Chapter 1 Oveniew - The Health Consequences of Smoking Source: 1975 Report, Overwew - The Health Consequences of Smoktng. pages 1 8. 1 OVERVIEW - HEALTH CONSEQUENCES OF SMOKING The statement, "Warning: 77re Surgeon General Has Determined That Cigarette Smoking Is Dangerous to Your Health," has been required by law on cigarette packaging since 1970 as a part of the Public Health Cigarette Smoking Act of 1969. This Act was a response by the U.S. Congress to the scientific information on the health consequences of cigarette smoking summarized in reports then avaiIabIe (the Surgeon General's Report of 1964 and the subsequent 1967, 1968, and 1969 PHS Health Consequences of Smoking). This Act was passed because a series of important questions concerning cigarette smoking and health had been answered. The following discussion summarizes the basic questions, the methodology used to determine the answers, and the answers themselves. The initial question to be answered concerning the health consequences of smoking was "`Are there any harmflt/heaIth effects of smoking cigarettes?" The answer to this question was provided in two ways. First, it was demonstrated that some diseases occurred more frequently in smokers than in nonsmokers. Second, a causal relationship was established between smoking and these diseases. Concern about the possible health effects of smoking started when scientists began looking for an explanation to account for the rapidly increasing death rate from lung cancer. The early retrospec- tive studies showed a link between lung cancer and smoking. The first prospective studies, however, found that only oneeighth_of.the excess overall mortality found among smokers could be accounted for by lung cancer; the rest was 1argeIy due to coronary heart disease, chronic respiratory disease, and other forms of cancer. They also found that the effect on overall mortality was largely confined to cigarette smokers rather than the users of other forms of tobacco. However, demonstrating an association by statistical probability is not enough to establish the causal nature of a relationship. Deterpining that the association between smoking and excess death rates is cause and effect was a judgment made after a number of criteria had been met, no one of which by itself is sufficient to make this judgment. These criteria as listed in the Surge0;: General's 3 Advisory Committee Report (1964) were the consistency, strength, specificity, temporal relationship, and coherence of the association. In addition, con.vincing theories about the mechanisms whereby smoking contributes lo the various diseases responsible for the excess mortality among cigarette smokers were developed from the evidence on the biochemical, cytologic, pathologic, and pathophysiologic effects of cigarette smoking, thereby providing the necessary support for the decision that the relationship was causal. The most important specific health consequence of cigarette smoking in terms of the number of people affected is the development of premature coronary heart disease (CHD). Boih prospective and retrospective studies clearly established that cigarette smokers have a greater risk of death due to CHD and have a higher prevalence of CHD than nonsmokers. Long-term followup of healthy populations has confirmed that a cigarette smoker is more likely to have a myocardial infarction and to die from CHD than a nonsmoker. Cigarette smoking has been shown to be one of the major independent CHD risk factors and to act in combination with other major alterable CHD risk factors (high blood pressure and elevated serum cholesterol). Autopsy studies have shown that persons who smoked cigarettes have more severe coronary athero- sclerosis than persons who did not smoke. Physiologic studies and animal experiments have indicated several mechanisms whereby these effects can take place. A second major health consequence of smoking is the develop- ment of cancer in smokers. Cigarette smoking was firmly established as the major risk factor in lung cancer. The risk of developing lung cancer was found to be 10 times greater for cigarette smokers than for nonsmokers. The risk of developing lung cancer increases with the number of cigarettes smoked per day and is greater in cigarette smokers who report inhaling, who started smoking at an early age, or who have smoked for a greater number of years. Smokers of filter cigarettes have been shown to have a lower risk of developing lung cancer than smokers of nonfiiter cigarettes, but the risk remains well above that for nonsmokers. The risk of developing cancer of the larynx, pharynx, oral cavity, esophagus, pancreas, and urinary bladder.was also found to be significantly higher in cigarette smokers than in nonsmokers. Pipe and cigar smokers were found to have elevated risks for the development of cancer of the oral cavity, pharynx, larynx, and esophagus when compared to nonsmokers. Fewer pipe and cigar smokers than cigarette smokers report that they inhale. As a result lungs of pipe and cigar smokers receive much less 4 exposure to smoke than the lungs of cigarette smokers. This is probably the primary reason for the lower incidence of cancer of the lung for pipe and cigar smokers compared to cigarette smokers. Women have had far lower rates of lung cancer than men. This has been attributed to the fact that fewer women than men smoke and the fact that women smokers generally select filter and low tar and nicotine cigarettes. However, the percentage of women smokers in the United States has increased steadily in the last 30 years, and since 1955 the death rates from lung cancer in women have increased proportionately more rapidly than the rates for men, reflecting this increased proportion of women smokers. The tar from cigarette smoke has been found to induce malignant changes in the skin and respiratory tract of experimental animals, and a number of specific chemical compounds contained in cigarette smoke were established as potent carcinogens or cocarcino- gens. Malignant changes including carcinoma in situ were found in the larynx and in the sputum exfoliative cytology. of experimental animals exposed to cigarette smoke. Nonmalignant respiratory disease is a third area of smoking- induced morbidity and mortality. Cigarette smokers have been shown to have more frequent minor respiratory infections, miss more days from work due to respiratory illness, and report symptoms of cough and sputum production more frequently than nonsmokers. Retrospective and prospective studies with long-term followup have found that cigarette smoking is the primary factor in the develop- ment of chronic bronchitis and emphysema in the United States. Cigarette smokers have also been found to be more likely to have abnormalities of pulmonary function and have higher death rates from respiratory diseases than nonsmokers. Data from autopsy studies have shown that cigarette smokers were more likely to have the macroscopic changes of emphysema, and that these changes are closely related to the number of cigarettes smoked per day. MUCOUS cell hyperplasia has been found more often in cigarette smokers. Cigarette smoke aIso inhibits the ciliary motion responsible for cleansing the respiratory tract. An additional area of health concern has been the effect of cigarette smoking during pregnancy. Mothers who smoke cigarettes during the last two trimesters of their pregnancy have been found to have babies with a lower average birth weight than nonsmoking mothers In addition cigarette smoking mothers had a higher risk of having a stillborn child, and their infants had higher late fetal and 5 neonatal death rates. There are some data to show that these risks due to cigarette smoking are even greater in women who have a high risk pregnancy for other reasons. These effects may occur because carbon monoxide passes freely across the placenta and is readily bound by fetal hemoglobin, thereby decreasing the oxygen carrying capacity of fetal blood. Having established that cigarette smoking is a significant causal factor in a number of serious disease processes, two additional questions became important. They are "Can the health consequences to the individual be averted by stopping smoking or by changing the cigarette. " and "What are the overall public health consequences of cessation and of the changes made in cigarettes?" The first question is the simpler of the two to answer. In the individual, cessation of cigarette smoking results in a rapid decline of the carbon monoxide level in the blood over the frrst 12 hours. Symptoms of cough, sputum production, and shortness of breath usually improve over the next few weeks. A woman who stops smoking by the fourth month of her pregnancy has no increased risk of stillbirth or perinatal death in her infant related to smoking. The deterioration in pulmonary function tests that occurs in some smokers becomes less rapid than that of continuing smokers. The death rates from ischemic heart disease, chronic bronchitis, and emphysema also become less than those of the continuing smoker. The risk of developing cancer of the lung, larynx, and oral cavity declines relative to the continuing smoker in the first few years after cessation and IO to 15 years after stopping smoking approximates that of nonsmokers. A smoker who switches to filter cigarettes and has smoked them for IO years or longer has a lower risk of developing lung cancer than a smoker who continues to smoke nonfilter cigarettes. The risk to a filter cigarette smoker, however, still remains well above that of a nonsmoker. The public health benefits of cessation are more difficult to determine than the effects of cessation on the individual. Just as cause-specific death rates have reflected the effect of cigarette smoking on certain diseases, they should also reflect any substantial benefits to be gained by cessation or reduction in cigarette smoking. Several factors combined to produce a reduction in per capita dosage of tobacco exposure in the United States for the years 1966-1970. First, per capita consumption of cigarettes declined from 4,287 cigarettes per person in 1966 to 3,985 in 1970. Second, during this period there was a slow but significant decrease in the average tar and nicotine content of cigarettes as well as a decrease in the amount of 6 tobacco contained in the average cigarette. The decline in per cnplfa consumption during those years occurred in the face of a substantial , increase in the proportion of young women becoming smokers as cornpared to women of previous generations and SO reflected t predominantly a decrease in cigarette consumption by men. Since 1970, although the per capita consumption of cigarettes has increased. the average levels of tar and nicotine have continued to decline, making it more difficult to predict what has happened to per capita dosage. Examination of cause-specific death rates for the period of this declining per capita consumption reveals that there was a downturn in the male death rate from ischemic heart disease beginning in 1966 which reversed the upward trend that had occurred over the previous two decades. This decline in the death rate from ischemic heart disease has not occurred in women. The male death rate from chronic bronchitis has also been declining since 1967, and the male death rate for emphysema has declined since 1968 when it was first recorded as a separate category. Female death rates for these two diseases have not shown these trends. Despite the impressive coincidences of the decline in death rates among males occurring at the same time that there was a decline in per capita cigarette consumption, it is impossible to be certain of the exact cause of the decline in the death rates. These diseases are influenced by a variety of factors in addition to cigarette smoking such as blood pressure and air pollution. Some of these factors have also been subject to major control efforts which may have contributed to the decline in the death rates. In addition, there have been therapeutic advances in the treatment of these problems which may also have helped lower the death rates. A decline in male death rates from lung cancer should also follow the decline in per capita consumption. This rate would not be influenced as much by changes in other etiologic factors or changes in therapy because cigarette smoking causes from 85 to 90 percent of all lung cancer and there have been no major improvments in survival due to changes in therapy. With lung cancer, however, two additional considerations must be kept in mind. A decline in death rates from lung cancer would be expected to lag several years behind a decline in per capita consumption. In addition, the decline in consumption and switch to low tar and nicotine cigarettes occurred 7 predominantly in the younger age groups where death rates from Lung cancer are low. For these reasons, it is necessary to look at lung cancer death rates by age group rather than total lung cancer death rates. The lung cancer rates by age groups for 1971 suggest a decline in the lung cancer rates for the younger males (under 4S), but the confidence limits on these trends at present remain wide enough that it is impossible to say whether this is a real decline or merely a leveling off. The national health statistics broken down by 5-year age groups are currently available only through 1971. The data by age group from a few more years will be necessary to determine whether the changes in smoking behavior which have taken place have reversed the trend of the preceding 4.0 years of continually increasing lung cancer rates in men. In 1971, the last year for which detailed mortality statistics are available, the accumulated exposure to cigarettes reached its peak among men born between 19 I5 and 1919, a group then in their early 50's. Cumulative exposure has continued to decline with each successive S-year birth cohort born since then. The trends of the last few years offer some hope that the peak of the "lung cancer epidemic," as some have termed this phenomenon, may have been reached with this group and that future years will show a slow but consistent decline. 8 Chapter 2 cardidar~s Pan I - 1971 Rspori, Chapter 2, 15 - 174. paQa Pan I1 - 1975 Remrt, Chapter 1. 9 - 38. paws Chapter 2 Cardiovascular Diseases Part I Contents Introduction Paga Smoking and Obesity . _ . : i - . . . . . . . . _`. . . . . . ii-; `. `. : :!; 39 Smoking and Electrocardiographic Abnormalities. I.--I; 43 Smoking and Heart Rate . : .`;-:t.`: ;:i;..' i, .;- .I ..,> _, .`_*.*._`. . . . . 43 The Effect of Cessation of Cigarette Smoking on Coronary i Heart Disease.. . .";. ; ::; ::`;f: _ 1';. e5'.:1'l . , . .". `: i 1` ; 5' . . :' . . . ,-.y'T. 43 The Constitutiona] Hypothesis ;: .;~J:-~-~,~: ;:!;:Y,< ,`t.: ;:,I )y.F.> 44 Autopsy Studies Relating Smoking, ~Atheros~lerosis, and ~' "- ti Sudden CHDDeath . . . . .`;:..`; .!..`~...`.~.~.;:`....~~`~.I':i'~'):: 48 Experimenta Studies Concerning `the `Relationship of ' Coronary Heart Disease and Smoking . . `. .: : : : : . ; : . `. .`." `.' 52 Cardiovascular Effects of Cigarette Smoke and Nicotine . * - , _ , -`.":" ." I `;I,' a;;:, . . .._.............._........ 52 Coronary Blood Flow _ . . . . _ . `. .I,o.y'L'; P .:t &j.`;;:!:`! *1! !&j `<>*<..a.irTJr; ;`- . . . . . . . . . . . ..-....... ) :54 Cardiovascular Effects of Carbon Monoxide . ;i .`i; I. 5 ::f. 1 .`i'.55 Effects of Smoking on the Formation of Atherosclerotic _,`. Lesions -- .-..- I-, II-- . .I `i . . . . . . . . . . . .._. . . ...`::. . . . . . ..-.. .:;r'.. . The Effect of Smoking on Serum Lipid Levels . . J:~!:~ ;; ?:s- 59 .f 61 The Effect of Smoking on Thrombosis . i; ;:;J.:. :Y,:.,`~~~~l~`~~~ 62 Other Areas of Investigation - _L. ._ . , : ., . . ., . . . . ., . . - - .-. :. 2 - , . . . , -* , ?Z I. . Iit. i . . . . . . ,:;-, '..,,' *- . :; 62 Nonsyphilitic Aortic Aneurysm . . y.;. . `. . . .:. ;`I-. . .,;r:t:!.r.~r.- .' 63 Peripheral Arteriosclerosis . ;`.`. .: ; . .-::`;:!u. ;. ;. . . .: ::1?-:3!;.$68 -`.,:r--`:;i~ ,`) -, .,? := i ,*,-' ,r` `. Experimental Evidence.`:".~~.;.",~,~!,I^;.!;.-f!~,.: ~~~;, ,:,r-: I- .69 Thromboan.itis ObIiteran;Y :`~:x-~iif*:i?~~. f;:F:nfi- ./-:s;f :+.3 `,;Q-j . . . . . . . . . ..`................ Summary and Conclusions . . . . . . -. .- `eiIj,ure -, `!::,y-;.p::2, . . . ...* :..- . . . . . s..: . . . . -. _ _...,, W..`.`. I-.--. 13 -Coronary Heart Disease . . . . _ . _ . _ . _ . . Coronary Heart Disease . . . . _ . _ . _ . _ . . Pap Pap ..-..-....a.. ..-..-....a.. 70 70 Cerebrovascular Disease . . . . _ . . _ . _ . . . . Cerebrovascular Disease . . . . _ . . _ . _ . . . . . . . ..-...... . . . ..-...... Nonsyphilitic Aortic Aneurysm . _ . . . . . . Nonsyphilitic Aortic Aneurysm . _ . . . . . . 71 71 . . . . . . ..---. . . . . . . ..---. Peripheral Vascular Disease _ . _ . . . ; -. . . Peripheral Vascular Disease _ . _ . . . ; -. . . 71 71 . . . . . ..-.... . . . . . ..-.... 71 71 References.. _ _ . : :... . . . _ ; :;.;+;ii;;T F References.. _ _ . : :... . . . _ ; :;.;+;ii;;~ F .' .' `,............~`.""" `,............~`.""" 71 71 ,.. ,.. FIGURES FIGURES `11 National Cooperative Pooling Project, Inter-Society Com- 3 ~ssion for Heart Disease Resources, :;. `!,: .+ ..; I, ,,., i c r . . .2-i.-. ,"`+."...j_.~ 1g p Risk of coronary heart diseas;?"(l2 years) according to .-- ..&; . . cigarette smoking habit and-presence of "p&&&ing j';. factors" .(men 30-59 at entry). Framingham Heart $!. cl -\- `Study. .`:`---.`:.`:`.`::"-"`:`::.-"` " a.. . . . . :. :. . . . . . . . -s- : I . - .;,;.-.;-;,' ratio: "i'ca 17-51 2. 3. Estimated coronary heart disease'death year follow-up, and frequencies of paired combinations of six high-risk characteristics in college, for all ages at death _ . . . .I ", `_ . . . . . . . . . . . . . . . . . . . . . . . ;..ii- ,-..... . . 21 4. Relationship between smoking status and serum choles- terol level at initial examination, and incidence of chn- ical coronary heart disease in men originally age 40-59 free of definite CHD. Peoples Gas Light and Coke Company Study, 1958-1962.. . . . -1.. . . . . . . . . .,. :. . . . . . ~. -39 6. Average annual incidence of first myocardial infarction among men in relation to overall physical activity, class, and smoking habits ,,(age-adjusted rates per 1,000) . . . . ..'.~.........; . . . . . . . . . . . . ..1..~.....-.'40 . :.: 1i- 1 _,a , . . ::._a , _ .;. _-<. .; :...I _, :-. aLIST OF kABiESs' -, . . ; . J. ~..~~j'~'.-~~~;jsij~ -: , : . (A indicates tables located in Appendix at end of Chatte;? ::, ji;L2,. .._ .._ . . . L . . . . ._. ,. I 1. Sudden death and acute mortality with first major.-: coronary episodes . 1 . ; :`; . ! :.I:. .e.:. :. ; ;r:`.`.-. . . r-y:: 19 2. Coronary heart disease mortality ratios related to smoking-prospective studies. _ -mci-J; ;IJedz:i.>< ..`;`.`.=~:rc-, ,.22 3. Sudden death from coronary heart disease related to :`. - ' smoking _ ..; -. ;r - - .-; . . . . :< ;`.-; . -`. ..-i;! _ ;`: /. `$i*;;. .`.:r!-!f; 26 4. Coronary heart disease morbidity as .-related .to .<%TL?-~ smoking. _ .; :. . . . .:. . . . . . .;. . . . . . . . -; 1 :.;-:-:,:.- ;,;~&;_?~~ 5. Coronary heart disease morbidity as related to smO~~,R~~.~ &d ing-angina pectoris-prospective studies Y.`: i -.-. .rX2 33 A 6. Coronary heart disease- morbidity and modid+- r retrospective studies `. . .-. . . . .`. . .' .`.- ; y'. ;-. ::w, ~.>,:Ai.:-,.L:~t8g . . . . . : . . - A 7. Differences in serum lipids between smokers and non- r"c!l'%. smokers. .1---- --. . . . . . . . . . . . . *.......-...... . :. . . -.94 EI ~_ - -- 14 usr 0~ TABLES (CONT.) [A indicates tables located in Appendix at end of CII~~~~, ^ Page A 8. Blood pressure differences between smokers and non- i smokers . . . .-;.: 7:. m-i,;`.-,r- :- .I.. -:..;; . . . . :.:.-.r`.-.::~):.`,, 99' 9. Death rates from coronary heart disease, by systolic - +J k -L - blood pressure: ILWU mortality study, 1951-1961 38 10. Death rates from coronary heart disease, by diastolic : !:J::' -, % ..L blood pressure : ILWU mortality study, 1951-1961 38 .-II. Death rates from coronary heart disease, among hy- ..?- ;;bl: pertensives and nonhypertensives : ILWU mortality ' 1 t-j ; study, 1951-1961_. ;:..:F:': ;`I. ;;;~;;.f~.i ;+ j: F?;< :i.yi-i.>{rg ,38 ,12. Death rates from coronary heart disease among men. ,a; without abnormabties related to cardiopulmonary `diseases by weight classification in 1951: ILWU morfa1if.y study, 1951-1961. : ;":`;`!?":?~~`:?;!:?;~-I:;`-.::`;:! 41 13. Death rates from coronary heart disease, by electro- : cardiographic findings in 1951: ILWU mortality study, 1951-1961............................. 14. 1958 status with respect to heart rate, blood pressure, cigarette smoking, and ten-year mortality rates, by cause (1,329 men originally age 40-59 and free of definite coronary heart disease) Peoples Gas Com- pany Study,1958-1968....................... 15. The effect of the cessation of cigarette smoking on the incidenceof CHD . . . . . . .._.._......._........ 16. Annual probability of death from coronary heart dis- ease, in current and discontinued smokers, by age, maximum amount smoked, and age started smoking A 17. Incidence of new coronary heart disease by smoking category and behavior type for men 39-49 years of age --.........................-.~........ A 18. Incidence of new coronary heart disease by smoking -- -- 101 category and behavior type for men 60-59 years of age . . . . . _ . . .`. . _ . .3 . . _`. . . .: .-T. .`1 .: . . . ..-. _ . . 302 19. Autopsy studies of atherosclerosis _ . . _ . . . . . . . . . . . . 49 A 20. Experiments concerning the effects of smoking and nicotine on animal cardiovascular function . . . . ; . 103 A 21. Experiments concerning the effects of smoking and nicotine on the cardiovascular system of humans. . 109 A22. Experiments concerning the effect of nicotine or smoking on catecholamine levels - 115 e.......,....... A 23. Experiments concerning the atherogenic effect of nicotine administration - .- 116 . . . ..-.................. 41 41 42 42 LIST OF TABLES (CONT.) (A indicates tales located in Appendix at end of Chapter) Page 24. Experiments concerning the atherogenic effect of carbon monoxide exposure and hypoxia _ 60 425. Experiments concerning the effect of smoking and nicotine upon blood lipids (Human Studies) *' rx.-.--rclf- .----s 119 C125a.Experiments concerning the effect of smoking and.lmPKG./DAY `1,' . 1 ' `.' 196' .s , . ,: .z..A:,, ___; 37 - 12 x7 - NONE ANY ONE . 7'. P PREDISPOSING FACTORS (CHOLESTEROL > 250. HYPERTENSION. DIABETES) *SIGNIFICANTLY DIFFERENf FROM "NONSMOKER" P<.D5 ,. .$. ._ = <. , 7 ,: :; : _ + 3 _- . . .= `.- E~CURE Z-Risk of coronary heart disease (12 years) according to cigarette smoking habit and presence of "predisposing factors" (men 30-59 at entry). Framingham Heart Study. . .: SOURCE: Kannel, W. B., et al. (9.4). _ $-, f `.: ; .I< 1.. -- _- :,;: _, :. ;. ,_* :: : : _ < . . ;;.. 1, .F : -`. I * ,`< : : ;' r.. -- ., _ : ; 1 s-j ^I __ .;,` -i I . _- I +. .Y Numerous epidemiological studies have indicated that cigarette smokers have increased mortality ratios for CHD ; that is, cigarette smokers show significantly increased death rates compared with nonsmokers (table 2). The risk incurred by cigarette smoking in- creases with increasing dosage and, as measured by mortality ratios, is more marked for men in the younger age groups, under age 60, although the absolute increment in death rates experienced- by smokers over that of nonsmokers continues to increase with increasing age. Table 2 lists the mortality ratios found in the major-' studies. Certain of these studies, including those at Framingham, Massachusetts, the Health Insurance Plan of Neti York City (HIP), and at Tecumseh, Michigan, have analyzed morbidity as well as mortality from CHD and have indicated that the risk of developing fatal and nonfatal CHD is greater among -cigarette smokers than among nonsmokers (tables 3 and 4). Conflicting etidence has been published concerning the relationship of ciga- rette smoking and the incidence of angina pectoris. While some 20 CI**nttn --I 3 SF. BP 130+ --B 2.4 . 131 2 140 1.4 1.4 LO 238 201 1 324 442 373 clI!Il 644 O- I CI~."ttsl `-A 3 H,ilhl <69 -B 2.0 2 ---.. 1.5 96 I.3 124 1.0 Z?? 1 Lllllh 199 346 468 394 875 0 no rpxt-A SP. BP no+ -6 . _- :`:. I O- i C' ! . k. .1. 2 1.1 1.9 ). 7b 1.3 124 102 1.0 1.1 - 149 1 232 4`2 ,- sp. BP 130+ _A hnnl dud --II : . . ; 2.5 3 2 ' 1 10 3 .._ 2 I -0 3 _ 2 I -0 3 2 1 -0 3 /- A+ A- A+ TABIF. 2.-Cormry heart disease mortality (Ati number of dathm [SM = SmoLcn AMhOG .* __. ,a=, amnh. Nmbcr,d .~. --. `: ; pOD&tiOn " Data rcfermm cdkctIon Hunmoad 187.7BS QucaLIm- ;"I a% 6.297 NS . . . . . ..!!l.OO (709) md rhItcmrkm nab.? md __-.___ -.----.-Msmokcn .1.70 (assl) - Horn. fne.t.ba - 1968. ' c&-69 ,e*n V.SA oflpr - mate. -\ (,,, ,I). _, _. , : : t `. `(v26 . . . . . . ..*.43 (50). : : ,, ,- I .- ,, . . ,(;:, 7 stmbel a.743 male Question- e 162 NS . . . . . . ..LOO md Gc.eU eSti phy- enrim and :.. i _ -;:,..>-.c -2 1966 skiam. fOUOW-Up I.__ _, l-20 . . . . ...1.48 swit.mr- of death hnd . -7 ' ">20 ________ 1.76 (`c: 1, crrti6ute. (150). .-- i ~~ Bat. Appmri- Quatioa- 6 mat.& `. , naircmd L :-7 j _ 2.000 NS . . . . .._. 1.00 1966 Allsmoker, .I.60 (1380) Ctnadn 78,cmo fOlhLWD c- ; ,tt,;j .-is ;, `Z I;,.. ;:_- 20 ..:..::1.78 (277) --,: returns. `- r. a: ; _L;;,~ -2 ,I ,kF ., lrdm 1966 U.S.A. . (88). us. In& Qoestion- 8% 10,890 NS ________ 1.00 (2997) vctcrula nrire and Allsmokcrs .1.74 (4160) : 2.266.674 fouoov-up :, -.. :" 1-3 ..-.__-. 1.39 (43SP ; :`..`. Del-m ~I. of dalb _ry t :- ..`I IO-20 _.._. .1.78 (2102) 1' : : i Jan. I ' ecrticlute. ' PI-39 . I ; I ___.._ 1.84 (1292) ; . . 1 fl .,y.-, : ; : : 7-q ;-`,l,. c 2 . . --?>39...... . .-.f.OO (266) i. Hhw. 266,118 Rmincd in- * 1 91 NS ____ ____ 1.00 fl7) . nmks LIcdiulu- l2 62 NS ..__ .-..l.OO (27)) ratios related to smoking-prospective studies dlcmn b parentheses)' NS = Nonamokenl - _.- . . .~ __-_ Cigars I. ,... NS..l.OO .- `- : NS ..`. so-Sb 6649 6-I 6548 . . . . . 1.00 190) 1.00 (142) 1.00 (204) 1.00 (273) . rI.C : b,.?zmG SM..1.28 (420) ..AUsmokcrs .193 (765) 1.85 (962) 1.66 (921) 1.41 (718) .<., .,,,:,!;,.; Pipu . . . . . . ..I.38 (36) 1.98 (60, 1.17 (49) 127 (68) NS..l.W - -""l20 . . . . i::.Z.Kl (203) 2.47 (199) 1.92 (129) 1.66 (78) .t z -s:. :;.$> ). ,, ' Data WDIJ : . . 7. . . . : : ~. ._ or& to maks . . 4red40-49 -. md irea CucED~t entw.NS Include Dive, .___ ~. ~----. ._.-._. --- __. _.._ -..- _. -. --._-. . ~~~___~ _ -- .- ..--- eksrmd : .-I : I a:;-. I, . ..-f.. er-amoken. Sd-bb bsmb 85-64 : . NS . . . . . . . ..l.OO 1.00 1.00 :t.: . I-14 . . . . . .x73 : 1.40 1.71 ! ? _ : lb24 . _. . .4.46 1.79 1.27 . . : i.%. >26 . . . . . ...1.36 1.92 1.68 --. -..-.- _ _. _ _ _. .~ _ .- _- - _- - - NS. .I.@, sy..1.46 .I : - ;.:-.. ._, : : Tllsu 2.-Coronaty heart disease mwtdity ratios (A&ml number of dacha (SM = Smokrn 5mond :c4*!`1L- :, C..,`.". ti-.:t !N-z _' ., ;-:-- -._ : . . . . `2 t:.!iJ` . : : . . I; ,.. :.., :. c i:..Z!.- :. . . . ._ :: Paffcnbu- 60.000 m& BUClIlIIT 17-61 1.146 NS . . . . . . . . 1.00 zcr md ._ former intervIew -..--r-mddxd 24 . . . . . ...1.60 (886) (D20 . . ..z.os 1970. men 8664 screeninp U.8& Jean of and follow- (zra). m. 09 of dcnth CcrtIflc~Cs. Tad.x _,K71 m.l* lntcrvlew. 6 ,_ 46 NS . . . . . .._ 1.00 (4) ,* ., o ? ?o?? railroad md rmulqr . <20 . . . . . . . .I.97 (20) I < i. 1970.. -Db?m foollaw-up - USA 4&69 ye=n ULPL- -.: :c, (-:, ;I! >2@ . . . . . . . .S.60 (22) c: (18s). of aamat Ln.t,on. ! : `.Z. :, 1 !I,i;; <.`.I . `:-, < , .:`. Pooh T.427 white XedIcrI a- 10 239 NS ._._ me m&s . . . . .I.00 (27) unIaatlm Amdan :.,_ `. :- 20 . . . . `. . . . S.00 (68) -:,,L. ___ .- _ .--w------y--_ .: -, <-; tJ=b -_. :. _ `) - ,,.. :-., I/ 1970. ., ... * ,,, US& :.. (Jr). - : _.! , _`., + I .). `- .; ,. _.' - r. , ,:I-; ,._ .. _-. ., _, 24 related to smoking-prospective ntudies (cont.) .hom in 9.~theses)I .,s'? ' NS = Nona.a~cn] ^ A'..- --.+-.. --. .- : T, `. : - I r - - ---~ --- -,o-" as--51 ,s-4* , .`-.. ----- - ------ - .. NS . ..`...... 1.90 1.00 1.00 ,:i, `I',3 ' .;.; (DA.: :. .>t,. - __. __ ._. . .:vl_.,: "I _ 7:..:..-?,1 ,r; -:; ;ic :I -,;.'z ,l?:.z:. : .' L-c,:-..- .?I- I(: ..`i -5 . ,,' ~. . . . _~ ~. ~. -. _ SC-II b6-6b 65-d& .86-m . ..NSincluda __ `. `5 .: us _ ,....... 1.00 1.00 1.00 .`: 1.00 -, i; ?: DfDa mad : I-.. 2 &IO . . . . . ...4.22 2.06 1.41 1.17 .I>l!~.`dpsm. `: ,I .- i- l. -, r: `.(T ___ 520 . . . . . ...6.14 a.17 1.64 .i 1.26 '!I!&:&. ml inchlda ^ ,.. 7.' -_-. *Jo . . . . . . ..I357 ldl 1.66 .,r 1.86 ..rrf?,eramoktn.- ' e.2 .ro . . . . . . ..i.sa a.16 1.42 :-I 1.42 <>,I! .- . :- 7 . r-' AU . . . . . . ...6.24 2.96 l-66 i 1.24 ..' _