higher for single than for married men. The size of the excess death rate for users of tranquilizers compared to men who do not use them is perhaps surprising 129.1 against 18.2 and 52.4 against 31.8). However, the tran- quilizers in question required a doctor's prescription, so that some men in this group are presumably under medical attention for illna. The group of users is small, comprising only about 10 percent of those who answered this question. Death rates tend to decrease slightly as the educational level increases; this association may represent some facet of the association of death rates with socio-economic level. Degree of exercise displays an inter- esting association with mortality, the death rate declining steadily with additional degrees of exercise. In particular, the two "no exercise" groups show marked elevations in death rates. These groups, however, amount to only 2 percent of the respondents to this question. From the same data, Ipsen and Pfaelzer (14) made a further analysis of seven variables that appeared to be related to mortality? in order to see whether any of the variables had a stronger association with mortality than did cigarette smoking. They concluded that apart from previous serious disease, none of the other variables examined had as high a correlation with mortality as smoking of cigarettes. Further, the correlation of any of these other variables with cigarette smoking was too weak to reduce markedly the correlation of cigarette smoking with mortality after adjustment for the other variable. In the analyses above, smoking was matched against each variable sep- arately. In addition, Hammond (11) carried out a "matched pair" analysis, in which pairs of cigarette smokers and non-smokers were matched on height, education, religion, drinking habits, urban-rural residence and occupational exposure. The percentage who had died in the 22 months was 1.64 for smokers and 0.88 for nonsmokers. These informative analyses are available, unfortunately, for only one of the studies. However, in order that the association of cigarette smoking with mortality should disappear when we adjust for another variable, the correlations of this variable with smoking and with the death rate must both be higher than the correlation between smoking and the death rate. Except for the breakdowns by longevity of parents and grandparents, the analyses throw little light, however, on the objection that a part of the differences in death rates may be constitutional, psychological or behavioral; i.e., that regular cigarette smokers are the kind of men who would have higher death rates even if they did not smoke. Further discussion of this Point appears in the next section. MORTALITY BY CAUSE OF DEATH In all seven studies the underlying cause of death, as specified in the Inter- national Statistical Classification of Diseases, Injuries and Causes of Death, Was abstracted from the death certificate. In the two American Cancer So- ciety studies, further confirmation of the cause of death, including histological evidence, was sought from the certifying physician for all cancer deaths; this 101 procedure w-as also followed in lthe British doctors' study for all certificates in which lung cancer was mentioned as a direct or contributory cause. With these exceptions the data presented here represent the results of routine death certification. For current smokers of cigarettes the total mortality, after adjustment for differences in age composition, was found previously (Table 2) to be about `70 percent higher than that of non-smokers in these studies. The primary objective in this section is to examine whether this percentage increase ap- pears to apply about equally to all principal causes of death, or whether the relative increase is concentrated in certain specific causes or groups of causes. RESULTS FOK CIGARETTE SMOKERS For 24 causes of death, plus the "all other causes" category, Table 19 shows summary data over all seven studies.* In four of the studies the data are those for current smokers of ciga.rettes only, but in the two California studies and the 25-State study the cause-of-death breakdown was available only for all cigarette smokers including "cigarette and other" smokers and current and ex-smokers. For each listed cause, Table 19 shows the total numbers of expected and observed deaths of cigarette smokers summed over all seven studies, and TABLE 19.-Total numbers of expected and observed deaths and mortality ratios for smokers of cigarettes only 1 in seven prospective studies Underlying cause of death Expected Observed - ---__ Cancer of lung (162-3) _............_. ~- ._.. Bronchitis and emphysema (502. 527.1) *..- Cancer of larynx (161)~ . . . . . .._.._....... Cancer of oral cavity (140-S) .- . . .._..___ -_ Cancer of esophaeus (1.50) ._~ . .._.... --. Stomach and duodenal ulcers (540-l) _ _ _ Other circulatory diseases (451468) _....... Cirrhosis of liver (5811... . . .._. . .._.... -._ Cancer of bladder (181) __.. _.._..__ Coronary artery disease (420) _ _.-.-_. Other heart diseases (421-2, 43a-41.. _...._. Hypertensive heart disease (44W3) General arteriosclerosis (450) . . . ..___ Canwrofkidney cls0) ~... ..__. -__ All other cancer.. ._._._... . . . . .._....... Cancer of stomach (151). . . . . . . .._ __.... -. Influenza. wwumonia (486-493) .-_. ____ 170.3 89. 5 14.0 E:`: 105.1 254.0 169.2 111.6 6.430.7 526.0 % ; 79.0 1.061.4 285.2 303.2 1,%x3.7 1.461.8 253.0 1,063.2 156.4 290.6 207. 8 422.6 15,653.Q Allothercauses-......_....-..-.-........- Cerebral vascular lesions (33~~4) .._._ ..-__ Canwr or prostate (177) ~~.._. . . .._.__..___. .4ccidents. suicides, violence (KGQ99~ _ _ _ Nephritis (592-4) ..__ -._- _.__... _..._ Rheumatic heart disease (400-416). .._..._. Cancerofrectum (154~~~ ..__.... .._____. Cancer of intestines (1.52~31.. _....._____.. All causes. _ ___.____._.__. --- ___.____...... I,=3 546 2; 113 El 379 216 11,177 E 310 120 1,524 413 415 1,946 1,844 318 1,310 173 ii 395 26,223 - I -- - Mortality ratio 10.8 6. 1 5. 4 4.1 3.4 2.8 2. 6 2. 2 1.9 1. 7 1. 7 1. 5 1. 5 1.5 1.4 1.4 1.4 1.3 1.3 1.3 1.2 1.1 1. 1 1.0 0.9 1.68 11.7 7.5 5.8 3.9 3.3 5.0 2.3 2. 1 2.2 1.7 1.5 1.5 1.7 1. 4 1. 4 1.3 ::3" 1.3 1.0 1.3 1.5 1.1 0.9 0.9 1.65 1 Current cigarettes only lor four studies: all cigarettes (current and ex-) for the two California studies and the study of men in 25 States. 1 "Bronchitis and emphysema" includes "olher bronchopulmonary diseases" for men in nine States and Canadian veterans. Median mortality ratio *The individual results for the seven studies are shown for reference purposes in Table 26. 102 the resulting mortality ratios, arranged in order of decreasing ratios. The combination of the results of the seven studies in this way is open to criticism, since it gives more weight to the larger studies than may be thought advis- able, and since the true mortality ratios for specific causes presumably differ somewhat from study to study. However, for some causes of death that are of particular interest the numbers of deaths are small in all studies, so that some procedure for combining the results is highly desirable. As an alternative measure of the combined mortality ratio, the median of the >even mortality ratios (obtained by arranging the seven ratios in increasing order and selecting the middle one) is also shown for each cause in Table 19. The median, of course, gives equal weight to small and large studies. Although there are some changes in the ordering of the causes when medians are used instead of the ratios of the combined deaths, the general pattern in Table 19 is the same for both criteria. Table 19 also presents the total numbers of non-smoker deaths on which the combined mortality ratios are based. Lung cancer shows the highest mortality ratio in every one of the seven studies, the combined ratio being 10.8. Other causes that exhibit sub- stantially higher mortality ratios than the ratio 1.68 for all causes of death in Table 19 are bronchitis and emphysema, cancer of the larynx, cancer of the oral cavity and pharynx, cancer of the esophagus, stomach and duodenal ulcers, and a rather mixed category labeled "other circulatory diseases," which includes aortic aneurysm, phlebitis of the lower extremities, and pulmonary embolism. For three of these cause-cancer of the larynx, oral cancer and cancer of the esophagus-the numbers of non-smoker deaths are small, so that the over-all mortality ratio cannot be regarded as accurately determined. The U.S. veterans' study and the 25-State study provide an additional breakdown for two of the causes listed in Table 19. For the rubric 527.1 iemphysema without mention of bronchitis), these studies give mortality ratios of 13.1 and 7.5, respectively. For ulcer of the stomach they give 5.1 and 4.3, whereas for ulcer of the duodenum their mortality ratios are 2.3 and 1.1. Bronchitis and emphysema also show a high rate, 12.5, in the British doctors' study. There follows a list of 14~causes whose mortality ratios are not greatly different from the ratio of 1.68 for all causes in Table 19. These causes range from cirrhosis of the liver, with a ratio of 2.2, down to a ratio of 1.2 for the miscellaneous class which contains accidents, suicides and violent deaths. Th' 1s group includes the leading cause of death, coronary artery disease, with a ratio of 1.7, cerebral vascular lesions with a ratio of 1.3, and the "all other causes" group with a ratio of 1.3. For each of these 14 causes the mortality ratio differs from unity, by the approximate statistical test of significance. Finally, th ere are four causes-nephritis, rheumatic heart disease, cancer of the rectum and cancer of the intestines-whose mortality ratios are close to unity. For smokers of cigarettes and other, the data from four studies agree in general with the ordering of causes in Table 19, although the mortality ratios for most causes are slightly lower than with smokers of cigarettes 103 only. These and the corresponding data for ex-cigarette smokers are shown in Table 20. Data on ex-cigarette smokers can be obtained from four studies. & causes of death with mortality ratios of 2.0 or higher are, in decreasing order, bronchitis and emphysema (7.6)) cancer of the larynx (5.4)) cancer of the lung (4.8), stomach and duodenal ulcers (3.1)) oral cancer (2.0) and other circulatory diseases (2.0). 1 The group of 17 causes with mortality ratios below 2 in Table 19 requires discussion. If cancer of the bladder (mortality ratio 1.9) and coronary artery disease (mortality ratio l-.7) are omitted, since they receive detail4 consideration elsewhere in this report, the numbers of expected and observed deaths for this group as a whole are as follows: Expected Observed Mortality Ratio 8,241.3 1.0,789 1.31 If we exclude from this total the four causes at the foot of Table 19, for which the mortality ratios are 1 and smaller, the corresponding totals become: Expected Observed 7,164.0 9,699 Mortality Ratio 1.35 In either case the excess of observed over expected deaths is close to 2,500 or about 25 percent of the total excess in observed deaths in Table 19. Thus, although the mortality ratios for these groups are only moderately over 1, the group as a whole contributes substantially to the total number of excess ob. served deaths. The group consists mainly of a miscellaneous collection of chronic diseases. Several tentative explanations of this excess mortality ratio can be put for. ward. Part may be due to the sources of bias previously discussed. It was indicated in the section on "Non-Response Bias" that the bias arising from non-response might account for a mortality ratio of 1.3. Relatively hi& mortality ratios in certain causes of death that have not yet been examined individually may also be a contributor, although as these causes are likely to be rare, the contribution from this source can hardly be large. Part may be due to constitutional and genetic differences between cigarette smokers and non-smokers. Except for the breakdown mentioned previously by longevity of parents and grandparents in the men in 25 States study, there is no body of data available that provides a comparison of cigarette smokers and non-smokers on these factors as they affect longevity. But it is not un- reasonable to speculate that the kind of men who become regular cigarette smokers are, to a moderate degree, less inherently able to survive to a ripe old age than non-smokers. We know of no way to make a quantitative estimate of the difference in death rates that might be attributable to such constitu. tional and genetic factors. Studies reported in Chapters 1.4 and 15 indicate that some average differ- ences can be detected between smokers and non-smokers on behavioral, psychological and morphological characteristics. Nevertheless, the same corn. parisons show considerable overlap between the individual men in a group of smokers and a group of non-smokers. For what they are worth, these corn. 104 TABLE 20.-Expected and observed dea.ths and mortality ratios for current smokers of cigarettes and other (three studies) 1 and for ex-cigarette smokers (four studies) 2 Underlying cause of death - Cmeer of lung (162-3)..-.---.. Bronchitis and emphysema (502, 527.1) a... . . . . . . . ..____ Cancer of larynx (161) _.... Carver of oral cavity (14&E) _ Cancer of esophagus (150) Bt?maeh and duodenal ulcers WC-1) _..________ --_- ___._. Other circulatory diseases (451468) .~ _.___.________._. Cirrhosis of liver (581)L .____.. Cancer of bladder 081) ..____.. Coronary artery disease (420. Other heart diseases (421-2. 4). _ __ _ ___ _ _ _ _ _. _ _ _ _ _ _ _ _ _ _ _. Cancer of prostate (177) __._. Accidents, suicides, violance o3no-Qw) ___ _______________ Nephritis (5924) .._________ Rheumatic heart disease (400- - .- Cigarettes and other - Number of deaths Expected -L 3bserved 60.9 510 8.4 30. 4 145 4.8 53.2 191 3.6 17. 4 133 7.6 1. 6 20 12. 5 1.3 7 5.4 11. 1 42 3.8 5.9 12 2.0 13. 1 57 4. 4 5. 4 6 1.1 23.0 99 40 3. 1 99.0 57.3 58.2 2,335.0 227 85 3,z 4.3 2. 3 1. 5 1.3 1.4 1.4 1.2 1.4 1. 5 1.2 1.4 0.8 1.0 1.0 1. 2 1. 1 1.4 0.9 0.7 1. 1 45.8 22.4 29.8 1,245.0 93 z 1,731 2. 0 1.2 1.0 1.4 225. 9 321 124.1 178 1.4 144.4 106.8 25.0 272.9 101.0 199.2 769.3 174 146 3;: 139 % 93.0 63.7 13.9 199.3 51.4 55. 1 308.1 1.4 1.2 1.8 1. 2 1.3 1.0 1. 2 634.0 97. 1 28.7. 1 30.7 96.0 89.7 149.6 605 118 321 57 316 44 169.6 21. 7 86 1E 47.9 43.3 85.8 159 23 59 i; 1. 1 1. 1 0.9 1. 1 1.2 0.9 1. 1 1.4 / 3,045. 5 1 4,107 1.35 I Mntish doctors, U.S. veterans and Canadian veterans. * British doctors. men in nine States, U.S. veterans, and Canadian veterans. ' "Bronchitis and emphysema" includes "other bronchopulmonary diseases" for men in nine States and Canadian veterans. Mortality ratio Ea.cigarette Expected _- 3hserved Mortality ratio parisons suggest by analogy that the differences in death rates from constitu- tional or genetic factors may be moderate or small rather than large.* Fur- ther, it seems unlikely that constitutional or genetic differences between cigar and pipe smokers and between these groups and non-smokers can have any substantial effect on their death rates, since the over-all death rates of these three groups differ only slightly. Finally, part of the difference may represent a general debilitating effect of cigarette smoking in addition to marked effects on a few diseases. Pearl's hypothesis that smoking increases the "rate of living" is of this type, though there are difficulties in making this hypothesis precise enough to be subject to medical investigation. Hammond (13) has suggested that the explana- tion might lie in the effect of cigarette smoking in decreasing the quantity of oxygen per unit volume of blood, but there are numerous medical objections to this hypothesis. This Committee has no information that would lead it to favor one or another of the possible explanations put forward above. `This question is discussed more fully in Chapter 9, p. 190. 105 h~oRT.amY RATIOS FOR CIGARETTE SMOKERS BY AMOUNT SMOKES For coronary artery disease and lung cancer, the mortality ratios are given by amount smoked in Tables 21 and 22 for current smokers of cigarettes only. In Table 21 an increasing trend with amount smoked appears in all five studies. The two California st-udies, in which the data are for all cigarette smokers (current and ex-smokers combined) show a less marked trend. TABLE 21.--Mortality ratios for coron.ury artery disease for smokers q cigarettes only by amount smoked Number of packs per da)- British Men in 9 U.S. doctors states veterans Canadian M;t",$a veterans -___ ---