e (een ()unted (ecause (ot" studies se)ected atients 'it" nor*a) ,P at (ase)ine desite "a&ing OSA- T"at is/ atients 'it"

OSA at "ig"est ris0 o+ de&e)oing "#ertension*a# "a&e (een e$c)uded (ecause t"e# 'ere a)read#

"#erten! si&e at t"e start o+ t"e stud#/ '"erease)igi()e su(ects '"o re*ained nor*otensi&e 'ere

so*e"o' *ore resistant to t"e "#ertensi&e e++ectso+ OSA- None! t"e)ess/ a)t"oug" t"e )ongitudina)resu)ts o+ t"e Wis! consin S)ee Co"ort Stud# areconsistent 'it" t"e )arge (od# o+ o(ser&ationa)e&idence )in0ing OSA to ris0 o+ "a&ing "#ertension/additiona) rosecti&e studies are needed toreconci)e t"ose ositi&e resu)ts 'it" t"e negati&eresu)ts o+ t"e S)ee Heart Hea)t" Stud#-

Effect of Continuous Positive Air$a" Pressure on %P

I+ OSA contri(utes to "#ertension de&e)o*ent

or rogression/ t"en e++ecti&e OSA treat*ent 'it"

continuous ositi&e air'a# ressure 7CPAP8 s"ou)d

)o'er ,P- Ho'e&er/ reorts are con+)icting- T"is

)ac0 o+ a consistent treat*ent e++ect *a# (e re)atedto *u)ti)e &aria()es/ inc)uding di++erences in stud#

design/ t#e and siGe o+ co"orts/ degree o+ CPAPco*)iance/ treat*ent duration/ and accurac# o+ ,Passess*ents-BF

Recent)#/ +our *etaana)#ses o+ rando*iGed con!

tro))ed tria)s on CPAP use "a&e (een u()is"ed 7Ta()e38- ,aGGano et a)53 ana)#Ged 3? rando*iGed c)inica)

tria)s u()is"ed (et'een 39F4 and 644?/reresentingF3F articiants/ t"at co*ared articiants treated'it" CPAP 'it" contro) su(ects/ t"at "ad a *ini*u*treat*ent duration o+ 6 'ee0s/ and t"at reorted ,Pc"anges during t"e inter&ention and contro) eriod-Mean net c"ange in s#sto)ic ,P +or articiantstreated 'it" CPAP &s contro) su(ects 'as 66-@?** Hg 795 CI/ 6@-B3 to 64-?6 ** Hg8% *eannet c"ange in diasto)ic ,P/ 63-FB ** Hg 795CI/ 6B-45 to64-?3 ** Hg8% and *ean net c"ange in *ean

arteria) ressure/ 66-66 ** Hg 795 CI/ 6@-BF to64-45 ** Hg8- T"e aut"ors conc)uded t"at t"eir ana)#sis ro&ided e&idence t"at e++ecti&e CPAP treat!*ent reduces ,P-

A)a*i et a)56 identi+ied 34 rando*iGed contro))ed

tria)s u t"roug" u)# 644? t"at inc)uded an aro!

riate contro) grou and reorted s#sto)ic and dia!

sto)ic ,P (e+ore and a+ter CPAP treat*ent and acon! tro) condition% data +ro* 5F> su(ects 'ereinc)uded- O&era))/ t"e e++ects o+ CPAP 'ere*odest and not signi+icant- CPAP treat*entco*ared 'it" t"e con! tro) condition reduced

s#sto)ic ,P (# 3-BF ** Hg 795 CI/ B-? to 64-FF** Hg8 and diasto)ic ,P (#3-56 ** Hg 795 CI/ B-3 to 64-4> ** Hg8- Reduc!

tions in ,P tended to (e )arger in atients 'it" se&ere

OSA 7AHI - B48/ and a trend +or s#sto)ic ,Preduc! tion 'as associated 'it" "ig"er CPAPad"erence-

Mo and He5B ana)#Ged rando*iGed contro))ed tria)s u()is"ed (et'een 6444 and 644?- Inc)usion criteria

inc)uded a treat*ent duration o+ @ 'ee0s and

5able 16 Summary of Metaanalyses of Ranom!"e Controlle Tr!als of Cont!nuous #os!t!$e %!r&ay #ressure 'se

Re+erence No- o+ Tria)s 7Patients8 ,P End Point Mini*u* CPAP Duration/ '0 Outco*e

,aGGano et a)53 3? 7F3F8 O++ice a*(u)ator# 6 S,P =6-@? ** Hg

D,P =3-FB ** Hg

More (ene+it in atients 'it" "ig"er (ase)ine

,P/ "ig"er ,MI/ and *ore se&ere OSAA)aH*i et a)56 34 75F>8 O++ice a*(u)ator# @ S,P =3-BF ** Hg 7not signi+icant8

D,P =3-56 ** Hg 7not signi+icant8

More (ene+it in *ore se&ere OSA% trend

+or (etter S,P reduction 'it" (etter CPAP

ad"erence

Mo and He5B > 7@>38 A*(u)ator# @ 6@!" S,P =4-95 ** Hg 7not signi+icant8

6@!" D,P =3->F ** Hg

Haentens et a)5@

36 75>68 A*(u)ator# 3 6@!" S,P =3-?@ ** Hg6@!" D,P =3-@F ** Hg

More (ene+it in *ore se&ere OSA and 'it"

(etter CPAP ad"erence

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CPAP5 continuous ositi&e air'a# ressure% D,P 5 diasto)ic ,P% OSA 5 o(structi&e s)ee anea% S,P 5 s#sto)ic ,P-


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*easure*ent o+ 6@!" a*(u)ator# ,P (e+ore and a+ter CPAP and non!CPAP treat*ent- Se&en studies 'it"

@>3 articiants 'ere inc)uded- O&era))/ CPAPreduced 6@!" s#sto)ic ,P (# 4-95 ** Hg 795 CI/66-F5!4-9@ ** Hg8/ 6@!" diasto)ic ,P (# 3->F **Hg 795 CI/ 6B-B@ to 64-66 ** Hg8/ and 6@!"*ean ,P (# 3-65 ** Hg 795 CI/ 6@-44!3-@9 **Hg8- T"e o&era)) treat*ent e++ects 'ere *odest and

signi+icant on)# +or 6@!" diasto)ic ,P-Haentens et a)5@ a)so )i*ited t"eir ana)#sis to

studies t"at "ad *easured 6@!" a*(u)ator# ,P/ '"ic"inc)uded 5>6 articiants +ro* 36 rando*iGed )ace(o!

contro))ed tria)s- T"e CPAP treat*ent conditionco*ared 'it" )ace(o reduced 6@!" s#sto)ic ,P (#3-?@ ** Hg 795 CI/ 66-?> to 64-?4 ** Hg8 and6@!" diasto)ic ,P (# 3-@F ** Hg 795 CI/ 66-3F to

64->F ** Hg8- T"e e++ect siGe 'as )arger +or da#!ti*e ,P/ 'it" on)# t"e c"ange in *ean ands#sto)ic ,P (eing signi+icant at nig"tti*e- In a

reseci+ied *etaregression ana)#sis/ greater CPAP

treat*ent! re)ated reduction in 6@!" *ean ,P 'aso(ser&ed in articiants 'it" *ore se&ere OSA andin t"ose 'it" t"e *ost CPAP ad"erence-

O&era))/ t"ese +our *etaana)#ses indicate/ at (est/ a

*odest anti"#ertensi&e e++ect o+ CPAP- T"ere ise&idence t"at indi&idua) &ariation in atients 'it" *orese&ere OSA and atients *ost ad"erent 'it" CPAPuse *ani+est greater (ene+it/ (ut t"is o&era)) s*a))treat*ent e++ect raises t"e uestion o+ '"# e++ecti&euse o+ CPAP does not )o'er ,P (etter- E&en s*a))reductions in ,P can resu)t in su(stantia) reductions in

cardio&ascu)ar ris0 suc" t"at s*a)) o(ser&ed e++ects

s"ou)d not (e discounted- W"# t"e treat*ent e++ects/"o'e&er/ are not )arger is an i*ortant c)inica) ues!

tion t"at at t"is oint re*ains an area o+ conecture-

A)t"oug" *u)ti)e ossi()e e$)anations need e$)ora!tion/ t'o issues *a# (e articu)ar)# re)e&ant- T"e +irstis t"e )e&e) o+ CPAP ad"erence needed to o(tain*a$! i*u* &ascu)ar and "e*od#na*ic (ene+it-Ad"erence 'it" CPAP use o+ten is )o'/ articu)ar)#in )ess s#*! to*atic atients- E&en in c)inica) tria)s/

CPAP ad"er ! ence o+ten "as a&eraged / @ to 5 "nig"t/5B *eaningt"at *an# atients are untreated +or se&era) "ours a

nig"t- It *a# (e t"at 'it" +u))!nig"t CPAP treat*entt"ere is a *ore!ronounced ,P e++ect- Data suggestt"at atients '"o are *ost ad"erent 'it" CPAP use

*ani+est t"e )argest decrease in ,P-5@

T"e ot"er consideration is t"e duration o+ treat!*ent- Most o+ t"e rando*iGed c)inica) tria)s o+ CPAP"a&e (een s"ort/ usua))# 36 'ee0s in duration-5@

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Ot"er at"o"#sio)ogic *ec"anis*s/ inc)uding

roin+)a**ator# *ediator e++ects/ increased o$ida!ti&e stress/ and increased &ascu)ar sti++ness a)so *a#

)a# a ro)e 7.ig 38- S*a)) CPAP inter&ention tria)ssuggest t"at eac" o+ t"ese e++ects can (e reduced'it" e++ec! ti&e CPAP use/ o+ten uite raid)#-5>!?3

OSA and Resistant H"#ertension

OSA is co**on in atients 'it" resistant "#er !tension/ '"ic" is de+ined as ,P t"at re*ains uncon!

tro))ed 'it" t"ree or *ore *edications- In a ro!

secti&e e&a)uation o+ @3 atients 'it" resistant"#ertension/ Logan et a)?6 +ound t"at 9? o+ t"e*en and ?5 o+ t"e 'o*en "ad signi+icant OSA7AHI 34 e&ents "8- In >3 consecuti&e su(ects

re+erred to t"e "#ertension c)inic at t"e :ni&ersit#o+ A)a(a*a at ,ir*ing"a* +or resistant "#erten!sion/ 'e +ound t"at 94 o+ t"e *en and >> o+ t"e 'o*en "ad OSA 7AHI - 5 e&ents "8-?B AsOSA se&erit# increases/ t"ere is an increasedneed +or additiona) ,P *edications% t"at is/ t"e *orese&ere t"e OSA/ t"e )ess )i0e)# ,P is contro))ed 'it" "ar*aco! )ogic t"era#-?@!?> A rosecti&e/ (utuncontro))ed CPAP tria) de*onstrated t"at CPAP usecan "a&e su(stantia) anti"#ertensi&e (ene+it in

atients 'it" resistant "#ertension- Logan et a)?F

reorted t"at CPAP use a+ter 6!*ont" +o))o'!u in33 atients 'it" resistant "#ertension )o'erednig"tti*e s#sto)ic ,P (#3@-@? @-@ ** Hg and diasto)ic ,P (# >-F ? B-4 **

Hg- T"e e$)anation o+ t"e e$traordinari)# "ig" re&a! )ence o+ OSA in atients 'it" resistant"#ertension re*ains o(scure- Data +ro* our

)a(orator#/ "o'e&er / suggest t"at it *a# (e )in0ed tot"e "ig" occurrence

.igure 6- P)as*a a)dosterone concentration ositi&e)#corre)ates 'it" anea!"#onea inde$ and "#o$ic inde$ in

atients 'it" o(structi&e s)ee anea and resistant "#ertension-AHI 5 anea! "#onea inde$% HI 5 "#o$ic inde$% PAC 5

)as*a a)dosterone concentration- Rerinted 'it" er*ission+ro* Pratt!:(una*a et a)-?@

o+ "#era)dosteronis* in atients 'it" resistant"#ertension- In an e&a)uation o+ 33@ atients 'it"resistant "#ertension/ 'e +ound t"at atients at "ig"

ris0 +or OSA 7(ased on t"eir resonses to t"e ,er)inuestionnaire8 "ad signi+icant)# greater 6@!" urinar#e$cretion o+ a)dosterone and 'ere a)*ost t'ice as)i0e)# to (e diagnosed 'it" ri*ar# a)dosteronis*

co*ared 'it" contro) su(ects 'it" resistant "#er !tension '"o 'ere at )o' ris0 +or OSA-?B In a su(se!

uent stud#/ 'e reorted t"at )as*a a)dosterone)e&e)s in atients 'it" resistant "#ertension are os!iti&e)# corre)ated 'it" se&erit# o+ OSA 7AHI and "#!o$ic inde$8/ t"at is/ t"e "ig"er t"e )as*a a)dosterone)e&e) t"e *ore se&ere t"e OSA 7.ig 68-?@

We "#ot"esiGe t"at t"e ositi&e corre)ation

(et'een a)dosterone )e&e)s and increasing se&erit#o+ OSA in atients 'it" resistant "#ertension issecondar# to

.igure B- E++ects o+ F 'ee0s o+ treat*ent 'it" sirono)actone on anea!"#onea inde$ 7AHI8% "#!o$ic inde$% suine AHI% and raid e#e *o&e*ent s)ee AHI at F 'ee0s 7)ig"t gra# (ars8 co*ared'it" (ase)ine 7dar0 gra# (ars8 in atients 'it" resistant "#ertension- REM5 raid e#e *o&e*ent-See .igure 6 )egend +or e$ansion o+ ot"er a((re&iations- Di++erent co*ared 'it" (ase)ine 7 P

/

-458- Rerinted 'it" er*ission +ro* 3


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a)dosterone!induced +)uid retention t"at )eads to an

increase in uer air'a# resistance due to greater ara"ar#ngea) ede*a- Suc" an increase in uer air !'a# resistance attri(uta()e to increases in intra&ascu)ar +)uid e$ansion "as (een descri(ed in "ea)t"# &o)un!teers su(ected to acute )o'er!(od# ositi&e

ressure-?9

In addition/ decreases in air'a# resistance and associ!

ated i*ro&e*ents in se&erit# o+ OSA are o(ser&edin atients acute)# diuresed +or e$acer(ations o+ conges! ti&e "eart +ai)ure->4 We (e)ie&e it )i0e)# t"att"e sa*e is occurring in atients 'it" resistant"#ertension (ut c"ronica))#% t"at is/ ersistentintra&ascu)ar +)uid reten! tion 'orsens OSA t"roug"increased uer air'a# resistance due to increased

ara"ar#ngea) ede*a- I+ so/ e++ecti&e diuresis/ articu)ar)# 'it" use o+ a)do! sterone antagonists/'ou)d (e e$ected to )essen t"e se&erit# o+ OSA in

atients 'it" resistant "#ertension- Suort +or suc"an e++ect is ro&ided (# a recent)# co*)eted stud#

in '"ic" 'e o(ser&ed an a)*ost54 reduction in OSA se&erit# in atients 'it" resis!tant "#ertension '"o 'ere treated 'it" sirono)ac!tone +or B *ont"s 7.ig B8->3 Not 0no'n at t"is oint

is '"et"er t"e sa*e (ene+it cou)d (e ac"ie&ed 'it"

ot"er t#es o+ diuretics-

Conc)usion

,P decreases during s)ee/ and reduced diingo+ ,P during s)ee increases cardio&ascu)ar ris0-Ha(itua) s"ort s)ee duration is associated 'it" "#er !

tension/ esecia))# during *idd)e age- Inso*nia 'it"o(ecti&e s"ort s)ee duration a)so is associated 'it"

increased "#ertension ris0- RLS "as a 'ea0 associa!tion 'it" "#ertension% "o'e&er/ PLMS increases

,P/ esecia))# '"en associated 'it" arousa)s-Moderate to se&ere OSA is associated 'it"

re&a)ent "#ertension% "o'e&er/ t"ere arecon+)icting resu)ts e$a*ining incident "#ertension-

Metaana)#ses s"o' t"at CPAP use reduces s#sto)icand diasto)ic ,P on)# *odest)#- OSA is resent in uto 94 o+ atients 'it" resistant "#ertension/ anddata suggest t"at it *a# (e )in0ed to

"#era)dosteronis*- More researc" is needed todeter*ine to '"at degree increased s)ee duration or treating s)ee disorders a++ects ,P-

Ac0no')edg*ents

Financial/non%inancial disclosures: T"e aut"ors "a&e reortedto CHES( t"at no otentia) con+)icts o+ interest e$ist 'it" an#co*aniesorganiGations '"ose roducts or ser&ices *a# (e dis!cussed in t"is artic)e-)ther contributions: We t"an0 Arren rando*ised tria)s in t"e conte$t o+ e$ecta!

tions +ro* rosecti&e eide*io)ogica) studies- %M) - 6449%

BBF7393836@5!365B-

34- Nationa) Center +or Hea)t" Statistics- uic0StatsPercentage o+ adu)ts '"o reorted an a&erage o+ ? "ours

o+ s)ee er 6@!"our eriod/ (# se$ and age grou ! :nited States/ 39F5

and 644@- MM*R Mor+ Mortal *l" Re#- 6445%5@7B>89BB-

33- %547@8?9B!>44- ;Erratu* H#ertension 644>%54758 e3>4-3B-

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Slee#- 6449%B67@8@@3!@@6-



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air'a# ressure treat*ent on o$idati&e stress and adionectin)e&e)s in o(ese atients 'it" o(structi&e s)ee anea-

Res#iration-

6434%>9758B>4!B>?-

59- P"i))is CL/ Yang / Wi))ia*s A/ et a)- T"e e++ect o+ s"ort!

ter* 'it"dra'a) +ro* continuous ositi&e air'a# ressure

t"era# on s#*at"etic acti&it# and *ar0ers o+ &ascu!

)ar in+)a**ation in su(ects 'it" o(structi&e s)ee anoea-

) Slee# Res- 644>%3?76863>!665-

?4- Drager L./ ,orto)otto LA/ .igueiredo AC/ rieger EM/

LorenGi 9!?F5-

??- La&ie P/ Ho++stein V- S)ee anea s#ndro*e a ossi()e

con! tri(uting +actor to resistant- Slee#- 6443%6@7?8>63!>65-

?>- E)ias RM/ Castro MCM/ de ueiroG EL/ A(ensur H/ Ro*Zo

E r/ LorenGi!.i)"o %

3B6768@@4!@@?-

>3-

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