PART 1 Current Information on the Health Consequences of Smoking Summary of the Report This report is a review of the pertinent medical literature on the health consequences of smoking which has appeared since the publica- tion of the 1968 Supplement to the 1967 Public Health Service Review. The 1964 Report of the Advisory Committee on Smoking and Health, the 1967 Public Health Service Review, and the 1968 Supplement have presented the broad base of converging epidemiological, physio- logical, pathological, and clinical evidence on which knowledge of the health hazards of smoking is based. Included in this evidence are data which show the magnitude of the excess mortality and morbidity among smokers. The following conclusions regarding the health consequences of smoking were summarized in the 1968 Supplement: General Mortality Information . Previous findings reported in 1967 indicate that cigarette smok- ,is associated with an increase in overall mortality and mor- EL 1 1 y and leads to a substantial excess of deaths in those people who smoke. In addition, evidence herein presented shows that life expectancy among young men is reduced by an average of 8 years in "heavy" cigarette smokers, those who smoke over two packsla day, and an average of 4 years in "light" cigarette smokers, those who smoke less than one-half pack per day. Smoking and Cardiovascular I&eases Current physiological evidence, in combination with additional epidemiolo ical evidence, confirms previous findings and suggests additional % iomechanisms whereby cigarette smoking can con- tribute to coronary heart disease. Cigarette smoking adversely affects the interaction between the demand of the heart for oxygen and other nutrients and their supply. Some of the harmful cardi- ovascular effects appear to be reversible after cessation of cigarette smoking. Because of the increasing convergence of epidemiological and P hysiological findings relating cigarette smoking to coronary leati disease, it is concluded that cigaret,te smoking can con- ,tribute to the development of cardiovascular disease and partic- ularly to death from coronary heart disease. Bnoking and Chronic Obstructiw Bronchqulmomry D&eases Additional physiolo !F `cal and epidemiological evidence confirms the previous findings t lat cigarette smokin 7 is the most important cause of chronic non-neoplastic bronchopu monary disease in the United States. 3 Cigarette smoking can adversely affect pulmonary function and disturb cardiopulmonary physiology. It is suggested that this qan lead to cardiopulmonary disease, notably pulmonary hypertension and car pulmonale in those individuals who have severe chronic obstructive bronchitis. Smoking am? Gamer Addi,tional evidence substantiates the previous fmdings that cigarette smoking is the main cause of lung cancer in men. Ciga- rette smoking is causally related to lung cancer in women but ac- counts for a smaller proportion of cases t.han in men. Smoking is a significant factor in the causation of cancer of the larynx and in the development of cancer of the oral cavit,y. Further epidemi- ological data strengthen ,the association of cigarette smoking with cancer of the bladder a.nd cancer of the pancreas. The most recent Public Health Service review of the effects of smoking on pregnancy was presented in the 1967 Report. The con- clusions of that review were as follows : Clearly, more research is needed to elucidate the significance of the relationship of smoking in pregnancy and low birth weight. Additional lon studies on the e -range morbidity studies are needed, -as well as fi ect of smoking on uterine activities and placental blood flow. Smoking does have an effect on t.he outcome of pregnancy. How- ever, it is not known whether this effect is deleterious or not. Until such evidence is presented so as to clearly define the role of smoking in pregnancy, it is more prudent at this time to advise pregnant women to stop or decrease their cigarette-smoking practices. No substantial negative evidence has appeared which refutes these judgments. On the contrary, studies made available since the publica- tion of the 1968 Supplement and reviewed by panels of experts in the relevant medical areas confirm previous findings and add new evidence that smoking is a health hazard. Highlights of the 1969 Supplement are as follows: I. Snwking and Cardiovamdar Diseases Further data from prospective studies confirm the judgment that cigarette smoking is a significant risk factor that contributes to the de- velopment of coronary heart disease, apparently by promoting myo- cardid infarct and cardiac arrhythmias. Analyses by several investi- gators of other associated factors (high serum cholesterol, high blood pressure and body weight) show clearly that the effect of cigarette smoking persists and is appreciable, even when these other factors are carefully evaluakd. Autopsy studies suggest that cigarette smoking is associated with a significant increase in atherosclerosis of the aorta and the coronary arteries. Experimental studies in animals have pro- 4 vided new information on the pathological effects of cigarette smoking on the arteries. This further supports the view that cigarette smoking promotes atherosclerosis. II. Smoking and Chronic Obetructive Bronchopdmwry DGenses Recent studies have demonstrated t.hat cigarette smokers may have significant disease of the small airways in the absence of bronchopul- monary symptoms. This disease is demonstrated by the finding of ab- normalities in t.he ventilation/perfusion relationships in the lungs of cigarette smokers. Animal experiments have demonstrated the path- ological effects caused in the lung by exposure to cigarette smoke or to specified concentrations of products found in cigarette smoke. Con- ditions similar to pulmonary emphysema in man have been produced in some of these experiments. Other studies have investigated the path- ological effects of smoking on pulmonary clearance mechanisms and demonstrated that pulmonary clearance may be significantly impaired by the effects of cigarette smoking. Epidemiological and laboratory evidence supports t.he view that cigarette smoking can contribute to the development of pulmonary emphysema in man. III. Smoking and Cancer A major pathological study of histological changes in the larynx has demonstrated a dose-relationship between smoking a.nd premalig- nant changes in the larnyx. New animal models for the experimental study of respiratory cancer, which may be helpful in elucidating the mechanisms of respiratory tract carcinogenesis, have been de- veloped and refined. More studies have been done to identify those substances in tobacco smoke which take part in carcinogenesis. These studies may help to define the exact biomechanisms involved in the cause and effect relationship between cigarette smoking and lung cancer. IV. Effect of Smoking on Pregnancy New data are presented which confirm the finding that maternal smoking during pregnancy is associated with low birth weight in infants and also indicate that maternal smoking is associated with an increased incidence of prematurity defined by weight alone. In addi- tion, it appears that maternal smoking during pregnancy may be as- sociated with an increased incidence of spontaneous abortion, stillbirth, and neonatal death and that this relationship may be most marked in the presence of other risk factors. V. Swwking and Noncancerous Oral Disease The chapter on noncancerous oral disease is the first Public Health Service review of this subject. The data available lead to the conclusion that ulceromembranous gingivitis, alveolar bone loss, and stomatitis 5 nicotina are more commonly found among smokers than among non- smokers. The influence of smoking on periodontal disease and gingi- vitis probably operates in conjunction with poor oral hygiene. In addition, there is evidence that smoking may be associated with edentulism nnd delayed socket healing. Tobacco smoke contains a large number and a wide variety of com- pounds which may result in complex and multiple pathophysiological effects on the various tissues and organ systems. While further research is needed to investigate the exact biomechanisms involved in the patho- logical effects of smoking, the evidence clearly shows that cigarette smoking constitutes a major health hazard in the United States. PART 2 Technical Reports on the Relationship of Smoking to Specific Disease Categories 260-2280--88----2 CHAPTER 1 Smoking and Cardiovascular Diseases Contents Ptlg.3 summary_----------T------~--------------------------- 11 Epidemiological Studies- - _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ - _ - - _ - _ _ _ - Atherosclerosis----------- _____________________ --_--_-_-_ ;i ThrombusFormationandBloodFlow __________ -_---_-__-- 27 Carbon Monoxide------------------------------- ________ Cited References---------------------------------------- E Cardiovascular Supplemental Bibliography----------------- 31 9 SMOKING AND CARDIOVASCULAR DISEASES Coronary heart disease (CHD) among men in the Western world is an epidemic which cuts short the lives of many in their prime produc- tive years. The evidence linking smoking and CHD has been reported not only from studies in the United States, but also from such diverse areas as West Germany, the U,S.S.R., France, Israel, Italy, and the British Isles. The 1968 Supplement (97) stated : Because of the increasing convergence of epidemiological and physiological findings relating cigarette smoking to coronary heart disease, it is concluded that cigarette smoking can contribute to the development of cardiovascular disease and particularly to death from coronary heart disease. The convergence of autopsy data and experimental data presented in this and previous reports suggests that cigarette smoking promotes atherosclerosis, including that of the coronary arteries. The results of physiological research and the findings of diminished risk of CHD in those who have stopped smoking indicate that t:here is also a more immediate mechanism operative. The mechanisms which might be re- sponsible for the promotion of myocardial infarction and fatal cardiac arrhythmias by cigarette smoking were extensively reviewed in the 1968 Supplement (27). Briefly stated, nutrient supply to the myocar- dium in general and, perhaps more importantly, to focal ischemic areas of the myocardium may be seriously compromised by a combina- tion of effects caused by smoking, and the deprived myocardium may become infarcted or develop an arrhythmia. These effects include diminution of blood flow through atherosclerotic coronary vessels and diminution of available oxygen for tissue use resulting from the bind- ing of carbon monoxide to hemoglobin in the place of oxygen and 11 possibly, although presently speculative, the poisoning of respiratory enzymes by hydrogen cyanide. Cigarette smoking has been shown to be an important risk factor in the development of CHD. It is important both by itself and in the presence of other significant risk factors. In combination with certain other risk factors, the joint effects appear to be even greater than those aocounted for by those risk factors independently. EPIDEMIOL~CZICAL STUDIES Hammond, et al. (11) have presented new da.ta on mortality from CHD, stroke, and nonsyphilitic aortic aneurysm among more than 800,000 men and women who were between the ages of 40 and 79 in 1959. The authors were attempting to evaluate the significance of multiple factors (sex, age, diabetes, high blood pressure, body weight, cha.nge in weight, exercise, cigarette smoking, sleep, and nervous tension) in the variations in death rates from these three diseases. It should be noted that this information consisted of self-reports obtained by ques- tionnaire and were not obtained from medical examination. Causes of death were based on deat.h certificate reports. As illustrated in table 1, coronary heart disease death rates and mortality ratios increased with increased cigarette smoking for men in all age groups and for women under the age of 70. Although the mortality ratios were higher in the younger age groups, the differ- ences in death rates between nonsmokers and heavy smokers became progressively higher with increasing age. Although CHD rates were higher for those who were 10 percent or more above the average weight for their height-age-sex group, and for those who reported having high blood pressure, the trend is clear that the effect of smoking persists and is appreciable, even when these other factors are held constant (table 2). 12 TABLE I.-Death rates and mortuLi& ratios for cormay haa? disease and sttoke, by anunmi of &are& smoking, sex, and age lZqnlarly smoked clgarettee Regularly smoked cigarettea scuandsge NeFW NWW smoked Number smoked daily smoked tzgiz$ l-9 cigerottel Number smoked daily lW19 al-39 4oor regularly 1-9 1lH9 W-39 400r more more 68 267 L: 18 li9 2ea 979 DEATH RATES 256 616 &Ml 2# 57a 47 163 663 1,243 3'16 718 1, MS z.w `43 2w `642 --_ 14 39 ' 16 a1 23 40 73 a 81 96 163 219 343 273 289 660 017 S93 793 ' 446 10 IS 3S 39 167 37 34 73 72 `95 110 139 33S !a1 -_ 4a7 404 `276 022 __ MORTALITY RATIOS 1 M&5: 40-49 years-. LOO L60 269 3.76 S.lil LOO 279 `Lll 221 1.64 so-69 years.... Loo 1.68 213 240 279 LOO 19s L43 293 240 w-69 years.-. Loo 1.43 1.32 LB1 1.79 Loo 1.30 L44 162 1.73 m-79 years-... 1.00 1.14 1.41 L49 147 LOO .9S .93 L33 r.63 Females: 4049 years.-. 1.90 L31 209 3.02 `8.31 LOO 1.&l 230 299 `h70 60-0-8 years.-. 1.09 1.16 237 263 3.73 Loo 1.26 270 267 `a.S2 w-e4 years-. l.M) Lo4 L79 208 `202 1.00 1.26 216 l-33 --_- 7w9 years.-. 1.00 .76 .98 tn ---_ LOO .33 I.67 1.23 --__ ' The mortality ratb Is the observed rata divided by the qectad rats. ' F&tee based upon only 6 to 9 deaths. Sowa: Hammond, E. C., et al. (II). 13 TABLE 2.-Coronary &art disease death rates for mm and wmen &x$ied by smoking habits, age, blood pressure, and relative weight Extent of No high blood pressure, by relative weight High blood ~rassnre, by relative weight Total t% 90-109 U-119 s% 90 OVBT Total tE 90-109 110-119 iii OVW MEN None or slight: 40-49yeers _______._-__ 62 `27 46 64 128 an _-_ 195 `210 _-___ 60-59~~ ____________ 226 140 216 283 a90 620 1686 611 643 609 60-69yesrs _____-___-__ 603 542 673 701 763 1,503 1,777 1,296 1,860 1,865 70..79p-... _________ i,m 1,467 1,555 1,840 1,868 2,7a8 3,342 5038 2,651 a, 100 IIlb~di8te: 40-49yefm __-__--- _--- 116 108 104 141 245 249 `a34 266 `288 _--__ la-59 years -_-___----_- 373 352 383 405 538 876 1,424 686 1,182 995 60-69yeaR _____-_----- 888 814 890 984 973 1,876 1,913 1,999 1,447 1,710 70-79year~ ____________ 1,973 ~237 1,778 1,953 &sol 3,220 3,700 3,172 gn3 6,461 20 or molv: 40-49 years. ___________ 222 123 235 309 276 647 687 650 765 89; bo-&i9yeal2 _____-______ 630 422 636 666 641 1,137 1.148 1,153 933 1,41 6049yt?ars ___-_-_-____ 1,047 978 1,019 1,249 1,307 1,986 &leo 1,993 1,744 2,076 70-79~~ ____________ ~236 %a46 5205 2151 ~846 4,123 5,141 4,205 13,692 ----- WOMEN None or slight: 40-49 years-. _ ___- _ _ __ _ SO-69yearS __---------- 60-69yem ___-------_ _ 76-79 yea's -_--- - - - --_ - Intam'ediate: 4049 yeara ---------__ so-59 years __-__ _ _ _--_ _ 60-69 yeal7L -________-_ 70-79 years --___------- mormom: 4cM9 yeara _--- ---- -- - so-59 years _-_-__- ____ _ e&w yeam _-_-_____-_ 70-79 yeara -_-- -_ _---- 8 `6 7 41 39 32 -ii 201 153 191 265 776 832 `179 667 16 17 12 -__ 76 69 70 153 284 a37 244 422 607 736 551 -__ 36 25 a8 `42 120 118 128 ___ 467 a41 636 `637 644 `866 `la6 -_- 22 68 323 754 --_ `73 `73 ' 135 --_ 63 -__ 53 ----- 161 100 142 167 469 400 495 462 1.338 1,313 1,217 1,449 86 --- `76 281 361 231 730 732 743 1,161 ' 1,854 1,014 .144 ___ 193 368 `26a 291 811 `788 1,100 5463 ___ `a,743 __-_- `23a 848 _-_-- `b94 76 229 469 1.626 ----- `198 `484 ---_- `706 ' Rates based apon only 6 to 9 deaths. SOUBCE: Hammond, E. C., et al. (21). Hammond, et al. also studied CHD mortality among men who were ex-smokers of cigarettes. The death rates from CHD were lower among the ex-smokers than among those still smoking at the beginning of the study, the size of the difference being larger the longer they had been off smoking (table 3). Some people stop smoking because of illness or symptoms and these people would be expected to have higher death rates than those who stop for other reasons. Early deaths among those with preexisting disease may account, at least in part, for the high death rates from CHD among ex-smokers in the early years of abstention. 14 Mortality ratios for stroke were higher among cigarette smokers with the exception of those over 70 years of age. Male err-cigarette smokers had mortality ratios for stroke approximately equal to those of nonsmokers. A clear increase in mortality from nonsyphilitic aortic aneurysms with increasing cigarette smoking among men aged 50-69 is seen in ta.ble 4. The mortality ratio for heavy smokers was 8.00. Hammond, et al. found that death rates from the three diseases var- ied considerably with relative weight, Iamount of exercise, amount of cigarette smoking, and hours of sleep per night. Subjects who were obese, took little or no exercise, smoked many cigarettes a day, or slept 9 or more hours per night had high death rates. Those with a combi- nation of these factors have especially high dea.th rates from the three diseases. TABLE 3.-Observed and expected number of deaths and mortality ratios for ex-cigareite smokers with a history of smoking only cigarettes, by number of years since last cigaretle smoking and for current cigarette smokers, coronary heart disease and stroke; compared to persons who never smoked regulurlyj in men aged 40-79 Type of smoker Coronary heart disease StiLe Observed Expectad Rati observed Erpeoted Ratio Ex-dgamtta smokera (former smokers of l-19 cigarettes a day) : stopped: Lea than 1 year.. ____________ 14 yeax _____________________ HI pears -_______--__-__-__---- 19-19 yeara _-__-___ _ ___ _ _ __ _- - 2oormoreytara --________-___ 29 17.9 162 ------ ------ ____-- b7 46.6 122 ______ ------ ._____ 55 46.7 L!a ___--- ------ _-_--- 62 b&l .9b ______ ----- - ______ 70 64.7 1.08 ._____ ------ -_____ Total. _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 263 226.9 1.16 57 b6.9 LO9 Cnrrenteigarettes ______--__-- 1,669 569.6 1.96 207 1316 1. b4 Nevex smoked regularly- __________ ___ L.srl 1,841.0 LOO Ml 601.0 1.09 Excigarette smokers (fmmw smokeus of 20 or more cigemtte a day) : mopped: Less than 1 year _-__-__-____-_ l-4 yw'rs.. _ ___ _ ___ ---___-_-_-- b-9 yelIla.-. -- -- - ---- _ -_- _ -- - _ - lo-19 Ye...-.-..-.-...------ 2oormoreyears ____-_________ 62 3R6 1.61 ______ ______ ______ lb4 101.9 Lb1 _----- ------ -_-___ 13b 116. b 1.16 ______ ___-__ -_____ 199 166.1 1.25 _----- _----- _-___- 80 76.4 Lob --__-- ___--- __-__- Tot& _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ 4a9.7 1.28 94 1OL 1 a98 C-t cigarstb smokers ____________ Z8: l,llu7 zbb 440 2517 L87 Never smoked regulsrlym _____________ 1,841 b841.0 LOO 501 b61.0 1.66 Somar: Hammond, E. C., et aL (II). 15 TABLE 4.-Aortic aneurpm death ratee and mortality ratios for men aged 50-69, classified by cigarette smoking habits [Ratas p?r1,ooopopulation] Cnrmnt smokers, by daily cigsrette consumption 1-Q IO-19 m-39 49 or more Death rate ___-__ _ _ _ _ _ _- __ _ _ _ ___ _ 13 34 50 59 104 Mortality ratio ___________ - ______ 1. 00 2. 62 3. 85 4. 54 8. 00 Son~mHammond,E. C.,et al. (21). They also found that death rates from CHD and stroke were lower in ex-cigarette smokers than in men who were currently smoking ciga- rettes at the time they enrolled in the study. The death rates of male ex- cigarette smokers who had not smoked for 10 to 20 years were no higher or only slightly higher than the death rates of men who had never smoked regularly. Death rates from the three diseases were lowest among subjects without a history of diabetes or high blood pressure who were not obese, took at least moderate exercise, never smoked reg- ularly and slept 6 to 8 hours per night. Nevertheless, even these sub- jects had substantial death rates from CHD, stroke and nonsyphilitic aortic aneurysm. Stamler (2.4) has anaylzed lo-year mortality data on a total cohort of men, aged 40-59 in 1958, who were employees of the Chicago Pea pies Gas Light and Coke Co. Of 1,465 men examined, 1,325 were found initially to be free of definite CHD and have been followed without systematic intervention. Higher overall death rates were found among the smokers in the study. Table 5 shows the death rates from CHD and from all causes for men with various risk factors. Recent papers by Thorne, et al. (a) and by Paffenbarger, et al. (19) report further results of studies of CHD among former college students. College health records and other college records were re- viewed to ascertain the presence or absence of factors under considera- tion. Cases were identified from death certificates in the study of fatal CHD (19) and from questionnaires and physical examinations in the study of nonfatal CHD ($?5). Matched controls were obtained for each case. In both nonfatal and fatal CHD, significantly more smokers were found among the cases than among the controls. Combinations of risk factors resulted in greater CHD morbidity and mortality ratios than did single factors. Figure 1 shows the morbidity ratios for corn- binations of pairs of risk factors in nonfatal CHD and table 6 shows mortality ratios for combinations of risk factors in fatal CHD. 16 TABLE &-lo-year mortality rates for sudden death, coronary heart disease, stroke, cardiovascular-renal, and all causes combined among men aged 40-69, classijied according to cigarette smoking, cholesterol, and blood pressure [Peoples C&s Light Co. Study, 1956-63. Men origInally free of coronary heart disease and followed without systematic Intervention,] l0-year mortality 19@3 risk factor status-cigarette smoking (10 or more a day], Sudden death All CHD Stroke All CVR All cause8 hypercholestemlemla, hypertension r Number Nyfber Death NuFfber Death Nur$ber Death NuFfber Death Nun$ber Death of mean rate 1 rate rate rate rate In cohort deaths deaths deaths deaths deaths Noriskfactor _______ _ _____________ _ __________________ _____ ____ ____ Hypercholesterolemia or hypertension only-1 factor. _ _______ _____ Cigarette smoking only (10 or more a day)-1 factor _______________ Hypercholesterolemia and hypertension only-2 factors ____ _ _______ Cigarette smoking (10 or more a day) and hypercholesterolemia or cigarette smoking and hypertension-2 factors... _ __ _______ _ _ _ ___ Cigarette smoking (10 or more a cay), hyperoholesterolemia, hypertension-a113.-.. _____________________ _ ______________ ______ ZU 0 0 1 3.0 2 6.9 4 11.9 13 42.0 216 4 19.6 13 63.1 6 19.6 19 726 27 101.6 405 4 10.0 16 37.1 5 11. g 20 46.9 44 107.7 60 1 9.9 3 2Q.6 1 40.7 4 70.3 8 121.9 293 11 37.2 17 67. 1 6 19.9 26 36.4 53 169.9 67 2 25.1 6 76.0 2 25.4 8 101.6 17 226.8 Total-.-... ___________________ _ ______ _ ____ ____ ______________ al,325 22 16.2 55 39.2 22 14.9 61 53.6 162 113.1 1 Risk factors include: Serum cholesterol 2&I or more mg./dl.; diastolic blood pres- 8 Smoking data were not obtained for 4 of the 1,329 men. sure QO or more mm. Hg; 10 or more cigarettes/day. I A" mtee m ~-adjusted by byear age groups to the U.S. male popuh3tion. lQ69. Souncs: Stamler, J. (84). All rates per thousand. T~~~~6.--Edimatedcoronaryhea~disease dmfhrattisinal7-61 year joUowup among former college students, cla.ssi$ed according to combined presence (+) or absence (-) of each of three speci$ed risk factors, and by age Risk factor Age (years) at death from coronary heart d&ease Clg*lLgtW Systolic BP, p;?$iep Total 130 or more more/day mm. Hg les$& 30-69 30-44 4654 55-09 yea- years Years years + + + 4. 3 l(l.9) 5. 7 ' (4.8) + - + 1. 8 2. 3 1. 6 ' (2.0) + + - 4. 2 2. 9 4. 5 5. 6 - + -I- l. 9 2. 9 1. 6 1. 8 + 1. 7 2. 2 1. 9 1. 3 - + - 1. 3 1. 2 1. 2 1. 4 - + 1. 1 1. 4 1.4 .8 - 1. 0 1. 0 1. 0 1. 0 1 Numbers in parentheses indicate expected number coronary heart disease decedents less than 5. SOUBCE: Paflenbarger, R. S., et al. (18). In a study of participants in the Health Insurance Plan of New York, Weinblatt, et al. ,($?9) reported that cigarette smoking males who developed angina pectoris were more likely to develop infarction than were nonsmoking angina1 patients, but there were not enough cases to draw definite conclusions. Weinblatt, et al. (30) also reported that the prognosis after the de- velopment of a myocardial infarction appears to be independent of smoking status prior to the infarct. In the absence of data indicating which patients stop smoking and how stopping smoking is related to the severity of myocardial damage, one cannot evaluate the effect of smoking on prognosis. If the persons who stop smoking tend to in- clude the most debilitated, the effect of continued smoking on prog- nosis would be underestimated. In a prospective study of over 3,000 men, Jenkins, et al. (14) re- ported that the incidence of CHD in men aged 3949 was three times higher among the cigarette smokers than among the nonsmokers (ta- ble 7). The incidence of CHD increased with increased daily cigarette consumption. For men aged 50-59, the relationship between cigarette smoking and CHD was found to be significant only for the heavy 18 4 3 * 1 0 . 3 B 2 3.: I 3 2 1 x0 ;: % 2 1 0 . 3 2 * 0 cl#wdta 10+/&y-A 6ys. 8? mo+mm. W-A Nd#lt/Q c 129-B spmn < 6 hr.,*-8 ciwuaa lo+/dq-A th&ht < 66 h-8 - < 66 h-8 < 6 llr./wk-8 b 3 2 1 0 6 3 2 1 0 1 3 2 1 0 4 3 2 1 0 4 3 2 1 0 Fmum l.-Morbidity ratios of coronary heart disease for paired combinations of factors in college. Souacx : Thorne, WC., et al. (2%). 19 smokers (table 8). Former cigarette smokers also had significantly higher CHD incidence rates, but no data are given on length of time since stopping smoking, or reasons for stopping. Pipe and cigar smok- ers did not have higher CHD incidence rates. After controlling for other risk factors such as lipid levels, diastolic blood pressure, and body build, the authors found that the association between cigarette smoking and CHD remained (tables 9,lO). The relationship between smoking and CHD was stronger among those men who exhibited be- havior type A than those exhibiting behavior type B (tables 11,12). Behavior type A is characterized by enhanced competitiveness, drive, aggressiveness, hostility, and an excessive sense of time urgency. Be- havior type B indicates an absence of these characteristics. Analysis of the data on behavior and cigarette smoking showed that both fac- tors have effects on the CHD rate. Again, these associations were stronger in the younger age group. 20 TABLE 7.-Annual incidence rates of coronary heart disease for men $9-49 years of age, clasti$ed by smoking hietory and by currint practices a8 to cigareth smoking I&J as of the b@miu# of the 4% year period ol ob+xvatlon] Morbidity etatue Total eublecte Never smoked Smoking history :lg%~ Former dgarette Current dgarette Current dgarette smoking by number per day None l-16 16-25 260rmore Nb;;- Rate 1 Nb::- Rate Nb;~ Rate Nby- Rate Nb;y Rate Nby Rate Nbr Rate Nb2- Rata Nby- Rate Totalnumberatrisk _--_-------- a258 e-m_- 540 _--__ 496 ___._ 239 -_--- 1,974 _____ 1,191 em._. 2Il ----- 484 .____ 422 _____ TotalnumberCHDc8sm ______. 62 6.2 7 `29 3 I.6 10 J9.3 43 82.9 20 `2.7 6 63 18 ` 9.2 20 `16.5 A~myocardtallnfarctbn -_----__ 32 5.1 4 1.7 3 1.6 10 9.a 35 7.2 17 3.1. 4 4.2 la 87 18 9.s Symptomatic ____ _ __________ 33 3.7 1 .I 2 1.1 8 7.4 27 6.8 11 20 4 4.2 11 3.6 12 6.3 Unrecognlmd _______________ I4 1.4 3 1.2 1 .6 2 1.9 8 1.7 6 I. 1 9 0 2 1.0 6 3.1 Fatal _______.__----- _ -------- 1" II", 0 0 0 0 1 de 8 1.7 1 .a 0 0 6 3 ~pectiody __._________ 3 1.2 0 0 0 8 1.7 a .6 I 1.0 5 z"t 2 ti 1 Annual rate per l,ooO men at rick. : Them distributions of casm for varlow emokiop cA2orleS are el2nlflcantlY dU- ferent from chance at P =O.oOl. a Dawns in CHD frequeucy between thla noup aud thoee who never emoked dgmttss (a11 .1 and 2 eomblued) la &nIficant at P-O.01 by cbl muare test corrected for continuity. 4 Differenca in CHD frequency between this group and cumut nouoigare.tb emokers is siguifkant at P -0.01. SOUBCC: Jenkln, CL D., et aI. (Id). TABLE 8.-Annual incidence rates of coronary heart disease for men 60-69 years of age, classajied by smoking hietory and by current practices as to cigarette smoking [Age as of the beginning of the 4% year period of observation] Morbidity statue Total eublecta Never smoked fhoklng history Pipe and Former cigar only cigarette current cigarette Current cigarette emoktng by number per day None 1-15 16-25 28 or more NW- Rate 1 Nun Rate Num- Rate Nbgv Rate Nun- Rate Nbr Rate Nby- Rate Nby- Rate Nby- Rate ber ber ber ber Total number at risk- _ ___ _ ____ _ 924 _---- 182 _---- 161 _-__- 137 ---_- 444 _____ 483 ___-_ 109 _--_- 167 --__- 165 _-_-_ Total number CHD ceeea _______ 70 18.8 9 tn.0 11 15.2 9 14.6 41 20.5 al 113.3 6 122 16 21.3 119 25.8 All myocsrdial infarction ________ 52 125 6 7.3 3 11.0 5 8.1 33 16.5 19 8.7 5 10.2 15 20.0 13 17. s Bymptomatlc _______ _ _____ __ 35 8.4 4 4.9 4 5.5 4 6.5 23 11.5 12 5.5 4 8.2 11 14.6 8 10.8 umwognlwd --________-__-- 17 4.1 2 24 4 s.5 1 1.6 10 5.0 7 3.2 1 20 4 s.3 s 6.7 Fatal __________ _ _____________ 3.4 14 0 0 3 4.1 3 4.9 8 4. 0 6 28 2 4.1 4 6.3 2 2. 7 AqInapectorisonly~~...~~...~. 18 4.8 3 3. 7 3 4.1 4 6. 5 8 4.0 10 4.6 1 20 1 1.3 6 8.1 ~Ammalrat8per1,OOOmenatrfsk. *Difference in CHD kequency between this group and current noneigaretts ' These distrfbutkne of owea for various amok.ing calories could occor 0.10 of smokers is significant at P=O.Ol. the time by chance, hence are not el@lcant at P-0.06. Bowa: Jenkins, C. D., et rd. (14). TABLE 9.-Annual incidence raies of new eorbnary keart disc&se, by smoking habits, adjusted for age and seradim, for speca$ed other risk factors [Rates are annual incidence per 1,OLkl men, aged 39 to 49 years at entry into 8tudy) Specified other risk factors Never Former Pipe and smoked sc;goyeT cigar only D~ycigr&t& - p.* 1-15 16-25 26or Cholesterol _______________________ _ _____ 33 vs 22 49 89 100 0.005 Betaf~pharstfo-..--.----.---.......... 31 91 18 49 91 102 .OOl Lipalbumin _______ __ _______________ _ ____ 31 95 18 51 89 102 .002 Systolic BP _____ _____ ____ __ __ ____ _______ 31 91 18 49 95 100 . 001 Diastolic BP _.__________________________ 29 89 16 49 95 104 .OOl Ponderal index __________________________ 29 91 16 49 95 107 .OOl Physical activity __________________ _ _____ 29 93 18 47 93 104 . 001 Amount of exercise _____ ____ ____ __ ___ ____ 29 91 18 49 93 104 .OOl lncomc level _____ _________________ _ ____ _ 29 91 18 49 93 104 .OOl Alloftheabove ___________ ________ 3s 93 20 51 89 93 .097 Triglycerides ______ _ _ ___ . _ __ _ _ __ __ _ _ _ _ _ _ _ 31 88 al 40 80 104 .002 r Level of significance of F-ratio for analysis of covariance. SOWCE: Jenkii, C. D., et al. (II). TABLE IQ.-Annual inci.dence rates of new coronary heart disease, by smoking habits, adjusted for age and seriadim, for specijfied other risk factors [Rates are annual incidence per 1,OQJ men, aged 50 to 59 years at entry into study) f3pecilled other risk factors Daily cigarette Never Former Pipe and consumption smoked ;kyk;t; crgar only - p.' l-15 M-25 28 or more Cholesterol. _ _ _ __ _ _ ___ _ ___ _ ___ _ __ _ _ _ _ __ _ 115 142 153 115 211 254 0.154 Beta/alpha ratio ________________________ 107 142 144 120 213 252 .127 Lipalbumin _____________________ __ ______ 109 140 151 122 218 262 .135 SystolioBP _____ _ _______________ ______._ 118 127 144 129 211 266 .136 Diastolic BP ____________________________ 109 127 135 127 2.26 273 .066 Ponderalindex-.---..----..------------ 107 131 140 122 222 269 .084 Physical activity _______________________ 113 142 149 115 213 249 .216 Amount Of exercise ___-__________________ 113 144 151 118 211 255 .203 Income level __________________ ____ _____ _ 113 138 147 120 2a-l 256 .156 All of the above __________ ____ _____ Triglycerides _______________________ ____ 113 113 118 147 138 140 213 258 .168 144 80 195 280 .121 1 Level of siguS5cance of F-ratio for analysis of covariance. SOUBCE: Jenkins, C. D., et al. (14). 23 TABLE 1 l.-Incidmce of new coronary heart disease, by smoking category and behavior type, for men aged 39-49 [Rates ere ege-edjusted annuel incidence per 1,ooO men] Behavior type Current and former Dally cigarette consumption Forz;o?AAette pipe end cigar only Total Never smoked 1-15 E-25 26 or more Ratea cases Rates Cases Rates cases Rates CsSeS Rates CaSeS Rates C&lSeS Rates Ceses A ______ _ ____ _ ________ _ ______________ 6.3 6 13.8 7 1.3 1 1.6 1 15.8 16 14.9 18 9.3 45 B __________________ _ _.____ __ ____ ____ 1.3 2 6.1 3 22 2 7.3 4 3. 1 3 4.9 4 3.3 18 Total _________________________ 29 7 9.1 10 1.8 3 4.9 6 9.3 18 10.4 20 6.2 63 BOWCE: Jenkins, C. D., et al. (4). TABLE 12.-Incidence of new coronary heart disease, by smoking category and behavior type, for men aged 60-69 [Rates are age-adjusted annual Incidence per l,@Xl men] Behavior type Current and former Daily cigarette consumption pipe end cigsr only Tote1 Never smoked Formero~@&te 1-15 16-25 26 or more ~- Rates cas%s Rates cases Rates Cases Rates Cases Rates Cases Rates Cases Rates CCl.WS A _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ - _ - 124 6 18.6 8 21.8 8 16.4 6 21.6 9 30.0 14 20.4 49 B ______.__-_ _ _______________________ 10.0 4 6.1 1 a4 3 4.7 1 21. 1 7 19.1 5 12.0 21 Total __.________ _ _____ __ ______ 11.1 9 14.2 9 14.9 11 11.6 6 21.3 16 28.0 19 16.8 70 BOWCE: Jenkins, 0. D., et al. (10. Epidemiological studies linking smoking and CHD have been car- ried out in various countries. In a retrospective study in Dublin, of 400 patients under the age of 65 who experienced myocardial infarc- tion, Mulcahy, et al. (18) observed a d&rite association between smoking and the development of the disease. A prospective epidemiological study of risk factors of CHD, in an Israeli population, indicates that smoking is associated with a higher risk of CHD (17). In a retrospective study of 503 male patients with myocardial in- farction and `114 age-matched controls in Munich, Schimmler, et al. (%Z') report that cigarette smoking plays a significant role as a risk factor. A recent paper by Cederlof, et al. (6) employs the twin-study method on a population of American twins, using a similar ,approach to that previously employed in a Swedish twin population. The pur- pose is to compare t.he contribution of genetic and environmental in- fluences to the development of angina pectoris. The authors imply that their study indicates a more important role for genetic factors than for smoking. However, this study can be criticized on several grounds. The authors based their detection of angina pectoris on the results of a self-administered questionnaire designed to elicit a history of chest pain of presumable cardiac origin; previous studies in Swedish twins have shown $a low rate of clinical confirmation of heart disease in those classified positive by questionnaire. No data are available on the health and smoking habits of 58 percent of the original group or the 41 percent of the "eligible twin pairs" who were nonrespondents. The authors' definition of a present smoker includes persons who have stopped smoking cigarettes for up to 3 years and thus includes per- sons who in other studies have been classified as ex-smokers. This definition of a cigarette smoker might contribute to an underestima- tion of the immediate effect of current cigarette smoking, since an unstated number of recent ex-smokers are included in the same cate- gory as current cigarette smokers. The relationship between cigarette smoking and the development of angina pectoris has not been clarified. However, Aronow, et al. (J) have shown that smoking one cigarette before exercising reduces t.he energy expenditure required for patients with classical angina pectoris to develop chest pain while exercising on a bicycle ergometer. AkTHEROSCLEROSIS A review of autopsy studies by Strong and auerbach, suggesting that cigarette smoking has a chronic effect leading to advanced degrees of atherogenesis, was presented in the Health Consequences of Smok- ing, 1967 (W). Further studies have recently been published in this area. 25