TABLE I.-Case-control studies of CHD risk among former smokers Reference Population Number of CBIC\ Willett et al. (19X1) Nurses Health Study: women aged JO-55 263 5.260 Nested m cohort 2Y Overall I .o 10.7-1.h) 2.0 (7.34.0) Quit I-4 yr I .s (0.7-3. I ) Rosenberg. Eastern US men aged 45 1.x73 2.775 Hwpitnl-bawd Kaufman. Helmrich. Shaptro (19x5) Rosenberg. &tern US women aped 40 5.55 1364 Ho\pitnl-bawd Kaufman. Helmrtch, Miller et al. ( 1985) LaVecchia et al. (10x7) Italian women aged 45 IhX 2.51 34x 3s @It S-4 yr I.3 to.x-3.0) Quit 210 yr O.h(O.l-1.3) I.1 (O.`J-1.4) I 0(0.7-1.0) I .A-7.0 depending 011 cig/da, TABLE I.--Continued @IIt oungcr age group. and the excess risk declined with increasing duration of abstinence. In men aged 31 to 53 year\. the relative rish among former smohers of I to 4 \ ears' duration M ;I\ I .Y compared u ith ne\ er smohers: relative ri$k further declined to 1 .4 to 1 .3 with a maximum of 20 years' duration ot abstinence. In contrast. persistent smohers had a relative rish of3.S. In this study. those who quit had smoked about IO percent fewer cigarettes per day before quitting than did persistent smokers. The British Physicians Study also included 6. IY4 women. for whom the data \h'ere reported sepsrately (Doll et al. 19X0). These women completedquestionnaires in IYS I. I Y61. and 1973. In contrast to most studies among adults. a substantial minority of nonsmoking women in this cohort initiated cigarette smohing between 195 I and 1961. Thus. the rates of smoking-related diseases among thoe classified as never smokers are likely to be overestimated because never smokers. defined according to the 195 I data. included a proportion of subsequent current smokers. Overall. the relative risk of CHD mortality among former smokers was 0.Y compared with I .O to 2.2 among current smokers. depending on the amount smoked. Because there were only 26 cases among former smokers. a detailed analysis was not performed. The first large-scale American Cancer Society (ACS) cohort was assembled in 1952 when 1X7.783 men aged SO to 6Y. living in 9 States, completed a questionnaire related primarily to smoking (Hammond and Horn 19SXa.b). The men were enrolled by over 22.000 ACS volunteers each of whom was asked to enroll IO individuals, excluding those who were seriously ill. There was no further update of cigarette uce. These men were studied for fatal outcomes for an average of 44 months. for a total of 667.753 person-years. Cause of death for 1 1,870 individuals was determined by death certifi- cate. Compared with never smokers. the relative risk of death due to CHD among current smokers of less than I pack per day was 1.75. Among former smokers of less than I pack per day, those quitting within the previous year had a relative risk of 2.09. those quitting 1 to 10 years earlier had a risk of 1 .S4, and those quitting for more than 10 years had a relative risk of I .09. A similar pattern was observed among smohers of 1 pack or more per day: among current smokers, the relative risk was 2.3: among quitters within the past year. 3.00: among quitters of I to 10 years. 2.06; and among quitters of more than IO years, I .60 (Figure 3). The authors speculated that the elevated 20s TABLE 2.--Cohort studies of CHD risk among former smokers Aged 55~64 Quit I 3 yr I .9 5 0 yr I.4 lO~bl4yr 1.7 ?I5 yr I.3 I.7 Awl 26.5 < Quit I ~4 yr I .O 5 Vyr I.3 IO l4yr 1.2 >lSyr I.1 I .3 TABLE 2.--Continued Reference Populallon Followup Numtwr of caes cinlollg former smohers Rcl:n~vc rd.\ compn~wtt \* irh nwcr w~,her\" Ftrrmer Currrm \mohrrs winher\ (`ommenl\ L)oll cl al. (10X0) Brni\h phyxicinns: 6. IYl women Hammond and Horn (1YSt-h.h) I X7.7X3 men aged SW50 44 mu for CUD denth\ 2.3 x0 40 IX fl4 40 Hammond and ACS CPS-I: 35X.533 men free of (iarflnhrl ( 1069) diagnosed CHD 6 yr for CIID mortatlty 7') 57 SS S2 70 0.01 Quit< I )r 2.OY I 10>1- I.54 >I0 y,- I.OY Prevlou\ly >I ppd Quit i I yr 3 (H) I-IOyr 7.06 >I0 yr I .hO Prevwu\ly I-t') clg/d:q Qull cl yr I.hl I--l\r I.21 5 Yir I.26 IO 141, ().%I >20 \r I .IlX TABLE 2.--Continued Reldive ri\ks compnred with never smoker\" Kelerrncc tlalnmond ;md (Llrllnhcl I IYW) ~C(IIltIIlUcd) anlonp former wlokerr 62 IS4 13s I33 x0 Former Current wlnher\ wwkrrs Comment\ 2.5s Prevlou\ly 220 clg/dsy Quit lhjr 1.17 I 76 Women 220 L?r/d;l) QW Nyr 1.10 0.Y I. I (W-2.7) 0.7 Aged 3Y40 I .Y Aged SOL5Y I. I 2.3 Only baseline kmohing data wed 2.0 3.0 depending on amount mokrd No data on duratwn I.3 Smohing intirrm;ttion upduted biennially 2.5 TABLE 2.-Continued Number of case\ Rclativr ri\h\ compared wuh never vnohcr\" Reference Population Followup among former \moher\ Former smoher\ Current 5moher~ Comments Cederlofet al. (lY75) Sample ofSl. 91 I Swedish IOyr 07 Quit I-Y yr I .s lOLlI 1.7 men aged I X49 Only hawlme Smoked . SOURCE. Hammond and Horn ( lY5Xhl. risk among recent quitters reflected the inclusion of men who stopped smoking because of early symptoms of heart disease. A second cohort study. the ACS Cancer Prevention Study 1 (CPS-I) (formerly called the ACS Z-State Study). was undertaken between 19% and 1972. Recruitment was by family, and eligible families had at least one person aged 35 or older. All family members aged 3.5 or older wtere asked to participate in the study: more than I million persons were enrolled. In a 6-year followup of 358.513 men free of diagnosed serious illness. clear reductions in risk ofCHD mortality were observed among former smokers compared with current smokers (Hammond and Garfinkel 1969). Among those smok- ing less than I pack per day. the relative risk among current smokers was I .90. Among those who stopped in the previous year. the relative risk v.as 1.61. and amon_e those with 10 years or more of abstinence. the risk was nearly the same a\ that for never smoher5. A similar pattern was observed among those smoking 1 pack or more per day. Current smokers at that level had a relative risk of 2.55. Quitters of less than 1 year had a relative risk of I .6 1. and those with between IO and 20 years of abstinence had only a slightly elevated relative risk of I .2S. Because of the very large number of deaths and the careful followup. the estimates of effect are relatively precise. In this period. cigarette smoking declined substantially. especially in the predominantly white, mid- dle- to upperclass groups represented by the study population. Hence. some misclas- sification of the current smoking group may have occurred. but the relative risks among former smokers. apart from the most recent quitters (some of whom inevitably resumed smoking). are likely to be accurate. In 19X2. a third ACS cohort. CPS-II. was initiated in SO States. The methods for recruitment and the population enrolled were similar to CPS-I. but the cohort was larger, vvith more than I .2 million participants (Chapter 3). Preliminary data based on 4 years of followup were published in the 19X9 Surgeon General`s Report (US DHHS 1989). Among men. former smokers aged 35 or younger had relative risks of CHD of 1.31. those aged 36 to 63 had I .7S. and those 65 or older had 1.29; the relative rijhs among current smokers were 1.94 . 3.X I. and I .62. respectively. A generally similar pattern wa\ jeen among women. When the data are examined by amount of previous smoking and time since quitting. the pattern of changing risk is influenced by the presence of disease at enrollment. When those who reported themselves a\ sick or as having previously diagnosed cancer. heart disease. or stroke at baseline were not excluded from the analysis, men who previou4y smoked fewer than 2 I cigarettes per day and who had quit smoking within the previous 3 years experienced a CHD mortality rate that was about 6 percent higher than that among current smokers. However, vvith increasing duration of abstinence, the risk among former smokers came very close to that of never smokers: after I6 years or more. the relative risk was 1.01 (US DHHS 1989). It is likely that the early peak in mortality among recent quitters partly reflects the effect of having included those vvho quit because of smoking-related illness. After excluding those with cancer. heart disease, and stroke at baseline, this early excess mortality is less apparent (Table 2). In all categories. those who quit 1 to 2 years earlier had relative risks substantially lower than those of current smokers. Findings are less consistent for those who quit within the past year. presumably because of a high incidence of smoking resumption in that group and the possible inclusion of persons who stopped smoking as a result of symptoms due to undiagnosed illness. A very similar pattern was observed among men who smoked 21 cigarettes or more per day, except that the relative risks were higher for all but those with the shorter period of abstinence. The absolute rates were lower for women, as expected, and the relative risks are thus statistically unstable. Neverthe- less, the overall patterns among female smokers were generally similar to those among male smokers. To examine the effects of smoking cessation at different ages. CPS-II data on cumulative mortality rates due to CHD were tabulated for 5-year categories of age at cessation. (See Table 3 and Chapter 3 for a description of the methods used to calculate these rates.) The mortality rates used for these calculations were based on subjects not TABLE 3.- Estimated probability of dying from ischemic heart disease in the next l&5-year interval (95% CI) for quitting at various ages compared with never smoking and continuing to smoke, by amount smoked and sex Age at quitting or at start of mterval Never smoker\ Continuing \moken Former smoker\ ,sician's orders were excluded from the analysis. Mortalit!, in this cohort uas monitored. and death certificates were obtained to assess cause of death. Smohing status after the baseline questionnaire was not ascertained. After 16 years offollo~up. quitters at enrollment when compared with never smohcrs had relative risks of I. IS for all cardio\,ascular mortality and I. 16 for CHD death specifically (Roget and Murray IYXO). In contrast. men who uere current smokers at baseline had relative risks of 1.5X for these two categories. Among past smokers. risk of death due to CVD increased with higher pre\,ious usual daily cigarette consumption. The relative risks among past smohers. compared Gth never smohers. ranged from I .02 for less than IO cigarettes per day to I .33 for 40 ciparettes or more per day. This gradient M as more pronounced among current smokers I Figure 1). A gradient was also apparent for decreasing rish with increasing duration of cmohing abstinence. For both cardiovascular and coronary mortality. there was a moderate decrease in risk with short duration of abstinence and a smaller. but consistent decline in rish uith longer periods of abstinence (Figure 5). After 20 years or more of abstinence. the relative risk of CVD was I .04. and for coronary death. the risk M as I .05. The major strength of the U.S. Veterans Study is the large numbers. M ith 2 I.1 Ii deaths from CVD among smohers and 9.077 among former smokers. The long followup period without reclassification of smokin, (7 status is a limitation. \\ hich M ill tend to lead to an underestimate of the effect of sustained smohing and an underestimate of the benefit5 of quitting (Chapter 2). This source of potential bias ma! not ha\e marhcdl~ distorted the estimates in this stud!: in the follo~up of this cohort (Roget and Murray 19X0). the relative risk for cardiovascular mortalit\ associated M ith current smoking at enrollment \\a\ I .h? at X.5 years and I .5X at I6 !ears: for coronar\ disease. the relative rish U;I\ I .6l at X.5 years and 1.5X at I6 vex\. Thus. the impact of misclassification of current smohers M ho quit (and therefore lowered their rish) as persistent smohcrs appears to be slight. A similar comparison of the relati\.e rishs among former smohers is less int'ormati\e in assessing the impact ofmisclassificati~,n. hfost quitters u ho resume smohins do 40 ~~ithin 2 years after cessation. Thcret'tore. IniscI~Issit`ication of e\-smoher5 betuecn X.5 and I6 fears of cessation is likeI> to he small. For both cardio\us~ular mortalit! and coronar! mortalit>. the relati\ e ri&\ among ex-smohers declined slightI> from I .2 I at X.5 hears of follo\vup to I. I5 and I. I6 at I6 yxrs of` follow up. This is consistent u ith the in\ crst` relation bet~reen duration of smohing cessation ;und mortalit\' ratio. Among current mohers In the l:.S. Veterans Stud!. the relati\.e rishs of coronar> disease \\ere slightI> hisher after X.5 years of follow up (relati\ e rish (RR )= I .Y5 for >20 cig/da\ ) than after 2.5 \cai-s of follo~up (RR=1 .75 I tDom 10.54). As expected. tho\e M ho stopped smohing on ;I ph\ slcian's orders v,ere at higher rish of death regardless of their smohinf statu\. An earl!, report of combined data from the Framinyham and Albany Heart Studies (Do! Ie et al. I Yh2) included 4. I20 men free from coronq di\easc at entr) into the stud!.. The Framingham Stud) data were bard on 6 lrars oft`ollouup and the Albany &art Stud! data on X bears of follo\~up. .4mong the 4 I I former smohers in the combined cohort. the rcIati\t' rish of Ml (age-adiusted) U;I~ 0.Y compared u ith nt'\`cr 71X . Gordon, Kennel. and McGee (1471) assessed the effects of \mol\ing cessation. In thi\ analysis. anyone who smoked for I lear or more during the mo\t recent ?-year interval between examinations was considered ~1 current moher. Ap- proximately 20 percent of men who reported that they had quit smoking a~ entr! into the studs resumed \mohing: about halfofthose smoked very little oronly intermittentI> after resumption. Compared with current smoker>. former smokers had B 30.percent reduction in fatal and nonfatal CHD (escluding angina): the relati\,e ri\h ;imong current smokers compared w>ith that among never \moken was 1.3. Other coronary ri4 factor\ were examined in detail: there uere no \ipnificant difference\ between per\i\tent smohers and those who quit. but those who quit Mere more likely to be ill. Hence. it would be expected that acl.justment for confoundin, ~7 would have revealed even greater benefit from cea\ation. The benefit of quitting seemed more marked in younger men. However. there w'ere only 73 cases ofCHD amon? the quitter\ \o that a detailed analysi\ could not be performed. The Western Collaborative Group Study monitored a cohort of 3.514 men for an average of X.5 years for CHD incidence (Rosenman et al. lY75). Information collected at baseline among men aged 3Y to 39 indicated that former maker\ had a relative rirh of 1.9 compared with that of never smokers . 30 percent lower than among current makers. For men aged SO to SY. former smokers had a relative ri\k of I. I compared with never smokers. 40 percent less than among current makers. Thih effect of cessation wa\ slightly greater than that observed after 4.5 years of followup (Jenkin\. Ro\enman. ZyLanski 196X). The difference between the age groups could be a true effect or may reflect different levels of misclassification: it is possible that a greater proportion of the quitters in the younger group than in the older group resumed smoking. In 1963. a prospective . Ury lY7Y ). The Seven Countrie\ Study (Keys IYXO) provided a valuable resource for analysis of rish factors for CHD. A total of I6 cohorts of men. aged 40 to 59. living in 7 countrie\. were examined and monitored for IO vear\ for CHD incidence. The cohorts were assembled between lY5X and 1064. and consisted of I ?.OY6 men free from CVD. In each rrouping of cohorts. former smohers had a lovver ri\h of CHD than did current c mohers. Houever. only about 7X case\ of CHD death among former smokers were reported: therefore. no detailed analysis w'as possible. Data on the health effects of smoking cessation are also available from the Health Insurance Plan of Greater Nevv York. The incidence of MI uas ascertained over a 17-J --- 3-year interval among I lO.OOO individuals (Shapiro et al. 196Y ). A total of 613 cake\ of MI were reported among men aged 35 to 6-l in this group. Compared u ith current smokers. those who quit in the preceding 5 years had a %-percent lower risk: compared with never smokers. the relative risk was 1.0. As in other studies. the percent reduction in ri\k associated with smoking cessation tended to be lower in the older age group>. but a decreased risk associated with quittin g wa\ apparent among all ages. Many studies of smoking cessation have focused on middle-aged men and women. Even as recently as the late 1970s. current smoking was considered to be a minor ri\h factor for CHD beyond age 65 (US DHEW 1979 ). and the benefits ofce\sation among older persons have been questioned (Seltzer 1971. 1975 ). Jajich. Ostfeld. and Freeman (1984) assessed the effect of quitting among 7 2.674 recipients of public as\i\tance aged 63 to 75 in Cook County. IL. Of the 2.674 individual\ studied. 770 were paht \moher\. 873 were current smokers. and 1.248 were never smokers. Participant> were screened at baseline and monitored for 4 years for CHD mortality. Overall. former smoher\ had a relative risk of CHD mortality of I. 1 I (based on 20 exposed cases). whereas current smokers had a relative risk of I .94. The number of cases was inadequate for a detailed analysis of the effect of duration of abstinence. Perjon\ with heart problem\ \vere not excluded at baseline. Approximately one-third of the CHD deaths were among those with such a history: therefore, it is likely that the apparent benefits of quitting may be understated because of the tendency of such individuals at high risk to quit because of illness. These data provide some evidence that the benefit\ of cessation extend to older adults. The British Regional Heart Study (Cook et al. 1986) monitored 7.735 men aged 10 to 59 who were randomly selected from general practice lists in the United Kingdom. The men were screened at baseline and studied for 5 to 7.5 years for incidence of fatal and nonfatal CHD; in this interval, there were 336 CHD outcomes. Those with CHD at baseline were not excluded. Compared with never smokers. quitters had a relative risk of approximately 2.5: compared with current smokers. the relative risk u'a\ approximately 30 percent lower. Men who quit smoking within the previou\ 5 years had a relative risk of approximately 3.3, compared with 3.6 among persistent smokers. Those who had quit more than 5 years earlier had a relative risk of approximate11 2.3. but there was no evidence for a trend of decreasing risk with increasing duration since cessation. Even those who had quit 20 or more years earlier had an elevated rish. After adjustment for other risk factors, the relative risk in this group was I .6 (p=O. I I 1. As expected, the prevalence of CHD at baseline among quitters was significantI> higher than for either current or never smokers. Presumably. the diagnosis of dihea\c provided a motivation to quit. When these men waere excluded. the relative risks were attenuated. Nonetheless. for those who had quit in the previous 5 years. the relative risk was still elevated at 3.2. The total years of smokin, (7 w'as suggested ah the mo\t important variable. It was also suggested that cessation lowered ri\k primarily b\, preventing the accumulation of further years of smoking. It i\ noteworthy that although results of this study are adequate to show an elevated risk among past \mhers. the number of cases among former smokers is too small to provide precise estimates of rish at the various durations since quitting. For example. there are only I I ca\es in the proup that quit 20 or more year\ earlier. Many studies of large cohorts examined the effects of smoking primarily among men. However, the Nurses Health Study investigators reported on smoking and CHD in a cohort of 12 I.700 women monitored through biennial questionnaires from I976 to 1989 (Willett et al. 1987). Women with previously diagnosed CHD were excluded from the analysis. Compared with never smokers. former smokers had a relative risk of I.5 (9S-percent Cl. I .&2. I ). In contrast. current smokers had a substantially elevated relative risk. ranging from 2. I for smokers of 5 to I4 cigarettes per day to 10.8 for those who smoked 45 cigarettes or more per day. There w'as no further analysis for the effect of duration of abstinence. The authors suggested that the slight elevation in risk of ex-smokers was due. in part. to resumption of smoking by some fraction of the former smokers. Adjustment for age: obesity; menopausal status; estrogen use: family history of MI: and personal history of diabetes. hypertension. and high cholesterol in a multivariate analysis led to an identical relative risk of 1 .S. demonstrating the absence of confounding by these coronary risk factors in this population. In another cohort study. Floderus. Cederlof. and Friberg ( 198X) monitored 10.945 twins born in Sweden between IX86 and 1925. Smoking behavior was ascertained at baseline in I96 1, and the cohort was studied for mortality for 3 I years using matched- pair analysis. Among the males. former smokers compared with never smokers had a risk of coronary mortality of 1 .O (95-percent CI. 0.X-I. 1). In contrast. current smokers had relative risks ranging from I .4 to I .8 depending on amount smoked. There were no data on duration of abstinence at baseline. and there may have been changes in smoking prevalence during the long followup that would tend to attenuate the relative risk. In a unique cohort design. Raichlen and coworkers ( 1986) examined progression of atherosclerosis among 33 men who underwent coronary angriographies at least 7 years apart. Among current smokers. progression of disease waj statistically significant and was correlated with pack-years smoked during the interval. Among pa\t smoker\. the degree of progression of atherosclerosi\ was far Ies\ than among current smokers: it w'as not statistically different from lack of progression. Several other cohort studies have reported on the relation of smoking cessation M ith risk of CHD: however. the number of sub.jects was generally too small to contribute substantially to knowledge in [hi\ area (Table 7). Intervention Trials In >everal clinical trials. an attempt has been made to ev aluatc the effect of altering ri\h factors for CHD. including smohing (Chapter 3). !Uost of the trials including smoking cessation have also incorporated interventions for other CHD rish factors mahing it difficult to assess the independent effect of quitting. Nonetheless. the\e data have extended the understanding of the effects of mohing ce\\ation on CHD rish. AssesGng \elf-report of smoking cessation or decrease in cigarette consumption is another potential difficulty. There may' be a tendency for sub.jects in a trial to seeh approv.al and avoid ne gative feedbach by, reportin, 17 le\s cigarette use than i$ actually the case (Chapter 2). Such a tendency would have the effect of miscI:t\\ification and would yield an underestimate of the benefits of cessation (Table 1). 72-l TABLE 4.--Intervention trials of smoking cessation and CHD risk Rcferencc Population Intervention oulcome caw\ among fwnmer moher\ Effect of wlohing ce\sttton (nonrandom~~ed) Hughe\ et al. ( I')81 ); MRFIT: I?,Xhh healthy US Diet, reduction in weight. CHD death\ I5 7% declme iI1 4J1k reduction MRFIT Research tnen aged 35-57 at high CHD hypertenswn, and smoktng interventwn group compared with Group ( 1982. I YX6): r&k peralwnt smokers Grimm (19X6): Ockene et al. MRFIT: 7,663 participant (IYYOI smokers at entry Diet. reduction in weight. hypertension. and smohmg (`HD dcnth\ 33 Quitter\ had 42% reduction t Ih~hO'% 1 MRFIT: h.Y43 participant smoker\ at entry Diet. reduction in weight, CHD death5 I2 hypertrn~ion. and amohlng Iljrrmann et al. (IYXI) Oslo study: I.232 healthy Diet and wioking Oslo men aged 4(WY 31 high C`HD risk Kornttxr et al. (IYX.31 I Y.409 male Helgian tlctory workers. aged 40-51) Anti\moking. hypcrtcn\ion control