tions in the upper and lower airways. Such alterations could be expected to interfere with the cleansing mechanisms of the lung. Pathological changes in pulmonary parenchyma, such as rupture of al- veolar septa and fibrosis, have a remarkably close association with past his- tory of cigarette smoking. Th I ese changes cannot be related with rertaint? IO emphysema or other recognized diseases at the present time. Chronic bronchitis and pulmonarv emphysema are the chronic hronrho- Ibulmonary disease* of greatest health significance. Epidamiologiral evidence provides the most important information relating cigarette Pmokinc to chronic bronchitis and emphysema. All seven of the major prospective qtudies show a higher mortality rate for chronic bronchitis and emphysema among cigarette smokers than among non-smokers. In the few studier; that have examined mortalitv rates separatelv for the tjro conditions. chronic bronchitis or emphysema, both rates ar, higher among cigarette smokers than among non-smokers. In one of the studies. the risk of mortalit!- from rhronic bronchitis was four times greater among cigarette smokers than among non-smokers. Emphysema was listed as a cause of death 13 times more frequentlv among smokers in one studv. and 71& times more frequpntlv among smokers in another study. Extensive prevalence studies. based largely on prevalence of specific Fymptoms and signs rather than imprecise diagnostic labels. show a consis- tently more frequent occurrence of cough, sputum, or the two symptoms combined. in cigarette smokers than in non-smokers. These manifestations are the clinical expressions found in chronic bronchitis. The results of the prevalence surveys. however. offer less direct evidence relating cigarette Smoking to pulmonary emphysema. as clinical diagnosis of this disease is less exact. Breathlessness, which may result from emphysema or airway obstruc- tion in chronic bronchitis, is associated with cigarette smoking -in males. Particularly in the older age groups. but not females. Similarly. a consistent association of cigarette smokin, w and chest illness is more evident for males. In the prevalence surveys in which various combinations of respiratory manifestations have been studied, a greater prevalence of these conditions is found consistently among cigarette smokers. The majoritv of clinical studies have noted a relationship between ciga- rette smoking and chronic bronchitis and emphysema. Cigarette smoking is a more Scommon habit in the United States among patients with chronic bronchitis or emphysema than in the control groups studied. The clinical studies also show a decrease in clinical manifestations of chronic broncho- Pulmonary disease after cessation of smoking. Examination of experimental evidence shows that the lung may be dam- aged by noxious agents found in either tobacco smoke or atmospheric pol- lution. In the United States, Ihe noxious agents from cigarette smoking are much more important in the causation of chronic broncho[mlmonar~ disease than are those present as community air pollutants. In the United Kingdom, persons who smoke cigarettes and are exposed frequentl! to at- mospheric pollutants are at greater risk of developing disabling respirator! di%se and death than those exposed to either alone. 301 The relative importance of cigarette smoking also appears to be mu,+, greater than occupational exposure as an etiologic factor for the chronic bronchopulmonary diseases. Cigarette smoking does not appear to cause asthma; in rare instances allergy to tobacc,o products has been ascribed a causative role in asthma: like syndromes. Evidence does not support a direct association between smoking and in. fectious diseases of the respiratory system. The category, influenza and pneumonia, contributes moderately to the excess mortality of cigarett? smokers but other data are r?ot available to extend this observation. Th,. sssociation of cigarette smoking and tuberculosis does not appear to be ;, direct one, but both are associated with the use of alcohol. Only for "stomatitis nicolina" and the epithelial changes in the laryn, i? there sufficient documentation to substantiate the clinical opinion that non. malignant alterations in the mouth. nose. or throat are induced by smoking. The changes in the mouth are more often associated with pipe smoking hut disappear after cessation of smoking. CONCLUSIONS 1. Cigarette smoking is the most important of the causes of chronic, bronchitis in the [-nited States. and increases the risk of dying from chronic bronchitis. 2. A relationship exists between pulmonary emphysema and cigarettp smoking but it has not been established that the relationship is causal. The smoking of cigarettes is associated with an increased risk of dying fronl pulmonary emphysema. 3. For the bulk of the population of the United States, the importance oi cigarette smoking as a cause of chronic bronchopulmonary disease is much greater than that of atmospheric pollution or occupational exposures. -L Cough, sputum production. or the two combined are consistently morr frequent amon? cigarette smokers than among non-smokers. 5. Cigarette smoking is associated with a reduction in ventilatory fun,.- tion. Among males, cigarette smokers have a greater prevalence of breath lessness than non-smokers. 6. Cigarette smoking does not appear to cause asthma. 7. Although death certification shoha that cigarette smokers have a motl. erately increased risk of death from influenza and pneumonia, an association of cigarette smoking and infectious diseases is not otherwise substantiatefl. REFERENCJ3 1. Abbott. C. A.. Hopkins, W. A.. Van Fleit. W. E., Robinson. J. S. :\ new approach to pulmonary emph)-sema. Thorax 8: llG-32: l!M. 2. Albert. R. E., Nelson. N. Special report to the Surgeon General'. IZd\ iaory Committee on Smoking and Health. 302 3. Altschuler, B. L. Personal communication to the Surgeon General's Advisory Committee on Smoking and Health. 4. American Thoracic Society. Definitions and classification of chronic bronchitis, asthma and pulmonary emphysema. Amer Rev Resp Dis 85: 762, 1962. 5. Amdur, M. 0. The effect of aerosols on the response to irritant gases. In: Davies, C. N. ed. Proceedings of International Symposium on Inhaled Particles and Vapors. Oxford, England: April 1960. Lon- don. Pergamon Press. 1961. p. 281-92. 6. Anderson, D. O., Ferris, B. G., Jr. Role of tobacco smoking in the causation of chronic respiratory disease. New En? J Med 267: 787-94, 1962. 7. Ashford: J. R., Brown? S.. Duffield, D. P., Smith. C. S.: Fay, J. W. J. The retention between smoking habits and physique, respiratory symptoms, ventilatory function, and radiological pneumoconioais, amongst coal workers at three Scottish collieries. Brit J Prev Sot Med 15: 10617, 1961. 8. Attinger, E. O., Goldstein, M. M., Segal, M. S. Effects of smoking upon the mechanics of breathing: I. In normal subjects. II. In patients w-ith cardiopulmonary disease. Amer Rev Tuberc 77: 1-16. 195s. 9. Auerbach, 0.: Stout, A. P.: Hammond, E .C., Garfinkel. L. Bronchial epithelium in former smokers. N Eng J Med 267: 119-25. 1962. 10. Auerbach, 0.. Stout. A. P.. Hammond. E. C.. Garfinkel. L. Changes in the bronchial epithelium in relation to cigarette smoking and in relation to lung cancer. New Eng J Med 265: 253-67, 1961. 11. Auerbach. O., Stout. &\. P.: Hammond. E. C., Garfinkel. L. Changes in bronchial epithelium in relation to sex, age, residence, smoking and pneumonia. New Eng J Med 267: 111-9, 1962. 12. Auerbach, 0.. Stout. A. P., Hammond, E. C.. Garfinkel, L. Smoking habits and age in relation to pulmonary changes: rupture of the alveolar septums. fibrosis and thickening of walls of small arteries and arterioles. New Eng J Med 269: 1045-53. 1963. 13. Hadham: C. Observations on the inflammatory affections of the mu- cous membranes of the bronchiae. London. Callow, 1808. 14. Badham, C. Practical observations on the pneumonic diseases of the poor. Edinburgh Med Surg J 1: 166-70. 1805. 15. Balchum, C. J., Dybicki, J., Meneely, G. R. The dynamics of sulphur dioxide inhalation. AMA Arch Industr Health. (Chicago) 21: 564, 1960. 16. Balchum, 0. J., Felton. J. S.: Jamison. J. N.. Gaines, R. S., Clarke. D. R., Owan, T. A survey for chronic respiratory disease in an in- dustrial city. Amer Rev Resp Dis 86: 675-85, 1962. 17. Ballenger, J. J. Experimental effect of cigarette smoke on human respiratory cilia. Yew Eng J Med 263: 832-5, 1960. 18. Baumberger, J. P. The amount of smoke prodmed from tobacco and its absorption in smoking as determined bv electrical precipitation. J Pharmacol Exp Ther 21: 47-57, 1927. 714-422 O-64-21 303 19, Bwklake. M. R.. Goldman. H. I.; Bosman, A. R., Freed, C. C. Long- term effects of exposure to nitrous fumes. Amer Rev Tuberc and Pul Dis 76: 398309: 1957. 20. Bickerman. H. A.. Barach, A. L. The effect of cigarette smoking on ventilator\ function in patients with bronchial asthma and obstructive pulmonary emphysema. J Lab Clin Med 43: 455-62, 1954. 21. Boake. W. C. A study of illness in a group of Cleveland families. New Eng J Med 259: 1245-9, 1958. 22. Borhe. R. D.. Quill&an. J. J. The effects of air pollutants on tissue cultures. Fed Proc Bull 18: 559, 1959. 23. Bokhaven. C., Niessen, H. J. Amounts of oxides of nitrogen acd carbon monoxide in cigarette smoke, with and without inhalation. Nature tlondon) 192: 458-9, 1961. 24. Boren, H. Carbon as a carrier mechanism for irritant gases. Pre- sented at California State Department of Public Health Sixth Air Pollution Medical Research Conference. San Francisco, 1963. 25. Boucot. K. R., Cooper, D. A., Weiss, W. Smoking and health of older men. 1. Smoking and chronic cough. Arch Environ Health (Chi- cagoi 4: 59-78, 1962. 26. Bower. G. Respiratory symptoms and ventilatory function in 172 adults employed in a bank. Amer Rev Resp Dis 83: 684-9, 1961. 27. Brinkman. G. L.. Coates, E. 0.. Jr. The prevalence of chronic bron- chitis in an industrial population. Amer Rev Resp Dis 86: 47-55, 1962. 28. Bronchitis. Report of a Sub-Committee of the Standing Medical Ad- visory Committee. Scottish Home and Health Department. Edin- burgh. H M Stationer). Off: 1963. 59 p. 29. Brown. K. E.. Campbell. A. H. T b o acco, alcohol, and tuberculosis. Brit J Dis Chest 55: 150-8, 1961. 30. Butler, W. T., Alling. D. W.. Knight, V. Special report to the Sur- geon General's .4dvisory Committee on Smoking and Health. 31. Chang. S. C. lIicroscopic properties of whole mounts and sections of human bronchial epithelium of smokers and non-smokers. Canrer 10: 121&61. 1957. 32. Chang. S. C. Studies of bronchial epithelium from smokers and non- smokers. [Abstract] Proc Amer Ass Cancer Res 2: 99-100, 1956. X Chang. C. S. Studies of subepithelial tissue of bronchi from smokers and non-smokers;. ( Ab-t c ract] Proc Amer Ass Cancer Res 2: 286-i. 1058. 34. Chapman. I.. Rrdish. C. H. T b o acco-induced epithelial proliferation in hutllan 5uLjtW. Long-term effects of pipe smoking on epithelium of hard palate. .\%IA Arch Path 70: 13310, 1960. %5. Chatgidakis. C. 8. A study of bronchial mucous glands in white South Afric,an pold miners. A>lA Arch Environ Health 1: 53% 12. 1960. XX Chi\tw. C. 1'. Respiratory function and disease among workers in alkaline (lust-. Brit J Industr Med 16: 51-60, 1959. ::;. Colle;t~ of Genrral Practitioners: Chronic bronchitis in Great Britain : A national sur\e\. Brit Med J 2: 973-9, 1961. 304. 38. Cross, K. R., Walz, D. V., Palmer, G. K., Warner, E. D. A study of the tracheobronchial epithelium and changes related to smoking. J Iowa Med Sot 51: 13730, 1961. 39. Dalhamn, T. The effect of cigarette smoke on ciliary activity in the upper respiratory tract. AMA A\rch Otolaryng 70: 166-8, 1959. -10. Dalhamn, T., Rhodin, J. M- ucous flow and ciliary activity in the trachea of rats exposed to pulmonary irritant gas. Brit J Industr Zled 13: 110-3, 1956. -El. Davies, C. M. The handling of particles by the human lung. Brit. Med Bull 19: 49, 1963. $2. Deichmann, W. B.. Kitzmiller. M. D., Witherup. S. The effects upon experimental animals of the inhalation of phenol vapor. Amer J Clin Path 14: 273, 1944. 53. Deirhmann, W. B.. Witherup, S., Dierker. M. Phenol studies 12. J Pharmacol Exp Ther 105: 265. 1952. -1-1. Densen, P. M., Breuer? J., Bass, H. E., Jones, E. W. New York City Health Department Chronic Respiratory Disease Survey. Interim Report. May 1963. 45. Devine, K. D. Pathologic effects of smoking on the larynx and oral cavity. Proc Mayo Clin 35: 319-52, 1960. 46. Djuric, D., Raicevic, P.. Konstantinovic, I. Excretion of thiocyanate in the urine of smokers. Arch Environ Health 5: 12-5, 1962. 47. Dorn, H. F. Personal communication to the Surgeon General's Ad- visory Committee on Smoking and Health. 48. Dorn, H. F. The increasing mortality from chronic respiratory dis- eases. Amer Stat Ass Proc Sot Stat Set p. 14%53,1961. 49. Dorn, H. F. The mortality of smokers and non-smokers. Amer Stat ,%ss Proc Sot Stat Set p. 34-71, 1958. 50. Dowling, H. F., Jackson, G. G., Inouye, T. Transmission of the experi- mental common cold in volunteers. 2. The effect of certain host factors upon susceptibility. J Lab Clin Med 50: 31625. 1957. 51. Dysinger, P. W., Lemon, F. R. Pulmonary emphysema in a non-smok- ing population. Dis Chest 43: 17-25, 1963. 52. Ebert, R. V.: Filley. G., Miller, W. F. Special report to the Surgeon General's Advisory Committee on Smoking and Health. 53. Ebert, R. V., Pierce, J. A. Pathogenesie of pulmonary emphysema. Arch Intern Med 111 I 34, 1963. 54. Edwards, F., M K c eown, T., Whitfield, A. G. W. Association hetweeir smoking and disease in men over sixty. Lanret 1: 196. 1959. 55. Edwards; J. H. Contribution of cigarette smoking to respiratory disease. Brit J Prev Sot Med 11: 10-21, 1957. 56. Eich, R. H., Gilbert, R., Auchincloss. J. H.. Jr. The acute effect of smoking on the mechanics of respiration in chronic obstructive pulmonary emphysema. i\mer Rev Tuberc 76: 22. 1957. 57. Ermala. P., Holsti, L. R. Distribution and absorption of tobacco tars in organs of the respi,-atory tract. Cancer 8: 673. 19.55. 58. Fairbairn, A. S., Fletcher, C. M.. Tinker, C. M., Wood. C. 11. ,A corn--_ parison of spirometric and peak expiratory flow measurements in men with and without chronic bronchitis. Thorax 17: 10%71. 1062. 59. Falk, H. L.: Tremen, H. M., Kotin, P. Effects of cigarette smoke and its constituents on ciliated mucus-secreting epithelium. J Nat Cancer Inst 23: 999-1012, 1959. 60. Fassett. D. W. Cyanides and nitrites. In: Patty, F. A. ed. Industrial hygiene and toxicology; Fassett, D. W. and Irish, D. D. eds. Toxi- cology. 2 rev ed. New York. Interscience Pub., 1962. Chapter 44, p. 1991-2036. 61. Ferris, B. G., Jr., Anderson, D. 0. The prevalence of chronic respira- tory disease in a New Hampshire town. Amer Rev Resp Dis 86: 165-77, 1962. 62. Ferris, B. G., Jr., Anderson, D. O., Burgess, W. A. Prevalence of res- piratory disease in a flax mill in the IJnited States. Brit J Industr Med 19: 18@-5, 1962. 63. Fletcher, C. M. Chronic bronchitis in Great Britain and America. An account of chronic bronchitis in Great Britain with a compari- son between British and American experience of the disease. Dis Chest 44: l-10, 1963. a. Fletcher, C. M. Chronic bronchitis: Its prevalence, nature and path- ogenesis. Amer Rev Resp Dis 80: 483-98, 1959. 65. Fletcher, C. M. Chronic Bronchitis, Smoking and Air Pollution. To- bacco and Health. Charles C. Thomas, Springfield, Illinois, 1962. p. 380-401. 66. Fletcher, C. M., Hugh-Jones, P., McNicol, N. W., Pride, N. B. The diagnosis of pulmonary emphysema in the presence of chronic bronchitis. Quart J Med 32-51, 1963. 67. Fletcher, C. M.. Tinker, C. M. Chronic bronchitis; a further study of simple diagnostic methods in a working population. Brit Med J 1: 1491-8. 1961. 68. Flick, A. L.. Paton. R. R. Obstructive emphysema in cigarette smok. ers. AMA Arch Intern Med 104: 51826, 1959. 69. Florey. H.. Carleton. H. M.. Wells. A. Q. Mucous secretion in the trachea. Brit J Exp Path 13: 269. 1932. 70. Forsey. R. R.. Sullivan. T. J. Stomatitis nicotine. Arch Derm t Chi- came I 83: 9X-50. 1961. r il. Foster. D.. Gassney. H. An investigation of the retention of smoke 1)articulate matter by inhaling and non-inhaling type of cigarette smoker. Presented at the Tobacco Chemists Conference. Hoboken: S.J.. Oct. 1958. 72. Frank. N. R.. .\mdur. 11. 0.. Worcester. J.. Whittenherger. J. L. Effects of acute controlled exposure to SO1 on respiratory mechanics in healthy adult males. J Appl Phy-siol 17: 232-8. 1962. 7.3. Franklin. W.. Lowell. F. C. L:nrecognized airway- obstruction asso- crated with smoking: A probable forerunner of obstructive pul- monary rtnphy scma. Ann Intern lied 5 1: 379-86. 1961. ill. Freeman. G.. Haydon. G. Effects of continuous low-level exposure to nitrogen dioxide. Presented at California State Department of Public Health Sixth Annual Air Pollution Medical Research Con- ference. San Francisco. 1963. 306 75. Fry, J. Chronic bronchitis in general practice. Brit Med J 1: 190-4, 1954. 76. Goldsmith, J. R. Special report to the Surgeon General's Advisory Committee on Smoking and Health. 77. Goldsmith, J. R., Hechter, H. H., Perkins, N. M., Borhani, N. 0. Pul- monary function and respiratory findings among longshoremen. Amer Rev Resp Dis 86: 867-X. 1962. 78. Gray, E. LeB. Oxides of nitrogen: Their occurrence toxicity, hazard. AMA .1rch Industr Health (Chicago1 19: 379-86, 1959. 79. Gross, P., Hatch, T. Pulmonary clearance: Its mechanism and rela- tion to pulmonary disease. J Occup Med 5: 191-4, 196.3. 80. Guillerm, R., Badre: R., Vignon. B. Inhibitory effects of tobacco smoke on the ciliary activity of the respiratory epithelium and nature of the responsible constituents. Bull Acad Nat Med (Paris) 145: 416-23, 1961. 81. Haagen-Smit, A. J., Brunelle. bl. F.. Hara. J. Nitrogen oxide content of smokes from different types of tobacco. AMA Arch Industr Health (Chicago) 20: 399-1.00. 1959. 82. Hammond, E. C. Special report to the Surgeon General's Advisor? Committee on Smoking and Health. 83. Hatch, T. Respiratory dust retention and elimination. Proc Pneumo- coniosis Conf Johannesburg, 1959. p, 133. 84. Hausknecht, R. Experiences of a respiratory disease panel selected from a representative sample of the adult population. Amer Rev Resp Dis 86: 858-66, 1962. 85. Heath, C. W. Differences between smokers and nonsmokers. AMA Arch Intern Med 101: 377-88, 1958. 86. Heimann, H. Effects of air pollution on human health. WHO Monogr Ser No 46: 159-220, 1961. 87. Higgins, I. T. T. An approach to the problem of bronchitis in industry : Studies in agricultural, mining and foundry communities. In : King, E. J., Fletcher, C. M., eds. Symposium on Industrial Pulmonary Diseases. London, Churchill, 1960. p. 195-207. 88. Higgins, I. T. T. Respiratory symptoms, bronchitis, and ventilator>- capacity in random sample of an agricultural population. Brit Med J 2: 1198-1203, 1957. 89. Higgins, I. T. T. The role of irritation in chronic bronchitis. In: Orie, N. G. M., Sluiter, H. J. eds. Bronchitis. Springfield, Ill., Thomas, 1961. p. 31-42. 90. Higgins, I. T. T. T b o acco smoking, respiratory symptoms, and venti- latory capacity. Studies in random samples of the population. Brit Med J 1: 325-9, 1959. 91. Higgins, I. T. T., Cochrane, A. L. Chronic respiratorv diseases in a random sample of men and women in the Rhondda.Fach in 1958. Brit J Industr Med 18: 93-102, 1961. 92. Higgins, I. T. T., Cochrane, A. L., Gilson. J. C., Wood. C. H. Popula- tion studies of chronic respiratory disease: 4 comparison of miners, foundry workers and others in Staveley, Derbyshire. Brit J. Industr Med 16: 255-68, 1959. 307 93. Higgins, I. T. T., Cochran, J. B. Respiratory symptoms, bronchitis and disability in a random sample of an agricultural community in Dum- friesshire. Tubercle 39: 296301, 1958. 94. Higgins. I. T. T., Oldham: P. D. Ventilatory capacity in miners. A five year follow-up study. Brit J Industr Med 19: 65-76, 1962. 95. Higgins, I. T. T., Oldham, P. D., Cochrane, A. L., Gilson, J. C. Respira- tory symptoms and pulmonary disability in an industrial town. Sur- vey of a random sample of the population. Brit Med J 2: 904-9. 1956. 96. Hilding, A. C. On cigarette smoking, bronchial carcinoma and ciliary action. 2. Experimental study on the filtering action of cow's lung, the deposition of tar in the bronchial tree and removal by ciliary action. New Eng J Med 254: 1154-60, 1956. 97. Hilding. -1. C. On cigarette smoking, bronchial carcinoma and ciliary action. 3. Accumulation of cigarette tar upon artificially produced deciliated islands in the respiratory epithelium. Ann Otol 65: 11630, 1956. 98. Hill, L. The ciliary movement of the trachea studied in vitro. Lancet 2: 802-5, 1928. 99. Hogner, R. Tobacco poisoning without using tobacco. Amer Med 26: 111-2, 1920. 100. Holland, R. H., Wilson, R. H., Morris, D., McCall, M. S., Lanz, H. The effect of cigarette smoke on the respiratory system of the rabbit. Cancer 11: 709-12, 1958. 101. Holland, W. W. A respiratory disease study of industrial groups. Arch Environ Health I Chirago) 6: 15-22, 1963. 102. Horton, A. W.. Tye. R., Stemmer. K. L. Experimental rarcinogenesis of the lung. Inhalation of gaseous formaldehyde or an aerosol of coal tar by C3H mice. J Nat Cancer Inst 30: 31-43, 1963. 103. Hyatt, R. E., Kistin. A. D.. Mahaw. T. K. Respiratory disease in southern West Virginia coal workers. Amer Rev Resp Dis (In Press). 104. Ide, G., Suntzeff. V., Cowdry. E. V. .\ comparison of the histo- pathology of the tracheal and bronchial epithelium of smokers and non-smokers. Cancer 12: .173&U, 1959. 105. Jimenez-Diaz. C., Sanchez Cuenca, B. Asthma produced by suscepti- bility- to unusual allergies. Linseed, insects, tobacco, and chicory. J Allerg 6: 39-103. 1935. 106. Joules. H. A preventive aljproach to common diseases of the lung. Brit Med J 2: 125963. 19.5-1. 107. Keith. C. H., New some. J. R. Quantitative studies on cigarette smoke. 1. An automatic smoking machine. Tobacco 144: i 13 ) 2632. Mar 29. 1957. 108. Kensler, C. J.. Battista, S. P. Components of cigarette smoke with ciliary-depressant activity. Their selective removal by filters con- taining activated charcoal granules. New Eng J Med 269: 1161-66, 1963. 308 109. Kleinerman, J., Wright, G. W. The reparative capacity of animal lungs after exposure to various single and multiple doses of nitrite. Amer Rev Resp Dis 83: 1X-2.1. 1961. 110. Kler, J. H. An analysis of colds in industry. Tr Amer Acad Opthal Otol 49: 201-7. 19.15. 111. Kordik, P.; Billbring. E.. Burn. J. H. Ciliary movement and acetyl- choline. Brit J Pharmarol 7: 67-79. 1952. 112. Krueger, L1. P.. Smith, R. F. Effects of gaseous ions on tracheal ciliary rate. Proc Sot Exp Rio1 Med 98: 112-I. 1958. 113. LaBelle. C. W., Long. J. E.. Christofano. E. E. Synergistir effects of aerosols. Particulates as carriers of toxic vapors. ?rrch Tndustr Health (Chicago I 11: 297-304. 1955. 114. Laennec, R. T. H. A treatise on the disease of the rhest. Translated by J. Forbes. Published under the auspices of the Librar! of the New York Academy of Medicine by Hafner. NY 81-97. 1962. 115. Landau, E., Morton, J. .4n epidemiologic view of chronic pulmonarv insufficiency in the United States. Amer Rev Resp Dis 83: 1057. 1961. 116. Langer, G.: Fisher, M. .4. Concentration and particle size of cigarette- smoke particles. AMA Arch lndustr Health t Chicago I 113: 372-y. 1956. 117. Leese, W. L. B. An investigation into bronchitis. Lancet 2: 762-5. 1956. 118. Leuchtenberger, C., Leuchtenberger, R.. Doolin, P. F. A correlated his- tological, cytological and cytochemical study of the tracheobronchial tree and lungs of mice exposed to cigarette smoke. Cancer 11: $90- 506, 1958. 119. Leuchtenberger, C., Leuchtenberger, R.. Zebrun, WY., Shaffer. P. A correlated histological, cytological, and cytochemical study of the tracheobronchial tree and lungs of mice exposed to cigarette smoke. 2. Varying responses of major bronchi. Cancer L<: 721-:<2. 1960. 120. Liebeschuetz, H. J. Respiratory signs and svmptoms in young soldiers and their relationship to smoking. J Roy Army Med Corps 105: 76-81, 1959. 121. Liggett & Myers Tobacco Co., Arthur D. Little, Inc. Special report to the Surgeon General's Advisory Committee on Smoking and Health. 122. Lindsey, A. J. Some observations on the chemistry of tobacco smoke. In: James, G., Rosenthal, T.. eds. Tobacco and Health. Springfield. Ill., Thomas, 1962. p. 21. 123. Loudon, R. G. Special report to the Surgeon General's Advisory Com- mittee on Smoking and Health. 124. Lowe, C. R. An association between smoking and respiratory tuhercu- losis. Brit Med J 2: 1081-6, 1956. 125. Lowell, F. C., Franklin, W., Michelson, A. I,., Schiller. I. W. Chronic obstructive pulmonary emphysema: 4 disease of smokers. .4nn Intern Med 45: 268-74, 1956. 126. Lowry, T., Schuman, L. M. Silo-fill er's disease- -a syndrome caused bv nitrogen dioxide. J.4M.4 162: 153-60, 1956. 127. Maliszewski. T. F., Bass. D. E. True and apparent thiocyanate in body fluids of smokers and nonsmokers. J Appl Physio18: 289-91,195s 128. Manos, N. E., Cooper, W. C. Special report to the Surgeon General's Advisory Committee on Smoking and Health. 129. McFarland, J. J., Webb, B. M. Special report to the Surgeon General's Advisory Committee on Smoking and Health. 130. Mellors, R. C. Microscopic localization of tobacco smoke products in the respiratory tracts of animals exposed to cigarette smoke. [Ab- stract] Proc Amer Ass Cancer Res 2 : 325,195s. 131. Mendenhall. W. L., Shreeve, K. Effect of tobacco smoke on ciliary action. J Pharmacol Exp Ther 69: 295, 1940. The effect of cig- arette smoke on the tracheal cilia. Ibid. 60: 111-2, 1937. 132. Merrill, M. H. Public health responsibilities and program possibilities in chronic respiratory diseases. Amer J Public Health 53: (3) C supp) ~ 25-33, 1963. 133. Mills, C. A. Tobacco smoking: Some hints of its biologic hazards. Ohio Med J 46: 1165-70; 1950. 134. Miller, D., Bondurant, S. Effects of cigarette smoke in the surface characteristics of lung extracts. Amer Rev Resp Dis 85 : 692-6, 1962. 134a. Miller, J. M. Special Report to the Surgeon General's Advisory Committee on Smoking and Health. 135. Mitchell, R. I. Controlled measurement of smoke-particle retention in the respiratory tract. Amer Rev Resp Dis 85: 526-33, 1962. 136. Mitchell, R. S. Personal communication to the Surgeon General's Ad- visory Committee on Smoking and Health. 137. AIitchell, R. S., Filley, G. F. P ersonal communication to the Surgeon General's Advisory Committee on Smoking and Health. 138. Mitchell, R. S.: Toll, G.. Filley, G. The early lesions in pulmonary emphysema. Amer J Med Sci 243: 409-18,1962. 139. Mork, T. A comparative study of respiratory diseases in England and Wales and Norway. Yorwegian Universities Press: 1962. Also: ACTA Med Stand 172 i Suppl384) : l-100,1962. 140. Morris, J. Iv. I-ses of epidemiology. Edinburgh, Livingstone. 1957. 135 p. 141. IIloriyama. I. M. Ch ronic respiratory disease mortality in the [-nited States. Public Health Rep 78: 743-8, 196:3. 142. Motley. H. L.: Kuzman, W. J. Cigarette smoke. Its effect on pulmo- nary function measurements. Calif &Led 88: 211-21. 1958. 143. Murphy, S. D., Klingshirn, D. A., Ulrich. C. E. Respiratory response of guinea pigs during acrolein inhalation and its modification h! drugs. J Pharmacol Exp Ther 141: 79-83, 1963. 144. Murphy-. S. D., Leng, J. K.- Ulrich, C. E., Davis, H. V. Effects on ex- perimental animals on brief exposure to diluted automobile exhaust. Presented at Air Pollution Research Conference, December 9, 1961. California. 116. Nadel. J. A., Comroe, J. H. Acute effects of inhalation of cigarette smoke on air\\ ay conductance. J Appl Physiol 16: 713-6. 1961. 310 147. Nakashima, T. Pharmacological studies on ciliary movement. Naga- saki Igasakkai Zassi 14: 2219-37, 1936. [Abstract in English] Jap J Med Sci, Sect pharmacol 11: ,12, 1938. 148. Olsen, H. C., Gilson. J. C. Respiratory symptoms, bronchitis and ventilator): capacity in men. An Anglo-Danish comparison, with special reference to differences in smoking habits. Brit Med J 1: 450-6, 1960. 149. Oswald, N. C., Harold, J. T.: Martin. W. J. Cliniral pattern of chronic bronchitis. Lancet 2: 539-13, 1953. 150. Oswald, N. C., Medvei, V. C. Chronic bronchitis; the effect of cigarette smoking. Lancet 2: 833%&y, 1955. 152. Pattle, R. E. Properties. function. and origin of the alveolar lining layer. Proc Royal Sot Biol 118: 21T--10, 1958. 152. Pattle, R. E., Burgess, F. Toxic effects of mixtures of sulfur dioxide and smoke with air. J Path Bact 73: 411-9,1957. 153. Payne, M., Kjelsberg, M. Respiratory symptoms, lung function and smoking habits in a total community-Tecumseh? Michigan. Paper presented before the Epidemiology Section of the .imerican Public Health Association in Miami Beach, October 17, 1962. 154. Pemberton, J., Goldberg, C. Air pollution and bronchitis. Brit Med J 2: 567-70, 1953. 155. Phelps, H. W., Koike, S. Tokyo-Yokohama asthma. Amer Rev Resp Dis 86: 55-63, 1962. 156. Phillips, A. M., Philiips, R. W., Thompson, J. L. Chronic cough: analysis of etiologic factors in a survey of 1,274 men. Ann Intern Med 45: 216-31, 1956. 157. Pro&: A. Some preliminary experiments in the study of cigarette smoke and its effect upon the respiratory tract. Ann Otol48: 176 94, 1939. 158. Rakieten, N., Rakieten, M. L.: Feldman, D., Boykin. M. J., Jr. Mam- malian ciliated respiratory epithelium. Studies with particular ref- erence to the effects of menthol, nicotine, and smoke of mentholated and nonmentholated cigarettes. Arch Otolaryng (Chicago) 56: 494-503, 1942. 159. Read, J., Selby, T. Tobacco smoking and ventilatory function of the lungs. Brit Med J 2: 1104-8, 1961. 160. Reid, D., Fairbairn, A. S. ,1ir pollution and other local factors in res- piratory disease. Brit J Prev Sot Med 12: 94-103: 1958. 161. Reid, D. D. General epidemiology of chronic bronchitis. Proc Roy Sot Med 49: 767-71, 1956. 162. Reid, L. Chronic bronchitis and hypersecretion of mucus. Lect Sci Basis Med 8: 235-8, 1958-59. 163. Reid, L. Measurement of the bronchial mucous gland layer: A diag- nostic yardstick in chronic bronchitis. Thorax 15: 132-41, 1960. 164. Reid, L. M. Pathology of chronic bronchitis. Lancet 1: 275-8. 195-1. 165. Revotskie, N., Kannell, W., Goldsmith, J. R., Dawber, T. R. I'ulmo- nary function in a community sample. Amer Rev Resp Dis fi6: 907-11, 1962. 311 166. Rigdon, R. H. Effect of tobacco condensate on the respiratory tract of the white Pekin duck. AMA Arch Path (Chicago) 69: 55-63,1960. 167. Rivera, J. A. Cilia, ciliated epithelium and ciliary activity. Int Ser Monogr Pure Appl Biol 15: 1-167, 1962. 168. Rosen, F. L. Bronchial asthma in the young male adult. Ann Allerg 4: 247-60, 1946. 169. Rosen, F. L., Levy, A. Bronchial asthma due to allergy to tobacco smoke in an infant. A case report. JAMA 144: 620-1, 1950. 170. Ryan, R. F., McDonald, J. R., Devine, K. D. The pathologic effects of smoking on the larynx. AMA Arch Path (Chicago) 60: 472-80, 1955. 171. Sanderud, K. Squamous metaplasia of the respiratory tract epithelium. 2. Relation to tobacco smoking, occupation and residence. Acta Path Microbial Stand 4.3: 47-61, 1958. 172. Saunders, W. H. Nicotina stomatitis of the palate. Ann Otol 67: 618-27, 1958. 173. Schoettlin, C. E. The health effect of air pollution on elderly males. Amer Rev Resp Dis 86: 878-97,1962. 175. Shah, J. R., Warawadekar, M. S., Deshumkh, P. A., Phutane, P. N. In- stitutional survey of pulmonary tuberculosis with special reference to smoking habits. Indian J Riled Sci 13: 381-92, 1959. 176. Short, J. J., Johnson, H. J., Ley, H. A., Jr. The effects of tobacco smok- ing on health. A study of 2.031 medical records. J Lab Clin Med 24: 586-9, 1939. 177. Simonsson, B. Effect of cigarette smoking on the forced expiratory flow rate. Amer Rev Resp Dis 85: 534-9, 1962. 178. Sollmann, T., Gilbert. A. J. Microscopic observations of bronchiolar reactions. J Pharmacol Exp Ther 61: 272-85, 1962. 179. Stokinger, H. E.. Wagner. W. D., Dobrogorski, 0. J. Ozone toxicity studies. 3. Chror?ic injury to lungs of animals following exposure at low levels. AMA Arch Industr Health 16: 51L-22, 1957. 180. Sweet, H. C., Wyatt, J. P., Fritsch, A. J.. Kinsella, P. W. Panlobular and centrilobular emphysema: Correlation of clinical findings with pathologic patterns. Ann Intern Med 55: 565-81, 1961. 181. Thoma. K. H. Stomatitis nictrtina and its effects on the palate. Amer J Orthodont 27: XLli. 1911. 182. Thurlbeck. W. RI. 4 cliniro-pathological study of emphysema in an .\merican hor;pital. Thorax 18: 59-67, 1963. 183. Thurlbeck. W. M.. Angus. G. E. The relationship between emphysema and chronic bronrhitis as assessed morphologically. Amer Rev Resp Dis 87: 815-3, 1965. 181. Thurlbeck. W. M.. i\ngus, G. E., Pare. J. A. P. Mucous gland hyper- trophy in chronic bronchitis, and its occurrence in smokers. Brit J Dis Chest 5i: 73-7X. 1963. 185. Truhart. H. Ein heitra;: zur nicotinwirkung. Dorpat, 1869. Thesis, 70 p. 186. U.S. Departnlrnt of Health. Education, and Welfare. Disability ap- plicants under the old-age survivors and disability program. 1960 selected data. Januar\- 1962. 312 187. Von Oettingen, W. F. Toxicity and potential dangers of nitrous fumes. Public Health Bull 272: l-34, 1941. 188. Vassar, P. S., Culling, C., S aunders, A. M. Flourescent histiocytes in sputum related to smoking. AMA Arch Path iChicago\ 70: 649-52, 1960. 189. Walker, I. C. The treatment of patients with bronchial asthma with subcutaneous injections of proteins to which they are sensitive. J Med Res 36: 423-80, 1917. 190. Westermark, T. Gaseous ions and their possible role in the etiology of lung cancer and some observations on free charges in cigarette smoke. Acta Med Stand 170: tSupp1 369) 119-20, 1961. 191. Wolff, W. -I., Tuttle. J. G., Godfrey, J. M. Radioautographic method for studying deposition of cigarette smoke in the dog lung. Abstract Fed Proc 13: 32-4, 1954. 192. Wolff, W. A.. Purdom. E. G.. Isenhower, J. A. The use of radio- isotopes as tracers in cigarette smoke. N Carolina Med J 15: 159- 63, 1954. 193. Wright, G. W.. Lloyd. T. Th e pulmonary reaction of normal and emphysematous persons to inhalation of SO,, fly ash. and moisture. 3d Air Pollution Research Seminar. U.S. Public Health Service. 194. Zamel, N., Youssef, H. H., Prime, F. J. Airway resistance and peak expiratorv flow-rate in smokers and non-smokers. 1960. Lancet 1: 1237-8, 1963. New Orleans, 313 Chapter 11 Cardiovascular Diseases Contents INTRODUCTION . . . . . . . . . . . . . . . . . . . . PERTINENT PHARMACOLOGY . . . . . . . . . . . . . GENERAL OBSERVATIONS ON CORONARY HEART DIS- EASE . . . . . . . . . . . . . . . . . . . . . . . . . SMOKING AND CORONARY HEART DISEASE . . . . . SMOKING AND NON-CORONARY CARDIOVASCULAR DISEASE . . . . . . . . . . . . . . . . . . . . . . . CHARACTERISTICS OF CIGARETTE SMOKERS . . . . PSYCHO-SOCIAL FACTORS OF SMOKING IN RELATION TO CARDIOVASCULAR DISEASE . . . . . . . . . . . SUMMARY . . . . . . . . . . . . . . . . . . . . . . . CONCLUSION . . . . . . . . . . . . . . . . . . . . . . REFERENCES. . . . . . . . . . . . . . . . . . . . . . List of Tables TABLE 1. Death rates per 100,000 from arteriosclerotic and degenerative heart disease by sex and age, United States, 1958-60 . . . . . . . . . . . . . . . . TABLE 2. Ratios of mortality rates for coronary heart disease, male smokers to non-smokers, by age and amount smoked, in selected studies . . . . . . . . . . . Page 317 317 320 322 325 326 327 327 327 328 321 324 316 Chapter 11 __ .- INTRODUCTION It has been suggested repeatedly that smoking may ha\-e adverse effects on the cardiovascular system. Recently. studies of large groups of people have shown that cigarette smokers in particular are more prone to die early of certain cardiovascular disorders than non-smokers. Chief among theFe dis- orders is coronary artery disease. and the present chapter deals mostly with this subject. The chapter begins with a summary of information ahout the acute effects of smoking on the cardiova.scular system. This is followed b\- a brief account of coronary disease, its frequency in different kinds of people. and the many factors known or thought to affect the likelihood of its develop- ment. The aim here is not to reviebj critically our knowledgr of coronary disease hut only to give background for what follows. Next is summarized the information currently availahle from study of large population groups on the association of cigarette smoking with an increased tendency to hal-e coronary disease. There follows a brief discussion of smoking and non- coronary cardiovascular disease. Finally, there is a short review of evidence relating to the question of whether cigarette smokers may, as a group, differ from non-smokers in ways not caused by smoking itself. Mortality ratios showing the association between cigarette smoking and deaths from cardio- vascular disease, especially coronary disease, do not indicate the magnitude of the burden. This can be better appreciated from consideration of the following facts: cardiovascular disease deaths now total more than 700,000 annually in the United States. Of these more than 660,000 were due to heart disease, with more than 500,000 due to arteriosclerotic heart disease includ- ing coronary disease. The remaining approximately 40,000 were ascribed to disease of other parts of the cardiovascular system. Deaths from lung cancer total approximately 39,000. A mortality ratio of 1.7 for coronary heart disease among cigarette smokers in the seven prospective studies repre- sents from 32.9 percent to 51.7 percent of all excess deaths: whereas the much higher lung cancer mortality ratio of 10.8 from the same studies repre- sents only 13.5 percent to 24.0 percent of total excess deaths (Chapter 8. Tables 19, 25). PERTINENT PHARMACOLOGY The acute cardiovascular effects of smoking in man and experimental ani- mals are like those caused by nicotine alone. A smoker who inhales gets usually l-2 mg of nicotine from a cigarette (56,57). Low concentrations of nicotine stimulate sympathetic ganglia, and high concentrations paralyze them. Parasympathetic ganglia respond in the same way but are less sensitive. iY ice ine t can also have a sympathomimetic effect 317 by causing the discharge of norepinephrine and epinephrine from chromaffin cells in various tissues, including heart: vessels, and skin (10, 11, 9). In addi- tion, nicotine produces effects reflexly by stimulating the chemoreceptors of the carotid and aortic bodies. Wh en nicotine is given intravenously in in- creasing doses to dogs or cats the first effects, at about 1 microgram,/kg body weight, are increased breathing and sympathetic stimulation, with predomi- nant vasoconstriction, cardiac acceleration, and rise in blood pressure, re- sulting from stimulation of the aortic and carotid bodies (17). Doses of 4 to 8 micrograms/kg can stimulate pulmonary and coronary chemoreflexes which produce opposite effects. If all these receptors are inactivated, much higher doses are needed to evoke the cardiovascular effects of sympathetic stimulation, presumably through action on sympathetic ganglia or chromaffin tissue. Intravenous administration of nicotine in the experimental animal causes a discharge of epinephrine from the adrenal medulla, and in man heavy cigarette smoking prnduces an increased urinary excretion of catecholamines (B&99). Smoking l-2 cigarettes causes in most persons, both smokers and non- smokers, an increase in resting heart rate of 1.5-25 beats per minute, a rise in blood pressure of 10-20 mmHg systolic and 5-15 mmHg diastolic (76, 78, 85, 86). and an increase in cardiac output of about 0.5 l/min/sq.m (75). There is a decrease in digital blood flow and a consequent drop in finger and toe temperature (31, 78,103). Th e d ecrease in peripheral blood flow which normally follows smoking does not occur in a sympathectomized limb, in- dicating that the effect is mediated primarily by the sympathetic nervous system rather than through the release of catecholamines from other sites or the direct effect of nicotine upon the smooth muscle of the blood vessels themselves (103) . Intravenous nicotine, and probably cigarette smoking as well, can produce a slight transitory increase in the blood flow to resting calf muscle (79). In the dog, nicotine and cigarette smoke cause an increase in coronary flow as the blood pressure, cardiac output, and heart work increase (30, 53). These effects. resemble those of epinephrine. Nicotine has been found to cause a transient decrease in cardiac oxygen utilization followed by a slight increase ( 53) . Relatively little information is available about the effect of smoking on coronary blood flow in man. In normal subjects it is re- ported that cigarette smoking produces an early increase in coronary flow as heart work increases. but there is little change in oxygen utilization by the myocardium i2). With continued "steady state" smoking the coronary flow and cardiac oxygen utilization are maintained at the resting level in both normal subjects and persons with coronary heart disease, despite in- creased blood pressure, heart rate, and heart work ( 74). A larger experi- ence must be gathered in this field before statements about the acute effects of smoking on the human coronary circulation can be made with assurance. The atherosclerotic rabbit heart, like the normal rabbit heart: shows an initial drop in coronary flow on administration of nicotine, but demonstrates less of a subsequent increase above the resting level than does the normal heart (97). These effects are said to be equivalent to those produced by norepinephrine in doses one-tenth as large as the nicotine dose. 318 Little or no change in the electrocardiogram of most normal persons or cardiac patients, except for an increase in rate, is produced by smoking or by the intravenous injection of an equivalent dose of nicotine (82, 98). In some persons there is a slight depression of the S-T segment and a flattening of l-2 mm in the T wave of the limb leads. These changes are not like those associated with my-ocardial ischemia. Rarely in persons with true angina. an attack of pain is precipitated by smoking. An ill-defined syn- drome consisting of chest pain. palpitation. and shortness of breath, known as "tobacco angina". has been described as occurring in smokers who do not have organic heart disease. but it is rarely diagnosed today (73, 82). Extrasvstoles and other cardiac arrhythmias have been reported to be caused bv smoking. but such cases appear to be unusual. I The b a IS ocardiogram obtained from a high-frequency table is some- II' t times changed by smoking a cigarette from a normal pattern to one said to be typical of coronary disease (78, 91 I Th is phenomenon is rare in healthy persons below 50, becomes increasingly common with advancing years in apparently healthy persons. but is particularly prone to occur at any age in persons with actual coronary disease. The effect has been used as a "stress test" to help uncover coronary disease. but false positive and negative results are common. The ballistocardiopaphic changes on smoking have been variously interpreted as resulting from impaired myocardial contractility I 78`)) from changes in the peripheral circulation (82), or from uncertain causes related to the physical properties of the high-frequency table as well as changes in the circulation. Cigarette smoking causes an increase in the concentration of serum-free fattv acids in man ( 50), apparently mediated by stimulation of the sympa- thetic nervous system (51). Although continued administration of epine- phrine to dogs over many hours can produce substantial increases in serum cholesterol, phospholipids, and triglycerides, such an effect has not yet been reported from nicotine or tobacco smoke (48, 92). The clotting time of the blood can be decreased 50 percent or more in ex- perimental animals by stimulation of the sympathetic nervous system or hy administration of epinephrine (12, 13, 14)) but attempts to demonstrate that cigarette smoking alters the clotting properties of the blood in man have been unsuccessful i5, 68). A decrease in platelet survival in viva has been found after smoking (68) . Cigarette smokers have been reported to show substan- tial decreases in hematocrit, hemoglobin, and platelet counts after abstinence of l-2 weeks (25)) but hemoglobin concentrations are alike in smokers and non-smokers of the same population group (4). Attempts have been made to induce atherosclerosis in rats by the chronic administration of nicotine for periods up to a year without sucwss (93). Tobacco has antigenic properties (29, 43). Rats can be sensitized to to- bacco extracts by intraperitoneal injection. Over a third of smokers demon- strate a positive-"immediate" skin reaction to such extracts while only about 10yc of non-smokers are said to give positive tests. The presence of serum reagins in persons with positive skin tests has been demonstrated by passive transfer techniques. Persons with thromboangiitis obliterans and smokers with occlusive vascular disease of other types are said to show a much higher incidence of positive skin tests than healthy smokers. The cardiovascular 7 14-422 O-64-22 diseases which have been related to smoking, however, do not in general resemble those usually ascribed to an immune mechanism. In man and experimental animals smoking or the injection of nicotine causes increased secretion of antidiuretic hormone. The renal effects of this are easily demonstrable but the quantity of hormone secreted in response to smoking is probably too small to have significant vascular effects (17 ) . In summary, the acute cardiovascular effects of smoking and of nicotine closely resemble those of sympathetic stimulation. and to a considerable extent are mediated by excitation of the sympathetic nervous system. No additional or unique cardiovascular effects have been demonstrated which. in the light of our present understandin,. 0 seem likely to account for the observed association of cigarette smokin, c with an increased incidence of coronar\- disease. CENERAL OBSERVXTIONS ON CORONARY HEART DISEASE Heart disease is the most common cause of death in our population. and coronary disease is the commonest variety of fatal heart disease (59'1. Iri 1961 there were 1:701..522 deaths from all causes in the United States. Heart disease deaths numbered 663.391 of which 502.351 were due to arterio- sclerotic heart disease. The disorder consists of obstruction or narrowing of the coronary arteries. reducing the blood supply to the heart muscle. The underlying cause of the obstruction is coronary atherosclerosis. but an acute coronarv artery occlu- sion is often caused by the formation of a blood clot in a d&eased arterv. The common manifestations of coronary disease are an$na pectoris. recur- rent brief attacks of chest pain caused by inadequate blood supply to the heart muscle: myocardial infarction, or necrosis of a portion of the heart muscle due to acute loss of blood supply; congestive heart failure, a chronic state caused bv inability of the heart to pump enough blood to satisfy the demands of thk body; and sudden death resulting from cardiac standstill or ventricular fibrillation. There are considerable differences in the prevalence of coronary heart disease in different countries, and often in different ethnic and socio-economic, groups within a particular country (ML 02 1. The reported death rate of arteriosclerotic heart disease. which is Ibrimarily coronary disease. is higher in the United States than in other countries. it is also quite high in Yew Zealand. Australia.`South Africa, Canada. and Finland. and moderately hi?h in Great Britain. The death rate in Norway, Sweden, and Denmark is roughI> half that in the high death rate countries I 1.5 I. The death rate in Japan appears to be about one-sixth that in the United States, although persons of Japanese origin living in the United States are said to have a death rate similar to that of the Fenera i)opulation of this country i.52). Because of changing diagnostic skills and revisions in nomenclature of disease, it is d&cult to be certain of the change in incidence of coronar! disease in the United States oter the pas! few decades, but there is a general opinion that the incidence is increasin, m in this country and in England. 320 particularly in the younger male group (59, 62, 65, 83). In 1955 the mortality rate from arteriosclerotic heart disease was reported to be about 240 per 100,000. Although this is an increase of more than 50% over the rate in 1940, it has been estimated that less than 157; of the increase represented a real chance in incidence of the disease, the remainder depending upon changes in diagnosis, in nomenclature and in the age of the population (59 1. Since 1955 the death rate from coronary disease (ISC 420) and from arteriosclerotic and degenerative heart disease (I%420 and 422) has con. tinued to increase gradually. In 1960 the age-adjusted death rate from 420 and 422 was 330 per 100,000 for white males and 150 for white females ( 55 ) . Although the basic cause or causes of coronary heart disease are obscure, certain factors other than smoking are known or thought to predispose to the condition or to be associated with an increased incidence. The incidence of coronary heart disease in men under 45 is about 5 times as great as that in women (Table 1) ( 15, 20,59, 62). In both sexes the inci- dence increases with advancing years. After the menopause the incidence increases rapidly in women, and at age 80 the death rates from coronary disease are about the same for the two sexes. Coronary thrombosis plays a relatively more important role in precipitating myocardial infarction in young men than it does in old men i 105 1. In studies of large population groups coronary disease has been associated with elevation of the serum cholesterol, hypertension, and marked overweight (19, 20, 24, 36,46, 59,62). Some individual characteristics have been said to be associated with coro- nary disease. There is a significant familial tendency to develop it (36, 69, 81, 96). Persons with a mesomorphic constitution are said to be more vul- nerable than endomorphs and ectomorphs (36, 62, 88). A coronary-prone 1)ersonality has been described as the aggressive, competitive person who takes on too many jobs, fights deadlines, and is obsessed by the lack of adequate time for the performance of his work (33,34,35). TABLE I.-Death rates per 100,000 f rom arteriosclerotic and degenerative heart disease* hy sex and age, United States, 195840 A c"' G roll p TMall= Frmah rloth SITC- Under 35------------------------------ 3.3 1.2 2.2 3544--------------------------------- 90.2 18.3 53.3 45-54 ------__-_-_____----------------- 353.7 79.3 213.5 55-64 -------___-----_----------------- 928.5 314.5 610.2 65-74 _________________________________ 2129.2 1082.0 1569.5 75orover------------------------------ 4765.1 3738.4 4179.7 *Includes IX numbers 420 and 422. Source: WHO Epidemiological and Vital Statistics Report, Vol. 16, No. 2, 1963. Certain occupations have been said particularly to favor the development of coronary disease, notably those which feature responsibility and stress (34, 81, 87), and which are sedentary in nature (71. Others (58, 72, 901 have not found that executives are more prone to coronary disease than non- executive 1)ersonnel. Ph; . ~slcians have been said to habe 3 or 4 times as much coronary disease as farmers or laborers 187): and general prac~titioners to 321 have 3 times as much as dermatologists (80). Occupations involving much physical activity are said to be protective (66, 67, 77). City life has been said to be more closely associated with coronary disease than suburban life, and men who drove more than 12,000 miles a year seemed, in one study, more 1Jrone to the disease than those who drove less (64). It has been widely held, and occasionally denied, that a diet high in saturated fat predisposes to the development of coronary disease (46, 52, 69, 81). A correlation between the national incidence of coronary disease and the percentage of food calories available as saturated fat has been re- ported among those countries for which adequate data exist (46). The serum cholesterol tends to rise when saturated fat is added to the diet, and it falls significantly when unsaturated fat is substituted (46). It has also been sug- gested that general over-nutrition? rather than excess saturated fat predis- poses to coronary disease, on the grounds that the correlation of coronary disease with total available calories or sugar consumption per capita is as good as that for percentage of calories in fat (106). In general, it is apparent that multiple personal and environmental factors can markedly affect the incidence of coronary disease. SMOKING AND CORONARY HEART DISEASE Over the last two decades a considerable number of epidemiologic studies on different populations, employing different techniques, have shown with remarkable consistency a significant relationship between cigarette smoking and an increased death rate from coronary heart disease in males, par- ticularly during middle life. There has been little dissenting evidence. The association of coronary disease with the use of tobacco in other forms has not been striking. The documentation for these statements is given in the following paragraphs. Particularly important is the information in Chapter 8, Mortality. English et al. 126) found the incidence of coronary disease in male patients at the Mayo Clinic about 3 times greater in cigarette smokers than in non-smokers in the 40-59 year age range, but found little relation to smoking above 60. Russek 181) reported a similar relationship, but less striking, in young men with coronary disease. Mills (64) in a study of reported mortality in a Cincinnati population found that heavy smokers in the 30-59 )-ear age range had twice as high a death rate from coronary disease as non-smokers. Male Seventh Day Adventists: who are non- smokers. were found by Wyrlder and Lemon (104) in a study based on hospital admissions to hale significantly less coronary disease and to de- velop it later in life than the general male hospital population. Haag and Hanmer I ST I reported that employees in the tobacco industry. \\ ho tend to smoke heavily. had a lower death rate for cardiovascular disease than the general population ill their geographic region. but no report was made of mortality rates within the tobacco-worker group, divided by smok- ing habits. The study has been criticized on this and other grounds ( 16 I. Large-scale prospective studies of mortality in British phyairians ( Doll and Hill, 21 I _ United States males 50-69 recruited by volunteer workers 322 ( Hammond and Horn, 38, 39.40.42) and \`.A. Life Insurance policyholders i Darn: 22) have confirmed the association of death from coronary disease with cigarette smoking. In the British study, a step-wise association was found between the amount of tobacco consumed (not entirel! cigarettes) and the mortality from coronary disease. The association occurred in the X-54 !-ear age range. but not in older men. Hammond and Horn found a similar graded relationship between coronary deaths and cigarette smok- ing. the death rate being more than twice ai great in men who smoked over a pack a da\- as in non-smokers. Men who had stopped smoking for more than a !ear at thr start of the study had a coronary death rate lower than those who continued. Studies on special groups of men. such as longshoremen (Buerhley et al. :: I membrrs of a fraternal order i Spain and Nathan. 89) and industrial employees (Paul et al. 71) which. in the latter two instances. incorporated clinical coronary disease. as well as coronary deaths. also have shown a relationship bet\\een coronary disease and smoking. The relationship It-as closer for men under 51 than for older men, and closer for myocardial infarcts and death than for angina pectoris (70,891. The long-term prospective studies of cardiovascular disease in Framing- ham (19, and in Albany 124) which have featured a painstaking sparch at regular interrals for clinical manifes;tations of disease. have. on pooling the data (Doyle et al. 23) shown a threefold increase in the incidence of myocardial infarction and coronary deaths in men who are hea\!- ciga- rette smokers as compared to non-smokers. pipe and cigar smokers. and former cigarette smokers. In the pooled data the incidence of angina per- toris did not shoM a significant association with cigarette smoking. The lack of this particular relationship had been suggested on the hasis of clinical experience (White and Sharber. 102 I. An apparent interplay of fa,ctors relating to smoking and occupation turned up in a short-term studv of the development of roronar) heart dis- ease in a general North Dakoia population (Zukel et al., 107). Farmers had about half the incidence of myorardial infarction experienced b!- others. In farmers. smoking had no appreciable effect on the incidence of infarc- tion. but in others the incidence of infarction was twice as high among smokers as among the non-smokers. The farmers who smoked cigarettes smoked less heavily than males in other occupational groups. In Chapter 8. Mortality, there is summarized the most recent infor- mation availahle from 7 large completed or current prospective smoking and death rate studies (Doll and Hill; Hammond and Horn ; Darn; Dunn, Linden and Breslow; Dunn. Buell and Breslow ; Best, Josie. and Walker; and Hammond ). The median mortality ratio for coronary disease of current cigarette smokers to non-smokers is 1.7 irange 1.5-2.01. Table 2 presents data from some of the large prospective s.tudies on the ratio of mortality rates due to coronarv heart disease of male qniokers to non-smokers, by age and amount smoked. The ratios tend in ;pnrral to increase uith amount smoked and to decrease with adl-anciq a;:r. The data from the first 22 months. of Hammond`s (41 I current study help to show the size of the coronary problem. For this purl)ose. actual uumbers of deaths ma\ be more informative than mortalit\- ratios. Of nearlv 10.000 deaths of men aged 45-i'). 40 percent were ascribed to coronaq disease. 51.i pervent of the 2.030 "excess deaths" associated with cigarette smoking were caused by coronary disease. In approximate terms, nearly half of middle-aged and elderly males in the United States die of coronarl disease. About half of the+,r males smoke cigarettes. Cigarette smokers ha\-e heen found it) several studies to have 1.7 times as high a coronar! death rate as non+mokers. If cigarettes actually caused the additional coronar\ deaths of smokers. they tvould account for many- deaths of middle-aged and elderly males in this countr). Like other studies (19. 21, 22. 23. $2'21 this one shows that the ratio of !smokers' coronary death rates to those of non- smokers inc,rcuses prog:`e+i\el, \\ ith tile [tail\ cigarette consumption. In addition. at each le\cl of consumption the ratio inrreases with the amount of inhalation reported I)\- the smokers. Others (21, 23. 26, 891 have indicated 324 that the risk of death from coronary disease in male cigarette smokers relative to that in non-smokers is greater in middle age than old age, and Hammond's current study supports this. Th e mortality ratio was 3.09 in the age range 4S49. and in successive decades t+as 2.20. 1.58. and 1.38. Men who stop smoking ha\-e a lower death rate from coronary disease than those who continue (23, 42. Si) . In the study of Hammond and Horn (42) the decrease in death appeared onI!- after a year. Angina pectoris is less closely related to cigarette smoking than myocardial infarction and sudden death. In the combined Albany-Framingham expe- rience (23)) angina pectoris showed no o\er-all relationship with smoking, and the association has not been strong in other studies (71, 89). In summary. a significant association has been established between cigarette smoking and the incidence of myocardial infarction and sudden death in males, especially in middle life. in population groups whose members appear so far to be liniilar except for sniokin,n habits. The question of whether they are, in fact, similar except for smoking is. of course, basic to the problem of whether cigarette smoking actually promotes the development of coronary disease or k-hether it is closeI\- associated with some other factor or factors which promote the development of coronary disease. It has been pointed out that angina pectoris, which indicates advanced coronary atherosclerosis. is less closely associated with cigarette smokin, 11 than is m!-ocardial infarction. and that this suggests that any etiologic role of smoking in myocardial infarc- tion should relate more to acute occlusive mechanisms, such as intravascular thrombosis or coronary spasm, than to the development of chronic arterial disease. SMOKING AND NON-CORONARY CARDIOVASCULAR DISEASE In surveys of large groups cigarette smoking has not been found to be associated with an incrra*ed pre\ alence of h\ pertension ( 3, 4. 19, 47, 49 1. The study of Hammond and Horn I 4.0, 42 I d;d not sho\v an increased death rate from hppertension in smokers. However. Darn 122 1 found that the death rate of cigarette smokers from h\ I)crtension with heart disease was 1.53 times that of non-smokers. and frhm h!-pertension without heart dis- ease. 1.41 time3 that of non-smokers. Hammond's current stud\ she\+ s similar figures I41 1 . Smoking has not been found to be associated with an increased mortalit!- rate from chronic rheumatic heart disea>e 122. 41. 42 1. Hammond and Horn ( !2) found a Inoderate increase in the mortalit) rate from cerebral vascular disease in cigarette smokers as compared to non-smokers I ratio 1.30 I. Darn (22 I reported a ratio of 1.33. and Ham- nlolld 141 1 a ratio of 1.43. Although non-HI philitir aortic aneurysm is a relatilell infrequent cause of death. the mortalit\ ratio for snlokrr; to non- smokers in thi:. diagnostic, c,ategor\ is larse in relation to the ratios in other cardiol ascular disorder>. In the stud\ of llalmnc~ncl atld Horn (,t2 1 it was 2.72. and in Hanl~t~ond's current .-tudv I I1 I it is 3.10.