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Ai+nucAN ' JoURNxli or EtIDEYtOLOGY VoL 121. No. 5 Copyrieht C 1'965 by'I'Ae Johns Hopkins UnivcriKty School of Hyrene and Public Healtb Prvuad in U.SA: f.ll *iibu :vaerved EFFECTS OF PASSIVE SMOKING ON ISCHEMIC HEART DISEASE MORTALITY OF NONSMOKERS A PROSPECTIVE ST4JDY' CEDRIC GARi.AN.., ELIZABE"I'H BARRETT-CONNOR, LUCINA SUAREZ, MICHAEL H. CRIQUI, ru+a DEBORAH L. WINGARD Garland, C. (D'rv: of Epiderniology„Dept of Community and Family Medicine, U. of Califomia, San Diego, La Jolla, CA 92093);,E. Barrett-Connor, L Swrez, M. H. Criqui, and D. L Wingard. Effects of passive smoking omischemic heart disease mortality of nonsmokers: a prospective study. Am J Ep/demb/ 1985;121:645-50. The mortality attributable to ischemic heart disease as a result of cigarette smoking is greater than that due to lung cancer. Between 1972 and'1974„ in a prospective study of a community of older adults In southern Califomia, llhe authors tested the hypothesis tAat nonsmoking women exposed to their hus- band's cigarette smoke would have an elevated risk of fatal ischemic hear3t disease. Married women aged 50-79 years who had never smoked cigarettes (n = 695),were classified'according to the husband's selt-reported smoking status at entry into the study: never, former, or current smoker. After 10 years, non- smoking wives of current or former cigarette smokers had a higher total (p S 0.05) and age-adjusted (p <_ 0.10) death rate from ischemit heart disease than women whose husbands never smoked. After adjustment for diffFrences in risk factors for heart disease, the relative risk for death frorn ischemic heart disease in nonsmoking women married to current or former cigarette smokers was 14.9 (p < 0.10). These data are compatible with the hypothesis that passive cigarette smoking carries an excess risk of fatal ischemic heart disease._ ischemic heart disease; longitudinal studies;,mortality; smoking, passive Although cigarette smoke contains by- drocarbons, nicotine, carbon monozide,. an&multiple carcinogens (1-4), interferes with pulmonary function (5, 6) and with cardiac function in persons with cardiovas- cular disease (7), and is a well established risk factor for emphysema (8), lung cancer Raceived for publication Au`nrt 23,,1984. '' From the Diviaion of Epidemiolo;y, Department of Community and Family Medicine, University of California, San Diego; La Jolla,,CA 92093. (Reprint requecu to Dr. Cedric GarLnd), This work .vas sapported by the Lipid Researr}t Clinics Piogram, National Institutes of Health Con- tract jlo. NIH-NHLBI-H1t-1-2I60-L; the National Iasti;ute of Artbritis, Diabetes, Digestive, and Kidney DiYeaee Research Career Development A.vard' Nb. 5 K04 : AJ+801063:02 (to Dr. Garland); and the Nauonal Ii?a.rt, Lung, and Blood~ lnatitute ResearcbCareer Development Award No. 5 K04 HL00946-03 (to Dr. Criqtu). (9), and cardiovascular disease (10) in smokers, the health effects of passive smok- ing are a subject of much controversy (1, 11-15): Nonsmokers in enclosed places with . smokers are regularly exposed to smoke (15-17), the concentration of noxious agents in the air exceeds that in inhaled smoke (1), and a significant amount of nic- otine is absorbed by exposed nonsmokers (18, 19). Recent studies suggest poorer pul- monary function in nonsmokers exposed to cigarette smoke at work (5), nonsmoking spouses exposed to smoking mates (6), and children exposed to smoking mothers (20- 2'2), and an elevated frequency of respira- tory tract symptoms in exposed child'ren (21, 23-25). Epidemiologic studies in 645

646 GARI.AND ET AL Greece (26, 27), the United States (28), Germany (29), Hong Kong (30); and Japan. (31-34) indicated an excess risk of lung cancer in involuntary smokers. A prospec- tive study by Garfinkel of' the American Cancer society cohort in the United States (13) found no excess risk of lung cancer from involuntary smoking, although the negative findings may be due, at least partly, to miscla.ssification of exposure to passive smoking (35). A cancer-registry-based study in Lancas- ter County, Pennsylvania, revealed no: cases of lung cancer in nonsmoking Amish persons (who are unexpose& to passive smoking because they live ia a closed soci- ety which forbids cigarette use) in a popu- lation of 12,000 observed for a seven-year period (36). We hypothesize& that an excess in is- chemic heartt disease might be, shown in passive smokers, even when the amount of lung cancer induced would be too low to detect. an excess risk„sirrce mortality attrib- utable to iscbemic heart disease as a result of cigarette smoking is greater than that' due to lung cancer (37). This is because lung cancer, even in heavy smokers, is less common than ischemic heart disease. We further hypothesized that nonsmoking women old enough to have died of coronaryy heart disease would have had spouses who provided the major source of cigarette smoke, because until recently most women had little exposure to cigarettes in the workplace. We report here a prospective study of mortality from ischemic heart disease, as well as lung cancer, bronchopulmonary dis- ease (chronic bronchitis, emphysema, and asthma), an& all-cause mortality, in non- smoking married women from a community of older adults who have been followed for 10 years. SUBJECPs AND METHODS Between 1972 and 1974, the entire adult community of Rancho Bernardo, Califor- nia, a predominantly white, upper-middle- class suburb of San Diego, California, was invited to participate in a survey for the prevalence of heart disease risk factors. Eighty-two per cent of adults in the popu- lation responded to the survey. Respond- ents were representative of the total popu- lation with regard to age and sex (38). All participants had a standardized in- terview including questions about age; cig- arette smoking-, history of past hospitali- zations for heart attack, heart failure, or stroke;,and duration of marriage. Cigarette smoking was assessed as current, former, or never. The number of cigarettes smoked per day was determined only for current smokers, and no data were obtained about duration of smoking. Weight and height were measured in light clothing without shoes, and obesity was d'efined by body mass index (weight/height= x 100). Before the interview, after the participant had been seated for at least five minutes, blood pressure was measured; with a standard mercury sphygmomanometer. Plasma cho- lesterol was measured by an Autoanalyzer in a standardized Lipid Research Clinic Laboratory.. Vital status was determined by an annual mailing for an average of 10 years with an overall ascertainment rate of 99.6 per cent. Death certificates„ obtaine& for all dece- dents, were coded by a certified nosologist according to the Eighth Revision of thE International ClassifCcation of Diseases. Adapted (ICDA) (39). Deaths were catego- rized as iscbemic heart disease (ICDA 410.0-414.9); cancer of the trachea, bron- chus, and lung (ICDA 162-163); chronic bronchitis, emphysema, asthma, chroni( obstructive pulmonary disease (ICDA 491- 493); and all causes. A death certificatE diagnosis of ischemic heart disease was val idated by interviews with next of kin, phy sicians, andJor hospita2l records in 85 pe: cent of a subsample of this cohort. Proce dures used~at the time of the survey and fo: follow-up have been described elsewben (40-42). After ezclusion ofwomen who had a prio 2023511723

PASSIVE SMOKING AT7D iSCHEM'iC HEART DISEASE history of heart disease or stroke or who reported that they currently or formerly smoked cigarettes, there were 695 currently married' nonsmoking women who were di- vided into three mutually exclusive groups based~ on their husband's self-reported smoking status at the time of entry into the study- never, former, or current smokers. Length of follow-up was virtually identical in aIl' groups. Differences in age-specific and total mortality rates were tested for significance by Fisher's exact test (43). Mortality rates were then age-adjusted by 10-year intervaTs„by the direct method and with the total study population~as the stan- dard The Mantel-Haensrxl test was used to compare age-adjusted rates (44). Coz's proportiona] hazards model (45) was used to adjust cumulative mortality rates and relative mortality risks for age, systolic blood pressure, plasma cholesterol, obesity indez, an&duration~ of marriage to current spouse. Regression coefficients were esti- mated by the method of maximum likeli- hood using a BMDP program (13MDP-2L) (46). Since we were testing previous find- ings concerning the risk of passive smoking, stat'istical significance was assessed at one- sided p levels of <_0.05 and 50.10. Since probability vallies from the Coz model are base& on asymptotic normality assumptions, the values must be inter- preted with caution when cell frequencies are as small' as those in the present study: The Coz regression was performed as a means of summarizing the results and con- trolling for simultaneous variation in pos- s1ly confounding risk factors. I RESULTS Characteristics of the 695 currently mar- ried women aged 50-79'years who reported thar they never smoked' cigarettes were ,1aAy7v-,ul according to husband''s smoking s-tab.as'at the initial examination (table 1). Women whose husbands never smoked or were former smokers were on the average older than wives of current smokers (p <_ 0.05). Wives of never smokers had been 647 married lbnger than wives of currentsmok- ers (p 5 0.05). Although other differences were not significant, wives of nonsmokers tended to have higher systolic blood pres- sure and were slightly heavier for height. Plasma cholesterol did not vary signifi- cantly accordicug to husband's smoking his- tory. Among nonsmoking women, those mar- ried to former or, current smokers had the highest age-adjusted death rates from is- chemic heart disease (table 2). Nearly one third of the age-adjusted mortality in women married to former smokers was at- tributable to ischemic heart disease. There were no deaths from bronchitis, emphy- sema, asthma, chronic obstructive pulmo- nary disease, or lung cancer in womenmar- ried to never smokers, but there was one death from lung cancer in the wife of a former smoker and one death from~chronic obstructive pulmonary disease in the wife of a current smoker. Age-adjusted all-cause death rates were higher in wives of current smokers of 21+ cigarettes per day compared with those of smokers of 1-20-cigarettes per day (table 3), but this result was not statistically sig- nificant. After adjustment for age, systolic blood pressure, total plasma cbolesterol,, obesity index, and years of marriage, the relative risk for death from ischemic heart disease for women married to current or former smokers at entry compared with women married to never smokers was 14.9 (p _< 0.10). The regression results showed that systolic blood pressure, which was on the average 3.$ mmHg higher in wives of non- smokers, significantly (p < 0.05) increased the risk of fatal ischemic heart disease. Women married to former smokers were not at excess risk of mortality from all causes (table 2). Because of reports in the literature of increased mortality during widowhood (47- 50), we examined whether bereavement might have explained the excess mortality in wives of current smokers. We reanalyzed -

648 GARLAND SrAL TAacz 1 Chcracteristia of nonsmoking women occ»rdinj to husband i cigarette smoking rtabu at entry, T972-I974 Hu.band. -mokint .um VrJ.'s d•a!![Serfsi70 Never (n - 203) Form.r (A - 395) Ctirre6t 40% - 97) M.an S.tand.rd deviatioa Meaa 2 s4nda:d darinion IYfaan S VAndard d.viat~on AP 64.6' :t 6.7 65.4' ± 6.9 62.1 2 7.4 Years of marriage 36.0' = 12.5 34.7 t 13.6 32.4 t 12.4 Systolic blood preasure 140.1 s 22+2 1387 :t 23.1 136.3 :t 20A Obesity iede: 3.50 s 0.58 3.43 t 0.49 3.41 ± 0.45 Plasma cholesterol 225.7 t 36.1 226.2 s 41.0 22fl.7 t 34.6 ' Signi6cantly greater than for wives of currrnt smokers at p S 0.05. Tast:e 2 Age-apecitic and age-adjusted 10-year morrelily rotea, 1974-1983, in nonsmoking monun occordind to husband's cigarette smoking status at enrry, ,1972-1974 Hi+sLaad'a smoking .ucus Ap poup of i Ne.+er Former Current w (7..rs) No. of deatha Po*luion at nak ~ No. of deaths Populatioa atri.k % No. of' dsstho Population at rn.k % Isebemic besrt d'uea.e 50-59 - - 0 41 0.0 0 62 0:0 0 34 0 0 6049 0 116 0.0 6 192 3.1 1 46 . 2.2 70-79 2 46 4.3 9 121 7.4 1 17 5.9 CrtAe rate 2 203 1.0' 15 395 3.8 2 97 21 Ase-adjussed rate 12t 3.6 2.7 All ntres 50-59 1 41 2.4 3 82 3.7 3 34 8.8 6049 12 116 10.3 21 192 10,9 6 46 13.0 70-79 9 46 19.6 21 121 17,4 3 17 17.6 Crude rate 22 203 10.8 45 395 11.4 12 97 12:4 Ace-adjusted rate 11.0 11.0 13.3 ' Io+er (p S 0.05) ~than combined rate for .vivea of current and former, ssmokers. t Lower (p s 0.10), than combined rate for wives of current and former smokers. the data excluding atl'deaths ( n= 29) which occurred at any time after that of the hus- band and observed no change ihthe relative mortality risks from ischemic heart disease or from all causes (not shown). There was therefore no evidence that bereavement fol- lowing the death of a spouse caused the excess mortality. DISCUSSION In this population of nonsmoking women aged 50-79 years, those married to current or former cigarette smokers had an elbvated' risk of death from iachemic heart disease compared with wives of never smokers. Furtbermore, the only two deaths attrib- utable to lung cancer, bronchitis, emphy- N sema, asthma, or chronic obstructive pul- monary disease in nonsmoking women ~ were in women married to current or former ~ smokers. Although we followed 695 women for 10,*e& years and observed: an adjusted relative risk of 14.9 for ischemic heart disease in non- ~ smoking wives of current or former smok-~ ers, the total number 'of deaths was rela-

PASSIVE SMOKING AND ISCHEMIC HEART DISEASE 64 9' TAa1.E 3 Ten-ymr al!-ocuse nlarsa!!ry mtes in nonsmohing, asvmen married to current srnokers, acroording to not supported by comparisons of obesity, plasma cholesterol, and'systoli'c blood pres- sure, all of which were similar or lbwer in number oF cigorrrres per day nnoked by /uu6Cnd No. of °9WR°ft ?i f Popu- Crudr Ayr-.djustrd• per day o. o d h Ltion Asatb deatb nte smak.d .at s at risk rate (%) (%) 1 by bmband 1-20 9 72 12.5 12.6 21+ 3 25 22.0 21L1 ' Adjusted for age by the direct method .vitb the total population at risk as the standard tively small, and the results must be con- sidered provocative rather than definitive. Nevertheless, we conclude that the associ- ation is real for the following reasons. First', it appears from the data (table 3) that a dose-response relationship ~ exists between quantity of cigarettes smoked by the bus- band and the age-adjusted mortality rate of the wife. Second, the association of is- chemic heart disease death with smoking by the spouse seems biologically plausible since carbozybemoglobia concentration doubles in the blood of nonsmokers exposed to smokers in a poorly ventilated room for two hours (51), moderately el'evate& room levels of carbon monoxide can precipitate attacks of angina pectoris in persons with preexisting disease (7), and elevatiom of carbon monoxide and carbozyhemoglobim have been shown to decrease cardiac con- tractility and to:raise left ventricular end- diastolic pressure in persons with cardio- vascular disease (8). Other explanations are possible (e.g., dif- ferent smoking patterns in men with chron- ically i]l wives) but seem unlikely, in that we excluded from the analysis all women witn; a history of cardiovascular disease. Widowhood, more common in the wives of saiokers, could have resulted in increased 6sk of death for these women because of t-he s>•c:alled "broken heart" syndrome (47- 50); however, bereavement was unrelated to the excess mortality in this cohort. Al- ternatively, cigarette smoking by a husband could reflect an otherwise less healthy life- style shared by the wife; this possibility was wives of current smokers compared with other women. We should'also note that the results of this study are confined to passive smoking exposures in the marriage in effect' at the time of entry into the stud'y, and exposures during previous (or subsequent)) marriages would be missed: This would tend'to have a generally conservative effect on the results. To our knowledge, this is the first report of an increase in mortality from ischemic heart disease due to involuntary smoking. We hope that others will ezamine their data to determine whether this effect is present in other populations. If this association is confirmed, a strong public health argument exists for prohibition of smoking in en- closed spaces. Legislation is presently un- der consideration or in effect in manyst8tes and localities to this end (5). RLfIIlBNclS 1. Shepard RJ! Tbe n.ks of passive smoking. New York: Oxford University Press, 1982. 2. Rylander R; ed. Environmental tobacco smoke effects on the smoker report of a workabop. Ge- neva: University of Geneva, 1974. 3. Schmeltx I, Hoffmann D, Wynder EL The influ- enae of tobacco smoke on indoor atmosphenx. L An overview. Prev Med 1975;4.'66-$2. 4. Hoegg UR: Cigarette smoke in closed places_ En- viron Health Perspect 1972;2:117-28. 5. White JR; Froeb HT. Small airways dysfisnction in nonsmokers chronically e:poaed to wbaox smoke.,N Engl J~Med 198(%302:720-3. 6. Kaufimann F. Tessier J-F, Oriol P. Adult passive smoking in the home enviivnment a risk factor for chronic airflow limitation. Am J Epidemiol, 1983;117:269-K. 7. Aronow WS, Kaplan MA, Jacob D: Tobacar a precipitating f.coor in angina pactoria. Ann Intern Med 1968;69:529-36. 8. US Department of Health, Education, and We)- fa,re, Public Health Service. Tbe health conse- quences of smoking. (DHEW publication no. (CDC)76-8704). W.shington„DC: US GPO, 1976. 9. US Department of Health and Human Services, Public Health and Human Services, Public Health Service. Surgeon General. The health conse- quences of smoking: cancer. (DHHS publication no. (PHS)82-50179): Washin;ton, DC: US GPO, 1992. 10. Libow M, Schlsnt RC. Smoking and beart disease. l.n: Yu PN, Good.vin JF, edc. Progress in cardiol- ogy: Vol 11. Philad'elphic Les & Febi,ger, 1982:131-61. 11. Lefcoe NM. Ashley MJ, Pederson L,L, et aL Tbe

650 GARLAND LR' AL baalth riska of puaive amokin` the gro..irtt caae for control measures in enclosed environmenta. Che,t 1983;8490-5. 12 Weiss ST,Ta=er IB„Scbenker M, et aL The health eflects of involuntary smoking. Am Rev R..pir Dis 1983;128933--42 13. Garfinkel L Ttme trends in lung cancer mortality among nonsmokers and a note on passive smok- ing. JNCI 1981;66:1061-6: 14. Hammond EC, Selikotf IJ. Pusive smoking and lung caacer with comments on two new papers. Enviton Res 1981;24:44M52 15. Friedman GD, Petitti DB, Bawrol RD. Prevalence and correlates of passive smokint. Am J Public Health 1983;73:401-5. 16, Repace JL, Lowrey AH. Indoor air pollution, to- bacco smoke, and public healts. Science 1980--208:464-72 17. Repace JL, Lo.rrey'AH. Tobacco smoke, ventila- tion, and indoor air quality. ASHRAE Trans 1982:88:894~-914. 18. Foliart D, Beno.vitx NI, Becker CE. Paaaive ab- sorption of nicotine in airline flight attendants. N En`1 J' Med 1983;308:1105. 19. 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