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Zp v The Health Consequences of Smoking 1 1977=1978 Prepublication copy: This copy is issued as a temporary_paper, preparatory to printing as a formal document. It omits the appendices and index which will appear in the final paper. Questions should be addressed the the Office on Smoking and Health, Rockville, Md. 20857 (301 - 443-1575). U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE Office of the Assistant Secretary for Health Office on Smoking and Health

, S THE SECRETARY OF HEALTH. EDUCATION. AND WELFARE WASHINGTON. O. C. 20201 c The Honorable Thomas P. O'Neill Speaker of the House of Representatives Washington, D.C. 20515 !=!`"' Dear Mr. Speaker: . As required by Section 8(a) of the Public Health Cigarette Smoking ' Act of 1969, I am submitting the 1977-191S~revert on the health --consequences of smoking. The report includes the "Bibliography on Smoking and Health--1976," the "Bibliography on Smoking and Health-- 1977," and "The Health Consequences of Smoking, 1977-1978." The report -bears a 2-year designation in order to return the series to an annual timetable which was altered because of the time required for the clear- ance processing of the 1976 report. The Bibliographies are prepared -annually and routinely to reflect the new acquisitions to the smoking- and health data base which operates at a cost of $200,000.00 per year; the health consequences of smoking report, which is a review of this new current information and prepared specifically for Congress, this year cost $9,800.00. "The Health Consequences of Smoking, 1977-1978" includes recently pub- lished data from three classic prospective studies of the mortality re- sulting from cigarette smoking. These studies, involving almost one and a half million persons, continue to document excess mortality among smokers as compared to nonsmokers. This part of the report also includes data on the established risks of low birth weight and increased perinatal mortality for offspring of women who smoke during pregnancy. In addition, the new evidence is reviewed that shows not only a high rate of heart attacks among women who smoke cigarettes, but that this effect is particularly critical in women who use oral contraceptives. The data in this report indicate that former smokers show lower death rates than continuing smokers and within 10 to 15 years after quitting come close to the low rates of those who never smoked. O W ~ W M N Mr

r Page 2 - The Honorable Thomas P. O'Neill One study supports previous evidence that there is a partial solution to the health problem in the use of cigarettes with lower emissions of "tar" and nicotine. As a result of public demand and a responsive industry, there has been over recent years a continuing decline in the emissions of "tar" and nicotine in cigarettes in use. The data in this report and in previous annual reviews of the health consequences of smoking have established cigarette smoking as a habit re- sponsible for an overwhelming level of premature death and disability in this country. To reduce this preventable and costly mortality and morbidity, this Department recently announced a new antismoking program. The program is one of public education, regulation, and research with special emphasis on children, teenagers, and young women, and on occu- pations where smoking increases risks from occupational exposure. In undertaking this program, I have invited the cooperation of the major broadcast networks, State and local school officials, the major corporations of this Nation, State Governors and legislators, the Federal Trade Commis- sion, the Federal Communications Commission, the Civil Aeronautics Board, and others whose involvement and cooperation are crucial to the success of this program. In response to the evidence linking the combined use of oral contraceptives and cigarette smoking, the Food and Drug Admin- istration, Public Health Service, HEW, has recently required that a warning statement to that effect accompany oral contraceptives as they are dis- tributed to those who use them. To provide leadership and to coordinate this program, an Office on Smoking and Health has been established in the Office of the Assistant Secretary for Health. As one of its first tasks, this Office will coordinate the production of a comprehensive document which reviews not only the biomedical but also the behavioral and control data about smoking and its effects on health. The report will be submitted to Congress in January 1979. As the principal health officials of this government, the Surgeon General and I are committed to fulfilling our responsibilities to provide infor- mation and direction to permit American citizens to make genuinely free choices about smoking and their own health. In this regard and as I am required by P.L. 91-222 to make such legislative recommendations that I deem appropriate based on the scientific data about the impact of smoking

A 1. Page 3 - The Honorable Thomas P. O'Neill on health, I will submit within the year a legislative package which I hope will meet with your approval. With appropriate coordination of legislative action and occ+cram, we can solve this difficult and important e public health probl~ Sincerely,' Joseph A. Califano, Jr. Enclosures . Identical letter sent_to The Honorable Walter F. Mondale l :.b:~> ..p ...~~. _ . , _ ..~:~

a PREFACE . J : . .. ..1. . ~ l ~ . ~t' ! .. i ~~ . . . . ,. . . . . This tenth report to tiie Congress on the health consequences of smoking discusses the special problems incurred by women who smoke and presents - recently published overall mortality data on smoking ,~,., - ~.... i,:~Smoking was first recognized as a health problem in the 1930's, when a sharp increase was noted in lung cancer rates formen. No similar : 'Tincrease was noted for women at that time for several reasons. First, as a group, women did not start smoking when men did, since such behavior was socially unacceptable for women at that time. Consequently, until the last decade, there were insufficient numbers of women who had smoked • .`u'1 -.. ...a_. _ . ..... , - . _ . ~ : ., . , - . for a long enough period of time to provide the size population necessary ... ,, .. . .- _. ~_ . ._ ... . ~ . for meaningful research. . _ _ c rt ., . .. , _ :. A .... . . . . '. . :' : . . .. . . . r., ,_ _. • v _ _ In recent years, however, the same health risks to men as a result of . f~ . . ,_. .- .. -. _ - - smoking have been documented for women who smoke. These include cardio- vascular disease, lung cancer, cancer of other specific sites, bronchitis _.. . . : ~, - . . .. ~ ~ . . , _ . . . ~ and emphysema. These diseases occur among smokers at rates far greater than those of nonsmokers. Additionally, women have been found to incur unique risks for themselves and for their offspring. For example, women over 30 years of age who smoke and use oral contraceptives have substan- w ~ tially higher risks of myocardial infarction. Moreover, the offspring C~ C.~ of women who smoke during pregnancy face greater risks of perinatal ~ 00b mortality and low birth weight. Further understanding of the mechanisms li

involved in these health consequences continues to evolve. Three large prospective epidemiologic studies demonstrate that overall mortality rates for cigarette smokers are approximately 70 percent higher than those for nonsmokers. These studies also document a decrease in overall mortality rates for those who quit smoking, provided they were not ill at the time of cessation. There is about a 15 percent reduction in overall mortality risk for smokers of low "tar" and nicotine cigarettes (less than 17.6 mg. "tar" and less than 1.2 mg. nicotine) compared to those who smoke high "tar" and nicotine cigarettes (25.8-35.7 mg. "tar". and 2.0-2.7 mg.:nicotine). Several publications have become available since the last report to Congress which review the social, behavioral, legislative, and health issues re- lated to smoking. A recently published paper by Daniel Horn, Ph.D., as part of his work with the World Health Organization, discusses the major barriers to be overcome if further progress is to be made against the threat of smoking to health. A copy is report. included as Appendix A to this Two other publications of note include the U.S. Public Health .,;; Service's "Proceedings of the Third World Conference on Smoking and Health, 1975," DHEW Publication No. (NIH) 77-1413, 1977, Volumes I and II, and . ., .. - ~ the World Health Organization's "Smoking and Its Effects on Health," Technical Report Series No. 568, Switzerland, 1975. iii , fS,

e Table of Contents . Preparation of the Report and Acknowledgments CHAPTER 1. Smoking-Related Health Problems Unique to Women . .,. Introduction . . . . . . . . . . . . . . . . . . . , , Effects of Smoking on the Outcome of Pregnancy . . . . . , . . , , , -Smoking and Birth Weight ., ; ; ; ; , , ; , ; , ; ; ; ; ; , ," , . Smoking and Perinatal Mortality . . . . . . . . . . . . . . . . Long-Term Effects on Physical and Intellectual Development ... Carbon Monoxide and Carboxyhemoglobin Levels in Maternal and Fetal Circulation and the Possible Mechanisms-of Smoking-Effects -- - ori Pregnancy ... . : . . . . . . . . . . : : . .- . . . . . Smoking and Its Effects on Cardiovascular Disease Among Women Taking Oral Contraceptives . . . . . . . . . . . . . . . . . . . : : : .: : Summary of Smoking-Related Health Problems Unique to Women Effects of Cigarette Smoking on Lactation , , , , , , , , , , , , , , What Women Know About Smoking and Pregnancy , , , , , , , , , , , , , References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CHAPTER 2. Smoking and Overall Mortality , , , , , , , , , , , , , , Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . Measuring Mortality . . . . . . . . . . . . . . . . . . . . . . . . . Mortality Ratios , , , , , , , , , , , , , , , , , , , , . Differences in Mortality Rates , , , , , , , , , , , , , , ~ ~ . . . Excess Deaths , , , , , , , , , , , , , , Life Expectancy . . . . . . . . . . . . . . . . . ... . . . . . Page

Description of the Studies , . . . . . . . . . . . . . . . . . . The American Cancer Society Study , , ; , , , , , , , , , , , , , The U . S . Veterans Study , , , , , , , , , , , , , , , , , , , , The British Doctors Study , , , ., , , , , , , , , , , Overall Mortality and Cigarette Smoking , , , , , , , , , , , , , Number of Cigarettes Smoked . , . . ', , , , , , , ,., Age --$egan Smoking . . . . . . . . . . . . . . . . . . . . . . . Inhalation Practice , , , , , , , , , , . . , "Tar" and Nicotine . . , ", , , , , , , , Ex-Smokers , . . . . . . . . . . . . .. : . .,. ,_ ~ Pipe and Cigar Smoking , , , , , , , , , , , , , , , , . , , , , , . Summary of Smoking and Overall Mortality References . I v . I rJ

f. CHAPTER 1 List of Figures Figure 1.-Risks of selected pregnancy complications for smoking and nonsmoking mothers, by period of gestational age at delivery for A, abruptio placentae, B, placenta previa, C, premature rupture of membranes (PROM) Figure 2.-Number of cigarettes normally smoked per day compared with Hb level at time of sampling in 93 pregnant women. mean and range of COHb levels for 129 nonsmokers Figure 3.-Oxyhemoglobin saturation curves of human maternal and fetal blood under control and steady-state conditions List of Tables Table 1.-Adjusted rates and F ratios for maternal smoking and _other_ important factors affecting birth weight, gestation, placental complications, and perinatal mortality Table 2.-Perinatal mortality and selected pregnancy maternal smoking levels Table 3.-Stillbirths according to cause during pregnancy complications, by in relation to maternal smoking Table 4.-Estimated annual mortality rate per 100,000 women from myocardial infarction and thromboembolism, by use of oral contraceptives, smoking habits, and age (in years) Table 5.-Estimated relative risks of nonfatal myocardial infarction, by use of oral contraceptives and cigarette smoking vi

CHAPTER 2 List of Figures Figure .-Annual probability of dying for current cigarette smokers, ex-smokers who quit less than 5 years ago, and never smokers, ages 55-64 Figure 2.-Annual probability of dying for current cigarette smokers, ex- smokers who quit 5-9 years ago, and never smokers, ages 55-64 Figure 3.-Annual probability of dying for current cigarette smokers, ex- smokers who quit 10-14 years ago, and never smokers, ages 55-64 Figure 4.-Annual probability of dying for current cigarette smokers, ex- smokers who quit more than 15 years ago, and ex-smokers, ages 55-64 List of Tables Table 1.-Age-adjusted mortality ratios for male cigarette smokers, by amount smoked, U.S. Veterans Study, 1954 cohort, 16-year follow- up Table 2.-Mortality ratios for cigarette smokers, by number of cigarettes smoked per day, British Doctors Study Table 3.-Mortality ratios for male cigarette smokers, by age and number of cigarettes smoked per day, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 4.-Age-adjusted mortality ratios for male cigarette smokers, by age began smoking, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 5.-Age-adjusted mortality ratios for male cigarette smokers, by number of cigarettes smoked per day and age began smoking, U.S. Veterans Study, 1954 cohort, 16-year follow-up C Table 6.-Mortality ratios for cigarette smokers, by inhalation practice,L,? British Doctors Study Q ~ W ~ N Cd vii

Table 7.-Mortality ratios for all cigarette smokers in two time periods, by sex and "tar" and nicotine (T/N) content in cigarettes smoked Table 8.-Mortality ratios for smokers of low "tar" and nicotine (T/N) cigarettes and nonsmokers in two time periods, by sex Table 9.-Mortality ratios for all cigarette smokers and nonsmokers in two time periods, by sex and "tar" and nicotine (T/N) content of cigarettes smoked Table 10.-Mortality ratios for ex-smokers who quit smoking on doctor's orders and for other reasons, by years since stopping, U.S. I Veterans Study, 1954 cohort, 16-year follow-up Table 11.-Mortality ratios for ex-smokers who quit smoking on doctor's orders and for other reasons, by number of cigarettes smoked per day, U.S. Veterans Study, 1954 cohort, 16-year follow-up ,Table 12.-Mortality ratios for ex-smokers who quit smoking on doctor's orders and for other reasons, by age began smoking, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 13.-Mortality ratios for ex-smokers of cigarettes only, by years since stopping, number of cigarettes smoked per day, and age began smoking, U.S. Veterans Study, 16-year follow-up Table 14.-Mortality ratios for ex-smokers compared to nonsmokers, by number of years since stopping and age, British Doctors Study Table 15.-Age-adjusted mortality ratios for pipe-only, cigar-only, and cigarette-only smokers, U.S. Veterans Study, 1954 cohort, 16- year follow-up Table 16.-Age-adjusted mortality ratios for current cigar smokers, by .,number of cigars smoked per day, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 17.- Age-adjusted mortality ratios for current cigar smokers, by age began smoking, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 18.-Age-adjusted mortality ratios for current cigar smokers, by number of cigars smoked per day and age began smoking, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 19.-Age-adjusted mortality ratios for current pipe smokers, by number of pipefuls smoked per day, U.S. Veterans Study, 1954 cohort, 16-year follow-up viii !

.Table 20.-Age-adjusted mortality ratios for current pipe smokers by age began smoking, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 21.-Age-adjusted mortality ratios for current pipe smokers, by number of pipefuls smoked per day and age began smoking, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 22.-Age-adjusted mortality ratios for current cigar smokers, by use of other types of tobacco, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 23.-Age-adjusted mortality ratios for current pipe smokers, by use of other types of tobacco, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 24.-Age-adjusted mortality ratios for current cigarette smokers, by use of other types of tobacco, U.S. Veterans Study, 1954 cohort, - . . . .+ - .. .. - . . . . . ~. _..._ .J . .. J .. ~ _ . _ . =- -_: 16-year- ,follow-up Table 25.-Age-adjusted mortality ratios for all smokers, by type of tobacco used, British Doctors Study ix

;;_~:; PREPARATION OF THE REPORT AND ACKNOWLEDGMENTS Previous Reports Reviews of the scientific information linking smoking to health problems began in 1964 with the publication of Smoking and Health,-Report of the Advisory Committee to the Surgeon General of.the Public Health Service, subsequently referred to as't-he"Surgeon General's Report." Thereafter, Public Law 89-92 was passed requiring supplemental reports to Congress on 1. The Health Consequences of Smoking, A_ Public Health Service Review; 1967. „ this subject, and the following three reports were published: 2. The Health Consequences of Smoking, 1968 Supplement to the 1967 PHS Review. . The Health Consequences of Smoking, 1969 Supplement to the 1967 PHS Review. ~ Public Law 91-22 amended the previous law in April 1970 and required , a comprehensive review within 18 months, with annual reports to be sub- mitted thereafter. The result of this review was The Health Consequences of Smoking, A Report of the Surgeon General; 1971. Since then, the following annual reports on the health effects of smoking have been published: 1. The Health Consequences of Smoking, A Report of the Surgeon General, 1972. 2. The Health Conseguences of Smoking 1973. , O W 3. The Health Consequences of Smoking, 1974. ~ 4 C.W . The Health Consequences of Smoking, 1975. f.~ N x

., 5. The Health Consequences of Smoking, A Reference Edition, 1976. Each report since t:~e original "Surgeon General's Report" has reviewed the scientific literature relevant to the association between smoking and cardiovascular diseases, non-neoplastic bronchopulmonary diseases, and " cancer. Smoking as related to the following diseases and conditions has been reviewed periodically in these reports: Allergy (1972) Exercise Performance (1973) Harmful Constituents of Cigarette Smoke (1972) Noncancerous Oral Disease (1969) Overview: The Health Consequences of Smoking (1975) = Overview: The Health Consequences of Smoking (1976) Peptic Ulcer Disease (1_967,_1971, 19__721 1973) - - . ~ Pipe and Cigar Smoking (1973) Pregnancy (1967, 1969, 1971, 1972, 1973) Public Exposure to Air Pollution from Tobacco Smoke (1972, 1975) Tobacco Amblyopia (1971) The 1977-1978 Report This publication, The Health Consequences of Smoking, 1977-1978, contains the most recent data on the health effects of smoking unique to women and on the effects of smoking on overall mortality. Although emphasis is on the most recent data, research from earlier years is included where neces- _sary for clarity. The report was prepared by the staff of the National Clearinghouse for Smoking and Health, Public Health Service, in the following way: 1. The Technical Information Center of the Clearinghouse continually monitors and collects the scientific literature on the health effects of smoking by means of several established mechanisms: xi

M S. a. An information science corporation is under contract to extract articles on smoking and health from the scientific literature of the world. b. The National Library of Medicine, through the MEDLARS system, provides a monthly listing of articles on smoking and health. Articles not provided by the information science corporation are obtained for review. c. Staff members review current medical literature and identify .pertinent articles. 2. Initial drafts for the present report were prepared by the staff of the National Clearinghouse and sent to experts in the content area for review and conanent regarding the format, the appropriateness of the articles selected for discussion, and conclusions. The drafts were then revised by the Clearinghouse to incorporate these comments. The final drafts of the complete report were reviewed by the National Cancer Institute, the National Heart, Lung; and B1ood Institute, the National Institute of Environmental Health Sciences, the National Institute of Child Health and Human Development, and by additional experts both inside and outside the Public Health Service. xll

ACKNOWLEDGMENTS The National- Clearinghouse for Smoking and Health Director, Daniel Horn, Ph.D., "~r '.~t'~,.-' ... ..~.. . _...~~,., ... . ~. : - . ' ... : ~ . . -. ~ : .. . . was responsible for the preparation of this report. Medical Staff Director was"John°J.' Witte, M.D. The consulting and technical editors were Elvin E. Adams, M.D., and Susan J. Dillon, respectively. The Technical Information :,G .._ ..i, . _ .. .. . _ • . . "~Officer responsible for the literature collection was Donald R. Shopland. '=The professional staff has had the assistance and advice of the following experts in the scientific and technical . gratefully acknowledged: ~ fields whose contributions AUERBACH,'Oscar, M.D. - Senior Medical Investigator, Veterans istration Hospital, East Orange, New Jersey =- .i : are Admin- COHEN,! Lawrence S., M.D.'- Professor of Medicine, Chief of Cardiology, Yale_University, School of Medicine, New Haven, Connecticut FITZPATRICK, Mark J., M.D., M.P.H. - Fairhaven, Massachusetts :. . ...: r _ . _ , ,.. . _ . - ' , . _ . FRAZIER, Todd M. - Assistant Director, Center for Community Health and Medical Care, Harvard Medical School, Boston, Massachusetts _ _.r _ a .. .. .. KRETCHMER, Norman, M.D., Ph.D. - Director, National Institute of Child Health and Human Development, Bethesda, Maryland KRUMHOLZ, Richard A., M.D. - Medical Director, Institute of Respiratory Diseases, Kettering Medical Center, Kettering, Ohio LEVY, Robert I., M.D. - Director, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland MARINE, William M., M.D. - Professor and Chairman, Department of Preventive Medicine and Comprehensive Health Care, University of Colorado Medical Center, Denver, Colorado O W McMILLAN, Gardner C., M.D. - Associate Director for Etiology of ~ Arteriosclerosis and Hypertension, National Heart, Lung, and Blood W rnstitute, National Instibutes of Health, -Benesda; PlaryIand M W C1t . xiii

MEYER, Mary B. - Associate Professor, The Johns Hopkins University, School of Hygiene and Public Health, Baltimore, Maryland NICHOLS, Ervin E., M.D. - Director, Practice Activities, American College of Obstetrics and Gynecology, Washington, D.C. PAFFENBARGER,.Ralph S.,;Jr., M.D. - Epidemiologist, Resource for;Cancer Epidemiology, San Francisco Bay Area, California State Department of Health, Berkeley, California L-,; PETERSON, William F., M.D. - Chairman, Department of Obstetrics and Gynecology, Washington Hospital Center, Washington, D.C. . PETTY, Thomas L., M.D. - Professor of Medicine and Head, Division of Pulmonary Medicine, University of Colorado Medical Center,:Denver, Colorado : RALL, David P., M.D., Ph.D. - Director, National Institute of Environ- mental Health Sciences, Research Triangle Park, North Carolina _ .. . ,... . . ,. , .,. . REINKE, William A., Ph.D. - Professor, Department of International Health, The Johns Hopkins University, Baltimore, Maryland „ RENZETTI, Attilio D., Jr., M.D. - Professor of Medicine and Head, Pulmonary Disease Division,.The University of Utah Medical Center, Salt Lake City, Utah SCHUMAN, Leonard M., M.D. - Professor and Head, Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, Minnesota ;, WYNDER, Ernest L., M.D. - President, American UPTON, Arthur C., M.D. - Director, National Cancer Institute, National Institutes of Health, Bethesda, Maryland - York City, New York xiv ...'.v: ~ Ll

CHAPTER 1 SMOKING-RELATED HEALTH PROBLEMS UNIQUE TO WOMEN _Eff ects of Smoking on the Outcome of Pregnancy . . . . . . . , . . Smoking and Birth Weight . . . . . . . . . :. . . . . . . . . . . Smoking and Perinatal Mortality . . . . . . . . . . . . . . . . . . . Long-Term Effects on Physical and Intellectual Development . . Carbon Monoxide and Carboxyhemoglobin Levels in Maternal and Fetal ...Circulation and the Possible Mechanisms of Smoking Eff ects on ,~. , ._._.. _ Pregnancy . .. , . . . Effects of Cigarette Smoking on Lactation . . . . . . . . . Oral CoAtracePtives Smoking and Its Effects on Cardiovascular Disease Among Women Taking What-Women Know About Smoking and Pregnancy Summary of Smoking-Related Health Problems Unique to Women Page

CHAPTER 1 List of Figures Figure 1.-Risks of selected pregnancy complications for smoking and nonsmoking mothers, by period of gestational age at delivery for A, abruptio placentae, B, placenta previa, C, premature rupture of membranes (PROM) Figure 2.-Number of cigarettes normally smoked per day compared ~OHb level at time of sampling in 93 pregnant women. = mean and range of COHb levels for 129 nonsmokers wi th - Figure 3.-Oxyhemoglobin saturation curves of human maternal and fetal blood under control and steady-state conditions List of Tables Table 1.-Adjusted rates and F ratios for maternal smoking and other ' important factors affecting birth weight; gestation,' placerital complications, and perinatal mortality Table 2.-Perinatal mortality and selected pregnancy complications, maternal smoking levels y Table 3.-Stillbirths according to cause in relation to maternal smoking during pregnancy ; ,..._•. , ~ : . : •. . , • . ~ Table 4.-Estimated annual mortality rate per 100,000 women from myocardial infarction and thromboembolism, by use of oral contraceptives, smoking habits, and age (in years) Table 5.-Estimated relative risks of nonfatal myocardial infarction, by use of oral contraceptives and cigarette smoking 2 n h)

10 SMOKING-RELATED HEALTH PROBLEMS UNIQUE TO WOMEN ;x ; ... . .: . - .: CHAPTER 1 INTRODUCTION Smoking habits and attitudes among women and teenage girls have differed in the past from the habits and attitudes among men:4x and teenage boys. .,,.. _ . 'Women tended to smoke fewer cigarettes, were less likely to inhale, and were more likely to smoke low "tar"and-nicotink and filter-tipped brands. Surveys-have indicated, however,-that the smoking habits of women are becoming ~.1. '7.;' _ . _ - . : . . - . . - - - . . . . . . . . ..~' .. . . . . _ . ... . . - . . . more like men's. Women are taking up the ha~it at an earlier age and have -,; V.. ; -- - --------------- become ~'leaVier- sino-ker - s . Ttiis T18s mSde tfieill mote kulnerable not only to lung cancer and other smoking-related_diseases,;but also to specific health problems that are unique to their sex. For example, research on the'relationship between cigarette smoking and the outcome of pregnancy has established that there are definite risks to both the fetus and the mother associated with cigarette smoking during pregnancy. Moreover, women who`use oral contraceptives are-at greater risk of.cardiovascular disease _. ~- .- .. .. _ if they-smoke cigarettes. There is also evidence that nicotine is present in the~-breast-milk of lactating"inothers who smoke. 2he following is a . _, . ...- . -.. .,.._ review of the current information on these and other health consequences of smoking unique to women. EFFECTS OF THE O ---ti'TCO-M-E OF -- --------PREGNANCY --- --- SMOKING ON There are definite health risks associated with smoking and pregnancy, w including effects on birth weight, perinatal mortality, 3 -111 and long-term C9 . w cn w c~

. <, physical and intellectual development of the child. This section reviews each of these subjects and also includes information about-the likely mechanism of action of smoke and its contents on the mother and the products of conception. Smoking and Birth Weight ~ In 1957, Simpson published her original finding that babies born to women who smoke during their pregnancy weigh on the average 200 grams (g) less than the babies born to women who do not smoke (35). Since then, more than 100 articles on this relationship have led to the general acceptance that smokers' babies generally weigh 150 to 250 g less than nonsmokers' babies, and twice as many of the former weigh less than 2500 g (14). The 1973 report of The Health Consequences of Smokin presented evidence to support a association between cigarette smoking and fetal growth retardation causal (39).' A strong dose-response relationship was also established in that , ,. ,. . . , , .. : ., report, with differences in weight being in direct proportion to the number of cigarettes smoked. The following additional points were summarized in the 1973 report to further support the causal association between cigarette smoking during pregnancy and lower birth weight: . ~ r_, _ .. .. 1. Results are consistent in all studies, retrospective and prospec- tive, from many different countries, races, cultures, and geo- graphic settings: 2. The relationship between smoking and reduced birth weight is , independent of other factors that influence birth wej.ght' ?1such as race, parity, maternal size, socioeconomic status, sex of child, and all others that have been studied. 4

Jf a woman gives up smoking by the fourth month of pregnancy, - her risk- of delivering a low -birth-weight -baby is!slmilar,toLthat iof a nonsmoker. ,Subsequent to the 1973 report, additional reports have further discussed and corroborated the association between smoking in pregnancy and low birth weight (20, 26,34,36). ''Smoking and Perinatal Mortalitv A strong, probably causal,association between cigarette smoking and higher late fetal and infant mortality rates among smokers' infants is now well es-tablished:_(-34)~-L~-Retrospective and prospective studies-have revealed ; a- - statistically significant relationship between cigarette smoking and an elevated mortality risk among the infants'of-smokers. ~In three of these studies of sufficient size to permit adjustment for other risk factors," a highly significant independent association between smoking and mortality was established. Part of the discrepancy in results between these studies and those in which a significant association between mortality was not demonstrated may be explained by a ,,for-risk factors other than smoking. smoking and infant The 1973 report also presented evidence indicating that the higher relative risks occurred among populations with risk factors other than smoking being present, such as socioeconomic status, age, parity, race, and previous pregnancy history. 5

Since 1973, a series of articles by Meyer,et al. analyzed data from the Ontario Perinatal Mortality Study of all single births in ten Ontario teaching hospitals in 1960-61 (27, 28, 29). The study involved 51,490 births, including 701 fetal deaths and 655 early neonatal deaths, and was of mothers in the hospital, interviews supplemented by clinical records with interviews~with anesthetists and attending physicians, and autopsy records (30). Perinatal mortality increased significantly with smoking, and was also affected by such factors as maternal age, parity, socioeconomic status,'previous pregnancy history, hemoglobin level, and other risk factors (29). Smoking fre- quencies also varied by many of these characteristics. Smoking and J' other risk factors were cross-tabulated among 52 data subgroups:"- In all subgroups, the mortality increase with smoking was dose related, but not in a simple, linear way. The increased risk of perinatal mortality = associated with light smoking among young, low-parity, nonanemic mothers s was less than 10 percent. At the other extreme, mothers with other risk factors of high parity, public hospital status, with previous low-birth- weight infants, or with hemoglobin less than 11 g had further increased perinatal mortality risks of 70-100 percent when they were smokers.' The most significant risk factor (mortality rate of 78 per 1,000 total births) was anemia,defined as a hemoglobin of less than 8.0 g. The failure of some earlier studies to find a significant increase in perinatal mortality with maternal smoking may be due to selection of study populations from the end of the spectrum, where light smoking is associated with only a 6

n slight increase in perinatal risk. This evidence points up how popula- tion selection could influence study findings and shows that exposure to the effects of smoking during pregnancy is much more dangerous for the babies of some women than for others. These findings are corroborated by a number of studies in which fetal, neonatal, or perinatal mortality rates are compared for smoking and nonsmoking women, controlling for the effects of various risk factors previously mentioned (1, 13, 23, 37). Additional data were published in 1976 and 1977 (27, 28) and revealed that frequencies of low birth weight (under 2500-!g), preterm delivery (<-38 weeks); perinatal mortality, ab=uptio placentae, placenta previa, I -bleeding during pregnancy, and prolonged and premature rupture of the -.-membranes increased directly and significantly (p< 0.00001) as the level of maternal smoking increased (Tables 1 and 2). ;The 1976 paper used multiple regression analysis to measure the independent effect of smoking on the various risk factors'. The probabilities of these complications were also compared (Figure 1). Risks of placenta previa and abruptio placentae were higher for smokers than for nonsmokers at all-gestations, ~ with relatively larger differences-in the earlier weeks of pregnancy. The risk of premature rupture of membranes was more than three times greater for smokers than for nonsmokers amone deliveries that occurred be- fore 34.weeks gestation and remained higher than the risk for nonsmokers through term (FigurelC).

A prospective investigation of 9,169 pregnant women was conducted by Goujard,et al. (16), and results showed a substantial increase in still- births among smokers. A large proportion of this increase was d'ue-to abruptio placentae. 'There were 100 stillbirths, classified into five categories of causes: vascular, abruptio placentae, mechanical, mis- cellaneous (syphilis, Rh, malformations, etc.), and unknown (Table 3). The abruptio placentae category exclusively represented cases without toxemia, the one toxemic case being classified with the vascular causes. The higher proportion of smokers is significant for only two of the categories: abruptio placentae (p = 0.005) and unknown causes (p = 0.0005). . _ . ~. . . .. _ . ; .. . • , . Although the numbers were small, the risk of stillbirths by abruptio pla- centae is six times higher among smokers. Long-Term Effects on Physical and Intellectual Development _ Three studies (7, 17, 41) report on long-term effects of smoking in pre nancy. Data from two of the studies presented below demonstrate an as- sociation between smoking during pregnancy and impaired physical and intellectual development in the offspring. Additional reports further substantiate this association (11,12). Butler and Goldstein (7) analyzed the National Child Development Study, a longitudinal study of 17,000 children born in Britain from March 3 to 9, 1958. The test procedures included a reading test at the age of 7 years, and a mathematics test, a reading test, and a general ability test at the age of 11. At both ages the height of the child was also measured. Analyses at both ages 8

r were based on smoking habits of the mother after the fourth month of pregnancy. ,., ~4 : - . . . Statistically significant differences in height and reading ability be- tween smoking categories (0, 1-9, or 10+ cigarettes daily) were found at both 7 and 11 years of age. r When account was taken for such factors as mother height, age, social :class as determined by father's occupation, number of older and younger children in the household, and the sex of the child, there was a deficit ~of height_and reading ability in the offspring of mothers who smoked, the extent of which increased with the amount smoked. _. ,,. ., . . These results establish an association of smoking in pregnancy. with later in- tellectual development, although the gap betweeen children of smokers (at a~li - levels of smoking) and nonsinokers does not appear to change between ~fi e ages of -- - 7 and 11 years. Smoking in pregnancy is associafed wiEh- ari-impairaient of boEh factors , tWe -effects are -small-: . , , .. .~ . . .. = _ ----- - mental and physical growth, alttiough compared wit~ other social and biologicaT .::,,----- ,In the study by Wingerd and Schoen (41), the net effects of various factors on length at birth and height at 5 years were determined in 3,707 single-born, white California children. Children of smoking mothers were found to be shorter (PG 0.001) at birth and at 5 years than children of nonsmoking mothers. (Intellectual development was not measured in this study.) 9

In contrast to these results, Hardy and Mellits (17) found very few significant differences in a number of body measurements and intellectual functions up to the age of 7 years between children of smokers and non- smokers. A possible explanation for this discrepancy is that their sample was too small, and a weight-matched control group could add a bias. Whereas the British study by Butler and Goldstein involved a sample size of over 5,000 children, Hardy and Mellits based their findings on only 88 matched pairs of children. Calculations by the authors of the British study show that with the small sample used by Hardy and Mellits there was only about a 20 percent probability of detecting statistically significant differences in the heights of children born to smoking and nonsmoking mothers. CARBON MQNOXIDfi. AND CARBOXYHEMQ~S._Q.$IN ~EVELS IN._MATERNAL_AND FETA_L QZI3CU_LA TION AND THE POSSIBLE MECHANISMS OF SMOKING EFFECTS ON PREGNANCY There is evidence to show that carboxyhemoglobin (COHb) levels are sub- stantially elevated in pregnant women who smoke and may result in damage to placental and fetal blood vessels. Higher levels of COHb in both fetal and maternal blood may also be a factor in the increased incidence of low birth weight of infants born to women who smoke. Cole, Hawkins, and Roberts (8) studied the smoking habits of a group of pregnant women and related these to the level of COHb in the circulating O blood. A group of 222 patients attending antenatal clinics at a London ~ 011 hospital were questioned about their smoking habits. Ninety-three (42 W 10

0 percent) were smokers, and 129 (58 percent) were nonsmokers. Simultaneous maternal and cord blood samples were taken at normal;delivery and at Caesarean section from 28 patients, and the COHb and fetal hemoglobin levels of the samples were measured. Results showed that women who smoke during pregnancy have a significantly higher level of COHb in their blood than women who do not smoke (p< 0.01). The mean COHb levels were 1.2 percent (range 0 to 2.4 percent) for the nonsmokers and 4.1 percent (range 0.5 to 14 percent) for the smokers. There was a positive correlation between the number of cigarettes smoked on the day of sampling and the COHb level (correlation coefficient 0.82) (Figure 2). With the exception of two patients, all the fetal COHb levels were demonstrably higher than the re- spective maternal ones. The mean fetal/maternal COHb ratio was 1.84 to 1 (standard deviation ±0.85). Hemoglobin has a 210 times greater affinity for,carbon monoxide(CO) than for oxygen. It is obvious, therefore, that cigarette smoking during pregnancy diminishes the oxygen carrying capacity of both fetal and maternal blood. This affects maternal oxygenation by increased pul- monary venous admixture and diminishes the oxygen available to the fetus at the tissue level by its effect on fetal oxyhemoglobin dissociation. In a 1975 report by Dow, Rooney, and Spence (10), a significantly greater rise in COHb concentration in response to smoking a single cigarette was shown in pregnant women (3.9 percent increase) as opposed to nonpregnant women (2.1 percent increase). This was more pronounced when anemia was present (5.0 percent increase) and appeared to be inversely related to the hemoglobin concentration. Three groups of women, all smokers, were 11

selected for this study. The first group consisted of 10 normal, pregnant women late in the second trimester of pregnancy,with hemoglobin levels of over 11 g per 100 milliliters (ml). The second group con- sisted of 10 women also late in the second trimester but whose hemoglobin levels were less than 10 g/100ml. Apart from anemia at the time of ad- mission to the study, these patients were normal. ThE, third group con- sisted of 10 normal, nonpregnant women with normal hemoglobin levels (over 11 g/100m1). The change in COHb was estimated spectrophoto- metrically in response to smoking the first cigarette of the morning, the women having rested for at least 30 minutes. A sample of venous blood was withdrawn before and 2 minutes after smoking the cigarette. The cigarettes were of a standard size and of a"non-mild" (i.e, not low "tar" and nicotine) variety. The women were instructed to take a puff every 40 seconds, inhaling as deeply as possible~to a total of 10 puffs. In the nonpregnant group, the mean rise in COHb concentration (+standard error of mean) was 2.1±0.2 percent. A significantly greater increase was found in the normal pregnant group ( mean rise 3.5±0.4 perc^nt; t=3.91; p< 0.005).. The effect was more pronounced in the anemic pregnant women, who had a mean rise of 5.0±0.2 percent (t=9.9; p c 0.0005). Longo (22) studied the effects of CO on oxygenation of the fetus in utero. Results showed that the partial pressure of oxygen in fetal blood decreases in proportion to the COHb concentrations in fetal and maternal blood (Figure 3). O W ~ ~ 12 W .A Gb

a This decrease in oxygen tension may be a factor in the low birth weight of infants born to women who smoke or are exposed to severe air pollution. These results suggest that significant increases in maternal and fetal COHb concentrations can signifi- cantly reduce oxygen delivery to the fetus. -Astrup, et al. (4) carried out experimental studies on animals which may have a correlate with other data based on human studies in this report. A brief description of his findings is included here. One investigation (4) studied the effect of moderate CO exposure (180p.p.m. and 90p.p.m. CO in atmospheric air) on fetal develop- ment in rabbits. Exposure to 180p.p.m. CO (16-18 percent COHb) during pregnancy resulted in a 20 percent decrease in birth weight and a neonatal mortality rate of 35 percent as against 1 percent in the control group. Exposure to 90p.p.m. CO (8-9 percent COHb) had a less pronounced effect. There was a negative correlation between birth weight and maternal COHb concentration (p.<0.05). The authors conclude that these results indicate that CO in tobacco smoke might be responsible for the reduced birth weight of babies whose mothers smoke during pregnancy. 13

A report from Denmark by Asmussen and Kjeldsen (2) studied the umbilical artery as a possible model for evaluating the vascular injury provoked by tobacco smoking in humans. Cords from newborn children delivered by 15 nonsmoking and 13 smoking mothers were studied in the transmission and the scanning electron microscope. The average weight of children born to smokers was 3,370 g and that children born to nonsmokers was 3,695 g, a difference of 325 g. A difference of 123 g was found in the weights of the placentas. Pronounced changes in the intima were found in the umbilical samples from smokers. The most important findings were degenerative changes in the endothelium, such as swelling, bleeding, contraction, and sub- sequent opening of the endothelial junctions, with formation of suben- dothelial edema. The basement membranes were considerably thickened. The smooth muscle cells in the edematous subendothelial space often showed vacuolization. Since similar changes can be induced in arteries of animals by exposure to CO or perfusion with nicotine, the authors conclude that cigarette smoking is harmful to the vascular endothelium and may provide some rationale for the mechanism behind low birth weights and increased perinatal mortality. SMOKING AND ITS EFFECTS ON CARDIOVASCULAR DISEASE AMONG WOMEN TAKING ORAL CONTRACEPTIVES . 03'763650 Smoking is a major cause of cardiovascular disease among women, and it has been found that the use of oral contraceptives potentiates its effect. Therefore, women who smoke and use oral contraceptives are at a much higher risk for cardiovascular disease and should be encouraged to stop smoking. In a review by Ory (31) of the original scientific data 14

r .. ._ . f '~': .* '[ .' , . , . . . . , . . . . .. _. . . that exists on the association between oral contraceptives and myocardial _..~c ...::. infarction, cigarette smoking was found to"be the most important factor in increasing the probability of women less than 50 years of age having myocardial infarction. Although this increased risk is independent of oral-'contraceptive use, oral contraceptive use appears to be an added risk factor.- The use of these drugs in the absence of other predisposinQ factors appears to have only a small effect on increasing the risk of dying from myocardial infarction. Jain (19) studied the risk of mortality associated with the use of oral 'contraceptives._: For women_40-44 who neither use oral contraceptives nor smoke cigarettes, the overall mortality rate from myocardial infarction is 7.4 per_ 100,000 (Table 4)._ The comparable annual mortality rate among women of this age group who use oral contraceptives but do not smoke is 10.7 per 100,000. This compares to a rate of 62 per 100,000 for women who take oral contraceptives and smoke. In a later study, Jain (18) analyzed the synergistic effect of smoking and the use of oral contraceptives on myocardial infarction. The relative risk of_nonfatal myocardial_infarction among those who use oral contra- ceptives and smoke is estimated to be 11.7 to 1(Table 5). The authors suggest that smoking should be considered as another contraindication for the prescription of oral contraceptives. 03763651 Results of a study by Beral (5) indicate that oral contraceptive users who smoke have a 10 times greater risk of dying from cardiovascular disease 15

., than women who neither smoke nor use the pill. Smoking by itself was re- sponsible for a 4-fold increase in the risk of dying from cardiovascular diseases. Oral contraceptive use in the absence of smoking also appeared to increase one's risk, but the differences were not statistically signi- ficant: Mann and his colleagues also studied the relationships between smoking and myocardial infarction in women (24,25). Their findings show an apparent but not a statistically significant increase in relative risk of nonfatal myocardial infarction for nonsmokers who use- oral contraceptives (2.02)with a 95 percent confidence interval of 0.5 to 8.5). In contrast, for smokers who use oral contraceptives, the relative risk was estimated to be 11.67 compared to that of the nonsmoking,• noncontraceptive user. In addition, these authors reported that the risk of nonfatal myocardial infarction was related to the amount smoked. It was found that in comparison with nonsmokers and ex-smokers, the relative risk of myocardial infarction in- creased significantly to 1.3 in women smoking fewer than 15 cigarettes a day, to 4.4 in women smoking 15 to 24 cigarettes a day, and to 11.9 in women smoking 25 or more cigarettes a day. Among nonsmokers, oral contraceptive users have 2.0 (95 percent confidence interval, 0.5 to 8.5) times the risk of having a myocardial infarction. (Because the confidence"interval includes 1.0,'chance variation is a possible explanation for this finding.) Among smokers, if a woman uses oral contra- ceptives, she has 5.4 (95 percent confidence interval, 2.0 to 14.7) times 16 .

N the risk of having a myocardial infarction than if she is a nonuser. This result is highly statistically significant (P= 0.001). 'EFFECTS OF CIGARETTE SMOKING ON LACTATION =Studies by Richer and Giudicelli (32), Rowan (33), and Vorherr (40), -further document the effects of nicotine in breast milk on infants of ;smoking mothers.' Since nicotine has been shown to cause nausea, vomiting, diarrhea, and tachycardia (39), it is recommended by the authors that lactating mothers refrain from smoking. .. ' 4~. . . . . . . . . . . .. ' . .. . . . . . Bradt and Herrenkohl (6) studied the relationship between cigarette smoking and DDT in human milk. A total of 55 human milk samples from eastern Pennsylvania were studied. Ten of the donors were cigarette smokers, and they donated 13 of the milk samples. Results of_the study showed that smoking was one of four variables which contributed to the increase in DDT. Mean total for the nonsmokers was .101 units versus .146 units for smokers. Four factors were identified statistically as accounting for 54 percent of the variance on total DDT levels in human milk. These factors are: (1) number of children nursed; (2) number of cigarettes-smoked daily; (3) use'of nonpersistent pesticides;-and (4)-' diet in calories. The relationship between the number of cigarettes smoked per day and the total amount of DDT in human milk suggests either that cigarette smoke may be a source of the human bodv burden of nnT or that cigarette smoke may cause more DDT to be excreted in the milk. 17

v WHAT WOMEN KNOW ABOUT SMOKING AND PREGNANCY There is much information circulating in the scientific community regarding the effects of smoking on health in general and, specifically, on the out- come of pregnancy. In a survey conducted by the National Clearinghouse for Smoking and Health (38), an attempt was made to find out how success- fully this information haa been disseminated to the general population and particularly to women. To what extent was the average woman informed about the consequences of her smoking on her own health and the health of her unborn child? The questions were designed to find out what women knew at the time of their last pregnancy (which in some cases was many years ago) and what they knew at the time of the survey. At the time of their last pregnancy, 24 percent said they believed smoking was hazardous to the health of a pregnant woman, and 31 percent said they believed it harmed the developing fetus. At the time of the survey in 1975, however, 53 percent reported that they knew smoking was harmful to a pregnant woman, and 60 percent believed it harmed the fetus. It is clear that the level of knowledge among women about the effects of smoking on pregnancy is appreciably lower than that in the scientific community. 18

r SUMMARY OF SMOKING-RELATED PROBLEMS UNIQUE TO WOMEN A strong, probably causal, association exists between cigarette smoking and higher late fetal and infant mortality among smokers' .infants. . Perinatal mortality increases significantly with smoking as well as with other risk factors such as maternal age, parity, socioeconomic status, previous pregnancy history, and hemoglobin level. :: A-dose-response relationship exists between smoking and the inci- dence of_low birth_weight,_preterm delivery,._perinatal_mortality, J abruptio placentae, placenta previa, bleeding during pregnancy, and prolonged.and premature rupture of the membranes. 4. In one study, the risk of premature rupture of inembranes was more than three times greater for smokers than for nonsmokers among de- liveries that occurred before 34 weeks gestation. 5. In another study, the risk of stillbirths by abruptio placentae was .__ s.ix times higher among smokers. There is an association between smoking during pregnancy and im- paired physical and intellectual development in the offspring. 7. COHb levels are substantially elevated in pregnant women who smoke O and may result in damage to placental and fetal blood vessels. GJ ~ ~ W 8. Higher levels of COHb in both fetal and maternal blood may be a ~ tll factor in the increased incidence of low-birth-weight babies amongV1 smokers. 19

9. The use of oral contraceptives potentiates the harmful effects smoking on the cardiovascular system. of 10. Results from one study showed that the relative risk of nonfatal myocardial infarction among women who use oral contraceptives and smoke is approximately 11.7 to 1. 11. Nicotine is present in the breast milk of lactating mothers who smoke and has been shown to cause nausea, vomiting, diarrhea, and tachycardia. 12. In one study, smoking was one of four variables which contributed to the increase of DDT in breast milk. 13. As recently as 1975, 40 percent of the women in the United States were not aware of the hazards to the developing fetus if they smoked during pregnancy. 20

r REFERENCES . AINDREWS, J. ,'_`icGARRY, J.M. A;community study of smoking in pregnancy. Journal of Obstetrics and Gynaecology of the British Commonwealth 79 (12):1057-1073, December 1972. 3. 115MSSEN, I., KJEtDSEi"G, K. Observations on arteries from newborn children of smoking and nonsmoking mothers. Circulation Research 36:579-589, May 1975. 1 ASTRUP, P. Carbon monoxide in tobacco smoke and its influence on the development of vascular diseases. Rehabilitation 1:11-12, 1972. • ASTRI3P, P., TROLLE, D., O1.SiEiV, H.M., KjEiBm, carbon monoxide exposure on fetal development. 1220-1222, December 9, 1972. K. Effect of moderate Lancet 2 (7789): 5. BERAL, V. Mortality among oral contraceptive users. Lancet 2 (8041): 727-731, October 8, 1977. . BWT, P.T,, HERRENKOHL, R.C. DDT in human milk. What determines the levels? Science of the Total Environment 6(2): 161-163, September 1976. 7. BUffLER, N.R., GOLDSTEIN, H. Smoking in pregnancy and subsequent child development. British Medical Journal 4(5892):573-575, December 8, 1973. 8. COLB~ P._V.1_H9WKI_NS, L.H., ROBERTS, D. Smoking during pregnancy and its effects -on the fetus. Journal of Obstetrics and ynaeco ogy o the British ----- - - Commonweal-th 79 (9):782-787, September 19T2. 9. COLLINGWOOn, J.M.: Smoking during pregnancy: effects on perinatal mor- tality and on subsequent intellectual and physical development. Health Visitor 47:68-69, March 1974. 10. DOW, T.G.B., R8©hiEY, P.J., SPENCE, M. Does anaemia increase the risks to the fetus caused by smoking in pregnancy? British Medical Journal 4(5991):253-254, November 1, 1975. 11. DEF132d, H.G., McBURNEY, A.K., INQXR9 S., H3lliTa , C.M. Maternal cigarette smoking during pregnancy and the child's subsequent development: -- -- ------- -- ---------- --- - -•--- -- I. Physical growth to the aQe_of_6-11~ year s` CanadIan Journa.l_of-_Public__.. 'Health 67(6):499-505, November-December, 1976. 21

12. DiNN , H.G. , McBURNEY, A.K. , IN0AM , S. , HUNT-Eg , C.M. . Maternal cigarette smoking during pregnancy and the child's subsequent development: II. Neurological and intellectual maturation to the age of 6~ years. Canadian Journal of Public Health 68:43-50, January/February 1977. 13. FABIA, J. Regression multiple dupoids de naissance utilisant dix variables "predictives." Canadian Journal of Public Health 64:548-551, November/ December 1973. 14. FIEL;DING, J.E., RUSSO , P.K. Smoking and pregnancy. New England Journal of Medicine 298(6):337-339, February 1978. 15. FORREST., J.M. Drugs in pregnancy and lactation. Medical Journal of Australia 2(4):138-141, July 24, 1976. 16. GOUJAi?dy , J., RUME14i1, C., BCHWARTZ, D. Smoking during pregnancy, still- birth, and abruptio placentae. Biomedicine 23(1):20-22, February 10, 1975. 17. HARnX, J.) MEILITS, E.D. Does maternal smoking during pregnancy have a long-term effect on the child? Lancet 2(7791):1332-1336, December 23, 1972. 18. JAIN, A.K. Cigarette smoking, use of oral contraceptives, and myo- cardial infarction. American Journal of Obstetrics and Gynecology 126 (3):301-307, October 1, 1976. 19. JAIN, A. K. Mortality risk associated with the use of oral_ contra- ceptives.Studies in Family Planning 8(3):50-54, March 1977. 20. XMINSKI, M., GOUJARD, J., RIFai6-ROUQUETTE, C. Prediction of low birthweight and prematurity by a multiple regression analysis with maternal characteristics known since the beginning of pregnancy. International Journal of Epidemiology 2(2):195-204, 1973. 21. KLINE, J., STEIN, Z.A., SUSBER, M., WARBURTON, D. Smoking:, a risk factor for spontaneous abortion. New England Journal of Medicine 297(15):793-796, October 13, 1977. 22. LQN~O, L. Carbon monoxide: effects on oxygenation of the fetus in utero. Science 194(4264):523-525, October 29, 1976. . 23. I,LMS, M. Racial differences in maternal smoking effects on the newborn infant. American Journal of Obstetrics and Gynecology 115(1): 66-76, January 1, 1973. 22

r. W.H.W.,THpROqOODr,M. Oral contraceptive use in 4 24. MANN, J.I, INMAN , _ older women and fatal myocardial infarction. British Medical Journal 2:445-447, 1976. 25. MANN, J.I., VESSEY, M.P •, 'nKROGMD, M•, DOLL, R. Myocardial infarction in V young women with special reference to oral contraceptive practice. British Medical Journal 2:241-245, 1975. 26. :MEREDITH, H.V. Relation between tobacco smoking of pregnant women and body size of their progeny: a compilation and synthesis of published studies. Human Biology 47(4):451-472, December 1975. 27. , 1SEYER, M.B., ,JAD+Ia16, B.S., TONASCIA, J.A. Perinatal events associated with maternal smoking during pregnancy. American Journal of Epi- demiology 103(5):464-476, 1976. ' 28. KXP, M.B., TON4S~IA, J.A. Maternal smoking, pregnancy complications, and perinatal mortality. American Journal of Obstetrics and Gynecology 128:494-502, July 1, 1977. 29. MEjfF.lt, M.B., TONASCIA, J.A., BUCK,C. The interrelationship of maternal smoking and increased perinatal mortality with other risk factors. Further analysis of the Ontario Perinatal Mortality Study, 1960-1961. American Journal of Epidemiology 100(6):443-452, December 1974. 30. `ONTAR=DEPART`3'EiQT a TH. Second Report 'of the Perinatal Mor- tality tality Study in Ten Teaching Hospitals. Toronto, Canada, Ontario Depart- -Me nr ot-ZieaIffi, Ontario Perinatal Mortality Study Committee, Vo1. I.,1967, 273 pp. 31. 4RY, H.W.. Association between oral contraceptives and myocardial in- farction. A review. Journal of the American Medical Association 237(24):2619-2622, June 13, 1977. 32. RICHER, C., CIiJDICELbI, J.F. Exretion des medicaments dans le lait maternal. Revue de Medecine 17(2):1149-1157, May 17, 1976. 33. ROWAY, J.J.. Excretion of drugs in milk. (Letter). Pharmaceutical Journal 217(5885):184-186, September 4, 1976. 34. RUSH, D. Examination of the relationship between birthweight, ciga- rette smoking during pregnancy and maternal weight gain. Journal of Obstetrics and Gynaecology of the British Commonwealth 81(10):746-752, October 1974. 35. SIMPSON, W.J.A. A preliminary report on cigarette smoking and the incidence of prematurity. American Journal of Obstetrics and Gynecology 78:808-815, 1957. . O W ~ ~ w ~ 23 ~ CD

36. SILVERMAN, D.T. Maternal smoking and birthweight. American Journal of Epidemiology 105(6):513-521, June 1977. 37. SPIRA, A., SPIRA, N., GOUJARD, J., SCHWARTZ, D. Smoking during preg- nancy and placental weight. A multivariate analysis on 3759 cases. Journal of Perinatal Medicine 3(4):237-241, 1975. " 38. U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, PUBLIC HEALTH SERVICE, CENTER FOR DISEASE CONTROL AND NATIONAL INSTITUTES OF HEALTH. Adult use of tobacco - 1975. Washington, D.C., June 1976. 39. U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, PUBLIC HEALTH SERVICE, HEALTH SERVICES AND MENTAL HEALTH ADMINISTRATION. The Health Consequences of Smoking, 1973. Washington, D.C., DHEW Pub- lication No. (HSM)73-8704, 1973, 97-149. 40. VORHERR, H. Drug excretion in breast milk. Postgraduate Medicine 56(4):97-104, October 1974. 41. WINGERD, J., SCHOEN, E.J. Factors inf luencing length at birth and height at five years. Pediatrics 53(5):737-741, May 1974. 24

e FIGURE 1.- Risks of selected pregnancy complications for smoking ' and nonsmoking mothers, by period of gestational age at delivery for A, abruptio placentae, B, placenta previa,, C, premature rupture of membranes ( PROM ) 0. 04: ~ 0.0 7 4- 0.01: 0.0081 0.006 0.004: 0.002' J; 0.00? 1$ 2i 0.0008 Q% 0.0006 m C~ 0.0004, . A: :- f t- 20. 241 ! a + I i 3 ( 1 f 281 321 36i 40i 44l, GESTATION. :wEEKS` 0.1 0.08~ 0.06r 0.04:+ 0.02i+ . 0.]l w 0.7^61 _ # „ C 0.00~ ~T z n.00^ } w U gf 0.01 O~ 0.00P• aI 0.00fi oi 0.004; } F- ~i 0.002 m ml 0.001oi 0.00081. f a1 0.0006i-} n Annetl . @' ( Q; 0.0002 ~ I;ONS".ZJKERS, 0.0002 4 9. r Oi r ¢ 0.0001 Source: Meyer, M.B., et al. (28). ' r . 25

FIGURE 2.- Number of cigarettes normally smoked per day compared with COHb level at time of sampling in 93 pregnant women. ~= Mean range of COHb levels for 129 nonsmokers 15 ~ t t 30' CIGARETTES SMOKED PER DAY ; Source: Cole, P.V., et al. (8). . . __.. 1. 26 1

0 22 20 E 18` 0 0 16 L ~ a = 14 C - 12 d C 0 U CN 0 10 +l 8 1~ I FIGURE 3. -Oxyhcniuollul,in sahrrafion curves of human niatr!rnal and . » fetal- bluod_ under control and steady -state co,iditions.' Fetus ---T.AF1 UM1,~ F2 0 M2 oj~ ~ V ------------------------------ / /v u ~ - O _Q ~ 6 E Ft'0/h/ F ,/ Mot!,~ l l . .~ 10 20 30 40 50 60 70 P02 (torr) 'With 10 percent fetal and 9.4 percent maternal HbCO concentrations. The maternal and fetal hemoglobin contents were assumed to equal 12 and 16.3 per 100 ml of blood, respectively• A normal 02 consumption of 5 ml per 100 ml of blood was assumed for both the uterus and its contents and the fetus. Source: Longo, L., (22). 80 90 100

r TABLE 1.- Adjusted rates and F ratios for maternal smoking and other important factors affecting birth weight, gestation, placental complications, and perinatal mortality a Factor *Adjusted Rates of Outcome t F Ratio Maternal Smoking Level Birth Weighz < 2500 Grams Per 1000 Births None 49.4 182.8 <1 Pack Per Day 75.7 >1 Pack Per Day 113.7 Previous Pregnancy History No Previous Pregnancy 70.0 123.5 Previous Pregnancy, 0 Loss 57.8 Previous Pregnancy, Loss 134.8 `Hospital Pay Status Private 60.0 84.0 Public 87.4 Gestation <38 Weeks Per 1000 Births Maternal Smoking Level None 77.1 50.6 <1 Pack Per Day 92.2 >1 Pack Per Day 115.9 Previous Pregnancy History No Previous Pregnancy 69.1 182.6 Previous Pregnancy, 0 Loss 85.7 Previous Pregnancy, Loss 193.9 O ~ .~ Hospital Pay Status W Private 78.9 ~Z120 . 3 1A Public 116.2 (continued) ~.e.....i`C/1s'

. TABLE 1.- continued Factor *Adjusted Rates of Outcome F Ratio ;' Placenta Previa Per 1000 Births Maternal Smoking None <1 Pack Per Day >1 Pack Per Day Previous Pregnancy History No Previous Pregnancy Previous Pregnancy, 0 Loss Previous Pregnancy, Loss 6.5 8.1 12.5 8.8 6.6 15.8 11.7 4.4 (Hospital pay status not a significant factor) Ii z. . Abruptio Placentae Maternal Smoking Per 1000 Births None 16.4 17.1 G 1 Pack Per Day 20.3 7 1 Pack Per Day 27.6 Previous Pregnancy History No Previous Pregnancy 18.8 25.6 Previous Pregnancy, 0 Loss 17.6 Previous Pregnancy, Loss 37.4 Hospital Pay Status Private 17.5 20.7 Public 25.0 Maternal Smoking Perinatal Mortality Per 1000 Births None 23.5 8.4 ~ 1 Pack Per Day 28.2 >1 Pack Per Day 31.8 ~ Previous Pregnancy History ~ W ~ No Previous Pregnancy 23.1 97.4 0 Loss Previous Pregnancy 23.6 Q+ , Previous Pregnancy, Loss 68.7 W ~ Hospital Pay Status ~ Private 23.3 44.2 Public 36.1 70

TABLE 1.-continued *Adjusted rates show independent effect of the factor given, adjusted for all other factors in regression. They are: maternal smoking, hospital pay status, mothers' birthplace, height, prepregnant weight, sex of child, previous preg- nancy history, and age-parity. fF ratio degrees of freedom: numerator = number of subgroups -1, denominator infinity. (All differences shown are highly significant. F ratios indicate the relative importance of the factor.) Source: Personal correspondence, based on data in Meyer, M.B., et al. f(27 iam 30

TABLE 2,- Perinatal mortality and selected pregnancy complications, by maternal smoking levels Smoking level (packs per day) (rates per 1,000 total births) Outcome 0 (23,358 Births) <1 (15,328 Births) >1 (6,581 Births) 2* X Perinatal Mortality 23.3 28.0 1 33.4 27.8+ Abruptio Placentae 16.1 20.6 28.9 47.3+ Placenta Previa 6.4 - 8.2 '13.1 -- 28.6+ ~ Bleeding During Pregnancy 116.5 141.6 180.1 201.9+ Rupture of Membranes 15.8 23.3 35.8 109.9+ > 48 Hours - Rupture of Membranes Only at Admission 30.3 39.3 45.0 45.7+ .*Cochran's chi square for trends. ±P <0. 00001. Source: Meyer, M.B., et al. (28). 31

4 TABLE 3,- Stillbirths according to cause in relation to maternal smoking during pregnancy Number of Stillbirths Deliveries Cause of Death: Vascular, 8 Abruptio,Placentae 13 Mechanical 13 Miscellaneous (Syphilis, Rh, Malformations,...) 24 Unknown 37 Detailed Records Not Available TOTAL 100 Livebirths 9069 Percent Smokers 25 46 Comparison With Live Births+ p = 0.005 . 15 13 35 p = 0.0005 26 n = 0.0001 12 + When p is not given, the difference is not significant. Source: Goujard, J., et al. (16). 32 t~: ,. _ : .... .. . , _. .,,...~ti . ,. .:,~:.

s TABLE 4.- Estimated annual mortality rate per 100,000 women from myocardial infarction and thromboembolism, by use of oral contraceptives, smoking habits, and age (in years) Myocardial Infarction Thromboembolism Women Aged 30-39 Women Aged 40-44 Women Aged 20-34 Women Aged 35-44 Smoking Habits Users Nonusers Users Nonusers Users Nonusers* Users Nonusers All Smokers 10.2 2.6 62.0 15.9 1.6 0.2 4.1 0.6 Heavy 13.0 5.1 78.7 31.3 4.4 0.2 11.4 0.6 Light 4.7 0.9 28.6 5.7 0.7 0.2 1.9 0.6 Nonsmokers 1.8 1.2 10.7 7.4 1.4 0.2 3.6 0.4 Smokers and Nonsmokers 5.4 1.9 32.8 11.7 1.5 0.2 3.9 0.5 *Estimated rates for smokers and nonsmokers were 0.24 and 0.16 respectively. Rates appear the same because of rounding. Source: Jain, A.K. (19). 699E9z4C0 w W

, TABLE 5.- Estimated relative risks of nonfatal myocardial infarction, by use of oral contraceptives and cigarette smoking Current User of Oral Contraceptives Smoking Data Yes No Smokers Total 11.67 2.15 Heavy* 14.81 4.23 Light+ 5.38 0.77 Nonsmokers 2.02 1.00 Based on data in Table VII by Mann and associates (25). *Heavy smokers: at least 15 cigarettes per day. +Light smokers: less than 15 cigarettes per day. Source: Jain, A.K. (18).

e CHAPTER 2 Page Smoking and Overall Mortality . . . . . . . . . • . . . • . . • • • . . Introduction Measuring Mortality . . . . . . . . . . . . . . . . . . • . . • • . . . ._ Mortality Ratios . . . . . . . . . . . . . . . . . . . . . . . . . . Differences in Mortality Rates ... . . . . . . . . . . . . . . . . .Excess Deaths . . . . . • . . . . . . . . . . . . • . . . . • . . • _. Life Expectancy . . . . . . . . . . . . . . . . . . . . . . . . . Description of the Studies • . . . . . . • . . . . . . . . .... . . . . The American Cancer Society Study . . . . . . . . . . . . . . . . . The U.S. Veterans Study . • . . . . . . . . . . . . . . . . . . The British Doctors Study . . . . . . .... . . . . . . . . . . . . . Overall Mortality and Cigarette Smoking . . . . . . . . . . . . . . . . Number of Cigarettes Smoked . Age Began .Smokin8 Inhalation-Practice . . . . "Tar" and Nicotine . Ex-Smokers Pipe and Cigar Smoking • . • . . • . . . . • . . . . Summary of Smoking and Overall Mortality . . . . . . . . . References 35

h. CHAPTER 2 List of Figures Figure 1.-Annual probability of dying for current cigarette smokers, ex-smokers who quit less than 5 years ago, and never smokers, ages 55-64 Figure 2.-Annual probability of dying for current cigarette smokers, ex- . smokers who quit 5-9 years ago, and never smokers, ages 55-64 Figure 3.-Annual probability of dying for current cigarette smokers, ex- smokers who quit 10-14 years ago, and never smokers, ages 55-64 Figure 4.-Annual probability of dying for current cigarette smokers, ex- smokers who quit more than 15 years ago, and ex-smokers, ages 55-64 List of Tables Table 1.-Age-adjusted mortality ratios for male cigarette smokers, by amount smoked, U.S. Veterans Study, 1954 cohort, 16-year follow- up Table 2.-Mortality ratios for cigarette smokers, by number of cigarettes . smoked per day, British Doctors Study Table 3.-Mortality ratios for male cigarette smokers, by age and number of cigarettes smoked per day, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 4.-Age-adjusted mortality ratios for male cigarette smokers, by age began sinoking, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 5.-Age-adjusted mortality ratios for male cigarette smokers, by number of cigarettes smoked per day and age began smoking, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 6.-Mortality ratios for cigarette smokers, by inhalation practice, British Doctors Study Table 7.-Mortality ratios for all cigarette smokers in two time periods, W by sex and "tar" and nicotine (T/N) content in cigarettes smoked ~ Q: W ~ 36 ~ N

r Table 8.-Mortality ratios for smokers of low "tar" and nicotine (T/N) cigarettes and nonsmokers in two time periods, by sex Table 9.-Mortality ratios for time periods, by sex cigarettes smoked Table 10.-Mortality ratios for orders and for other Veterans Study, 1954 all cigarette smokers and nonsmokers in two and "tar" and nicotine (T/N) content of ex-smokers who quit smoking on doctor's reasons, by years since stopping, U.S. cohort, 16-year follow-up Table 11.-Mortality ratios for ex-smokers who quit smoking on doctor's orders and for other reasons, by number of cigarettes smoked per day, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 12.-Mortality ratios for ex-smokers who quit smoking on doctor's orders and for other reasons, by age began smoking, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 13.-Mortality ratios for ex-smokers of cigarettes only, by years since s,topping, number of cigarettes_smoked per day, and age began smoking, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 14.-Mortality ratios for ex-smokers compared to nonsmokers, by "' ~~number of years since stopping and age, British Doctors Study Table 15.-Age-adjusted mortality ratios for pipe-only, cigar-only, and cigarette-only smokers, U.S. Veterans Study, 1954_cohort, 16- year follow-up Table 16.-Age-adjusted mortality ratios for current cigar smokers, by .... _ . _, _ , number of cigars smoked per day, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 17.-Age-adjusted mortality ratios for current cigar smokers, by age began smoking, U.S. Veterans Study, 1954 cohort, 16-year follow-up O ~ ~ 37 GJ ~ ~ W

Table 18.-Age-adjusted mortality ratios for current cigar smokers, by - number of cigars smoked per day and age began smoking, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 19.-Age-adjusted mortality ratios for current pipe smokers, by number of pipefuls smoked per day, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 20.-Age-adjusted mortality ratios for current pipe smokers, by age began smoking, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 21.-Age-adjusted mortality ratios for current pipe smokers, by number of pipefuls smoked per day and age began smoking, U.S Veterans Study, 1954 cohort, 16-year follow-up Table 22.-Age-adjusted mortality ratios for current cigar smokers, by ' use of other types of tobacco, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 23.-Age-adjusted mortality ratios for current pipe smokers, by use of other types of tobacco, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 24.-Age-adjusted mortality ratios for current cigarette smokers, by use of other types of tobacco, U.S. Veterans Study, 1954 cohort, 16-year follow-up Table 25.-Age-adjusted mortality ratios used, British Doctors Study 38 for all smokers, by type of tobacco c E

t' CHAPTER 2 SMOKING AND OVERALL MORTALITY INTRODUCTION In 1964; the subject of smoking and overall mortality was examined in the Report of the Advisory Committee to the Surgeon General of the Public Health Service (9)."-This subject was reviewed in 1967 and 1968 in The Health Conse- quences of Smoking (6,7). Since then, the updated results of three prospective, epidemiologic studies concerned with tobacco use and overall mortality have been published (1,3,5). The following is a review of work previously reported as well as an analysis of the three more recent studies. Summary of the 1964 Report (9): . The death rate for male cigarette smokers was about 70 percent higher than that for nonsmokers.* . The death rates increased with the amount smoked.* . The ratio of the death rate of smokers to that of nonsmokers was highest at the earlier ages (40-50) and declined with increasing age.* . The mortality ratio was substantially higher for men who 5. . In two studies which recorded the degree of inhalation, the mortality ratio for a given amount of cigarettes smoked was greater for inhalers than for noninhalers. started smoking before the age of 20 than for men who started after 25. The mortality ratio increased as the number of years of smoking increased. o3'7s3s'75 *Data are derived from seven major prospective studies of male smokers and nonsmokers. The rate is for smokers of cigarettes only at the time of entry into the study. These are obtained by subtracting the yearly death rate for nonsmokers from the death rate of a comparable group of smokers. This meas- ure reflects the added probability of death in a 1-year period for the smoker over that for the nonsmoker. 39

7. Cigarette smokers who had stopped smoking had mortality ratios of 1.4, compared to 1.7 for current cigarette smokers. The mortality ratio declined as the number of years of "cessation .; : . . . _ increased. 9. Death rates for men smoking less than five cigars daily were about the same as those of nonsmokers. For men smoking five or more cigars daily, death rates were slightly higher (9 to 27 percent) than those for nonsmokers. Death rates for.ex-ciQar smokers were higher than for current smokers in all four studies in which this comparison could be made. One possible explanation may be that a substantial number of cigar smokers quit smoking due to illness. 10. Death rates for current pipe smokers were little if at all higher than for nonsmokers, even for those smoking 10 or more pipefuls per day and for those who had smoked for more than 30 years. Ex-pipe smokers, on the other hand, showed higher death rates than both nonsmokers and current smokers in four out of five studies. As similarly noted above, one possible explanation may be that a substantial number of cigar and pipe smokers qu:bt smoking because of illness. In the 1967 report of The Health Consequences of Smoking, additional con- clusions were made relative to the effect of smoking on overall mortality (6). The highl ights of that report are presented below: C 1. The previous conclusions with respect to the association between smoking and mortality were both confirmed and strengthened. ~ Qw., 40

With respect to effects of smoking on specific age groups, men 45 to 54 years of age were at greatest risk, both in terms of -mortality ratios and excess deaths expressed as a percentage of total deaths. Nevertheless, although both of these measures declined with advancing age, the increment added to the death rate, which reflects one's personal chances of being~affected, continued to increase with age. . Women who smoked cigarettes had significantly higher.death rates than those who had never smoked regularly. The magnitude of the relationship varied with several measures of dosage. The same overall relationships between smoking and mortality were observed . for women as for men, but at a lower level. Previous findings on the lower death rates among those who had discontinued cigarette smoking were confirmed and strengthened by the additional data reviewed.. The 1968 report of The_Health Consequences of Smoking (7) reported that the life expectancy 8.3 years less than for a two-pack-a-day or more smoker at age 25 is that for the corresponding nonsmoker. (those smoking less than 10 cigarettes per day) had 2.8 Even light smokers to 4.6 fewer years O of life expectancy than corresponding nonsmokers. G: Q a) c.w 17; MEASURING MORTALITY ~ ~ Overall mortality is a term familiar to epidemiologists and statisticians but one which is not commonly used or appreciated by many who are concerned with the health of the public. To many physicians, dentists, nurses, and 41

other health professionals who have a primarily clinical orientation, the concept of overall mortality is often not clearly understood, since it has no immediate application to their practice. Individuals die of specific diseases. Disease-specific mortality rates are of more immediate interest to many in the health care field. Overall mortality rates are particularly useful in measuring the effect of agents which affect multiple organ systems and which are capable of causing or contributing to the cause of several diseases. In contrast, disease-specific mortality rates measure the effect of an agent on a specific cause of death but fail to measure the total impact of an agent on the public health. Overall mortality is, therefore,. a good measure of the cumulative or total effect of an agent on health. The problem of how best to measure the relationship between smoking and mortality has been discussed in previous reports, as well as in some of the prospective study reports. A brief discussion of some of the measures of comparison available and their utility is presented below. Mortality Ratios: These are obtained by dividinQ the death rate for a classification of smokers by the death rate of a comoarable Qroup of nonsmokers. A mortality ratio has been considered to reflect the deQree to which a classification account for variations in variable (e.tz., smokinQ) identifies or mav death rates. which indicates the relative that other important factors effect of affecting As such, it is a measure of risk that variable on mortality, g;ven mortality (e.Q., a2e) are parable in the numerator and denominator groups. 42 cnm- r .

f Differences In Mortality Rates: These are obtained by subtracting the yearly death rate for nonsmokers from the death rate of a compa- rable group of smokers. This measure reflects the added probability of death in a 1-year period for the smoker over that for the non- smoker. As such, it is a measure of personal health significance, a means for the individual to estimate the added risk to which he is exposed. Excess Deaths: These are obtained by subtracting from the number of deaths occurring in a group of smokers the number of deaths which .would have occurred if that group of smokers had experienced the same ~ mortality rates as a comparable group of nonsmokers. This measure s an indicator of the public health significance of the differences found,`since it measures the number of people affected and therefore quantifies"`the magnitude of the problem for society as a whole. Life Expectancy: This is a concept which is easier to understand tfian it is to calculate. uAt a given age, it represents the average number of years one might be expected to live. It identifies the point in time at which half the population in question theoretically will be dead and the other half will be alive. DESCRIPTION OF THE STUDIES 03'7636'79 The following is a brief description of the design and methods used in each of the three studies which are reported in this chapter. Some com- ments are made concerning the relative strengths and weaknesses of each study. 43

The American Cancer Societv The largest of the three studies discussed here is the American Cancer Society (ACS) Study (4,8). In late 1959 and early 1960, volunteer workers of the ACS enrolled 1,078,894 men and women in a prospective study. In- formation was solicited on age, sex, race, education, place of residence, family history, past diseases, present physical complaints, occupation, occupational exposures, various smoking habits, and other factors. Information concerning smoking habits included: type of tobacco used, number of ciga- rettes smoked per day, inhalation practices, age at initiation of smoking, and the brand of cigarettes smoked from which the "tar" and nicotine con- tent of the cigarette could be calculated. All segments of the population were included except migrant workers and similar groups that could not have been traced easily. Also excluded were mental patients and those receiving long-term medical care in institutions. Enrollment was by house- holds, with the specification that there be at least one person over age 45 in each household enrolled.The study area covered 25 states. At the time of enrollment, each person completed a lengthy questionnaire. At 2- year intervals, for a period of 6 years, brief repeat questionnaires were administered to each surviving subject. In the follow-up questionnaires, information was obtained concerning current cigarette usage, hospitalization, diseases acquired in the interval between questionnaires, and several other items. Almost 95 percent of survivors were successfully traced the first 6 years, (that is, through June of 1966). In October 1971 and September 1972, further follow-up questionnaires were distributed to the nearly 900,000 individuals who had been last 44 contacted in September 1965. Nearly

93 percent of the survivors were successfully followed for the entire 12 years. The time period from July 1, 1960, to June 30, 1966, is referred to as Period 1 and that from July 1, 1966, to June 30, 1972, is referred to as Period 2. The positive features of this study include its prospective design, the unusually large population enrolled~ which included all major segments of society, the frequency of the follow-up periods, the variety of the data collected, the thoroughness of follow-up with loss of but few enrollees, and the relatively long period of observation. Ae U.S: ~#e~erans Stti~d y The U.S. Veterans Study (4,5) was initiated by Dorn in 1954 and continued by Kahn and later by Rogot. This study describes the overall mortality experience of about 250,000 U.S. veterans who held Government Life Insurance policies in December of 1953. Beginning in January 1954, questionnaires on smoking habits were mailed to these policy holders and nearly 175,000 (68 percent) responded. These individuals comprise what in this report is called the "1954 cohort." In January 1957, a second questionnaire was mailed to those not responding in 1954, and an additional 50,000 replies were obtained, raising the response rate to 85 percent. These are referred to as the "1957 Cohort." The annual probability of dying for the 1957 cohort was somewhat greater than that of the 1954 cohort. Because of this, the mortality experience of these two cohorts was examined separately. C C.: Only the data from the 1954 ~johort will be considered here, as a sepa- J rate analysis of both cohorts is beyond the scope of this paper. The V~ GA study o ulation was uite select; • almost all p p q policy holders were white ~ 4~-

. males. Most were white-collar, skilled workers who were veterans of World War I. This group was questioned as to sMoking habits, etc., and followed for 16 years. Since significant changes have occurred in the smoking practices of white males in the United States over the past 20 years, it is likely that similar changes also occurred in the smoking habits of the subjects of this particular study in the study period. It is unfortunate, therefore, that the recent mortality experience of this population has to be correlated with smoking practices of many years*ago. The strengths of this study include its large population, its prospective design, and its long period of follow-up. Its weaknesses include its narrow population, which limits the applicability of the results to the general population, and the lack of information about more recent changes in smoking habits among members of the study population which would affect the mortality experience of the group. The Briti$n:Dobtors Study. In 1951, a total of 34,440 male British doctors responded to a questionnaire distributed by the British Medical Association relative to smoking habits (1). Nearly all of those enrolled were followed for a period of 20 years. Updated information concerning smoking practices was obtained in 1957, 1966, and 1972. More than 10,000 deaths occurred in this population in the period of observation. Information was obtained on the type of tobacco used, inhala- tion practice, the use of filter cigarettes, and the number of cigarettes O smoked per day. The usual demographic data concerning the background of ~ ~ the individual were also obtained. W Q) ~ 46 ~

d The strengths of this study include its large size, prospective design, the unusually long period of follow-up, the frequent determination of smoking habits of the subjects enrolled in the study, and the thoroughness of follow- up. Perhaps the only significant drawback is that the study population was so narrow. The most recent analysis has been limited to overall mortality, since death certificates were not obtained for those who died in the last half of the study period. Smoking classifications used in the latest paper are some- what different from those used in previous reports. The occasional smoker was grouped with the nonsmoker, since their mortality experience was es- <. sentially similar. As a result, occasional smokers who had quit smoking were grouped with those who had never smoked, and regular smokers who became occasional smokers were grouped with ex-smokers. OVERALL MORTALITY AIND CIGARETTE SMOKING Cigarette smoking as related to overall mortality was examined in these three studies using several different measures of dosage. Number of Cigarettes Smoked In the study of U.S. veterans, mortality increased with the number of cigarettes smoked per day. The mortality ratio was 1.25 for smokers of less than 10 cigarettes per day and increased to 1.89 for men smoking two packs (40 cigarettes) or more per day (Table 1). In the study of British ~ Q doctors, the mortality ratio was 1.41 for smokers of 1-14 cigarettes per day W 09 and increased to 2.16 for smokers of 25 or more cigarettes per day. The mor- (Z W tality ratio for all cigarette smokers compared to nonsmokers was 1.63 (Table 2). The mortality experience of U.S. veterans by age and the number of ciga- 47

rettes smoked per day are presented in Table 3. Cigarette smoking appears to have a stronger effect on the mortality of younger smokers than on older smokers. The death rate for smokers increases with age, but since the risk of dying in general increases more rapidly with ad- vancing age than the risk associated with smoking, the relative contri- bution of cigarette smoking to overall mortality decreases with time. This relationship is imperfectly demonstrated when mortality ratios are used. Age Besan Smoking The earlier one begins smoking, the more exposure that individual will have had to cigarette smoke at any subsequent age. In the U.S. Study, the overall mortality ratio for those men who began before the age of 15 was 1.86. This decreased to 1.32 for Veterans smoking those who did not start smoking until after the age of 25 (Table 4). Table 5 presents the mortality ratios for males by number of cigarettes smoked per day and age began smoking. The lowest mortality ratio (1.36) wac ex*+erienced by those men who smoked less than 21 cigarettes per day and who were more than 20 years old when they began smoking. The highest mortality ratio (1.82) occurred among those who smoked more than 21 cigarettes per day and began smoking before the age of 20. Inhalation Practice Death rates by inhalation practice were examined in the study of British doctors (Table 6). The mortality ratio for those who did not inhale was 1.28. This increased to 1.43 for those who did inhale. 9 y 48

! "Tar" and Nicorine--- The "tar" and nicotine content of cigarette smoke in relation to overall mortality was examined by Hammond, et al. (3) using the ACS data. Several important issues relative to the concept of less hazardous were settled in this study. It has been smoking generally accepted that the harmful effects of cigarette smoking are proportional to the "tar" and delivered by the cigarette. For several years, the "tar" nicotine levels and nicotine levels of all the popular brands of cigarettes have been checked periodically by the Federal Trade Commission. This information has been made available to the public through various public and private agencies and is included in cigarette advertisements. Those who have decided not to quit or who have not been able to quit have been encouraged to switch to brands of cigarettes which deliver less "tar" and nicotine. This pattern of smoking is thought to be one way of partially reducing the risks associated with smoking. Some persons in the scientific community have questioned whether or not there would be any substantial reduction in risk of mortality associated with such a switch. Smokers might increase the number of ciga- rettes smoked per day, thus keeping their intake of "tar" and nicotine relatively constant. Smokers switching to low "tar" and nicotine cigarettes may inhale the smoke more deeply into the lungs, thus tending similar exposure .to. -tfie •tnxic__elements ;ia -the smoke. to mintain a In the study by Hammond, et al.(3), "tar" and nicotine (T/N) levels were de- fined fined as follows: High T/N: 25.8-35.7 milligrams(mg.) "tar" and 2.0-2.7 mg.~ nicotine ; Medium T/N:17.6-25.7 mg. "tar" and 1.2-1.9 mg. nicotine; Low T/N:(„7~ 0~ less than 17.6 mg. "tar" and less than 1.2 mg. nicotine. A matched ~ 49

S group analysis was utilized. Subjects within each group were matched for: (1) age, (2) race, (3) number of cigarettes smoked per day, (4) age began smoking, (5) place of residence (urban or rural), (6) history of hazardous occupational exposure, (7) education, (8) history of lung cancer, and (9) history of heart disease. Matching was done separately for men and women in both time periods of the study. Within each matched group, the subjects were divided into three subgroups according to "tar" and nicotine (high, medium, or low). The entire group was discarded if it did not contain at least one subject in each "tar" and nicotine category. The adjusted number of subjects in Period 1 was 14,688 men and 30,176 women. In Period 2, there were 6,475 men and 15,342 women. The mean age of subjects in Period 1 was 53.6 years for -men and 51.6 years for women--"; in Period 2, the mean age was 58.4 years for men and 56.7 years for wgffigAe,, Table 7 shows mortality ratios by sex and "tar" and nicntine cnntent of the ciea- - rettes smoked. In this instance, the mortality ratio for the hi2h T/N smokers is represented as 1.00. There is a small but significant (p < 0.0005 ) reduction in the risk of dying with the use of lower T/N cigarettes. The mortality ratio was reduced to 0.91 for the medium T/N smokers and was further reduced to 0.84 for the low T/N smokers. A comparison was also made between the mortality experience of low T/N smokers and nonsmokers. Subjects were matched according to the same factors as the previous analysis with the exception of the number of cigarettes smoked per day. The adjusted number of subjects for Period 1 was 15,346 men and 32,702 women. For Period 2, adjusted numbers were 6,822 and 16,803 for men and women, respectively. 0 The mean age of subjects in Period 1 was 53.8 years for men and 52.3 vearq ~ ~ 50 Q' 4

for women. In Period 2, the mean ages for men and women were 58.7 and 57.3 years, respectively. The mortality ratios for these matched groups are presented in Table 8. The death ratio foc the low T/N group is 1.00, and that for nonsmokers is 0.66. The mortality ratio for the low T/N Qroup is, therefore, approximately 50 percent higher than that for the zonsmokers. Assuming that the composition of the two low T/N groups were quite similar in these separate analyses, these two sets of data can be combined to com- pare mortality rates of smokers of various levels of "tar" and nicotine with those of nonsmokers (Table 9). These results are approximate, however, and are subject to some error. Anoth er matched group analysis was done comparins mortality ratios of smokers of relatively few (1-19) high T/N cigarettes with those smokers of relatively large numbers (20-39) of low T/N cigarettes. The mortalitv of these two groups were very similar,and the difference between them was not statistically significant. ratios EX-SMOKERS The mortality experience of ex-smokers is a subject in which there has been increasing interest in the past several years. When the harmful effects of smoking were initially suspected and examined, the question at first was one of the magnitude of the problem. More recently, there has been a nationwide recognition of the adverse morbidity and mortality C which results from smoking. As a result, more than 30 million Americans ~ have quit smoking, and millions more anticipate quitting within the next C.7 ~ 51 ~ ~

e several years. One of the questions of greatest concern to the smoker at this time is not, "How bad is my smoking for my health?" but rather, "After all these years of smoking will it make any difference if I quit?" The bene- fits of stopping smoking are more clearly understood as a result of the studies reviewed here. The relationship between cessation of smoking and overall mortality was examined in considerable detaill in the study of U.S. veterans. A differentiation was made between ex-smokers who stopped smoking on the recommendation of a doctor and those who quit for other reasons (Tables 10, 11, 12). In each cohort, about 10 percent of the ex-smokers had stopped on doctor's orders, and this group had much higher mortality levels than those who stopped for other reasons. There was a direct relationship between mortality levels and the maximum amount previously smoked-, an inverse relationstiip between mortality and years since stopping smoking, and an inverse relationship between mortality and`age when smoking began. The combined effects of these three factors on mortality are presented in ratio (1.03) Table 13. The lowest mortalityqwas experienced by ex-smokers who began smokiniz after the age of 20, smoked fewer than 21 cigarettes per day, and had stopped smoking for more than 10 years at the time of enrollment in the study. Conversely, the highest mortality ratio (1.45) was exDerienced bvYex-srrokers ~•7ho began smoking before the age of 20, smoked more than 21 cigarettes per day, and had stopped smoking for less than 10 years at the time of enrollment in the study. 52

r A detailed study of the mortality experience of ex-smokers who stopped smoking forvarious reasons other than a doctor's order is given in Figures 1-4. This information is derived from the U.S. Veterans Study for men aged 155-64 who used to smoke from 21-39 cigarettes per day. The years since stopping smoking is considered as a variable, and the mortality rates are compared _with those of current cigarette smokers and nonsmokers. Annual probabilities of dying are plotted on a logarithmic scale. This results in a fairly smooth, linear pattern for both smokers and nonsmokers. The posi~ive slooe indicates increasing mortality with the passing of time for both smokers and nonsmokers. These lines also appear to run,parallel or perhaps diverge slightly. This indicates an approximately constant or slightly increasing excess probabilitv of dying between cigarette smokers and nonsmokers over the 16- year period. For ex-smokers who quit less than 5 years prior to the beginning of the study, the probabilitv of dvinQ is at first nearly identical to that of smokers (Figure 1). Over the years, the probabilitv eradnallv falls to a position approximately halfway;- between that of smokers and nonsmokers. Figures.2 and 3 show that with longer periods of cessation the probability of dying more nearly approaches that of nonsmokers: -The prob ability of dyingVfor ex-smokers 'who had stopped smoking for 15 or more years is virtually the same as~__ as that for nonsmokers for the entire 1A-year period (FieurP 4). The mortality experience of British doctors who quit smoking indicates that there are benefits to quitting no matter how long one has smoked O W ~ W ~ Cd (Table 14). After 10-15 years of not smoking, the risk of dying for ex-smokers (1.1 compared to 1.0). is similar to that of those who have never smoked^ It should be remembered that overall mortality examines the probability of dying from all causes. 53

f This masks the relative benefits of quitting for specific diseases. It is known that the risk of dying from ischemic heart disease is reduced almost immediately after cessation of smoking, while the risk of dying from lung cancer decreases more slowly. Only the net or total effect is demonstrated in overall mortality figures. PIPE. AND CIGAR• SMKING ; Pipe and cigar smoking as related to overall and specific causes of mortality was last reviewed in the 1973 report of The Health Consequences of Smoking (8). The combustion products of pipe and cigar smoke',. contain many of the same chemical compounds found in cigarette smoke condensate. Since pipe and cigar smokers are less likely to inhale than ciga- rette smokers, they experience much lower mortality from certain diseases strongly associated with cigarette smoking. These include lung cancer, ischemic heart disease, and chronic obstructive lung disease. They do have death rates that are virtually similar to those for cigarette smokers,-howaver, 'for cancers of the oral cavity, pharynx; larynx, and esvphagus. -- -- It should'not be inferred from the above that switching to a pipe or cigar will necessarily reduce the mortality risks experienced by a current cigarette smoker, particularly one who inhales. The reason for this is that a cigarette smoker who inhales would •p•robably, ' continue to inhale after switching (8). Lower risks for pipe and cigar smokers may be associated with the lower prevalence of inhalation among these smokers•and' not with less hazardous tobacco products. The U.S. Veterans Study contains the most detailed information concerning the mortality experience of pipe and cigar smokers. The mortality ratios 54

. I for both pipe and cigar smokers are predictably greater than those for non- smokers, and they are less than the mortality ratios of cigarette smokers (Table 15). Significant dose-response relationships were demonstrated for both pipe and cigar smokers by amount smoked and age began smoking. -- The mortality ratio for cigar smokers increased from 1.11 for those smoking 1-2 cigars pex~day to 1. 39 for•=those smoking nine or- mo=rC cigar§ per ~day '(-'fat3'le 16) . The mortality ratio was 1.13 for those who began smoking after the =' age of 25 and 1.22 for those who began smoking befiore -.~ the age of 15 (Table 17). Table 18 combines these variables and shows that the lowest mortality ratio for cigar-only smokers is 1.07 for those who smoked less than five cigars per day and began smoking after the age of 25. The highest mortality ratio of 1.28 was experienced by those who smoked more than five cigars per daq and begavg smoking~teferb~ the age of/25. Somewhat similar dose-response relationships were demonstrated for pipe- only smokers; however, the risk associated with pipe smoking is slightly less than that with cigar smoking-(Tab,les 19,20, and 21). The above discussion relates to those who have limited their lifetime smoking to cigars only or pipes only. Frequently, however, a smoker will have used tobacco in several different forms. For instance, a cigar smoker may be a former cigarette smoker and may occasionally smoke pipes. The C C.% U.S. Veterans Study contains data on the mortality ratios of individuals ~ W who use tobacco in various forms. These data have been arranged so that ~ GD N the various patterns of smoking are arranged by increasing risk of mortality. Table 22 shows the age-adjusted mortality ratios of current cigar smokers 55

. who have or are using pipes and/or cigarettes. Smoking cigarettes and cigars is more risky, and smoking pipes and cigars is less risky, than smoking cigars alone. The mortality experience of pipe smokers is shown in Table 23. Pipe smoking alone is the least hazardous form of smoking. The combination of pipes and cigars is a less risky combination than the combination of pipes and cigarettes. It is interesting to note that when the pipe smoker divides his smoking three ways and uses both cigarettes and cigars in addition to pipe smoking) the mortality ratio is less than if the time devoted to smoking is split two ways between pipes and cigarettes. Evidently to the extent that cigarettes are replaced there is a reduction in risk. The mortality ratios of current cigarette smokers who, have or are iasirng s o,xi cigars !ha ghown. in Tab.1e 24 , In the study of British doctors, Doll and Peto (1) reported that those who smoked only pipes or cigars experienced mortality rates which were similar to, or only slightly above, those of men who did not smoke at all. Pipe and cigar smokers who also used cigarettes had mortality ratios which were intermediate between those who only smoked pipes and cigars and those who smoked cigarettes. These figures are presented in Tab1e,25. 56

SUMMARY OF SMOKING AND OVERALL MORTALITY 1. Overall mortality rates for cigarette smokers are about 70 percent higher than those for nonsmokers. 2. Overall mortality risk increases with the amount smoked. For the two- pack-a-day cigarette smoker, the risk of premature death is approximately .twice that of the nonsmoker. 3. Overall mortality ratios of smokers compared to nonsmokers are highest -at earlier ages and decline with increasing age. For cigarette smokers, the risk of premature death is twice that of nonsmokers at age 40. 4. Overall mortality ratios are higher for those who begin smoking at -- a young age compared to those who begin later. For those who begin smoking before the age of 15,the risk of premature death is about 86 percent higher than that for nonsmokers. 5. Overall mortality ratios are higher for those smokers who inhale than for those who do not. There is about a 15 percent reduction in overall mortality risk for smokers of low "tar" and r.icotine cigarettes (less than 17.6 mg. "tar" and less than 1.2 mg. nicotine) compared to those who smoke high "tar" and nicotine cigarettes (25.8-35.7 mg. "tar" and 2.0-2.7 mg. nicotine). 7. Overall mortality rates of low "tar" and nicotine cigarette smokers are about 50 percent higher than for nonsmokers. 57

S 8. Overall mortality rates of former smokers decline as the number of years of cessation increase. After 15 years off cigarettes, death rates for former smokers are nearly identical to those of nonsmokers. 9. Overall mortality rates of former smokers are directly proportional to the number of cigarettes the person used to smoke. 10. Overall mortality rates of former smokers are inversely proportional to the age at which the person began smoking. 11. Regardless of length of time smoked or number of cigarettes smoked, former smokers have lower mortality rates than continuing smokers, provided they are not ill at the time of cessation. 12. Overall mortality ratios - ~ for cigar smokers are somewhat higher than for nonsmokers. The U.S. Veterans Study showed a mortality ratio of 1.16, compared to 1.0 for nonsmokers. The overall mortality ratio was 39 percent higher than the ratio in nonsmokers for men smoking nine or more cigars a day. A positive dose-response relationship exists between cigar smoking and mortality. 13. Overall mortality ratios for male cigar smokers are inversely proportional to the age at which the individual began smoking. 14. overall mortality ratios for pipe smokers are only slightly higher than for nonsmokers. The mortality ratio in the U.S. Veterans Study was 1.07. Overall mortality ratios were 21 percent higher than nonsmokers for men who smoked 20 or more pipefuls a day than for nonsmokers. O A positive dose-response relationship exists between pipe smoking and ~ mortality. W~ 58 ~ rA

I / 15. Overall mortality ratios of men who s,moke cigarettes in combination with pipes and/or cigars are intermediate between those who smoke pipes or cigars only and those who smoke cigarettes only. Cigarette smokers who also smoke cigars or pipes have overall mortality rates approximately 30 percent higher than nonsmokers. 59

. REFERENCES 1. DOLL, R., PETO, R. Mortality in relation to smoking: 20 years' observations on male British doctors. British Medical Journal 2(6051):1525-1536, December 25, 1976. 2. HAMMOND, E.C. Smoking in relation to the death rates of one million men and women. In: Haenszel, W., Editor. Epidemiological approaches to the study of cancer and other diseases. Bethesda, U.S. Public Health Service, National Cancer Institute Monograph 19, 1966, pp. 127-204. 3. HAMMOND, E.C., GARFINKEL, L., SEIDMAN, H., LEW, E.A. "Tar" and nicotine content of cigarette smoke in relation to death rates. Environmental Research 12(3):263-274, December 1976. 4. KAHN, H.A. The Dorn study of smoking and mortality among U.S. veterans: report on 8-1/2 years of observation. In: Haenszel, W., Editor, Epi- demiological approaches to the study of cancer and other diseases. Bethesda, U.S. Public Health Service, National Cancer Institute Mono- graph 19, 1966, pp. 1-125. 5. ROGOT, E. Smoking and general mortality among U.S. veterans 1954-1969. U.S. Department of Health, Education, and Welfare. Washington, D.C., DHEW Publication No. (NIH) 74-544, 65 pp. 6. U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. A Public Health Service Review: 1967. Washington, D.C., Public Health Service Publication No. 1696, 1967, pp. 7-17. 7. U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. 1968 Supplement to the 1967 Public Health Service Review. Washington, D.C., 1968 Supplement to Public Health Service Publication No. 1696, 1968, 117 pp. 8. U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, U.S. PUBLIC HEALTH SERVICE, HEALTH SERVICES AND MENTAL HEALTH ADMINISTRATION. The Health Consequences of Smoking, 1973. Washington, D.C., DHEW Publication No. (HSM) 73-8704, 1973, 249 pp. 9. U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, U.S. PUBLIC HEALTH SERVICE, CENTER FOR DISEASE CONTROL. Smoking and Health. Report of the Advisory Committee to the Surgeon General of the Public Health Service. Washington, D.C., Public Health Service Publication No. 1103,1964, 387 pp. 60

FIGURE 1.-Annual probability of dying for current cigarette smokers, ; ex-smokers who quit less than 5 years ago, and never ; smokers, ages 55-64 * I qx 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.9 0.8 a i 0 2 4 6 8 10 12 14 16 YEARS OF FOLLOW-UP > Never smokers *U. S. Veterans Study, 1954 cohort, 16-year follow-up. 61

FIGURE 2.-Annual probability of dying for current cigarette smokers„ qx 9.0 8.0 7.0 z 6.0 ~ 5.0 O J 4.0 Q H ~ 3.0 CD 0 o J 2.0 a o Q v D z z Q 1.0 0.9 0.8 ex-smokers who quit 5-9 years ago, and never ', smokers, ages 55-64 * ~ ommmno Current smokers --- Ex-smokers a Fi 0 2 4 6 8 10 12 14 16 YEARS OF FOLLOW-UP > Never smokers * U. S. Veterans Study, 1954 cohort, 16-year follow-up. 62

FIGURE 3.-Annual probability of dying for current cigarette smoicefs, ; ex-smokers who quit 10-14 years. ago, and never ~ smokers, ages 55-64 * I (9 z tl. W O J qx 9.0 8.0 7.0 6.0 5.0 4.0 ~. a F- U) 3.0 1.0 0.9 0.8 owm~o Current smokers M-- Ex-smokers ommmot> Never smokers 0 2 4 6 8 10 12 14 16 YEARS OF FOLLOW-UP 03'763G99 * U. S. Veterans Study, 1954 cohort, 16- year follow-up. 63

FIGURE 4.-Annual probability of dying for current cigarette smokers, ! ex-smokers who quit more than 15 years ago, and never; smokers, ages 55-64 * I qx 9.0 8.0 7.0 z 6.0 ~ 5.0 v, W OJ 4.0 F- U) 3.0 J a ° o^ 2.0 t o ~ ~e I / ; :D z 1.0 Q 0.9 0.8 C 0.1 A o~o Current smokers Ex-smokers Never smokers I 0 2 4 6 8 10 12 14 16 YEARS OF FOLLOW-UP U. S. Veterans Study, 1954 cohort, 16-year follow-up. 64

t .) ,, TABLE 1.- Age-adjusted mortality ratios for male cigarette smokers, by amount smoked, U.S. Veterans Study, 1954 cohort, 16-year follow-up Number of Cigarettes Smoked Mortality Per Day Ratio < 10 1.25 10-20 1.51 21-39 1.69 > 40 1.89 Nonsmokers 1.00 Total 1.55 TABLE 2.- Mortality ratios for cigarette smokers, by number of cigarettes smoked per day, British Doctors Study Number of Cigarettes Smoked Mortality Per Day Ratio Mixed (Cigarette & other) 1.21 1-14 1.41 15-24 1.57 > 25 2.16 Nonsmokers 1.00 Total 1.63 TABLE 3.- Mortality ratios for male cigarette smokers, by age and number of cigarettes smoked per day, U.S. Veterans Study, 1954 cohort, 16-year follow-up Number of Cigarettes Smoked Age Per Day 30-34 35-44 45-54 55-64 65-74 None 1.00 1.00 1.00 1.00 1.00 O < 10 1.94* 1.44 1.44 1.20 1.15 L; 10-20 1.27 1.79 1.64 1.49 1.30 ~ 21-39 1.76 2.23 2.10 1.67 1.42 ~ C.~ > 40 2.33** 2.72 2.13 1.86 1.65 ~ Total 1.52 1.95 1.83 1.53 1.32 O N *This which **This figure is why figure is it is calculated on the basis of 140 individuals and nine may appear to be somewhat unstable. calculated from 68 individuals and five deaths. deaths, 65

TABLE 4.- Age-adjusted mortality ratios for male cigarette smokers, by age began smoking, U.S. Veterans Study, 1954 cohort, 16-year follow-up Age Began Mortality Smoking (Years) Ratio < 15 1.86 15-19 1.64 20-24 1.51 > 25 1.32 Nonsmokers 1.00 Total 1.55 TABLE 5.- Age-adjusted mortality ratios for male cigarette smokers, by number of cigarettes smoked per day and age began smoking, U.S. Veterans Study, 1954 cohort, 16-year follow-up Number of Cigarettes Smoked Age Began Mortality Per Day Smoking (Years) Ratio < < > > 21 > 21 < 21 > 21 < 20 20 20 20 1.36 1.56 1.59 1.82 Nonsmokers --- 1.00 TABLE 6.- Mortality ratios for cigarette smokers, by inhalation practice, British Doctors Study Inhalation Practice Mortality Ratio Smokers Who Inhaled 1.43 Smokers Who Did'Not Inhale 1.28 Nonsmokers 1.00 66

TABLE 7.- Mortality ratios for all cigarette smokers in two time periods, by sex and "tar" and nicotine (T/N) content of cigarettes smoked* Mortalit~ Ratio Sex Period High T/N Medium T/N Low T/N Male 1 1.00 0.90 0.88 Male 2 1.00 0.98 0.81 Female 1 1.00 0.89 0.84 Female 2 1.00 0.87 0.82 Total 1.00 0.91 0.84 Source: Hammond E.C., et al. (3). *A matched-group analysis adjusted for several factors. See text. TABLE 8.- Mortality ratios for smokers of low "tar" and nicotine-(T/N).cigarettes and nonsmokers in two time periods, by sex Mortality Ratio Sex Period Low T/N Nonsmokers Male 1 1.00 0.57 Male 2 1.00 0.64 Female 1 1.00 0.76 Female 2 1.00 0.71 Total 1.00 0.66 Source: Hammond E.C., et al. (3). *A matched-group analysis adjusted for several factors. See text. TABLE 9.- Mortality ratios for all cigarette smokers and nonsmokers in two time periods, by sex and "tar" and nicotine (T/N) content of cigarettes smoked Mortality Ratio Non- Low Medium High Sex Period Smokers T/N T/N T/N Male 1 1.00 1.75 1.80 2.00 Male 2 1.00 1.56 1.89 1.92 Female 1 1.00 1.32 1.40 1.57 Female 2 1.00 1.41 1.49 1.73 Total 1.00 1.52 1.64 1.80 O G: Source: Hammond E.C., et al. (3) Q Q: 67 W ~ O W

TABLE 10.- Mortality ratios for ex-smokers who quit smoking on doctor's orders--• and for other reasons, by years since stopping-, U.S, Veterans Study, 1954 cohort, 16-year follow-up Mortality Ratio Years Since Stopping Quit on Doctor's Orders Quit for Other Reasons < 5 1.55 1.23 5-9 1.43 1.23 10-14 1.77 1.14 15-19 1.35 1.04 > 20 1.16 1.06 Total 1.52 1.18 TABLE 11.- Mortality ratios for ex-smokers who quit smoking on doctor's orders and for other reasons, by number of cigarettes smoked per day, U.S. Veterans Study, 1954 cohort, 16-year follow-up Mortality Ratio Number of Cigarettes Smoked Per Day Quit on Doctor's Orders Quit for Other Reasons < 10 1.42 1.00 10-20 1.48 1.17 21-39 1.53 1.30 > 40 1.60 1.32 Total 1.52 1.18 TABLE 12.- Mortality ratios for ex-smokers who quit smoking on doctor's orders and for other reasons, by age began smoking, U.S. Veterans Study, 1954 cohort, 16-year follow-up Mortality Ratio Quit on Quit for Age Began Smoking (Years) Doctor's Orders Other Reasons < 15 1.59 1.36 15-19 1.55 1.20 20-24 49 1 12 1 0 > 25 . 34 1 . 1 15 G: 'z . . a: Total 1.52 1.18 W ` O .01 68

. vj .> TABLE 13.- Mortality ratios for ex-smokers of cigarettes only, by years since stopping, number of cigarettes smoked per day, and age began smoking, U.S. Veterans Study, 1954 cohort, 16-year follow-up Years Number of Since Cigarettes Smoked Age Began Mortality Stopping Per Day Smoking (Years) Ratio < < < < > > > > 10 10 10 10 10 10 10 10 > 21 < > 21 > < 21 < < 21 > > 21 < > 21 > < 21 < < 21 > 20 20 20 20 20 20 20 20 1.45 1.27 1.21 1.12 1.19 1.07 1.08 1.03 Nonsmokers 1.00 Total 1.18 TABLE 14.- Mortality ratios for ex-smokers compared to nonsmokers, by number of years since stopping and age, British Doctors Study Years Mortality Ratio Since Age Age All Stopping 30-64 >65 Ages 0* 2.0 1.6 1.8 1-4 1.7 1.4 1.5 5-9 1.6 1.4 1.5 10-14 1.4 1.2 1.3 >15 1.1 1.1 1.1 Nonsmokers 1.0 1.0 1.0 *Current Smokers 69

( TABLE 15.- Age-adjusted mortality ratios for pipe-only, cigar-only, and cigarette-only smokers, U.S. Veterans Study, 1954 cohort, 16- year follow-up Type of Mortality Tobacco Ratio Pipe Only 1.07 Cigar Only 1.16 Cigarettes Only 1.55 Nonsmokers 1.00 TABLE 16.- Age-adjusted mortality ratios for current cigar smokers, by number of cigars smoked per day, U.S. Veterans Study, 1954 cohort, 16-year follow-up Number of Cigars Smoked Per Day Mortality Ratio 1-2 1.11 3-4 1.13 5-8 1.22 > 9 1.39 Nonsmokers 1.00 Total 1.16 TABLE 17.- Age adjusted mortality ratios for current cigar smokers, by age began smoking, U.S. Veterans Study, 1954 cohort, 16-year follow-up Age Began Smoking (Years) Mortality Ratio <15 1.22 15-19 1.23 20-24 1.16 >25 1.13 Nonsmokers 1.00 Total 1.16 70 M

a TABLE 18.- Age-adjusted mortality ratios for current cigar smokers, by number of cigars smoked per day and age began smoking, U.S. VeteranG Sturiy, 1954 cohort. 16-vear follow-uo Number of Cigars Smoked Per Day Age Began Smoking (Years) Mortality Ratio <5 >25 1.07 <5 <25 1.16 >5 >25 1.28 >5 <25 1.23 Nonsmokers 1.00 Total 1.16 TABLE 19.- Age-adjusted mortality ratios for current pipe smnkerc, by number of pipefuls smoked per day, U.S. Veterans Studv, 1954 cohort, 16-vear follow-up Number of Pipefuls Smoked Per Day Mortality Ratio <5 0.93 5-9 1.12 10-19 1.08 >20 1.21 Nonsmokers 1.00 Total 1.07 TABLE 20.- Age-adjusted mortality ratios for current pipe smokers, by age began smoking, U.S. Veterans Study, 1954 cohort. 16-vear follow-uo Age Began Smoking (Years) Mortality Ratio <15 1.04 15-19 1.12 20-24 1.06 >25 1.06 Nonsmokers 1.00 Total 1.07 O W ~ ~ 71 W ~

TABLE 21.- Age-adjusted mortality ratios for current pipe smokers, by number of pipefuls smoked per day and age began smoking, U.S. Veterans Study, 1954 cohort, 16-year follow-up Number of Pipefuls Smoked Per Day Age Began Smoking (Years) Mortality Ratio <10 >25 1.03 <10 <25 1.05 >10 >25 1.12 >10 <25 1.12 Total 1.07 TABLE 22.- Age-adjusted mortality ratios for current cigar smokers, by use of other types of tobacco, U.S. Veterans Study, 1954 cohort, 16-year follow-up Type of Tobacco Used Cigarettes Pipes Mortality Ratio Never Never 1.16 Never Current 1.10 Never Former 1.10 Former Former 1.10 Former Current 1.13 Former Never 1.23 Current Current 1.21 Current Never 1.30 Current Former 1.33 TABLE 23.- Age-adjusted mortality ratios for current pipe smokers, by use of other types of tobacco, U.S. Veterans Study, 1954 cohort, 16-year follow-up Type of Tobacco Used Cigarettes Cigars Mortality Ratio Never Never 1.07 Never Current 1.10 Never Former 1.11 Former ._ Former 1.14 O Former Current 1.14 W Former Never 1.10 ~ Current Current 1.21 W Current Never 1.28 ~ Current Former 1.36 O ~ 72

,TABLE 24.-'Age-adjusted mortality ratios for current cigarette smokers, by use follow-up of other types of tobacco, U.S. Veterans Study, 1954 cohort, 16-year : Type of Tobacco Used Cigars Never Never Never Former _ Former Former Current Current Current Pipes Mortality Ratio Never 1.55 Current 1.28 Former 1.47 Former 1.48 Current 1.36 Never 1.53 Current 1.21 Never 1.30 Former 1.33 TABLE 25.- Age-adjusted mortality ratios for all smokers, British Doctors Study Type of - Mortality Pipe or Cigar Never Cigarettes 1.09 Pipe or Cigar and Cigarettes 1.31 Tobacco Used Ratio Cigarettes Only 1.73 Nonsmokers 1.00 73