Association Between Sleep Apnea, Sleep Duration, and Serum Lipid Profile in an Urban, Male, Working Population in Japan

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1 CHEST Original Rsarh Assoiation Btwn Slp Apna, Slp Duration, an Srum Lipi Profil in an Urban, Mal, Working Population in Japan SLEEP DISORDERS Yoshiro Toyama, MD ; Kazuo Chin, MD, PhD ; Yuihi Chihara, MD, PhD ; Misa Takgami, RN, MP ; Kn-ihi Takahashi, MD, PhD ; Knsuk Sumi, MD, PhD ; Takaya Nakamura, MD, PhD ; Yukiyo Nakayama-Ashia, MEng ; Itsunari Minami, PhD ; Sahiko Horita, RN, MN ; Yasunori Oka, MD ; Tomoko Wakamura, PhD, RN ; Shun-ihi Fukuhara, MD ; Mihiaki Mishima, MD, PhD ; an Hiroshi Kaotani, MD, PhD Bakgroun: Dyslipimia is oftn omorbi with obstrutiv slp apna (OSA), but fw populationbas stuis hav invstigat thir rlationship. Short slp uration is assoiat with hyprtnsion an iabts; howvr, its assoiation with yslipimia is not wll known. W invstigat rlationships among OSA, slp uration, an th lipi profil in a ommunity-bas stuy. Mthos: W masur th rspiratory isturban inx (RDI) an slp uration by a typ 3 portabl vi an atigraph in 275 mn in a Japans ompany. Fasting bloo paramtrs wr obtain from prioi insption ata. Rsults: Aoring to Japans ritria, 143 subjts ha yslipimia. Prnt slp tim of oxygn saturation as masur by puls oximtry (Sp O 2 ), 90% an prvaln of svr OSA wr gratr an slp uration an man Sp O 2 uring slp wr lowr in subjts with yslipimia than in thos without. Univariat analysis show that th RDI was positivly orrlat with srum triglyri (TG) lvls ( r , P,.01), an slp uration was ngativly orrlat with srum total holstrol (TC) lvls ( g , P 5.03) an srum low-nsity lipoprotin holstrol lvls ( g , P 5.04). Stpwis multipl rgrssion analysis rval that TG was orrlat with RDI ( b , P 5.02), BMI ( b , P,.01), an alohol intak ( b , P,.01), an that TC was orrlat with slp uration ( b , P 5.03), ag ( b , P 5.02), an waist/hip ratio ( b , P 5.02). Conlusions: Short slp uration was assoiat with TC lvls an RDI was positivly assoiat with TG lvls among working-ag mn in an urban Japans ompany. Corrting th status of OSA an/or short slp uration might improv th lipi profil an ariovasular onsquns. CHEST 2013; 143(3): Abbrviations: CVD 5 ariovasular isas; DL 5 yslipimia; DM 5 iabts mllitus; ESS 5 Epworth slpinss sal; FBG 5 fasting bloo gluos; FFA 5 fr fatty ai; HDL-C 5 srum high-nsity lipoprotin holstrol; LDL-C 5 srum low-nsity lipoprotin holstrol; OSA 5 obstrutiv slp apna; %T, 90 5 prnt slp tim of oxygn saturation as masur by puls oximtry, 90%; PM 5 typ 3 portabl monitor; RDI 5 rspiratory isturban inx; Sp o 2 5 oxygn saturation as masur by puls oximtry; TC 5 srum total holstrol; TG 5 srum triglyri Obstrutiv slp apna (OSA) is haratriz by rurrnt pisos of apna an hypopna uring slp, whih aus intrmittnt hypoxia an frqunt arousals. Many stuis hav shown that OSA is a risk fator for hyprtnsion, ariovasular onsquns, 1 iabts mllitus (DM), 2,3 an mtaboli synrom. 4,5 A rlationship btwn OSA an lipi mtabolism was shown in animal mols, in whih intrmittnt hypoxia aggravat lipi mtabolism. 6,7 720 In human stuis, most of whih wr lini bas, yslipimia (DL) was foun mor frquntly in patints with OSA than in subjts without OSA. 5,8 Howvr, it is still ontrovrsial whthr OSA orrlats inpnntly with th srum lipi profil or what omponnts of th lipi profil ar assoiat with OSA. 4,9-15 Similar to finings for OSA, a larg numbr of stuis monstrat that short slp uration is assoiat Original Rsarh

2 with hyprtnsion, 16,17 ariovasular onsquns, 18 DM, 19,20 an mtaboli synrom. 21,22 On th othr han, th rsults of stuis about rlationships btwn slp uration an th srum lipi profil wr inonsistnt It shoul b not that all but on of ths stuis valuat slp uration by qustionnair, whih is unaptabl as an objtiv masurmnt. 28 Thus, th rlationships btwn lipi mtabolism an OSA or slp uration ar not wll known. W prviously rport that slp uration was signifiantly shortr in subjts with svr OSA than in thos with mil or no OSA. 29 To our knowlg, howvr, th assoiations among slp uration, OSA, an lipi mtabolism hav not bn valuat simultanously. W hypothsiz that OSA an slp uration afft th lipi profil inpnntly of othr onfouning fators. To tst this hypothsis, w analyz ata from a ross-stional pimiologi halth survy of mil-ag mal mploys in Japan, in whom w masur slp uration an th rspiratory isturban inx (RDI) by portabl hom-monitoring vis.30 Manusript riv Fbruary 9, 2012; rvision apt Sptmbr 15, Affiliations : From th Dpartmnt of Rspiratory Miin (Drs Toyama, Chihara, an Mishima), Rspiratory Car an Slp Control Miin (Dr Chin), Horizontal Mial Rsarh Organization (Ms Nakayama-Ashia an Dr Minami), Cntr for Gnomi Miin (Dr Kaotani), Environmntal Halth Nursing, Human Halth Sins (Dr Wakamura), Grauat Shool of Miin; Dpartmnt of Epimiology an Halthar Rsarh (Ms Takgami an Dr Fukuhara), Grauat Shool of Miin an Publi Halth, Kyoto Univrsity, Kyoto; Dpartmnt of Prvaln Miin an Epimiologi Informatis (Ms Takgami), Rsarh an Dvlopmnt Initiativ Cntr, National Crbral an Cariovasular Cntr, Osaka; Dpartmnt of Rspiratory Miin (Dr Takahashi), Otsu R Cross Hospital, Shiga; Dpartmnt of Rspiratory Miin (Dr Sumi), National Hospital Organization Minami Kyoto Hospital, Kyoto; Dpartmnt of Rspiratory Miin (Dr Nakamura), Kyoto City Hospital, Kyoto; Dpartmnt of Human Nursing (Ms Horita), Faulty of Human Halth, Sonoa Womn s Univrsity, Hyogo; an th Dpartmnt of Slp Control Miin (Dr Oka), Grauat Shool of Miin, Ehim Univrsity, Ehim, Japan. Funing/Support : This work was support in part by grants from th following: Japans Ministry of Euation, Cultur, Sports, Sin, an Thnology [ , , an ]; Japans Ministry of Halth, Labor, an Wlfar (Rspiratory Failur Rsarh Group an Halth Sin Rsarh grants: Comprhnsiv Rsarh on Lifstyl-rlat Disass inluing Cariovasular Disass an Diabts Mllitus ); th Japan Vasular Disas Rsarh Founation; PRESTO JST (Prursory Rsarh for Embryoni Sin an Thnology, Japans Sin an Thnology Agny); Suzukn Mmorial Founation; Taka Sin Founation; Mitsui Lif Soial Wlfar Founation; Chiyoa Knko Kaihatsu Jigyoan Founation; an Halth Sin Cntr Founation. Corrsponn to: Kazuo Chin, MD, PhD, Dpartmnt of Rspiratory Car an Slp Control Miin, Kyoto Univrsity Grauat Shool of Miin, Shogoin 54, Kawahara-ho, Sakyo-Ku, Kyoto, , Japan; -mail: hink@kuhp.kyoto-u.a.jp 2013 Amrian Collg of Chst Physiians. Rproution of this artil is prohibit without writtn prmission from th Amrian Collg of Chst Physiians. S onlin for mor tails. DOI: /hst Subjts Matrials an Mthos Stuy subjts wr mal mploys of an urban wholsal ompany in Japan as srib lswhr in tail. 30 All of th mal mploys wr invit to partiipat in th stuy btwn January 2004 an Dmbr Of th 466 mal subjts who wr invit to partiipat, 396 answr th baslin qustionnair (85.0% of ligibl subjts). Of th qustionnair rsponrs, 322 (69.1%) unrwnt monitoring with hom-bas portabl monitors. Thr wr no signifiant iffrns in haratristis (suh as ag, BMI, Epworth slpinss sal sors, an numbrs of urrnt smokrs, habitual snorrs, alohol rinkrs, an subjts with hyprtnsion) btwn ligibl subjts an partiipants. 30 Of thos 322 mploys, 47 wr furthr xlu from th analysis ithr baus bloo paramtrs wr not masur (n 5 29) or baus som of th omponnts of mtaboli synrom, suh as bloo paramtrs an waist irumfrn, wr not trmin (n 5 18) ( Fig 1 ). Thr was no shift workr in this population. Th prvaln of DL, istribution of OSA svrity, an man uration of wkly slp i not iffr signifiantly btwn th inlu subjts an th xlu subjts ( P 5.69 an 0.85 by x 2 tsts an P 5.63 by unpair t tst, rsptivly). W analyz ata on th rmaining 275 subjts rgaring th rlationships among th lipi profil, slp uration, an OSA. Writtn inform onsnt was obtain from all subjts. Th stuy protool was approv by th Univrsity Grauat Shool an Faulty of Miin Ethis Committ, institutional rviw boar approval numbr E-37. Anthropomtri an Biohmial Masurmnts Train rsarh staff prform masurmnts of wight, waist irumfrn, an BP. BP was i bas on th avrag of th last thr of svn masurmnts ma aftr th subjts rst a fw minuts in a sitting position. Hight an fasting bloo paramtrs, inluing fasting bloo gluos (FBG), srum triglyri (TG) lvls, srum total holstrol (TC) lvls, an srum high-nsity lipoprotin holstrol (HDL-C) lvls, wr obtain rtrosptivly from prioi insption ata. Whn TG lvls wr, 400 mg/l, srum low-nsity lipoprotin holstrol (LDL-C) lvls wr alulat by th Friwal formula (LDL-C 5 TC 2 HDL-C 2 TG/5). Aoring to iagnosti ritria of DL for Japans popl, 31 DL was fin by LDL-C 140 mg/l, HDL-C, 40 mg/l, an/or TG 150 mg/l, or by th urrnt us of lipi-lowring rugs. Hyprtnsion was fin by BP 140/90 mm Hg or by th urrnt us of antihyprtnsiv rugs. DM was fin by FBG 126 mg/l or by us of gluos-lowring rugs. Estimation of Slp Duration, Slp Disorr Brathing, an Slpinss Eah subjt wor an atigraph (Atiwath AW-Light; Koninklijk Philips Eltronis N.V.) for 7 ays to stimat slp-wak tim 32 an a typ 3 portabl monitor (PM) (Morphus; Tijin Pharma Lt, whih is th sam as Somté; Compumis Lt) for two nights at hom as an altrnativ to polysomnography in th iagnosis of OSA. 33 Slp uration was stimat from analysis of atigraphy traings in onjuntion with a slp iary. RDI (numbr of apna an hypopna pisos pr hour of th analyz tim) was alulat from ata aquir from th atigraph an th PM. PM rors wr inspt visually an sor by at last two mial otors spializ in rspiratory miin. Apna (ssation of brathing for at last 10 s) an hypopna (. 50% rution in journal.publiations.hstnt.org CHEST / 143 / 3 / MARCH

3 tsting for normality an quality of varian. Whn a signifiant iffrn was obsrv, th Tuky-Kramr tst or Stl-Dwass tst was prform. For atgorial variabls, th signifian of an intrgroup iffrn was trmin by x 2 tsts. To tst our hypothsis that th srum lipi profil was assoiat with OSA an slp uration, w prform univariat an multivariat analyss. First, rlationships btwn ah srum lipi lvl an th othr variabls wr analyz by Parson orrlation offiints or Sparman rank orrlation offiints following tsting for normality an quality of varian. Nxt, to intify thos variabls that oul bst prit ah srum lipi lvl, stpwis multipl rgrssion analyss wr prform an offiints of trmination wr alulat. Th variabls ntr in ths analyss wr thos yiling a P valu,.10 by univariat analysis, an whn two inpnnt variabls ha vry strong ollinarity ( g. 0.70), on was slt. Cutoff valus st in th stpwis analysis wr P 5.05 for both th forwar an bakwar prosss. Intrations btwn any two sts of th variabls rmaining in th stpwis mols wr assss by ntr ross trms. P valus,.05 wr onsir statistially signifiant. All analyss wr prform using JMP, vrsion (SAS Institut, In). Figur 1. Flowhart of stuy subjts. th amplitu of nasal prssur or rspiratory ffort assoiat with. 3% rution in oxygn saturation as masur by puls oximtry (Sp o 2 ) for 10 s) wr sor whil assssors wr blin to othr information xpt for slp-wak tim by atigraphy. Data without Sp o 2 valus, illgibl rorings, an ata from rorings of, 2 h wr xlu from analysis. Whn ata from both ror nights wr availabl, rors from th son night wr analyz furthr. No OSA an mil, morat, an svr OSA wr fin by RDI, 5, 5 to, 15, 15 to, 30, an 30, rsptivly. Th moifi Japans vrsion of th Epworth Slpinss Sal (ESS) was us to assss subjtiv slpinss. A sparat slp iary was also omplt uring th survy prio. Statistial Analysis Rsults ar xprss as th man plus or minus SD or th numbr of subjts. W ompar th iffrns in haratristis btwn th subjts with DL an thos without DL. Following tsting for normality an quality of varian, ontinuous variabls wr ompar by unpair t tsts, th Wlh tst, or th Mann-Whitny U tst, an atgorial variabls wr ompar by x 2 tsts. It has bn rport that th prvaln of DL an that of svr OSA wr approximatly 50% 34 an 7%, 35 rsptivly, among ault mn in th gnral population an that th rat of DL among subjts with svr OSA was 70%. 5 Bas on ths ata, th sampl siz was st to ahiv 80% powr at a 5% signifian lvl, an it was trmin that thr shoul b a sampl siz of 40 patints with svr OSA. Subjts wr also atgoriz into four groups by wkly, man slp uration as follows: slp uration, 5 h, 5 to, 6 h, 6 to, 7 h, an 7 h; two subjts slpt longr than 8 h. Th signifian of an intrgroup iffrn was trmin by an analysis of varian, Wlh tst, or Wiloxon rank-sum tst for th ontinuous variabls following Rsults Charatristis of Stuy Subjts Charatristis of stuy subjts with an without DL ar shown in Tabl 1. Thr wr only four subjts whos LDL-C oul not b alulat baus of TG 400 mg/l. Of th 275 subjts, 148 (53.8%) ha DL. Bsis valus for th lipi profil an anthropomtri paramtrs rlat to obsity, prnt slp tim of Sp o 2,90% (%T, 90), systoli BP, iastoli BP, FBG, prvaln of svr OSA, an rat of urrnt smoking wr signifiantly gratr, man Sp o 2 uring slp an slp uration wr signifiantly lowr, an RDI tn to b gratr in th subjts with DL than in thos without DL. Thirtn subjts with DL (8.8%) wr bing trat with lipi-lowring rugs. Whil thy ha signifiantly highr TG lvls than th othrs (man SD, mg/l vs mg/l; P,.001), TC, HDL-C, an LDL-C lvls i not iffr. Charatristis of th four groups atgoriz by slp uration ar prsnt in Tabl 2. TC lvl was gratr in th subjts who slpt 5-, 6 h than in thos who slpt 7 h. LDL-C lvls tn to iffr among th atgo ris. All subjts with morat to svr OSA slpt, 7 h, an 7 (44%) of th 16 patints with svr OSA slpt, 5 h. On th othr han, 14 of th 19 subjts (73.7%) who slpt 7 h i not hav OSA ( Tabl 2 ). Rlationships Btwn Srum Lipi Lvls an th Othr Variabls, an Multivariat Rgrssion Analysis for Priting Eah Srum Lipi Lvl Th assoiations btwn srum lipi lvls an th othr variabls xamin ar summariz in Tabl 3. TG lvl was positivly an signifiantly orrlat with BMI, nk irumfrn, waist/hip ratio, RDI, 722 Original Rsarh

4 Tabl 1 Charatristis of Stuy Subjts With an Without Dyslipimia Charatristis Without Dyslipimia With DyslipimiaP Valu Subjts, No. (%) 127 (46.2) 148 (53.8) Ag, y Nk irumfrn, m ,.001 BMI, kg/m ,.001 Waist/hip ratio ,.001 RDI, vnts/h a Man Sp o 2 uring slp, % Lowst Sp o 2 uring slp, % Slp tim of Sp o 2, 90%, % a No OSA, No. (%) 57 (44.9) 57 (38.5).285 Mil OSA, No. (%) 46 (36.2) 56 (37.8).782 Morat OSA, No. (%) 21 (16.5) 22 (14.9).704 Svr OSA, No. (%) 3 (2.4) 13 (8.8).023 Slp uration, h ESS sor Triglyris, mg/l ,.001 a Total holstrol, mg/l ,.001 b HDL holstrol, mg/l ,.001b LDL holstrol, mg/l ,.001b Fasting bloo gluos, mg/l a Systoli BP, mm Hg Diastoli BP, mm Hg Alohol intak, g/ a Currnt smokr, No. (%) 62 (49.6) 93 (63.3).023 Us of lipi-lowring miations (statin/fibrat/unknown), No (6/2/5) NA History of CVD (CI/IHD/HF), No. 2 (0/1/1) 8 (3/5/3).091 Data givn as man SD unlss othrwis iniat. CI 5 rbral infartion; CVD 5 ariovasular isas; ESS 5 Epworth Slpinss Sal; HDL 5 high-nsity lipoprotin; HF 5 hart failur; IHD 5 ishmi hart isas; LDL 5 low-nsity lipoprotin; OSA 5 obstrutiv slp apna; RDI 5 rspiratory isturban inx; Sp o 2 5 oxygn saturation as masur by puls oximtry. amann-whitny U tst was us for omparisons. b Wlh tst was us for omparisons. Two subjts ha both IHD an HF, an on ha both CI an IHD. %T, 90, FBG, iastoli BP, an alohol intak, ngativly with man Sp o 2 uring slp an lowst Sp o 2 uring slp, an tn to b orrlat with urrnt smoking. TC lvl was positivly an signifiantly orrlat with ag, BMI, nk irumfrn, waist/hip ratio, RDI, FBS, systoli BP, an iastoli BP, ngativly with slp uration, an tn to b orrlat with th lowst Sp o 2 uring slp an a history of ariovasular isas (CVD). HDL-C was ngativly orrlat with BMI, nk irumfrn, waist/hip ratio, an urrnt smoking, positivly with man Sp o 2 uring slp an with alohol intak, an tn to b orrlat with %T, 90. LDL-C was positivly orrlat with ag, BMI, nk irumfrn, an waist/hip ratio, ngativly with slp uration an alohol intak, an tn to b orrlat with RDI an FBS. With th xption of nk irumfrn an iastoli BP, ths variabls wr ntr into stpwis multipl rgrssion analysis for priting ah srum lipi lvl for strong ollinarity with BMI or systoli BP. Ths analyss intifi BMI ( b , P 5.002), RDI ( b , P 5.024), an alohol intak ( b , P,.001) as inpnnt xplanatory variabls for TG lvl; ag ( b , P 5.019), waist/hip ratio ( b , P 5.019), an slp uration ( b , P 5.030) for TC lvl; an BMI ( b , P,.001), alohol intak ( b , P 5.026), an urrnt smoking ( b , P,.001) for HDL-C lvl ( Tabls 4-8 ). Stpwis analysis gav no multivariat mol that show statistial signifian for LDL-C, but slp uration ( b , P 5.052) tn to orrlat with LDL-C lvl ( Tabl 9 ). Th rsults of analysis using nk irumfrn insta of BMI ar shown in Tabls 5 an 8. Almost non of th rsults hang whn systoli BP was hang to iastoli BP. Thr was no signifiant intration btwn any of two sts of th variabls in ah stpwis mol. Evn xluing th 13 subjts who us lipi-lowring rugs, th rsults of stpwis rgrssion analysis i not hang xpt that urrnt smoking bam orrlat with TG lvl. Disussion This was a ross-stional pimiologi survy that us portabl hom-monitoring vis for assssmnt journal.publiations.hstnt.org CHEST / 143 / 3 / MARCH

5 Charatristis Tabl 2 Charatristis of Stuy Subjts Catgoriz by Slp Duration Slp Duration, 5 h 5-, 6 h 6-, 7 h 7 h P Valu Subjts, No. (%) 30 (10.9) 92 (33.5) 134 (48.7) 19 (6.9) Ag, y Nk irumfrn, m BMI, kg/m a Waist/hip ratio RDI, vnts/h b,, Man Sp o 2 uring slp, % Lowst Sp o 2 uring slp, % Slp tim of Sp o 2, 90%, % No OSA, No. (%) 9 (30.0) 40 (43.5) 51 (38.1) 14 (73.7).015 Mil OSA, No. (%) 9 (30.0) 34 (37.0) 54 (40.3) 5 (26.3).535 Morat OSA, No. (%) 5 (16.7) 14 (15.2) 24 (17.9) 0 (0.0).253 Svr OSA, No. (%) 7 (23.3) 4 (4.4) 5 (4.4) 0 (0.0),.001 ESS sor f Triglyris, mg/l Total holstrol, mg/l f HDL holstrol, mg/l LDL holstrol, mg/l Dyslipimia, No. (%) 21 (70.0) 50 (54.4) 67 (50.0) 10 (52.6).265 Fasting bloo gluos, mg/l Systoli BP, mm Hg Diastoli BP, mm Hg Alohol intak, g/ Currnt smokr, No. (%) 20 (66.7) 51 (56.0) 75 (56.8) 9 (47.4).594 Us of lipi-lowring miations (statin/fibrat/unknown), No. 0 5 (2/2/1) 6 (4/0/2) 2 (0/0/2) NA History of CVD (CI/IHD/HF), No. 0 3 (1/1/2) g 7 (3/4/2) h 0 NA Data givn as man SD unlss othrwis iniat. S Tabl 1 lgn for xpansion of abbrviations. a Wlh tst was us for omparisons. b P,.05 vs 5-, 6 h P,.05 vs 6-, 7 h P,.05 vs 7 h Wiloxon rank-sum tst was us for omparisons. f P,.1 vs 7 h g On subjt ha both IHD an HF. h Two subjts ha two CVDs (IHD an HF, CI an HF, rsptivly). of slp uration an OSA, an, to our knowlg, is th first stuy to valuat th rlationship among th lipi profil, OSA, an slp uration simultanously. This stuy of mil-ag mn monstrat that TG lvl was orrlat with RDI ( P 5.02), BMI ( P,.01), an alohol intak ( P,.01), an that TC lvl was orrlat with slp uration ( P 5.03), ag ( P 5.02), an waist/hip ratio ( P 5.02). DL is on of th major risk fators for CVD. Among lipi lvls linially masur, LDL-C has bn shown to b th strongst risk fator for CVD an TG is also bliv to avan athroslroti hang Rntly, two ranomiz, plabo-ontroll stuis rport improvmnts in th srum lipi profil of patints with OSA by CPAP thrapy. Phillips t al 39 rport that 8 wks of CPAP thrapy for svr OSA ras postpranial TG an TC lvls, but that fasting TG lvls i not hang signifiantly with suh tratmnt. Howvr, Sharma t al 40 rport improvmnts in fasting TG, TC, an LDL-C lvls aftr 3 months of CPAP thrapy for OSA of morat or gratr svrity. Thrfor, it is still ontrovrsial how th lipi profil is afft by CPAP thrapy in patints with OSA. On th othr han, svr OSA was rlat to short slp uration ( Tabl 2 ). It has bn rport that slp uration lngthn aftr aoption of CPAP thrapy for OSA. 41 Thrfor, th improvmnts in TC an/or LDL-C lvls by CPAP thrapy might b partly aus by xtnsion of slp uration. In, aily us of CPAP for. 5 h in th subanalysis in th Sharma t al stuy inu improvmnts in fasting TG, LDL-C, an TC lvls 40 ; howvr, ths valus i not hang signifiantly with 4.4 h of CPAP tratmnt pr ay in th rport by Phillips t al. 39 Bsis obsity, inrass in srum fr-fatty-ai (FFA) lvls by sympathti nrvous ton, 42 ativation of TG biosynthsis in livr through a pathway from hypoxia-inuibl fator-1, 6,7,14 an rass in lipoprotin lipas ativity 43 hav bn avoat 724 Original Rsarh

6 Tabl 3 Corrlation Coffiints With Srum Lipi Lvls Charatristis TGa TC HDL-C LDL-C Ag, y b b BMI, kg/m Nk irumfrn, m b Waist/hip ratio RDI,a vnts/h Man Sp o 2 uring slp, % b Lowst Sp o 2 uring slp, % b Slp tim of Sp o 2, 90%, a % Slp uration, h ESS sor Fasting bloo gluos, a mg/l 0.17b 0.17b Systoli BP, mm Hg Diastoli BP, mm Hg Alohol intak, a g/ Currnt smoking a b 0.05 History of CVD a HDL-C 5 high-nsity lipoprotin holstrol; LDL-C 5 low-nsity lipoprotin holstrol; TC 5 total holstrol; TG 5 triglyri. S Tabl 1 lgn for xpansion of abbrviations. a Th orrlations btwn ths variabls an srum lipi lvls ar prsnt by Sparman rank orrlation offiint ( r ), an th othrs ar prsnt by Parson orrlation offiints ( g ). b P,.01 P,.05 P,.001 P,.1 as possibl mhanisms for th lvation of srum TG lvls in OSA patints. Barló t al 44 rport that patints with OSA ha highr srum FFA lvls than ontrol subjts, an that this inras in srum FFAs may rsult in lvat TG lvls. Svral stuis hav rport assoiations btwn TG lvl an OSA, but most wr linially bas. 4,9,11,14,15 Nwman t al 10 rport that in an pimiologi survy, a orrlation btwn TG lvl an apna-hypopna inx was sn only among fmal patints. Thrfor, our stuy is th first to rport a rlationship btwn TG lvl an OSA in a gnral mal population. To our knowlg, svn stuis hav rport assoiations btwn th lipi profil an slp uration, but thir rsults wr inonsistnt. In aition, six of th svn stuis stimat slp uration only by a qustionnair. Our stuy population was omparabl in ag to that of Bjorvan t al 23 an rlativly los to that of Choi t al. 21 Consiring that th subjts in our stuy inlu fw long slprs ( 8 h), our finings wr onsistnt with th finings of thos rports. Two of th svn stuis analyz ata spifially aoring to sx 24,25 an both rport a rlationship btwn slp uration an HDL-C lvls in a fmal population. It is known that faturs of th lipi profil iffr aoring to sx 45 ; th influn of slp uration on lipi mtabolism may also iffr btwn mn an womn. Katano t al 27 stui 4,356 halthy workrs (inluing 800 womn) from Japan. Thy stui th orrlation btwn slp uration an DL an foun that thos with th lowst slp uration (, 6 h/night) ha DL, whih supports our rsults. Thr hav bn svral rports of los rlationships btwn OSA an mtaboli synrom, inluing svral fators that ompos mtaboli synrom. 4,5,8,15 Data show that 3 months of CPAP thrapy lowrs BP an partially rvrss mtaboli abnormalitis an mtaboli synrom in patints with OSA. 40 In that subanalysis, subjts with man ahrn to CPAP Tabl 4 Stpwis Linar Rgrssion Mol to Prit Srum Triglyri Lvls: Mol 1 Variabls b R 2, %P Valu BMI RDI Alohol intak ,.001 Cumulativ R b 5 stanariz rgrssion offiint; R 2 5 offiint of trmination. S Tabl 1 lgn for xpansion of abbrviations. Tabl 5 Stpwis Linar Rgrssion Mol to Prit Srum Triglyri Lvls: Mol 2 Variabls b R 2, %P Valu Nk irumfrn RDI Alohol intak Cumulativ R S Tabl 1 an 4 lgns for xpansion of abbrviations. journal.publiations.hstnt.org CHEST / 143 / 3 / MARCH

7 Tabl 6 Stpwis Linar Rgrssion Mol to Prit Srum Total Cholstrol Lvls Variabls b R 2, %P Valu Ag Waist/hip ratio Slp uration Cumulativ R S Tabl 4 lgn for xpansion of abbrviations. Tabl 8 Stpwis Linar Rgrssion Mol to Prit Srum HDL Cholstrol Lvls: Mol 2 Variabls b R 2, %P Valu Nk irumfrn ,.001 Alohol intak Currnt smoking ,.001 Cumulativ R S Tabl 3 an 4 lgns for xpansion of abbrviations. for 5 h ha suprior improvmnts in mtaboli paramtrs to thos with man ahrn to CPAP of, 5 h. Thus, onsiring prvious rports, OSA 4,9,10,12-15 an slp uration, inluing th tratmnt uration for OSA, 40 may hav signifiant ffts on mtaboli paramtrs, inluing bloo lipi lvls. In aition to rlationships with mtaboli synrom, 29 BP, 46 an bloo gluos, 47 w hav rport rlationships among slp apna, slp uration, an lipimia in this stuy. Thus, w propos that slp uration shoul b onsir for rlationships btwn OSA an mtaboli paramtrs whthr ths onitions ar trat or untrat. In this stuy, man slp uration in urban subjts in Japan was 6.0 h. It was rport that th avrag slp uration by slf rport was 7.2 h/ among mil-ag Japans popl. 48 Atigraph-masur slp uration was rport to b shortr than slfrport slp. 28 In aition, rntly it was rport that 30% of mploy ivilian workrs in th Unit Stats wr short slprs (slp uration, 6 h/). 49 Although it is sai that th slp uration among Japans is on of th shortst in th worl, 50 subjts in Wstrn ountris might also hav vlop slp pattrns similar to thos shown in th prsnt stuy. Thrfor, our rsults might apply to urban subjts in Wstrn ountris. Limitations of this stuy shoul b mntion. First, w annot know ausality or th mhanisms of our finings baus this was a ross-stional stuy. Rsults of th prsnt stuy wr simpl pimiologi ata. Son, th stuy population was limit to working-ag mn from an urban ompany in Japan an inlu fw long slprs ( 8 h). This bias of th stuy population oul hav afft th Tabl 7 Stpwis Linar Rgrssion Mol to Prit Srum HDL Cholstrol Lvls: Mol 1 Variabls b R 2, %P Valu BMI ,.001 Alohol intak Currnt smoking ,.001 Cumulativ R S Tabl 3 an 4 lgns for xpansion of abbrviations. rsults an thy annot b gnraliz to womn, th lrly, long slprs, or othr thni groups. Howvr, limiting th haratristis of stuy subjts might hav nabl us to mor larly intify th rlationships unr stuy baus lipi mtabolism woul likly iffr onsirably in stuy subjts with a mor htrognous bakgroun. Thir, w oul not stimat th lifstyls of th partiipants, namly, itary habits, xris habits, an so forth, whih ar bliv to influn lipi mtabolism. It is vry iffiult to valuat ths fators quantitativly by a qustionnair alon. Subjts of th prsnt stuy, howvr, wr limit to thos mploy by on ompany in th srvi inustry, so w might think that thir lifstyls, physial workloa, an soioonomi status wr rlativly similar ompar with subjts in prvious pimiologi ohort stuis. In aition, th inis assoiat with obsity, whih ar usually bliv to strongly rflt a aily nrgy balan, i not iffr aoring to slp uration. Fourth, th stuy population was small, spially rgaring th numbr of patints with svr OSA, baus this was an xhaustiv survy an th numbr of ompany mploys that w survy was smallr than th alulat sampl siz. Thrfor, futur tsting shoul inlu many mor subjts among whih thr is a suffiint numbr of patints with svr OSA that woul orrspon to th stimat sampl siz. Finally, w i not prform polysomnography. Howvr, th intrsorr an night-to-night rliability of th RDI wr xllnt (intrlass orrlation offiints of 0.98 an 0.95, rsptivly). 30 In aition, it has bn rport that th nonattah PM is rliabl unr th spifi onitions in whih our stuy was onut. 33 Tabl 9 Stpwis Linar Rgrssion Mol to Prit Srum LDL Cholstrol Lvls Variabls b R 2, %P Valu Waist/hip ratio ,.001 Slp uration a Cumulativ R S Tabl 3 an 4 lgns for xpansion of abbrviations. a Slp uration was mhanially slt by th stpwis analysis in whih th utoff valus wr st at P 5.05 for both forwar an bakwar prosss. 726 Original Rsarh

8 In onlusion, w show that slp uration was ngativly assoiat with TC lvls an that RDI was positivly assoiat with TG lvls in mil-ag mn working in an urban Japans ompany. For working-ag mn with DL, CPAP thrapy for svr OSA may improv th lipi profil an subsquntly ru risk of ariovasular vnts. Furthr stuy is n to trmin th assoiation among lipi mtabolism, OSA, an slp uration. This will rquir survys of various populations with iffrnt bakgrouns. Aknowlgmnts Author ontributions: Dr Chin ha full ass to all of th ata in th stuy an taks rsponsibility for th intgrity of th ata an th auray of th ata analysis. Dr Toyama: ontribut to ata analysis an intrprtation, raft th manusript, an srv as prinipal author. Dr Chin: ontribut to th sign an suprvision of th stuy. Dr Chihara: ontribut to rafting th manusript an approv th manusript. Ms Takgami: prform th primary statistial analysis an approv th manusript. Dr Takahashi: valuat rors of portabl vis visually an linially an approv th manusript. Dr Sumi: valuat rors of portabl vis visually an linially an approv th manusript. Dr Nakamura: valuat rors of portabl vis visually an linially, an approv th manusript. Ms Nakayama-Ashia: ontribut to ata aquisition an approv th manusript. Dr Minami: ontribut to ata aquisition an approv th manusript. Ms Horita: ontribut to ata aquisition an approv th manusript. Dr Oka: ontribut to ata aquisition an approv th manusript. Dr Wakamura: ontribut to ata aquisition an approv th manusript. Dr Fukuhara: prform th primary statistial analysis an approv th manusript. Dr Mishima: ontribut to th stuy sign, an approv th manusript. Dr Kaotani: ontribut to th stuy sign an ata aquisition an approv th manusript. Finanial/nonfinanial islosurs: Th authors hav rport to CHEST th following onflits of intrst: Dr Minami has riv a rsarh grant from Suzukn Mmorial Founation. Th rmaining authors hav rport that no potntial onflits of intrst xist with any ompanis/organizations whos prouts or srvis may b isuss in this artil. Rol of sponsors: This publiation was ma possibl by grants from th following: Japans Ministry of Euation, Cultur, Sports, Sin, an Thnology [ , , an ]; Japans Ministry of Halth, Labor, an Wlfar (Rspiratory Failur Rsarh Group an Halth Sin Rsarh grants: Comprhnsiv Rsarh on Lifstyl-rlat Disass inluing Cariovasular Disass an Diabts Mllitus); th Japan Vasular Disas Rsarh Founation; PRESTO JST (Prursory Rsarh for Embryoni Sin an Thnology, Japans Sin an Thnology Agny). This was not an inustrysupport stuy. Th sponsors ha no rol in th sign of th stuy, th olltion an analysis of th ata, or in th prparation of th manusript. Rfrns 1. 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