TABLE %-Percent of persons 17 years old and older, who perceive their health to be "excellent," by cigarette smoking status, sex, and age: United States, 1974 Sex and age TOt2.1 Present Former Never smoker smoker smoked 17+ 174 454 65+ 17+ 17-44 45-64 65+ 17+ 1744 4.544 65+ Both Sexes 42.7 51.3 34.0 27.1 Male 46.8 56.7 36.9 25.5 39.0 33.7 41.2 33.7 46.3 42.0 49.2 43.7 31.3 33.0 34.1 23.9 28.3 32.4 29.3 21.7 41.5 47.1 32.6 24.7 44.1 52.9 32.3 19.2 43.0 55.4 36.7 26.5 44.0 59.9 36.0 25.4 42.8 53.1 32.0 28.2 52.0 60.8 40.9 30.0 SOURCE: Wilson. R.W. (16). been analyzed to determine if this increased hospitalization is for diseases usually associated with smoking.1 While smokers tended to report more hospitalizations than did persons who had never smoked, there was no tendency for smokers to report more frequent visits to physicians than those who had never smoked, although former cigarette smokers reported the largest proportion with five or more physician visits during the past year (Table 10). Respondents in the 1974 Health Interview Survey were also asked whether they had ever tried to quit smoking, whether a doctor had advised them to quit, and whether they had been advised to quit because of specific health conditions. Just under a quarter of all persons who had ever smoked reported that they had been advised by a doctor at one time or another to stop smoking (Table 11). Surprisingly, at least from a public health point of view, at those ages at which the effects of smoking often begin to manifest themselves, 45 to 64, less than one-third of the smokers reported that they had been advised by their physicians to stop smoking. This would appear to indicate a need `There are many types of analyses that wuld be performed on these data that have not been done became of differing priorities and Ia& of resources. Fw example, one inter&ing ar?.a of investigation that wan begun, but not mmpleted beeawe of the apparent complexities of the issue. in the relationship between cigarette smoking, he&b "titi&, and weight. However, NCHS doa make available to researchers public-use data tapes from the various s"~eyS, 80 that they can conduct their own snaly3es (la). 3-15 TABLE 9.-Percent of persons 17 years old and older, with one or more hospital episodes in the year prior to interview, by cigarette smoking status, sex, and age: United States 1974 Sex and age Both sexes Total Present Former smoker smoker Never smoked 17+ 1744 4.544 65+ Male 13.1 13.5 14.4 127 12.3 13.8 11.7 120 12.9 12.3 15.1 l2.1 16.5 16.5 19.7 15.3 17+ 10.2 10.5 ml 8.3 1744 7.0 8.6 8.0 5.3 4M4 13.1 12.4 14.5 125 El+ 17.4 19.0 18.5 14.9 17+ 15.7 16.9 17.5 14.7 17-44 17.2 19.5 16.8 15.9 4&64 12.8 12.3 16.2 X2.0 65+ 15.8 129 23.1 15.4 SOURCE: Wilmn. R.W. (16). not only for increased public education, but also for increased educational programs among health professionals. About two-thirds of all present smokers had tried to stop smoking at some time (Table 12). Since detailed smoking history information was not obtained, it is difficult with these data to determine the more precise relationships between illness, physicians' advice to stop smoking, and actual attempts to stop. Some of the studies conducted in the past by the National Clearinghouse for Smoking and Health and reported elsewhere in this report have attempted to investigate these relation- ships as well as some of the more attitudinal and psychological aspects of smoking. Respondents to the Health Interview Survey were asked if a doctor had ever told them they had heart trouble. Among persons under 65 years of age, a larger proportion of both present smokers and former smokers had been told that they had heart trouble compared with persons who had never smoked (Table 13). For example, 15 percent of the male former smokers aged 45 to 64 had been told they had heart trouble compared to 10 percent of those who had never smoked. There is some difficulty interpreting the data for persons over 65 years old, where a higher proportion of those who had never smoked report heart 3-16 TABLE lO.-Percent of persons 17 years old and older, with five or more physician visits in the year prior to interview, by cigarette smoking status, sex, and age: United States, 1974 Sex and age Total Present smoker Former smoker Nl?V6T smoked Both sexes 17+ 17-44 4544 65+ 24.8 23.7 27.0 26.1 22.0 23.0 23.4 a.3 25.5 24.3 26.4 272 34.2 27.0 37.1 34.9 Male 17+ 17.9 16.9 22.9 17.3 17-44 13.4 14.1 16.1 13.1 4544 21.3 20.7 24.1 20.8 65+ 30.2 24.8 33.5 39.4 Female 17+ 30.8 31.3 34.5 30.0 17-44 29.9 32.9 33.5 27.6 45-64 29.2 28.3 31.1 29.4 65+ 37.0 30.1 46.8 36.3 SOURCE: W'ilmn. R.W. (16). trouble, since many of the smokers with heart trouble have already died. Of those smokers who have been advised by a doctor to stop, about 28 percent were advised to stop because of respiratory disease. About 23 percent of the smokers 65 and older were advised to stop because of circulatory problems, but this proportion drops for the younger smokers. Hardly any smokers reported they were advised to stop because of cancer. However, these data on cancer are also misleading; since the survival rate for lung cancer is relatively low, many smokers would not live long enough to report that the doctor had told them to stop smoking. The first cycle of the Health and Nutrition Examination Survey contained a number of questions that, when combined, formed an Index of General Psychological Well-Being.2 This measure provides data on another dimension of the relationship between cigarette smoking and health. In general, current cigarette smokers were found ' The Index of General Psychological Well-Being ia compcmed of 18 items with a total of 128 response optiona. The "%`JnSe Option for each item that indicates the greatest diitrea is scored zero. Some of the items and their response V-iOM &o permit representations of high-level positive well-being. The total index area rangv from 0 thou 110. ritb low acres indicating diatregl and high area indicating positive well-being. Gaerelly positive affect is mhd by acorn above 78 and marginal well-being by scared of 73 to 77. The median more for the population `=`hte. Of adults, 25 to 74 yearn old, was between 83 and 84 (3). 3-17 TABLE Il.-Percent of persons 17 years old and older who have ever smoked and who were ever advised by a physician to stop smoking, by smoking status, sex, and age: United States 1974 Smoking status All ages and sex 17+ 17-44 45-m 65+ Total ever smoked Both sexes Male Female Former smoker 23.9 19.6 292 30.1 23.5 17.8 29.2 32.4 24.4 21.8 29.2 25.3 Both sexes 21.3 14.2 26.3 28.2 Male 22.7 13.5 23.0 29.6 Female 18.9 15.0 22.6 24.2 Present smoker Both sexes 25.2 21.5 31.1 32.6 Male 24.0 19.4 39.2 37.0 Female 26.6 23.9 32.1 262 SOURCE: Wilma, RW. (16). TABLE 12.-Percent of present cigarette smokers 17 years old and older who have tried to stop smoking, by sex and age: United States, 1974 sex All ages 17 1744 4s64 65+ Both sexes 64.7 66.0 62.8 61.1 Male 66.0 66.7 65.1 63.3 Female 63.3 65.3 69.2 57.9 SOURCE: Wilson. R.W. (16). to have a slightly lower level of well-being than were nonsmokers. Heavy smokers (more than 1 l/2 packs a day) under 65 years of age report the lowest levels of general well-being and report mean levels of general well-being at marginal levels or lower. Conclusions The available evidence in the relationship between cigarette smoking and illness and disability has increased markedly since the first 3-18 TABLE lh-Percent of persons 17 years old and older who have been told by a doctor that they had heart trouble, by cigarette smoking status, sex, and age: United states, 1974 Sex and age Both sexes Total Present Former smoker smoker Never smoked 17+ 9.0 7.8 12.9 9.4 1744 4.2 4.3 4.7 4.1 45-64 11.1 11.6 14.9 9.9 65+ 22.9 17.9 28.5 23.3 11+ 8.9 8.2 13.8 8.4 17-44 3.8 4.5 4.7 3.6 4544 12.0 13.0 15.2 10.0 65+ 24.5 18.6 28.5 26.5 Female 17+ 9.0 7.4 11.4 9.9 1744 4.6 5.1 4.9 4.4 45-64 10.3 10.0 14.3 9.9 65+ 21.8 16.8 23.5 22.4 SOURCE: Wilson, R.W. (26). Surgeon General's report was issued, largely as a result of data collected from national probability surveys conducted by NCHS. These data range from the standard health indicators, such as measures of chronic and acute illness and measures of disability days, to less commonly used indicators of lifestyles. The results of analysis performed on these data vary from the more frequently reported findings on disability to data from the Index of General Psychological Well-Being, first reported in this chapter. The findings tend to be consistent with the large amount of evidence on the relationship between cigarette smoking and mortality, i.e., people who smoke cigarettes report more illness and disability than people who have never smoked cigarettes. While many studies show a reduction in the risk of mortality among former cigarette smokers, data on disability and illness often show continued high risk for former smokers, indicating both a lack of refinement in the current data to distinguish between types of former smokers as well as the fact that Once certain diseases occur they do not go away. The most important aspect of these data collected by NCHS lies not iu the substantive analysis prepared by the NCHS staff, but in the 3-1s analytic potential of the data to other researchers in the smoking area through the use of NCHS's public-use data tape program. 3-20 Morbidity: References (1) AHMED, PI., GLEESON, G.A. Changes in Cigarette Smoking Habits Between 1955 and 1966. U.S. Department of Health, Education, and Welfare, Public Health Service, Health Services and Mental Health Administration, National Center for Health Statistics, Series 10, No. 59, PHS Publication No. 1900, April 1970,33 pp. (2) BELLOC, N.B. Relationship of health practices and mortality. Preventive Medicine 2: 6%81,1973. (5) FAZIO, A.F. A Concurrent Validational Study of the NCHS General Well-Being Schedule. U.S. Department of Health, Education, and Welfare, Public Health Service, Health Resources Administration, National Center for Health Statistics, Series 2, No. 73, DHEW Publication No. (HRA) 78-1347, September 1977,53 pp. (4) HAENSZEL, W., SHIMKIM, M.B., MILLER, H.P. Tobacco Smoking Patterns in the United States. Public Health Monograph No. 45. U.S. Department of Health, Education, and Welfare, Public Health Service, PHS Publication No. 463,1956,111 pp. (5) HAMMOND, E.C. Smoking in relation to death rates of one million men and women. In: Haenszel, W. (Editor). Epidemiological Approaches to the Study of Cancer and Other Chronic Diseases. National Cancer Institute Monograph No. 19. U.S. Department of Health, Education, and Welfare, Public Health Serviw, National Cancer Institute, January 1966, pp. 127-204. (6) HAMMOND, EC., HORN, D. Smoking and death rates - Report on 44 months of follow-up of 187,783 men. Journal of the American Medical Association X6(10): 1159-1172,1958. (;) MADOW, W.G. Net Differences in Interview Data on Chronic Conditions and Information Derived From Medical Records. U.S. Department of Health, Education, and Welfare, Public Health Service, Health Services and Mental Health Administration, National Center for Health Statistics, Series 2, No. 57, DHEW Publication No. (HSM) 73-1331, June 1973,58 pp. (8) MILLER, H.W. Plan and Operation of the Health and Nutrition Examination Survey: United States, 1971-1973. U.S. Department of Health, Education, and Welfare, Public Health Service, Health Resources Administration, National Center for Health Statistics, Series 1, Nos. lOa, lob, DHEW Publication No. (HSM) 73-1310, February 1973,123 pp. (5) MOSS, A.J., SCOTT, G. Characteristics of Persons with Hypertension: United States, 1974. U.S. Department of Health, Education, and Welfare, Public Health Service, National Center for Health Statistics, Series 10, No. 121, DHEW Publication No. (PHS) 79-1519,197s. (In press) (IO) NATIONAL CENTER FOR HEALTH STATISTICS. Cigarette smoking: United States, 1970. U.S. Department of Health, Education, and Welfare, Public Health Service, Health Services and Mental Health Administration, National Center for Health Statistics. Monthly Vital Statistics Report 21(3)(Supplement), June 2,1972,8 pp. (11) NATIONAL CENTER FOR HEALTH STATISTICS. Health, United States, 19761977. U.S. Department of Health, Education, and Welfare, Public Health Service, Health Resources Administration, National Center for Health Statistics, National Center for Health Services Research, DHEW Publication No. (HRA) 77-l232,1977,441 pp. (l2) NATIONAL CENTER FOR HEALTH STATISTICS. Standardized Micro-Data Tape Transcripts. U.S. Department of Health, Education, and Welfare, Public Health Service, National Center for Health Statistics, DHEW Publication No. (PHS) 78-1213, June 1978,36 pp. 3-21 (IS) NATIONAL CLEARINGHOUSE FOR SMOKING AND HEALTH. Smoking and Illness. U.S. Department of Health, Education, and Welfare, Public Health Service, Bureau of Disease Prevention and Environmental Control, National Center for Chronic Disease Control, National Clearinghouse for Smoking and Health, PHS Publication No. 1662, July 1367,6 pp. (14) WILSON R.W. Cigarette Smoking and Health Characteristics United States, July 1964-June 1965. U.S. Department of Health, Education, and Welfare, Public Health Service, National Center for Health Statistics, Series 10, No. 34, PHS Publication No. 1600, May 1967,64 pp. (15) WILSON R.W. Cigarette smoking, disability days and respiratory condition. Journal of Occupational Medicine X(3): 236246, March 1973. (16) WILSON R.W. Testimony presented at Regional Forum sponsored by the National Commission for Smoking and Public Policy. Philadelphia, June 16, 1977,27 pp. 3-22 4. CARDIOVASCULAR DISEASES. - National Heart, Lung, and Blood Institute CONTENTS Atherosclerosis ............................................................ `7 The Nature of Atherosclerosis in Man.. ................... `7 The Effect of Smoking on Atherogenesis.. .............. 10 Experiments in Animals ................ . ...................... 16 Research Needs ................................................... 18 Conclusions ......................................................... 19 Myocardial Infarction .................................................. 19 The Nature of Myocardial Infarction.. .................... 19 Summary of Epidemiological Data ........................ .20 The Effect of Smoking on Myocardial Infarction in Man.. ........................................ L .. 38 The Effect of Smoking on Myocardial Infarction in Animals.. ..................................... .40 Research Needs .................................................. .40 Conclusions.........................................................4 1 Sudden Cardiac Death .............................................. .41 The Nature of Sudden Cardiac Death in Man.. ....... .41 Sudden Cardiac Death in Animals.. ....................... .43 Summary of Epidemiological Data ........................ .43 The Effect of Smoking on Sudden Cardiac Death in Man.. ............................................... .44 The Effect of Smoking on Sudden Cardiac `Death in Animals.. .......................................... .45 Research Needs .................................................. .45 Conclusions ........................................................ .45 Angina Pectoris ....................................................... .46 The Nature of Angina Pectoris in Humans ............ .46 Summary of Epidemiological Data ........................ .46 The Effect of Smoking on Angina Pectoris.. .......... .48 Research Needs .................................................. .48 Conclusions ........................................................ .49 Cerebrovascular Disease ............................................. .49 The Nature of Cerebrovascular Disease in Man.. ..... .49 Summary of Epidemiological Data ........................ .50 The Effect of Smoking on Cerebrovascular Disease . .50 4-3 Research Needs .................................................. .52 Conclusions ........................................................ .52 Peripheral Vascular Disease ....................................... .52 The Nature of Peripheral Vascular Disease in Man . .52 Summary of Epidemiological Data ........................ .53 The Effect of Smoking on Peripheral Vascular Disease ............................................. .53 Research Needs.. ................................................ .54 Conclusions ........................................................ .54 Aortic Aneurysm of Atherosclerotic Type.. ................... .55 The Nature of Atherosclerotic Aortic Aneurysm ...... .55 Summary of Epidemiological Data ........................ .55 The Effect of Smoking on Aortic Aneurysm.. ......... .56 Research Needs .................................................. .56 Conclusions ........................................................ .56 High Blood Pressure ................................................. .56 The Nature of Hypertension ................................ .56 Summary of Epidemiological Data ........................ .57 The Effect of Smoking on Blood Pressure ............. .58 Research Needs .................................................. .58 Conclusions ........................................................ .58 Other Conditions ...................................................... .58 Venous Thrombosis.. ........................................... .59 Thromboangiitis Obliterans (Buerger's Disease). ....... .66 Oral Contraceptives, Smoking, Myocardial Infarction, and Subarachnoid Hemorrhage Among Women ..... .66 The Effect of Smoking on Blood Lipids.. ............... .61 Other Constitutents of Smoke .............................. .62 Discussion and Conclusions.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 LIST OF TABLES Table l.-Autopsy studies of atheroclerosis.. . . . . . . . . . . . . . . . . . . 11 4-4 Table 2.-Coronary heart disease mortality ratios related to smoking-prospective studies.. . . . . . . . . . . . . . . . . . . . .22 Table 3.-Coronary heart disease morbidity as related to smoking.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .27 Table 4.-The effect of the cessation of cigarette smoking on the incidence of CHI?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 Table 5.-Annual probability of death from coronary heart disease, in current and discontinued smokers, by age, maximum amount smoked, and age started smoking.... 35 Table 6.-Coronary heart disease morbidity as related to smoking-angina pectoris-prospective studies.. . . . . . . . . . . .47 Table `7.-Age-standardized death rates and mortality ratios for cerebral vascular lesions for men and women, by type of smoking (lifetime history) and age at start of study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 4-5 Atherosclerosis Most studies of the pathology of atherosclerosis have been based on autopsies of coroner's or hospital populations in which only a limited fraction of decedents have been examined. They have been valuable for an understanding of the pathogenesis and complications of atherosclerosis. Such studies cannot be taken to represent the prevalence of atherosclerosis in the general population. Studies which attempt to minimize selection bias at autopsy by examining the great majority of decedents in a defined population are rare (66,114). The most extensive and comprehensive autopsy study that has been conducted is the International Atherosclerosis Project, which collected data from 15 cities in 14 countries and recorded more than 21,000 autopsies according to a standardized protocol and method of evaluation (85). The study found a remarkably frequent occurrence of atherosclerotic lesions in the United States; detailed international or geographic differences in the severity of atherosclerosis; raised the issue of whether childhood atherosclerosis evolves into adult forms of atherosclerosis; and documented that, on the average, there are more frequent and extensive coronary plaques in cases with coronary heart disease than in comparison cases regardless of age, sex, geographic location, or race. Approximately the same prevalence and extent of advanced atherosclerosis were seen in coronary heart disease cases regardless of age, sex, and, with few exceptions, of geographic location. While individuals may show considerable variability in the severity of atherosclerosis, the conclusion is that coronary atherosclero- sis is of primary importance in the development of coronary heart disease in a population (133). Another extensive study in five towns in Europe has been reported by the World Health Organization (WHO) ( W. The Nature of Atherosclerosis in Man Information about atherosclerosis in man derives from pathological studies and from associations observed in clinical or epidemiological studies. The lesion or plaque is a cellular proliferation in the arterial intima. It contains chiefly smooth muscle cells, but also fibrocytes and cells typical of chronic inflammation. Lipid is commonly present along with cehlar products such as collagen, elastic tissue, glycosaminoglycans, and cellular debris from necrosis. Elements of thrombus are common both in and on the plaque. Focal calcification is frequent. Thus, a highly variable and complex range of lesions can be considered under the term atherosclerosis. The concept of the development of lesions is a synthetic one derived from the observation of many lesions rather than from the actual observation of a single lesion over time. At present, there is 4-7 controversy over whether the fatty streaks seen in childhood are the precursors of the more fibrous, raised, and complex adult lesions, or whether some or many adult lesions arise independently of fatty streaks (which also occur in adult life) (89). The usual prevalence of atherosclerotic lesions in adult life is such that the aorta and carotid arteries are affected about a decade before the coronary arteries and cerebral arteries, and the latter are affected a decade in advance of the arteries of the leg. However, such relationships are not constant; individual variations are common and, indeed, specific clinical syn- dromes of localized atherosclerosis are recognized. Atherosclerotic plaques distort and narrow the calibre of the affected arteries. This reduces the flow of blood through them and creates the condition called ischemia. When &hernia becomes severe, the organs and tissues deprived of blood no longer function properly and clinical disease occurs in the form of coronary heart disease, stroke, or peripheral vascular disease. The occurrence of severe &hernia may arise because of the enlargement of plaques, or it may be precipitated by the development of thrombosis (clot) on plaques, or by other complications that can affect them. The various diseases resulting from &hernia are considered subsequently in this chapter. Conditions that predispose to the onset of disease in the future, increasing the risk of its occurrence, are spoken of as "risk factors". The concept of risk factors arose from clinical experience with cardiovascular disease, particularly coronary heart disease, rather than with atherosclerosis itself. Prospective population studies such as those considered in the Pooling Project (107) further developed the predictive value of selected factors such as cigarette smoking and levels of blood pressure and cholesterol. Risk factor associations for atherosclerosis as distinct from coronary heart disease are limited in their documentation. The International Atherosclerosis Project (85), dealing with autopsy data, concluded that the severity of atherosclerosis is closely associated with the proportion of total calories derived from saturated fat in the diet of the population, with the serum cholesterol levels measured in the population, and with hypertension. The association with smoking was not examined. The WHO (66) study documented the association of a number of disease states and conditions with the extent and severity of atherosclerosis. A recent report has described the associations between several variables measured during life and the extent of atherosclero sis of the aorta and coronary arteries seen at autopsy in Japanese- Americans participating in a prospective cardiovascular risk factor study (11.2). Statistically independent associations were found by multivariate analysis between aortic atherosclerosis and age at death, cigarettes smoked per day, serum cholesterol concentration, and blood pressure level. Coronary atherosclerosis was related to relative body 4-g weight, cigarettes smoked per day, and serum cholesterol concentra- tion. Models of experimental atherosclerosis in species as different as birds, rodents, dogs, swine, and nonhuman primates have been developed. The majority of these models have been induced by feeding saturated fat or cholesterol leading to fat-rich plaques that resemble the fatty streaks of childhood or the very fat-laden plaques occasional- ly seen in adult life, Other experimental techniques of inducing lesions are: the use of physical injury to arteries leading to acute proliferative plaque development with little or no hpid accumulation; the induction of intimal thrombi with their tissue organization yielding fibro-fatty plaques; immunologic vascular injury with lipid or cholesterol feeding; and, recently (in chickens), viral infection. Among different species of nonhuman primates, the same dietary regimen will produce character- istically a somewhat different distribution of plaques in the arterial tree. Different experimental diets will produce lesions that are characteristically more fatty or more fibrous. Spontaneous fibrous or fibro-fatty plaques occur in many species including birds, rabbits, swine, and nonhuman primates. The enhancement of spontaneous atherogenesis in chickens by polycyclic hydrocarbons has been reported (1). A strong genetic control exists in pigeons both for the expression of experimental atherosclerosis and for its localization predominantly either in the aorta or in the coronary arteries. Thus, there is a wide variety of experimental and spontaneous animal models available with which to study atherogenesis. A huge body of literature deals with the pathogenesis of human and experimental atherosclerosis. Several recent reviews provide a detailed and critical consideration of current concepts (3,21,22,84,89, 117,119,126,155,156). The various interrelationships of different patho- genetic processes such as cellular proliferation, lipid accumulation, and thrombotic phenomena are not fully understood. Nevertheless, it is Possible to synthesize available data into a frequently explored major working hypothesis of the initial stages of atherogenesis based on extensive experimental data (see particularly 117,155,156) that support the Pathogenetic concept that the arterial endothelium functions normally to separate the intima and media from the blood. The hypothesis holds that local injury results in failure of this barrier function or in loss of endothelial cells and exposure of the subendothe- hum to whole plasma and to blood platelets. Platelets and plasma contain growth factors capable of inducing smooth muscle cells in the mtima and adjacent media to multiply. This loss of barrier function also allows macromolecules such as fibrinogen and very low density (VLDL), intermediate, low density (LDL), and high density (HDL) liPoProteins freer access to the vessel wall. More lipid is internalized by intimal smooth muscle cells and macrophages than their lysosomal digestive systems can catabolize, and they become overloaded with fat 4-9 and cholesterol. The amount of sterol externalized metabolically by such cells may exceed the local capacity of HDL to accept and transport it away. Cellular necrosis occurs and both intracellular and structural lipids spill into the extracellular compartment of the intima where they contribute to the lipid burden. The sequence in this hypothesis is endothelial injury, impaired barrier function, and subendothelial exposure to plasma and to platelets, followed by cellular metabolic overload, failed homeostasis, cellular proliferation, and necrosis. In addition, the stigmata of mild chronic inflammation occur promptly, and appearances suggestive of a migration of smooth muscle cells to the lesion are seen. Local cellular production of glycosaminogly- cans, collagens, and elastin follows. Progression of the lesions can be through a continuation or cyclical repetitions of the same processes or by thrombosis. Thrombosis, necrosis, calcification, hemorrhage, and ulceration may further complicate the lesion. A large number of agents are suspected to be capable of injuring endothelium and altering its barrier function. It should be noted that the foregoing views are derived from animal experimentation but appear to be congruent with the nature of atherosclerosis in humans. A novel theory of atherogenesis has been proposed recently that does not necessarily contradict the concepts stated above, but which designates a prior abnormality of the smooth muscle cells that proliferate to form plaques. It has been found that the cells that constitute individual fibrous atherosclerotic plaques in adults are homogenous for an isoenzyme marker. That is, each plaque must either be monoclonal or initially polyclonal with the development of a monotypic character as it has developed (21, 22, 104, 105, 135). If the correct interpretation is that plaques are monoclonal, it is necessary to consider whether this represents a mutation or transformation of vascular cells leading to a local proliferation analogous to benign smooth muscle cell neoplasia. In this view, environmental agents capable of inducing somatic cell mutation, including mutagens derived from tobacco, could be fundamental to the pathogenesis of atheroscle- rotic plaques, and might cause the primary cellular changes facilitating other conventional risk factors or agents to produce lesions in man. At the present time, data to settle the validity of these interpretations are not available. The Effect of Smoking on Atherogeneais Autopsy studies in which smoking behavior has been recorded are not common. Table 19 (pp. 49-51) of the 1976 reference edition of the report, The Health Consequences of Smoking (138), lists several investigations into this aspect of smoking. This table is reproduced below as Table 1. These investigations compare, within their particular group of study cases, smokers with nonsmokers and different levels of smoking, 4-10 TABLE l.-Autopsy studies of atherosclerosis. (Figures in parentheses are number of individuals in that smoking category)1 [SM = smokers NS = nonsmokers] Wilern and Plair. Mz L' S.A 989 consecutive male autopsies at New York City VA hospitals. s?verity of aort,r rlemis The authors conclude that Ahove averagt: AMXp Lklow awragp in 60 @mnt of caws. the NS. 9.9(X1) 60.2 29.8 degree of ~elems~~ at `#I Uw4) 18.1 35.4 45.9 The authors mncludc that the percentqe of men with an advanced degrre of coronary athemeekmnir was higher among EIR" mtk smokere than among nonsmokers and that the percentage "Creased with amount of cigarette smoking. This relrtion- ship plrJisted even when eases were matched for a(p and cause of death. Avtandilov. wk Russia 259 mate and 141 female autopsies. Not spwihed. hut then welt. 180 SM and 220 NS Comparative size of mean area of athemxlemtic legions in inner mat of wonmy arteries. Right mromuy tiry Left coronary artery SM NS SM NS 3&3!. t15.5@w 1.3(32) t6.3 22 4%49 Kww 11.X27) t15.g 4.4 5&59 t36.3(39j 14.8@9) tn.9 9.9 6iM9 t31.9w ZWW t26.5 a5 7079 41.9(18) X1(36) 26.1 35.8 The author concludes that the war-at changes WR found in the left and right mmnary arteries with lea were chanp in circumflex artery and aorta. Causes of death 96athem &rote, 1~accidental. 202-various di-. tT-tat for signifiince of difference between means is significant at p