Document 6424288
Transcription
Document 6424288
FROM BLDSC.RGENT \ ACTION SERVICE 93'54 3%I (YIED)~2 . ?TH 15 :21 T. ;5 :23/'N0. 35?G13553o P PAPERS Cigarette smoking, tar yields, and non-fatal myocardial infarction : 14 000 cases and 32 000 controls in the United Kingdo m S Parish, R Collins, R Peto, L Youagnan, J Barton, K Jayne, R Clarke,, P Appleby, V Lyon , S Cederholm-Williams, J Marshall, P Slight for the International Studies of Infarct Survival (ISIS) Coliaborctor s Abstract Obfecdeas-To sasses the effects of cigarette B8F/rcami Rc Mrs. Gllnlol Tr l$ Service Unit agd XOA.ealoloalal Studio Unit, Naffuld Depart mean ofC ha l ha+didas, Rsddife Iatlrasuy, cached o116flL said CsrdLn Depar , me r, john Eadeli>feHoepitsl, Otdtsrd OXI 9011 S Parrish, terser r+wmeh kaoa R CoUina, Brivish Room Fa9sdaias wniar rovarak few R Pcta,prvJrrror vfmdicd xaasde and sprdrarfslear LYourgman, wafer raeamh tffa w jbartvn,,anrisr .r ltiiyuk swrctar os6,rpeisr*amr R Cbrtss, rasach f lks , P Appleby, ,aws .rJ, fdlorrr of Lpoa, "amok 1d1,n P SldgfG prgi ;uur oetrina of rmdivoa k'raadaors Osfmd Bb-Research Leboratary, Magdalen Sdem*Pesb,, Oi&rd Oxe 4GA S t oderholin- ilhsmt, swam 1MarehaU, rare ci faao w Contspoodcacr W : Dr pm" arq,Nlpu_tert_s BMJ VOLUME 3I1 Introduction In countries such as the United Kingdom, wher e smoking on the incidence of nonfatal myocardial cigarettes have been used widely for several decades, inf rudou, and to compare tar in different types of tobacco now accounts fat about 30% of All deaths in mwmfacsmed dpreucs. middle age, with lung cancer and coronary heart Methodt-In the early 19906 responses to a postal disease the most common fatal conditions." Over the queednnnalre were obtained from 13 926 survivors of pest few decades cigarettes have been altered in various wyoe+sdiat laf>uctioa (tetra) recendy discharged ways, reducing the to celled yields of tar and nicotine from karpir:sls In the United Riagdom and 32369 of when smoked in a standard way by a machine. Typical British c,gareaes had tar yields of 25-3 S mg during the their rdstlves (controls) . Blood had been obtained hum cues soon after ad,at den for ebe index 1950s and 5-15 mg In 1990' Buy partly becsosc myocardial infaretien and was also sought from the the chief toxins in e{garere smoke are uneanin and controls . 4923 eases and 6SSO cv nfrols were current partly because smokers may compensate for reduced emokars of manufactured cigaratrer with known yields (or other changes) by smoking cigarettes more rear yields. Almost all tar yields were 7-9 or 12-15 actively,- the health aft= of 21r mores in cigarette mgfciprette (mean 7•S mg for low tar (< 10 mg) and manufacture arc unpredictable . Low rat cigarettes do 13 .3 for medium tar (a10 mg)) . The cited risk cruse substantial take of cancer and heart disease, autos were standardised for are and sax and comalthough the risk of lung cancer is less than with high paasd myocardial infarction rafts In current tar cigarettes ."'-" For heart disease, however, thug dsaret*a simwkan *ith those in non-smoker who remains uncertainty"-" about whetter the rats he's had nor ap+q)xd cigaremes regularly In the past been decreased, increased, or not changed by alte 10 yearn . :etti Composition oser the past few rationseg, ReedtrAt agd 30-49 die rases of nsi+oea dial deeadee . Nato" heart disease mortality rarest and .Qtiefi in makers were chant five times these In trends are fiat ififen7tative because ocher factors arse ten-smokers (as deeaed) ; at ages 50-59 they were such large differences in coronary heart disease thew times those in non-smokers, and even at ages between different populazovs and time periods . 60-79 they were twice as greet as in non-rockers Instead, concurrent epideauologicsl comparisons (risk ratio 6 .3, 4-7,1-1, 2 .5, and 1 .9 at 30-19, 40-49, within one population are needed. 50-59, 60.69, 70-79 respectively; each 21v<0.00001) . But, although tobacco is a major cause of heart Ater eamdardiasrion for age, eta, and amount disease, particularly among young and middle aged emoksd, the rate of mm-fetal myocardial infsrcdon adults, it 13 difficult for conventional prospective or was 1d-40/6 (SD 5 .4) bigmer In medium tar *an In low retavspeUvc ewdks to compare the risks from diftar cigarette smoker, (2P•0.06) . This peaeenrage ferent types of cigarette . Only a narrow range of was not egalSrsndy greater at ages 30-59 (16•ff,L cigarette tar yields is eoneutreedy available withic one (7.1)) than at 60-79 (1.0'/. (S'S)) . In bade up ranges population, and the tar yields of cigarettes smoked by cite difference in risk between cigarette smokes and people in 1990 might correlate poorly with the tat netts-smokers was much larger than the difference yields smoked by these people years earlier. Hence, even large differences in dsk between prolougod use of between one We of cigarette and another (risk ratio low, medium„ and high at cigtrccces might produce 3 .39 end 3 .95 et ages 30-59 for smokers of similar members of Saw and of medium nor ciger .we,, and only small dl$irvnces in risk between cgrrenr use of risk ratio 2 .35 and 2.37 et ores 60-79) . Mum possible low and medium tar digarettes. At younger ages the conAppadvRg facmfs dot could be rested for were proporoopal difff=cr id rated of eere:ury heart similar in low and medium bar users, with no disease between seokets and em1-smokers is pardatufgfalSotmt dl>seseaces in blood lipid or albtmmdn lady ewe, so any cffu t of cigarette type may also eeaceeaadeas. be extreme . Thus, to minimise the chances of a false negative result in a study of tar yields, the number of Candxefove--The present study indicates that the cases of myocardial iufarcoon in middle aged dgarecre basmodrsent change of tar yields In the European Unions srnolcers should be large--preferably scvail thousand to comply with an upper limit of 12 mgfcigaretee will not Increase (and may somewhat decrease) the -with at least as many controls . We achieved this by studying subjects from the United Kingdom facidmcc of myocardial imdarcdoo, ettlesa they imb'ssedy help pc rpematc tobacco use . Seen low tar who patdeipated in the large ISIS (ratarnstional Studies of infarct survival) vials of the vestment agsratsee rem greedy Increase rates of myvcardiel infierctlon, bowrsr, especiuw -m ovig people in of acute myocardial 41fatftioo,"0 by using Postal their 30a, 409, and SOs, and far more risk is avoided qucatlothaaires (copies available an request), rather by not amoidng than by eheaging frees one typo of than inueviews, and by eimplifyicg blood collection cigarette to anotlser . procedures. 19 AUausr 1995 http://legacy.library.ucsf.edu/tid/vla14a99/pdf 47 1 325300249 FROM E ,DSC URGENT ACTION SERVICE ~3'S4G321 V ;'itiED) 02 . J' 99 15 :21/ST. 15 :20/NO . 3586135585 P 3 Pa eacsaad urcdsoda CASES AND CONTROL S a a/ in a atodifteatioa for plasma of their uriaacr radioimmunoaseay ." Rciv1 With this plaspha a}Uv correlate closely with those with gas chromarogtaphr .Bcckrnatl CX-4 and CX-5 autosnalysers were used for measuring concentrations of cholesterol and albumin (both path Becl®sn reagents) and apolipoproteins At and B (suits Immune reagents) . To corms for discoloration from haemolycis, an initial blank reading was subs acted from the final reading. 5ampia from a large plasma pool were included in each analytical run, yielding coefficients of variation o f 2 for cholesterol and albumin and 46/6 for epolipopmrrins. Cases were the survivors in the Uniird I(ingdom aged 30-79 from the ISIS-3 or ISIS-4 trials who completed an epidemiological qucadonnaire sent to them a few months sfatx diet infarction . Those who was asked to complex it were all Ole survivors from ISM-3, but from 15154 only the survivors aged 30-59 who on adahissian to hospital were reported to be ciareete ,molars. Thus, although only eases from ISIS-3 can be used to compare smokers with nonsmekers, the ease from 1315-4 strengthen the analyses of tar yields among cmakers shed 30-59. The ISIS-3 questionnaire asked the rases to identify all their brothers, ilitas, and children aged at least 30 who were resident in the United Kingdom . A similar "control" quesdonnaire was then seta to such relatives, accompanied by a second copy, which the rclnweu, if marred, were to ask their spouse to complete- One reminder was seat to cases and relatives who did not reply, and inconsimuclae or omissions were queried once. Of the 20 691 ISIS-3 patients in the U aired Kingdaem, 19065 who were oar known to be dead were posted the ease questionnaire, of whore 1346 were found to be dead and 13 969 (79% of presumed survivors) completed it. The control questionnaire was sent to 30 247 relatives of ISIS-3 cases, of whom 75 were found to be dead and 21995 (73% of presumed survivors) and 14 245 of their spouses completed it. Patients with a history of titrvke, gastointesdnal bleeding, or ulcer tended not to have been recruited into the ISIS-3 uial," and so pcoplc with such conditions were not digs'bJc aS c49e$ or controls . Of those who completed questionnaires, 2002 cases and 3851 controls were excluded because they were under 30, over 79, or of unknown age or because they had a self reported history of "delralu stroke" or of "bleeding or ulcer in (or near) the stomach . " MS-4 patients in the United Kingdom aped 30-59 who were described at trial entry as current amokas were also aeat the questionnaire . The response rest for such patients was similar in both trials . Any of theca ISIS-4 pagears whose questionnaire zcipoese indicarod *et they were not cigarette smokers at the pmt of their infarction were excluded . 1513-4 (and, to some extent, ISIS-3) tended to exclude patchier with chock or pervisaersr byparension,' but such exclusions should not bias the epidemiological analyzes of tobacco tae. Information was sought on sex, age, batik- size . smoking, dcin1S1ng, past health, and relatives. Cease were ,eked about their habits and hisboty jets before their index myocardial infarction (because haring a heart attack may ulcer a pedant's habits), while contzn{cr were asked about their present habits . Kence, questions to cases often began, "Before your recent hospiai admission. . . ." Roth cases and controls west asked to lilt how many relatives of certain types then bar . but only cases acre to provide contact details . In other respects case and control queadomaicoa weze' . ore was nenidcnrkaL The inc" history se technical and recorded various conditions that mid be assocismd with exclusion from the randomised trial (see above) or that might affect, or be affected 17, stroking. After the question of whether they had "env smoked regularly Cie on meat days for at least a F=,~^ the rest of tau cigarette section was to be coeplent ! only by those who replied 'yes ." It dealt with the age az which the subject hid first and last smoked regale==, whether any cigarettes had been smoked in rte k.evious month, the number smoked per day wb.m 16 -subject had WE smoked cigarettes segsdady. and the way in which ciguccres were smoked. People was to rick against 137 derailed brand rimes the ace &e•, what they Inc smoked, they usually smoked most eat, if it was not an the list, to write out its eaatu I-fY (and, whenever possible, to enclose the peclbgiag of that brand with she qucstionnsimr) . For the caw wso listed more than One brand, the average of the yi&S was taken- Ninety eight per cent of controls and 9°'' . of cases who Currently stroked only mamtfscr>z-d curettes with a )maim tar yield, and both :s tmt using their corrects: brand for, an average, the parr 1i) or 11 years . .4015 aAA@rala >3t D2¢r.mmtONS OF CtOAPFrrg SMOALNO STATL3 Blood was to be taken froth p2tirm5 in ISIS-3 ismediately after randomisation but before the anal Qeswents and eolleeeed in a 10 ml vecurainer conraining 0-I2 ml presarvative (15011 potassium EDTA a+kfi aptmtimiss: 0 .34 mnlol/l: Becton Dickinson), on reeurming their quecdonnsire, controls were sate an identical container for their general practitioner to collect blood . Case and control containers ware sent by Scat class post m Oxford . Controls were sent one reminder about giving a aapsple, A her a moan of two days in the post the blood was centrifuged, the packed ell volume was recorded, &Ad dhe plasma and huffy coat were aficluoted for storage at -405C . Blood arrived from 97% of ISIS-3 cases and 45% of controls, but breakages or haemolysis rendered 5% of that samples onusable . The present blood analysts involve only correlations of smoking with blood biochemistry results, and these analysed abould not be materially blued by low response rates . Respondents were daeifed as Current e4mraz z (26% of the commas : those who had smok cigarettes m the previous month, plus the few who failed to answer ibis ym/ne queston but germ ad= evidence of current cigarette use) ; other eobacoo testa (3% : pipes, cigars, or smokeless tobacco in the px year); or as not using tobacco Cllr/-: all oh=s)_ I-cable I these are further subdivided. Because of the poapble confusion between those who vsapt smoking ad" years ago and thou who never smokae, the train compais si group was defined as rrcCr smokers who had not used cigarettes regulary hi 1c past 10 years. Plasma eodnine concentration was measured in controls who were current cigarette smykeas, and in a 3% sample of oontroIs who repotted no current use of tobacco, by means of antibodies developed by Knight 472 http://legacy.library.ucsf.edu/tid/vla14a99/pdf I QL'V9TtO3tNAmvs SSITMAT D1995TARVs1nDS The tfnktsd Kingdom's government chc%6~v% eve ducts surveys of common cigarette brands, .. . -s tar, aleoleme, and carbon moddiddt yieIdsy,twfiee a (R We,, personal communication) . Duiitn to Um 19809 the apaual dusts in sales weighted yids about 2-30/. for tar, 1-29/6 for nicotine, and gnu 7th carbon mofOZide (j Renteul, personal coI D don) .' Most 1313-3 cases replied in 1990 eb ez t .cccsr 1°95 BMJ voL(Ji4n 311 19 . 325300250 FROM l %DSC URGENT ACTION SERV CE ^1 : 33' V»5 Jc I t ;WED) 02. 13'991 15 : 22/ST. 15 : 2J,'NC. 358C ,13558t ? inyararrlisl ln&redon (wain Ante of ittiltredort! Pebrnaty 1990), most controls replied in 1990-1(meam November 1990), and mostlSLS-4 -see replied in I992-3 (mean date of infarction : July 1992) . To avoid secular treads in yields introducing minor biases, the slid-199O sun, results for each cigarette brand were used (R Waller' . personal comunlcatlan) . If a brand was assayed only earlier or later then midL990, yidda flvm die dvscet survey were eatrapoiamrd eo meld-1990 by animal dcacases of 2 .5% in tar and 1 .5%. in nicodne . a8ST RVSY O? COM7lO .! A P2w YuARS LATan To diode mepredt eibllity, about 2000 co ols who originally returned both qu€stionaalre and blood sample (and whose replies indicated no previous vascular disease) were scut the same gnettiooneis and blood kit spa about 2-3 ytats lira. To avoid over. sampling yunng cononIs, the random sample wa s I 'god with reap= r to vex and age in groups of an yeas. Severity per cent (1388/1996) tealwrned the qucidmaaire, 95% (1324(1388) of whom Save blood. LTATl4TiuaL agrwODS The anslyvee are ell tla2matcbed-hat is, they compare cases with all controls, not just with their own r alseva--6nd. for tar yield analyses among male" tha console are as relevant to ISI5 4 as to ISIS-3 cases . All analysts of myocardial in&redon rates were stratified either for r and five year age poup or for three factors and amount smoked (five categories; see below). Calculaioas of risk rado*-or, equisaleady, relative vials--erlta0ed soma lad stratified Iogisdc is Tars (famed by uaomditional muimum like!!hood), with ova cans ra177r included for eaclt st2avrm . Risk ratios pee often worn with 95'/0 confidence iatervala. Tana aided probability thirds (2P) are used. ran 1-R0eY BY mnoetr u t PR Ad moon am= #dy . (g Aspeedd deny AWA,v t av (d4% epwrid 20 par jp' . s,dd'57ia lepmmd 10-3W. (6) Taryiddras 1950 ofdas bamdt r4wrmd do, of (a) the reported number smoked per 44y and (b) the e:dmated 1990 of yield. Self repoeoed 4p0ette constunpdan was caegaeiaed a 1-9, eaectly 10, 11-19, eseeriy 20, and 2121 agerenes a day; 85% reported smoldng 10.30 ogarecua a day. The tar yields show a bimodal distribution, with contmoneet values 7-9 or 12 .15 tng/cjpxr e . Tar yields of 10 mg were rare, which manses this a natural point of subdivision, unaffected by stay slight difc men in data of a3e and coutrol responses, to ddnle two mak camgorissi low :ar (< 10 w& mean 7-5 sslg) and medium tan (s 10111& mean 13-3 mg) . Meditrall tar is :Omenmen split imrm 1012,13, and 14 iddprette. This dellnidoa of low tar is also used by tits Depaaeat of Keith (R Wailer, personal omemunimtion)! Twenty fm per amt of the smokers in figure lb use low at cigarettes, as in [bit nsmonslly representative survey in 1990 . !most al l FMQvm4crDLYrp.u moMaofsr4Q1Gy4Ogoofi s Table r shorts the numbed of controls 2nd cases in various categories of tobacco use subdivided by vat and by ate. The ace range of ditefrdevance to the tar yield analyses is 30-59, andaa:tong controls in this tangs 25% beds of moo. sad of women were alarm dpreae smokes, is dose ag eepent with pappnlly rcpreecuunfm e, hmarviewa administered arrays is the arly 1990x .+ Twenty two per cent of that cresols were cum= usara of mam&wntred eipfemes only with knows mr yields. Figure I tivm for controls who cutretady used nraoa gwssd. dprvtn only, the frequency disuibw?AaiaF-Tu6 gar it ems mdemmu4 . ed!O-? cad Inudmmaku nowned Cm,mr da -Me>•+nlm Noe ai as aaeb,ee s adarmbe m .l oi~gv+a~ Ae 6mRreeoseo Ta n 11m Caeadr U~ " -6mm 70-79 Mw 6001 wwso 60 .79 1m7 awsc $a 70-7+ 00104 90•@1 O ahe q..ns mss NN •r!"Mar .4 , 9--b-COP. 71 40 1 91 2 3111 5502 41 fill 2010 162 33 13e9 4" 26 za 1031 676 60 133 11 943 660 21 w 28 3459 1351 65 251 27 1063 419 33 7M 20 11 3e 46 60 27 is 39 35 0 470 4 25 - - 5 430 2S - - 2d1 2907 - 1690 o®R 30 •m 163 11607 23 t 11 laeeeeopI dpma. +wo ks emdahm tabreeseel9 am 2194 320 WOE a dvirxaaaa dpeeam 3264 Mw 60-79 655 wove 40-79 726 218 gas t4?6 Ma 70-19 1117 Tar r= ®lmaem K 317 7 eat 408 <l0yrrsep sins ijOymvlMO 719 NO 1165 1 468 1566 447 676 Now r gNi s dprers easbm Tasl• 14173 4391 6695 906 39719 11161 12575 4077 4971 2541 5046 11967 z 434 647 NO 47 977 1266 272 226 504 236 f17s - - - 4702 7206 1919 1576 air 4192 7779 17271 44315 26 0 20 ant 411 4 14 2 -C+matmen std a0ames. RMI voWM16 3 L 1 19 Avctser 1995 http://legacy.library.ucsf.edu/tid/vla14a99/pdf 47 3 325300251 sso3~eydjwaP. In Satire 2b the mean eoonine values wsse aboin a third higher ametog the controls who emoked medissas tar dermas (low tar 217 ng/mI v mcdhuo tar 292 ngtml) . But the smokcm of low tar dgarcrtm rtpoeed smoking 15.8 elgareaes a day compared with 19-7 a day for those in the modium w group . Afro standardisation )br age, act, sod amount stroked, however, t))c mean Plasma cunel c coaeennkvOn was suf 19% higba with medium tar ciprettes . This difference in w ire is sdU highly 9iptg5Cant (2P <0.00001), which helps validdatt the aregtlewadon of tar yield based on the qutseionnaite . Bat it is less ocLtee than The d&rencc of aver 506/r in the nicodms yldd Per cigarette measured by machine (0 .73 mg and 1 .18 rpg) . This may be partly because the cazcgorisatioa of - yields is impeded, and partly because smoke's of low yield cigarettes compensate by sa y 490-1 (b) C.Caolvrr arise dpb'rilr~r l~u .~p(~~ryCdai~we w.W r-yi,id in mete smoke per cigarette . Buts dncc this caregnrisa iron predkrs highly ng stream biechcmicii differences in blood taken months laces (figtac 2b), it Me some validity- Cab Uft esvwhatred drrems o1Jy (or - Tabaan) wrJ: .Y,va aleeukesl6f uelta>asdary~saert Jim., ' a4vZ17aodZ9]ri e4amine gts®s adq .ar JS4d Je•7,andMU= ' Qrpw gk_w, .-,. 7.4asdJ3.3 wt 370, 0.734wd J-Jd art rais,dar, .4ee 4 JS.O iget2(aid '4oe rr6da 151osdarm odtw sa Ci&&ItFrra USi ANDAION-FATAL1,97OCARDIAL D"ARCTION Lew nr 6LfYY(4 rjaj~r r,s.ir 9/es► quanxNakiv, Nadia 1 0 20 Md ble&taiadavlaroli lea u emmmmim (pp- 2oa wp4p kdicead souse t6ias6p tier 0203 No owrrnttobaae (3%21l051$ o i ID Tar y (nwft rrra) TAMS v-Nwrfaas1 eyo,-U i daIdow: £es'nwadt 0100 4(tmatc toe in PWk midi av Xm y uJ >Regw MropldlPie asa,elaEa~tYrerFe a Llalml GZWW d CIPINIedaNlf A. bras) C . OMMON Nmaadcew7sw --PJm ds•ara a6ampaa l0 y,M„ W-4 .1010 1195% COMMON Toss r-s eoanDL mrMwD mdoel 17x6 1407 ss 20 199 4" 061 561 Arts 6-35(441e6.91) 24 4306 4 .66 6Vtm3-6o 15-1 2701 3.10 66 .3.49) 13-7 30.29 ev6 4142 733 I1lLD }es CHI w4•343 221 6040 436 111 693 163 636 767 369 1074 2299 436 (216 W 2 9p 1) 4 SO-SO ei949 9040 5x19 79 362 1-92(14302-ft 44 9241 207 (200w2•72) 12-1 337 •3arhr r ns .rd6t,a s.r aaaadrdir00 ear eau red res. When those using maaufacmred cigarettes only were compared with ==-mlokcts who had not smoked agarettey regularly in the past 10 yews (eaehlding w both cases those using any otbar type Of Tebaoco), the relative risks for non-&W myocardial inft+etion in people With no precious neoplaetic or maw vascular diseaso depended strongly on age (rablt IX, fig 3) . As is the cane for mortality from eeronary 'heart diwase,' 1 the risk ratio ce, i aring smokers with n0A'makers was grow a younger ages, reinforcing the need for the role w,ce of tar yields to be eoasidered saparately at younger and older ases . TAR YIEID$ AND NOIJ-7ATALMYOCAAL1Ai1NaAA,C77CELZ InfOtmauon about the ralcvanct ofear yield . comm . from cum= users of mamlifacenred Cigarettes 0sno . Of these, much the moat mfo=ative pre the 9000 aged 30 .59, lather than the 3000 aged 40 .79. Tltisis not only bccaalse the aumbxit are Inger but also because the risk r ado whm 6mokers m compared with non- Mroaeriei inbreo m std elglratra migkag• 12 0(10 mw sM 32 ODD cw&vl s I f$we .draea.d' '- br+d>~d6lracttaeartrrlibdi><en9ramnw. used filtcod bands (100% of the low tat group, 9694 of the medium nr pup), so Slurs accounted for lisle of the di$cace in ylelda betweee low grid mcdinm tar aiparaacs in 1990 . 3tt(ATION VZrWzor QU2frIDNr•3Avm AND wrnn2 63 &au-igh of r6RI UN Ales maid by lrrloldra 4.7 0 3-i 3. I cVN (rMTIDNi Figure 2 shows the relation between plena c opine eances=tlonf and (a) reported daily ciprczra file and (b) tot yield for conuols reporting use t f manufacruad cigarettes only or no current tobacco use . The man eorminc couccutredon was very low in the self reponed non-zmoketa, which helps validau both quesdonnoire and laborawsy avuhD. Among dpmtte smokxw then was a swag Z&6 0A between cot one mncennJtlun and dig ga oust reposed to be smoked, which spin helps validpte the guecriotraaire. The downward ruvantrc It figure 2a sllggees that those who smalls mote dgarnctes may absorb lets nicotine from each one or that those reporting Imp numbers include duproporvonarely many who overrepme4 cite both . Hoge way, self repotted cigarette consumpdon prow dot only appro 'CUM information about The rsal dosds of ulconne and of other sobsTaacda. 474 ~' 4 33.9 4Wl 50 .9 1 70-9 tt AV W79 abk reap 383 &,k , 237 too 3--Cwsarama and not-!d xveaftw ijpr at efipe tease Ad ,eon or vs,.wt earn Ronde n3 MOO aa* sspnvbw 11ipe.y of MW eagpla m lsQadto &1061. 304 FU roe . It Aw,oas16ad for as and /br gwgaaavame of egg eeld aarWWW diver mutt WWWA.oeo avy MA 46M arrr ors Mae aa,.rrbr we . OW nold ple wMBV sad had Mar halls rrtwlor dpi .dM an6Rst a MY Mod w AO P" JO jeavL Rid coin u thins ad i garb rolrao . (A, all WO MR&O dJr ,,1SIF-4 so" ataradr ol5Ya16 dwftt+r salbat Q6w r .byrdISJS3) SAIJ vowxa 311 l9 Atzt=1999 .~i (; V71.I J yC. ,01'1/•l.l?•c i ,~4~•VV : ' ./r ,U I •vO1C~ 1 I . .v7~~Ct'6L M~J`i :I3S 1CV~J. .i• http://legacy.library.ucsf.edu/tid/vla14a99/pdf .L A~~JU :3 Jt~l~~ ~0r r 325300252 FROM B D$C URGENT ACT I O\ SERV'. CE 9371 4632 I ; NED) 02 . 10' 99 15 :23Isis ! 5 : 2,110. 3580135535 P C TAers ,,,, IV n m,fid rotes n a .nov imaAe7r df nTorw and hen tar semester l•vgw9mo,awes .NWAl mot 60 ¢snsW6vahem 1990 meyd R.b. of wm .6ed 'a,aeIdML klfue.ae ;a ametlaa Ord"= tar samoken efles, pualeeret.ee (aith h7u c naarnre .tend aid dp,tr6ma) SCadadbcd for ere.-Nan d crasser 'CesW4t Grade 5enda Lae diet mm&wseeee& mh,edses 1a611e6de (n . 'n.d-dh tithe nspc,*,, , 5%4 1534 ta£ .ewea) stesa4szom, wnewatmaoed dicoset AI0"f VR1t M.mamrr 274 399 1796 1512 1203 1 .166 1 073 (1961 .1•x64) (t•O25w.1 .324) (09cwwt•zi7 ) )26 5 416 e 1P.-0004 3PQ-az ~1+>0 L AP 6&79, La.tts Mdlawor A,e s0-7v: lewtr Med.,rtavr - 438 1144 433 999 274 Lift 757 rase 170 1 1179 1400 1.019 1 .010 (0.590001 .230) (0.3761 1 .191) (0177L to L-325) 21Oae-1 2PeO .1 aP3'. e . 1 1 .142 1 .104 14Y35 (I'034 m i •255) (0998 e .1-2227 (0-910 0o 1 .173) W.500! ZP.O-06 2070• 7 IftOPINGUS ~! m ,dus e d omeer drMUlor ur yWd o IM 133-11 ffte, slee.rdus .yen . oft N A rdd , t muet .dt f~ od no ..d)..se 1000 (Sb Oby )). trw cw0asabm OUR R a oft irda.e ar yktda, ted.aaet et)ne .ae .ids seine per. aesplasea as sea . dies. a,., wll omdax es m-Ll b ..d Mype,a(Tir. d. crma.n. TMS2 tw-.4naieees bd- --).v kaki, ad 1&.d rived m..rn.eaowv. Ydwr .>, suonr CS$) Gme:we aw C,arost . to w Non-rrsekerwkss CWWv*o rtWd dms.&ea .=d aadp e e .,e dpnorenly iapaniar .t Lowow Mcdlamor (_1156) (0.3123) SipaaMeee (0.295) (o.942) Stsaaaee Lipidma owuncm r holeleeel (a e .Yq 5-02 (095) 341 th•02) Ns 6-01 (946) 6-05 (ads) Na AP°CP°P1O . At (dA 1 .277 (0006) 1`185 (9.094) 2F=0.03 1 266(0013) 1-x64(0007) N3 Apoapepeewbll ()01) 1 .354(0 .009) 1 .165 (0005) 29.01004 1422(0014) t-226 (e 009)9 N N Tealiv-AVrVd-N-ty e(f Nt90ikf Rmpome warIAN1 gae,deemiee e mre.9,De"lbsav E Ret9.ate msepmt goaeocmwim 4d,sus lsett ~t..,odv •,ipuOa,, .,y Omsmbeu:onsrr Pemw eipteetr m,.ie.r. <lo)7e efntews eat, oma tabacra ONE Not mtiaa :oeaao 6103aea s l0, ., was much larger dean the differrnce between one type of cigarette and another the risk ratios were 3,39 and 3 .95 for smokers of similar numbers of low and of medium tar ciVt,ntcs at sgcs 30-59 and wt arc 2 .55 and 2 .37 at saes 60-79_ (Table I i shows that results Were similes when these compariso))s wee : based on the sma lee numbers of cigarette smokers with no Sported history of neoplasne or mifor vascular disease . ) p071iiNr1Lcor.mu DacOMCIORa Table [V relates smoldog to blood lipid eonc dntradons among ISIS-3 cases entering the trial tsfthin 0-4 hours of pain onset whose blood spent only one or two days In die pos , and among one randomly chosen control per case (matched for age, sex, and days sample spent in the post)- Apolipoprotein Al was 1-a%lower and apolipoprotein B 24% higher in smokers than in non-Smokes llVr Cuss` di=c" sr wo small to aeea,alc for much of the excess risk among smoltets . There netts no significant differences in blood lipid concentrations (Or albumin concentration, data not shown) between smokers of law and of medium tar cigarettes, either overall or in these aged 30-59 (dsz nor shown) . For many factors theft wan likewise no significant dldbre ces between smokers of low and medium tar eigareaes. These include self repulsed height, weight, loneliness, depression , wt)rry, insomnia, teenage acre, tell consumption, alcohol coaatrmpds , and whether living with a apotlse. For a few &-on, however, there Wee definite diffareecea even after stands di,aden for age sad sae . (Multivariate adjustment for these observed differences would make little difference, but these differences point to the powlbllity of others adorns.) Those who smoked low tar dgarrttea were, on average, almost six months olds when they left full time educedon (Mean Leaving ape 15-9 pars for low ta r group o 15 .5 years for 1Dcdlalm tat), was more likely to ivy that they had matured physically 'law than "ero de" (13 .4% . 10 5%), had "so&sr hands the n rw average" (14.40/0 a, 11 .00/.), had been regular drinkers of cofee (75% u670/#), were older when they faerrCd to . 9 smoke (18,9 a 17 .9 yon old), and had changed to their 1 es 7 3 3 current brand more recently (7.9 v 10 .1 years pre29 1s 50 rl o viousiy) . Thew suggest a general tendency for thos e who smoke medium tar dprevrea to include a slightly tte,e~ 2 10 r 374 is larger proportion Of manual workers, and to have x..Qetp. 4~ea .2 .Nes f s a >9l skigtly less education . (Likt:wtae, unpublished "mww any net ee lad rs,o.01s91sId an beds egslew (6S d.,)6ed . in un w oetdt.ly as41e<tArm w 1.6r. 21 w 1e. d.ea Is. a m medLm e.o 1.., 5,, b . do= abalhw) . smokers Is more elttrame in middle than in old ago As there was no aignkilant difference between the tar yields of cases aged 30-59 in MS-3 and in 1515-4 (table m), the groups were combined. Table La provides age-set standardised comparison, of aaa-5►mi atyocerdial Infarction in smokers of low tar vases smokers of medium tar cigarettes . Overall, there were only slight effeees of the air yield . The mm daffy ml-be of tenures smoked *aa dighrly higher in the medium tar than in the law nr Cigarette smokers (19 .0 v 17.1). When standardised not just for age and sus: but also for the daily dumber of (dgasetra smoked, the incidence of myocardial inlhee don was 10 .06 (SD 5.4) higher in medium than in low tar dgaltutc smokers (zPao•o6) . This di&renee was non-> alllaatty geeeecr at ages 30-59 (16 .0% (7.1) higher 2P=0.02) than as 60-79 (1 .04/. (S-5) higher, 2P>0-1) (fig 4) . As threes two "auks are no t hil y dArenc fiom eask other, they do not prove tha t tar yield, in of pew peCpornodll itltpottannce to tba eardibtaacity of cigarettes in middle than in old age, especially since the smoker versos non-smoker risk ratios are low ewetteme in old age . In both age ranges the difference between cigarette smokers and non-smokers B11Q VIOLU es 311 19 tumors 1995 http://legacy.library.ucsf.edu/tid/vla14a99/pdf analyses by M Jarvis of the 1990 and 1992 general household surveys in the United Kingdom fotlad eignillda,etly higher "indices of depre eton" in user;, of medieuse than of law tar eipretres .) ARMDUCm1 .rTT Ora MOttn404x ASSMICATION A total of 1388 controls repeated the questionnaire t few years lacer, and table V compares their two replies . When subdivided three ways (men ilIcni ed cigercucs only, ocher tobacco or a -atests smol9a c to year5i resesainder), 900/, r+ealained in the same axgog of the 97 who smoked pnly menufactgred cigarettes with tar known on both occasions, 890/. bad continued to smoiae medium or low at cigarettes as originally . Overall, there was a 56/4 shift towards the low tar calagory, in line with national osuda, and the coarelsdon eoeJiSc ienr between the two assessments of err yield was 0-71 . Discussion When cigarette amolters are compared with non- smoker the risk ratio for m7umrdiel infarction is mulch mote e)e,seme in early adult lift than in old age . The numbers eomtributing to figure 3 are unusually loge (12000 eases and 32000 controls) and so the pattern of seedily ineseasing risk ratio with younge r 47 5 325300253 FROM BLDSC URGENT ACTION SERVICE :'937546.3'21 : E9132. J' 9 15 :214/ST. i 5 : 2- 0, 31H0135586, P age is put cularly reliably demonstrated, as are the hazzrds at the extremes of the age range of 30-79 . The risk ratio is twofold at ages 74-79, but It is almost fourfold at ag , 30-59 (dsroefoid at 50-59 but 5 ►cfold If 30-49), }burn these large differesees hew probably beep somewhat dllutcd by the tniselsssi}leanon of some smokers or non-smokers. Had it been possible, with no claaificat on errors, to Compare p tangent agamte smokers with lifelong non-smokers then the risk ratios would probably have been still mots extreme than those in figure 3, and would have been at least Wurfcid at ages 30-59 . As moat ofthe excess risk associated with smoking is caused by smoking," this fourfold risk redo implies that about three quarters of he myocardial bfarcdons among c1prstte smokers aged 50-'59 wtxe caused by tobacco (two L A at ages 50-59, but four fifflu at ages 30-49) . Any di;ffetenees In the risk of heart disease between those who are smoking differcat types of cigarette must be mach la-se earente than the diffeatnces between smakert and ionrsmokere so especially large studies are needed to assess them. Moreover, epidemiological media that were undertaken when tar yields below 15 mg were still uacnmmon (N j Wild er al, tutpublished data)- are of limited contemporary relevance in countries such as the United Kingdom where tar yields above 15 mg have already virtually disappeared (fig Ib) and where a European United upper limit of 12 rag is soon to be eefoered . As no other line recent studies ace aveilabla, our current lfndings stand aloneFor me yields the rested finding is that sf smndardisedon for age, tax, and number of ggarettcs, the incidence of a,on-atal aryocardial infarction seemed m be about 10% greater with medium tar then with low tar cigsrttms (95% confidence interval 0 to an ., time UJJ .1gvra If this toy. difference was highly staristical(y significant (which it is not 211-0-06) ye would call not be epidemiologically secure. It is uncertain )tow much sdeed .e empbuis to put on the data at ages 30-59 as opposed to thou at 60-79, how much seleeelve emphasis to put on the die from people with no previous disease, and how much to empheeie e Nlreetrde In kWoa and d ur Pd ta+ or (<10 mg mine 75 mg ) nedlua or (>lo mg mw 133 too hF c Ik4% (SD 7.t) more irduttr. br .maWna 339 1.0% (so 0-b) moat siV . NS 2 9 cif ALa 36,9 Asa 60-79 PKr or yield, a,d rvi it no»~r! r 4w,Jim _q-Pfi Atired for use, ts, led macaws -AU 4 mntyansu at aim 10-1/ &-r- .r that wma-f ayo .a ^'m a" 1-166 (SD 0071) roan Serra macaw sradawt rant mrasar loseerr aem®i mwmlarr (SP-O'01; mabk L . TA* sera tv"d•&Mj mmparuear at yw 60-99 - 1 .010 M-OAS) (NS) . Thee An amts (1-1 d6 asd l'Ol Q) wr atnotuwd aide cis . F&k rvwot y3*31 and 2.3? .r d,swet, Weak", va,w a aaae.Aw all ) to AW ON rid riots P1AX fro ae.tdt•r of lot. madrrsd6na rm ajvmra 3 39 std 3 9S s qsw 10,T9+vt 0- 75 e,d7 .37x taw 6479 ICQy masavpee • Non-fatal myocardial infarction rates are five times as great among cigarette smoitas as among non-smokers at ages 30-49, three thncs as great at ages 50-59, and twice as great or age 60 .79 • Among cigarette smokers four fifths of myocardial lnfarctions at ages 30-49 were caused by tobacco, two thirds at ages 50-59, and half at ages 60.79 I a The risks seem to be ll%lttly greater with medium tar than with low tar cigarettes, but this difference is not definit e • Didrrences in risk between cigarette smokers and son-smokcre are far greater than any differvncca ip risk between one We of cigarette and inether • Far More myocardial infarctions could be avoided by not smoking than by changing from one type of cigarette to another analyses that tee staadirdiaed for the amount smoked . (Those using low tar cigarettes reported smokes slinky fewer than those smoking medium tar cigarettes, and if lower daily consumption is chiefly a consequence of tower yields of tar, nicotine, and other smoke components then it should not be standardised for.) Hence, table III reports several' diferent comparisons of disease rates in smokers and in non smoltcrs, wit1 h, differences that are somedmee more and sometimes leas than [0%. Also, there was a slight geodency fur tar yields to be inversely related to education sod eg various other aspects of toast tat . It is di£=ulr to see how :case of these uncertainties can be resolved: large scale eandomissidon is impracticable, and even if the present study could have been much larger, thereby narrowing the confidence intervals, the possibility of confounding would rtmlain . Despite these uncertainties, however, the present results provide some reassurance to those in government or in iadusay who could direct decreases in cigarette to yields to reduce cancer iAejde tee .''h" . They indicate diet such changes will not subsrrntisily increase the incidence of myocardial jujigetfon and miy well decrease it. Tlhus, the limit of 12 mgrcigarstte an tar yields that is now bed introduced in the European Union should help limit the number of premature deaths from tobacco, unless govcmmcm3 or smokers come to retard reduadons in tar yield as substitutes fur she avoidance of ageretras, for in developed crannies tobacco remains much the most impostamr rinse of premature death. T W ii pardeulsdy so for mere, with toboeoo now causing about a third of all deeths in middle aged men- But where women lave been smoking cigarettes for some decades (as, fior example, in the Ualred Kingdom or the United Surer) tobacco also already causes about 3 quarter of all the deaths in middle aged women,' For the general population, therefore, the most important finding is not the slight and rsnratsia difference in figure 4 bow= out type of cigarette and anathes but the lard and definite difference in fgtme 3 between cigarette smokers and doe-smokers, particuujady in early middle age IrrecpeCdve Of whether low or medium tar cigarettes are used, about due quarters of the smokers who bavt la heart stuck in their 30e, 40a, or 501 need not have done so, and far more heart attacks eoeld be prevented by not ,molting than by reducing cigarette tar yields . The Aid ockaowledgmmt is to erne patients and fib t 476 EM vor nsor 31 t 19 AUGUST 199 5 http://legacy.library.ucsf.edu/tid/vla14a99/pdf 325300254 FROM B_DSC URGEN ACTION SERVICE 019375"'r-321 (WED) 022 . 1'T 99 15 :24,iST . 1.5 :2ci/NO. 35810135585 P 8 rtIadraa wh6 m(kbor red in this amdy, and ro ft 1nOdisl Lod unrdq I from more than 100 hapir&L id rite United Kln tom tared in the IS 1S report ." It We pardcutidy dunk Peers Faogiyatt, Cheryl Sweep, and Rob= Waff of the Indgmdedi Scimtifie Comeaieree on Sawiml6 and lialfb, De rams of Kellett ; Keith Dahill 6f the I b6ratOty of the Gtl.anlamc Chemia* M2cdn Jail of the rmpastal cancer Resserh Fugdi and Kaldip Bhamee, (entail Borg . Lee Beelal)shsm, Macy B,atnn, Sarah Clark, Sarah, Edward,, Shrill Foster, Heaters Halls, Maya Kies, Keen Kaarril lay Clultdoe Maraden, Gale Mad, Kavtp Murphy Muds Radler, and Karl Wa11rndeays of rite Qzbrd ClFoicol Trial Service Unit and Fpida, i616pal Studiy Unit . 1 Faadlne The ISIS dials end epidaatiolopfeal awdiu wee 9oppQrrd by the daanurcatas of the study dap"" and by the Bridah Heft Foutldedoa, Imperial Cancer Raeat& Fund. Mcdicx) Research Council, and Tobacco Produen Roeatch Tttaat of the Independenr Sdefldfic Commlmee on Smoidng and Hce1tl., Deparg0pen( Of Hid,, Ca MdEct :ofh9oetegG Now. ..M....a,.j e.••••t••aa I POOP. LAD.ltadrwf.Tt.wad,e..hC7 lmdp,d -Roue /110.rdtt who md,war Jb>a oammd mad amide(? f7Pfad:0*d U .uolOPh ,1996. 20.1RP.- 4Wh-&•s1,onrit talmdI .M.m&pI,relda .aw POrlkv; 40 7we oata•.dar an aela 111991 4aaao. daq 1194809for-11 . 1 Z-M- D, Pw 1, Oder 1Laronu . .0br .eo.d I..M U.dad. LTaPc T,a ;v.dlod Aemq for ebsch an Comm. IPee . OARG sdnm& PM bs(om loo 74.) A ®dd X. Mdal-Wa le..,rA. 91R,..,Ahe die. a.d .4. Orea,d : Gaf rd 7 area NI, ID! 3M, MUatY1R eC Iaad P_ OUe U9 AL s ee ., d b+faid a=.ma do as s,pme leer 8010oe K E* Y M.d loom.) 6 vWN. I20aatt P l9eoefac MMW ar Ma 4a b pup=ae adhWL Odwd poem, tIm. I fctrl>h= oM 1S. Smalbr mad Ikdt de ammdm harem aa.elhii hean4aer, 160d mma&y and .aded9cedrdl ldo4.tC ...,.,rp ffwie 11141!'240 4 I walwn4 7L Tama;-Padre K. emdsb PCs, 7a/09* R Saunas .L __. 1dm and UMM4na bie~ a die 1 t Momded Jed AKA-41"I,dkjdal-16. wsdl-m4 PI, Tvd19a0-raft tL Ito mom, ofbaz err Seaton adsme 10 .11 moans of aml2 WW*WAwO ReWIN Sam dm Seeadi Unn 9e06 Sa(p.d7A, Ie4W.421 l 19 ww&-d N, Taaodhtodoc tL 3dtlnvoa doimdoc oIdaeor Ann ft SaedaeMantNamNo*, AAAd,e I993a enl-3o- I I l/cre C, Kwme M Tat field . of mean me rude .aaa ea,o. *X YAW Cemtae 101100c-7. 12 Peas Dw, P.rwa 10 . R---" IL, SW-W r, wrrrhmw 1, Mb VW 9 . Tar mama of Spurr in Matlen to lay mac An 1 Qordree 19ro.IH70H1 . .3 3edlmao SD, Gadlid,d I . I,aa eamear M/ . II p..paahosd m tlplaap6 Yr /fc d cW4.aac ham 7 pr0.peed.e sandy. Ph,Mof l9e9e7a'SI 1-23. 14 Winds It. Sdb,w, . it. h .p.r Xleefmm 0 -*d -w e m t°°9 wa l.T.a .~ ,sa . awm,.af may, 7 Nerd Cam 1,ar IMAM 47).7. 15 K.oi,r DO, NehmdaY !!. ee.eelkra 4 Aaacmr OS, farpa aWm" aA mtq% gdnw9t aaga of Opron Sashed ad .ht or aeenrialr ere am,a ,ma.M1efJMoU 34J4I 09-Ii. 1d Pdms pt, R.eeene L *,Mw J. -'Le.-tor Riser ad dr ne of em-Mid I dla iidaavwr ewer. 7Nmilrlfadd 19f°a19r15M-73 . 17 Neaef L Fncrosm MC. rAvrcdsa G same I, Maki A, Tlaw 0 w bdoI .! C.t§SS-a1QM T. .m4. Ter Odd .f ...sneer. mad .1* at aoaralalomaialafa~ .Da[71913iIN1707-1 0 Is Z .2 6Smaaad lnsrre00ed flit ' K Wise 9isol ► CaaAmb,. f 14d.mb.d "wI did....d.._ ddpckb.q s .1 .,p6M, bad,, reamer amsat »,197 p.ee KtMgftaci Blum mpmi*l MYmdm; IDS., teem 198air349i0. t0 T !4 (TAai Tmtroodaoo Smdy of I.&- 6a.1-.A 04W.Pd..c on* L9a-I A Ifldgarltd old of .a , nar R SOUR plodwUm errant w uIaeplam ad of wprM plat %epmb of tgMS AM WAN 44199 a.o .f ..p.lad,. .mabom,0l.ta,t.m .e.r-wa1U2,10 :I11,40_ 29 1304 a ado, lommada,at Sa . Of TO& a 3or9k11) C0116W sit Greta 13144 A r.OaMeeea fir .~l eat ~a .elr dew pp, rd --W. d f....aeoq MP04 sae nbhm r flog Painds -M* 21 reloR eel „re P, ~"Me.o MS . wd" Ja. Loppee.d "-dbe od-1- by ,dded .r fia"4l N trdef tw0e .i'ia. ter., tab. lle3~l:uasl . 22 l4Tnaha i C. Idsae MAIL A w14d p .-I.S.id iwm.bpap6,c s,.d+d kv ,he as-b.dw of meads m dao,ae to Wolapa 9 .Idh 1/'#11 f°eaw.aef 191eb" Ult . 25 DmP.rm,ee d Iead& "-" , w, a .sl. - SOwf f9Td a l.la. ta,.dae On -3.496W 9a- .err, t .RS_(fad,dal eo9C0n 1991114.1 . 24 Ise PP4 Oisfr t . hbrmlO tad ape of op<eme lonat . J 1)p Caawaaglfitd 193171:16.22 . >! OT.da It, 1Ialba. D.'FobdBl .M ecru . ..seer; eti.Swye. NAl J 26 Kamnaa0 C, OednW L Sdde a A. Lo' EL "Pa" of deice a.r.ke k ad.aen o e.ade r. b$w lv 1976,0303-7' . 27 Padtd Da, lM Sow GD . C. .dwmiea. .r mad one deem In area, of 1"vWceeam.JCA.MaDIv 101SailSa l . L 20 C.s4tt VP, Gad.,. e1 fl ..4rr?P, Mdt.dada PM, Pddeb M, Ravel we. tla fie dtStw ma maaoay h is Shear;: ft Mra;dreh.n ah.Li' L.wI a1F100-11. 56 !SIW.haaw T, Sapley nq, Pm . Q. Opmn% tar tame q rd -wary am a oc is. deem of dhdmoa and to Thad I dtPdlt•fd Gmammdb Hfdd,)90Z 113-7. (Aaaad 7SA,6,II) A 2S year follow up of mortality among women who smoked during pngnmcy U Paula Rentekllilio, Em Isari, Max** Kcwsnon Ol f,etiae-To iavatigure 16pg term mortality atitaa' wmil7dn who smoked daring preoancy and dew who mopped Umoldog. Detigo-A fdlldw up of a geographirQy 4Rfinird cohost from 1961 through to im . 3,4/tctfi--11994 wemm is oer wn FisLnd aq scsed t o deliver in 1966, cA®ptisiog 9Q/. of all woman giving birth In the wee during that year. Smoking habits were reeonded during pregnancy but not later. AapxmmmWd/1&i RcOth QSeisaas mind Gaserairraedw, hula; ehysfOulu, s4pilde 1, FIN-0120 oats, Flabmd P:vla RrvJ atlio, yrrlfErmr Bea Lyana, Mot o Harlot KniTmee . epAuniorf *differ C6nefpcmdmu WC Dc Rallrzbliio. t471n50111477-W 8MJ vari'.4fi 311 Mawr oatcoms rndoaure-3Kartelit7 by cause (571 diode) . Ria iLto-T a mortality reds ad uetad the age, plw of raW nee, yeas of edncado and marital MEW war 2.3 (9Sa/4 coa$dencd lacdtvai 1-d to 1-3) for the weslien who soeok>ed during pregnancy and 1 .6 (1 .1 to 2.1) for those *ho stopped nolring before the mend moats of pregnant , both eou plead with tan-smolcves . Among the oetd!!s the r save mortality sae higher for typical disease* related to tobacco intake, Butch u respiratory and oesophageal aefscer and discasrs of the cardiovascular and digestic orbs and ahu for acddumt: and suicides. Conclusion-The risk of premature death oecem a 19 Atmurr 1995 http://legacy.library.ucsf.edu/tid/vla14a99/pdf to be hfOuer in women who emeriti dnriyag prepaney than to other wonaet7a who smoke. This stay be explained either by the low proportion of those who O11op laser and the high proportion of heavy emoks3s or by odor rhaaaaaa4adcs of these aabjecta that hMW"se the rink . latrodnction The o®sequencee for the child of marexaal unitin g during pregnancy have been well documented,' but less interest has been directed towards the morherLprogrlosis. We analyse here 28 yew mortality data on ;L geagaphirally defined population of women who smoke during prt:wsaucy; many background vanables were recorded pr-pee vely . Methods Pop,det m -The cohort eonaileed of 12 CIS 5 pre®naut women (13 of them delivering twice) in the two most norcherD provinces In 1?ialaad, OWu sad Lapland, whose expected dam of delivery fell in 1966 and when the pregnancy Iriulced in a birth . The cohort covered 96'h of all delfveties in the rq;ion in 1960 Th e 477 325300255
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