B&B lmpormikreom ImAmE MAmAscmEmT 300 "#"CZ M=Ituclls aou&XVARD Ulmosca M.%"Lnovto, M.%w emo Z0772 0 USA tac 1) 24@ 1 1 0 P R-F T 1 C@',,! 0-F ITL- AT-,,i RDSI-__ -,OILIC Position Paper for the ):NTER-SOCI@ cO',%t%IISSIO"' FOR HEART DISEASE PLE '"'CURCF S Prep3red by the Atherosclerosis S@Ltidv GROUD -Chairman: Jeremiah Qtamler, M.D.' MeiTibers: Rodney R. Beard, M.D. William E. Co-,i nor, M.D. Victor G. deWol'Lce, @vi.D, -Joseph Stokes-III, FL.D. Park W. Willis III, iNI.D. Epid@-m@lo y Studv GrouD Chai--man: Abraham M. L-ilienfeld, YA.D. embers:, Thomas D,-.@,ber, M. D. Joseph T. Doyle, M.D. Frederick H Epstein, -L4.D. -i. Kuil.-ii Lewis r, Warren 'Wi n k e I s t"e'i n',. 'Tr., @fL. D. r) I . Q . I . . 1. "Xn view of the fact that atherosclerotic complica- --@tions cause a majority of the deaths in this country and a substantial proportion of the disability, it is recommended that immediate efforts be made to prevent premature athero- Sclerotic complications." Second National Conference on Cardiovascular Diseases, Surnnary Papers. 1964. o'Co.rona.ry Heart Disease has zeached enormous propor- .tions, striking more and more at younger subjects. It will result.in coming years in the greatest epidemic mankind has faced unless we are able to reverse the trend by concentrated ,research into its'cause and prevention. "The Board expressed a wish that countries most affected by cardiovascular diseases increase their efforts both to set @p efficient services for control and to carry out more exten- sive research prograimes.11 Executive Board, Plorld Health Organization, 1969. Contents The Need.for a National Commitment to Primary Prevention as the 'eans of Controlling a Major Public Health Problem Principal 1, Coronary Heart Disease and Other Atherosclerotic Diseases .......... P- The Possibility of Achieving Primary Prev'ention of Atherosclerotic Diseases.... .................... ....... ......................... -A. Association of risk factors with atherosclerot.Lc--da-seases \major risk factors...,@, ....... 0................. ............ Diet and serum lipids ..................... 6 .................. 3 Hypertension ........................... O..* ................... 6 Cigarette smoking ............................................. 6 Combinations of major risk factors ........................... 7 B. Association of risk factors withatherosclerotic diseases other risk factors .............................................. 8 Diabetes mellitus and asymptomatic hyperglycemia ............. 8 Obesity ....................................................... 8 Sedentary living ................. ............... .......... 9 Psycho-social tensions... ................ ............... 9 Family history ......................... ..................... 10 C. Modification of risk factors ............ ............... 0.0 10 Changes in diet composition.... ............ o ................. ii. Control of cigarette-smoki.ng ..... ......... ........ *90 13 Drug treatment of hypertension .......... 14 Control of multiple risk f'actors... ...................... 1.5 Summary ........................................ .............. 16 III. Recommendations for Primary Prevention ....... ...... 00 ................. 17 A. A National Policy Commitment to a'Strateg'y of Primary Prevention... ............. ........ ............. ........ i7- B. Definitive Field Trials o.f.Pri,-,iary Prevention ................. p. 17 C. Diet and Food Modifications ................................... 17 1. Calories ...... ................. 0.0 ................... 18 2. Cholesterol ..................................... ...... 18 31. Sit:urated fats .......................................... 18 4. Meats ................................................... 20 S. Dairy products ............. ............................ 21 6. Baked goods ........................................... 22 7. Fats and oils ...................... .................. 22 8. Egg yolks .......... ................................... 22 9. Definition and labeling of foods. ...................... 23 -10. Gover=ent food and nu6rition programs .............. 24 11. Public and professional nutrition education ............ 24 D. Elimination of cigarette smoking ....... 0 ....................... 1. Advertising and sale of cigarettes ..................... 26 2. Mass media education 26 program ........................ 3. Education program in the schools ........................ 26 4. Cigarette vendin-'machines .............................. 27 C> 5. Smoking in public facilities., ........ 0 ................ 27 6. Use of tobacco tax funds ............................... 27 7. Government subsidies for tobacco cultivation and export .................. ........................ 27 8. Socioeconomic planning for the phase-out of the tobacco industry ....................................... 27 E. Detection and control of hypertension, ....... 27 F. Community programs for individuals highly susceptible to premature atherosclerotic diseases ...... 4..................... . 28 G. Drugs for the treatment of hyperlipidemia; exercise programs.* 29 IV. Primary Prevention of Premature Atherosclerotic Dis&ases -- Perspective. 30 I. THE NEED FOR A NATIONAL CON,,vITViENT TO PRDARY PREVE@\'TIO@N AS THE PRINCIPAL ilEA,,,S OF CDNT,@C)LLI-i%-G A iic' OR PUBLIC ALTII PRO LE, 0 HE B li CORONARY HEART DISEASE LN-D OTHER ATHRR' OSCLEROTIC DISEASES. Atherosclerosis i's the major specific type of arteriosclerosis' afflicting mankind. Its hallmark is an accumulation of fatty materials (lipids), cholesterol most prominently, in the walls of medium and large arteries. The clinical manifestations of this disease reflect the ischemic complications of severe atherosclerosis. The central problem, therefore, is the prevention of the severe form of this disease, particularly.its premature occurrence, e.g., befo re age 65. Morbidity, disability and mortality rate s from atherosclerotic diseases -- coronary heart disease (CHD)@ cerebrovascular, aortic, renal vascular and peripheral vascular disease -- remain extremely high in the United States and constitute one of the principal challenges to medical science and public health. This. report is based principally on the extensive research data available concerning the critical problem of coronary heart disease'. However, its conclusions are probably applicable to atherosclerosis wherever it occurs. The National Health Examination Survey of 1960-62 estimated that 3.1 million American adults age 18 to 79 had definite coronary heart disease and 2.4 million had suspect-CHD, together representing about 5 per cent of t@ population (Table 1 1 It was further estimated that of Americans under age 65, almost 1.9 million had definite C@ and 1.6 million had suspect CHD. Every year about a million persons in the United States experience either a myocardial infarction or sudden CHD death. There are over 600,000 deaths each year due to CHD. (Table 2) (2). Over 200,000 more succumb t.o. atherotliro-nbotic disease of major.arterial vessels (2, 3). in other parts of the bodYA Approximately 165,000 of the coronary deaths occui7 in persons under 65 years of age, with a greater toll (3 to 1) among men than women. For middle-aged men, the United States has one of the highest CHD death rates in the world (Table-3) '( 4j, .5 Analysis of mortality trends give no sign-that these high death rates are decreasing (Fig. 1 3 A North American man has about one chance in five of developing clinical CHD before age 60, mostl:y in the form of myocardial -Lnfarction (Fig. 2 6, 6a-k About 25 per cent of those experiencing a first premature heart. attack die within three hours of onset of symptoms, often prior to hospitalization and before medical care can be obtained (Table 4 ) (6,, 6a-k, 7). Another 10 pe'r cent die within the first Weeks after their attack. For those middle-aged persons fortunate enough to recover, prognosis for longevity is markedly impaired. They are approximately five times as likely to die within the next five years as those without a history of previous coronary disease (6,..6a-k, 7-9)... In most cases death is due to recurrent acute coronary episodes. Clinical atherosclerotic disease in the arteries of other organs is similarly associated with a reduced life expectancy. These facts strongly indicate that major progress in controlling atherosclerotic diseases is possible only by primary prevention reducing first clinical episodes by preventing severe atherosclerosis and its complications. This must be the main strategic thrust of a national effort to control coronary heart disease during the years ahead. II. TIIE POSSIBILITY OF ACHIEVING PRL@Y PREVENTION OF ATIIERO- SCLEROTIC DISEASES. A. Association of @i-sk factors with atherosclerotic diseases major risk factors: Many studies conducted over the past 25 years have demonstrated associations between certain biochemical, physiological and environmental factors and the development of premature coronary heart disease. Numerous risk factors for CHD.have been identified-,such as habit nsion, cigarette smoking, hyp:erglycemia (diabetes mell4.tus), obesity, sedentary living, psycho- ka positive; social tensions d/\fa-,nily history of premature atherosclerotic disease. Of central importance-in evaluating the association between risk factors and CHD is the finding that arterial lesions cannot generally be produced experimentally in'animals without a substantial modification of 'the diet involving increased intake of cholesterol and fat, leadin- to elevation of serum lipid levels.* Similarly, with very few exceptions, human populations consuming diets high in saturated fat and cholesterol have high mean serum cholesterol levels and high +"Hyperlipidemia" is the generic term for elevation of one or more of the blood (serum) lipids, i.e. cIholesterol, triglycerides, phosphol-"pids. The most extensive res-earch on the relationship between the blood lipids and the atherosclerotic diseases has involved serum cholesterol. Recent eN,idence suggests that elevated serum triglyqerides may also be related to increased risk of CHD. The water-insoluble serum lipids are dissolved in the blood stream'by combination with proteins to form several types of serum lipoproteins. 'The association between lipodrotein patterns and CHD is currently under further study to assess whet@er any of the types have predictive or diagnostic value over and above that of serum cholesterol and triglyceride levels alone or in combination 38 *Comprehensive reviews of research (animal, experimental, clinicopathologic and epidemiologic) on the atherosclerotic diseases are available in the recent scientific literature (10-37). This section summarizes evidence considered most ertinent to the matter of achieving primary- prevention. p 3 ,-ncidence and mortality rates from premature CHD. ilu-,nan populations consuming diets'low in cholesterol and saturated fat have low mean serum cholesterol levels and low i,-icidend e-and mortality rates from prematur& CHD. Within a@y-population group, again with few-exceptions) the risk'of developing' premature C,'M increases as the serum cholesterol' level rises. This fact has been extensively documented for the American male population in several prospective epidemiologic studies (Fig. 3 cf. also' Fig. 11 below 6, 6a-k The relationship between level of serum cholesterol and disease is continuous. With increasing cholesterol concentration risk is increased. There is no evidence of a critical level of serum cholesterol which separates high from low risk individuals. Detailed data on relationships among.diet, serum.lipids and premature CHD are available from many studies. For example, the International Atherosclerosis Project quantitated the degree of athero- sclerosis of the aorta and coronary arteries at autopsy in over 31,000 persons age 10 to 69 who died during 1960-65 in 15 cities throughout the world. Yiarked.geographic differences in the extent and severity of atherosclerosis were observed (Fig. 4 22... Populations in those countries with a high intake of saturated fat and high serum cholesterol levels had more severe atherosclerotic lesions than did populations in countries with low saturated fat intake and low serum cholesterol levels. Decedents from the United'States showed the greatest degree of -involvement. Repeated analyses of international mortality statistics have yielded comparable findings. The most recent data deal with mortality' rates for 22 developed countries including the'British Commonwealth, '4., .,5 Europe and North America (Table 3 The sizeable 4 differences in CIID mortality rates for -,iid d males correlate dle-age positively with differences in nutritional factors, e.g., total calories, saturated fat, and cholesterol. The United States is near the top of.tbe list with high per capita levels for all of these indices and fo rmortality. Data collected in research on living populations' are consistent with those obtained from autopsy studies'and mortality statistics. An extetLSive report from a prospective international study of 18 population samples in seven countries Finland, Greece Italy, Japan, Netherlands, United States and Yugoslavia -- deals with observations on approximately 12,000 men originally age 40-59 who have been studied for about a decade 39, 40 On initial examination, marked differences in prevalence of CHD were recorded 'among the population samples from the seven countries '(Fig. 5 40 For samples with high prevalence of CHD, including middle-aced American men, the rate was over four times greater than for those from countries with low prevalence. Data on five year CHD incidence.and mortality rates are consistent with the prevalence data (Fig. 5 'and Table 5) '(40). The"highest five year incidence rates were recorded for men from Eastern Finland and the United States -- over 120 and 80 per 1,000 respectively. In contrast, five year incidence rates were about.20 per 1,000 or less for men in Corfu, Crete,.Dalmatia and Japan. Differences in CHD mortality rates were frequen ly paralleled by differences in total mortality rates (Table .5) .40 This finding supports the conclusion that the differences in CHD rates were not due to diagnostic variability. Differences in CHD prevalence, incidence and mortality rates among the populations of these countries were significantly related to saturated.fat intake and serum cholesterol level (Pigs.'6-8 .40@. e '5 Recent-clinical studies using angiography to asstess narrowin@ of coronary arteries have further strengthened the evidence on the association between ser= lipid levels and CHD'. Middle-aged patients with substantial narrowing of the coronary arteries had levels of serum chol esterol triglycerides or both significantl y higher than those Of patients with- out such narrowing 41 also aggravates the atherosclerotic process, particu.1 arly in the presence of hyperlipidemia. Thi s conclusion is supported by impressive clinical-and experimental data as well as by prospective epidemiologic findings demonstrating significant correlations between blood pressure and the subsequent development of CHD (Fig. 9, 11 .).(6,, 6a-k). This relationship between blood pressure and CHD risk is continuous. At each higher step of the blood pressure scale risk is increased. Hypertension has also been established as a major risk factor for .cerebrovascu'Lar disease, including atherothrombotic cerebral infarction and cerebral hemorrhage (Fig. 9 (6,.6a-k). The 1964 Surgeon General's report on rette kin established that on the average cigarette smokers in.the United States have a 70 per cent greater chance of developing C,'M than non-smokers 42 Recent data from several prospective studies in this country have con- firmed this finding and strengthened the association between smoking and h argest of these has involved atherosclerotic diseases_ (6,. 6a-k. .43-45)-. -T. e 1 one million men and women 46 This showed that for each sex and age group CHD mortality increased with increased intensity of cigarette smoking (Table 6 46. Men age 45-54 smoking two or more packs of cigarettes a day were at highest risk. The younger the age group, the higher the relative risk 6 47, 48). It has also bee.-, associated with'ci,ar@tte smolrin@ (Table 7) (6, 6a-k demonstrated that the association between cigarette smoking and CILD risk is inde- ..pendent of such other risk factors as serum cholesterol level and blood pressure (Fig.10 ) (6$ 6,a-k, 49, 50). In addition, three studies have recently shown -that,atherosclerosis of aorta and/or coronary arteries is more severe at autopsy L. in persons who had been habitual cigarette Smokers prior to death compared to those who had never smoked (Fig.11 51, 54). !:'s report have Finally, as the annual supplements to the Surgeon Genera noted, research progress has been recorded in elucidating possible mechanisms 'whereby smoking may exert its deleterious effect on the atherogenic process (43-45). I Morbidity and mortality rate's from CHD among Americans living in the same communities differ markedly particularly when classified with respect to all three of the foregoing risk factors serum cholesterol, blood sure and 'rette considered simultaneously. Detailed data are now availa- ble from the pooled findings of six major U. S. prospective studies deal-@nc,,, with 7,594 middle-aged American men free of clinical CHD at initial examination (Fi,, 12 (6 6a-k). Those free of the three risk factors - hypercholesterole-,nia ci-arette smoking and hypertension - experienced much lower CHD morbidity.and mortality rates over a ten-year period than did the groups of men with any two or all three of these traits. CHD,. mortality rate was one-third to one-sixth as hi-h and th'e suc death rate was o'ne-fourth to one-sixth as high. As a result of the 13w mortality rate from atherosclerotic diseases,.the men free of these major risk factors had less than one-third the ten-year mortality rate from all.c auses than the ""- men with these traits and about one-f if th the total mortality rate of those witli"'all three risk factors.: These impressive findings indicate that these three risk factors ,bypercholesterolemia, h-vi)ertension and cigarette smoking are 12ri 7 f designated ri'sk factors for --especially coronar@, -heart disease. This designation is appropriate, first becau'se of the impact of these factors on ri k, particularly s when presen't in combination, second because of the consistency of the findings from multiple studies and third because of the frequency-of IL occurrence of these factors singly and in combination in the L-aerican population. All three are potentially amenable to prevention and control.- B. Association of risk factors with --theroscl rotic diseases other risk factors: Clinical diabetes mellitus has been recognized for years as a serious risk factor for atherosclerotic disease. This relationship has been extensively documented in retrospective studies dealing with coronary, cerebrovascular and peripheral vascular disease 29,. @5' These investigations have shown that diabetics have atherosclerotic disease more often, more severely and more prematurely than nondiabetics. A long-term prospective study in industry of persons age 25-64 involving an average of more.tha'n 73,000 men and women has confirmed the role of diabetes as a risk factor, especially v7hen hyper- tension is also present (Table 8) 56). Recent retrospective studies also indicate that persons wiL-.h mani- festations'of atherosclerotic disease (coronary, peripheral and cerebral) exhibit abnormalities in glucose tolerance more frequently than clin4-cal controls 29, 55 Finally, long-term prospective studies in U.S. population groups indicate that asymptonatic hypergl-vccmia - so-called chemical or sub-clinical diabetes is also an independent risk factor for atherosclero@;c ...,Lase of major coronary, cerebral and peripheral arteries Figs. 13 and 14) (29$ 55s 57 - 59). Obesity i@ another trait implicated as a significant coronary risk factor. For many years data have been available from life insurance actuarial studies indicating that overweight persons i-,ave an incrcascd risk of dying from 6oronary and cerebrovascular disease. Risk 4-S -a function of degree of over-weight 60. Although these data indicate an increase in risk, it is smaller than that recorded for such factors as hypercholesterolemia, hypertension and cigarette smoking. @ong-term prospective'st.udie@ hav@ @@lso-rioted an increased risk of CHD in overweight men in the United States ( 6, @a-k., 29, 61). However, the findings are not entirely consistent. They suggest that the association between overweight and CHD risk may be largely attributable to the increased proneness of overweight men to,h pertension, hyperlipidemia y and diabetes. Moderate overweight -- in the absence of these risk factors and cigarette smoking -- apparently is associated with only a modest increase in risk. Epidemiological evidence suggests that sedentary livin2 contributes to the'risk of premature atherosclerotic d--seases in the economically developed countries This evidence is not entirely consistent nor has the role of possible confounding variables been fully clarified. Furthermore, the apparent impact-of sedentary living on risk of coronary heart disease observed in some studies is less than that for the major risk factors. Psycho-social tensions related to personal life situations and/'or those inherent in cultural circumstances have long been suspect as factors related to premature CHD. This view has recently received support from several studies. For example, data from investigations on personality-behavior-patterns and social incongruities are consistent with this hypothesis. Data have also been obtained indicating a detrimental effect of social and geographic mobility and urbanization '(16,"25,, 29, 68-71)... These various'p.sycho-social influences may be conditioning 9 or aggravating risk factors in our society, particularly in the pres- 'f other traits enhancing proneness to premature CIU). Clinical ence o 'and unusual fatigue experience indicates that emotional cri cute events (e.g., myocardial infarction, stroke) in persons with pre-existing severe atherosclerotic disease. Most of the positive findings indicating association between various psyc@@social factors and pre-nature CliD have been recorded in single investigations and they require confirmation. This is-under- standable in view of the complexity of measurement in this area Coronary heart disease has long been thought to be related to il history. Evidence exists indicating an increased risk of C.qD in close relatives of persons who experience a heart attack early in life, e.g., prior to age 50 (20 28 29, 35 @@,.72-75). There are numerous examples of multiple premature attacks within families. In contrast there is little evidence for familial aggregation when the disease first occurs late in life. It is likely that some of this predisposition is mediated by familial resemblances in risk factors, e.g., hypercholesterolemia, hyper-. tension and diabetes. Most of the predisposing influences are under both genetic and environmental control; families share not only genes but also living habits 'such as eating patterns and smoking. C. Modification of risk factors: Certain risk factors can be avoided, controlled or corrected by appropriate changes in mode of life. Thus prevention or control of hyper-lipidemi.a may be effected for most 34 19 persons by acceptable modification of the di-et 24 25, 28, 29, 33 64, 76). Weight, one frequently lowers elevated serum triglycerides, blood pressure and plasma glucose levels of obese patients. In addition, well-tested pharmacologic measures are available for the control of hypertension 10 not responsive to d,ietary @na ement alone (Fig. 15) '(29, 64, 77., 78). smoking is also amenable to prevention or correction on a large scale, as shown by recent declines in the proportion of cigarette smokers in the American population -82). -(Fig.,,_16 and Tables 9, 10) (79 Research studies have been done to evaluate Ion--term, effects. of modifying diet composition, cigarette smoking and hypertension. n es in diet co-,nT)osition: Studies have been conducted in both animals and man to determine whether chan-es in composition'L' the diet have an effect on the atlieroslcerotic process, and on incidence and mortality from CHD. Change from a high to a low cholesterol diet has resulted in a decrease in size of atherosclerotic plaques in experimental animals (18, 26,. 29). Evidence on this matter,.available for many years from research with non-primate species has recently' been supplemented by significant confirmatory findings on reversibility of lesions in primates Table 11 and fig. 17) (83). In man, data on the opposite trend i.e., effects of increasing saturated fat and cholesterol intake' -- have been reported in several epidemiologic studies. For example, migrants (e.g., Japanese, Neapolita-Lis) to the United States from areas with low coronary heart disease death rates have higher serum lipid levels and higher CHD death rates, especially for males, as compared to rates in their native countries (i@2,..27 29). Reports are also available-indicating that reduction in calorie, fat and cholesterol intake can lead to regression of lesions in man .29. Data on this matter in the older literature have recently been supplemented by physiologic evidence suggesting partial regression of peripheral athero- sclerosis in persons with Type III hyperlipoproteinemia treated by diet and a drug to lower serum lipids, 84 Results of experimental studies of dietary changes in man have recently been reported. Studies in Los Angeles, Helsinki and \eN,7 York have dealt with primary prevention of CIM 85-8.7.. ). All three investigations utilized j2'-@ts reduced in saturated fat and cholesterol. Polyunsaturated fat was added to replace saturated fat removed from the diet. As a consequence the diets'-- particularly in the Los Anceles study were high in polyunsaturated fat. In the New York Anti-Coronary Club,, polyunsaturates were used for partial replacement of saturates. This study also placed obese volunteers on weight reducing diets durinc, their initial months in the project. The Los Angeles study was a double blind random trial anona C> veterans living in domiciliary facilities. The Helsinki study is,a comparison of two mental hospital populations. The New York study compared volunteers placed on a fat modified diet with a somewhat similar group of volunteers on their usual diet. Several hundred men have participated in each study for several years. These three studies reported a sizeable.decrease in the.incidence of new coronary events in the experimental compared with their respective comparison groups (Figs'. 18-20) 85-87 In the Los Angeles study, t@e effect appeared to be substantially greater in men under age 65 at entry. Two studies (Los Angeles and Helsinki) also reported mortality findings. Their data indicate that.-diet change was associated with -lthough statistical significance reductions in CliD mortality rates, a was not reached. The Helsinki study also recorded a sizeable reduction in total mortality rate, paralleling the decrease in CHD death rate but again, statistical significance was not reached. The Los Angeles study did not note any decrease in total mortality. The lower death rate fro-Li 12 -atherosclerotic diseqse was offset in the experimental group by a higher death rate from non-cardiovascular causes, including a statistically ,,a-,it neoplasms. _3 question concerning possible carcinogenic effects of j3'-ets very high in polyunsaturated fats. The results of these three studies are encouraging with regard to the possibility of preventing CHD and other atherosclerotic diseases by dietary fat modification. However, they are not conclusive as to the preventive value of dietary chance. Each dealt with a C> relatively small group and had one or another additional flaws, 'e.g., high drop-out rates, absence of a suitable control group, lack of double blind .design (88.,89).Nonetheless, all are consistent in showing a reduction in CIID incidence and indicate the potential for CHD prevention through modification of dietary fat composition.' Control of cigarette smokin@: The Surgeon General's reports on "The Ilealth Consequences of Smoking" have concluded that cessation of cigarette smoking is followed by a reduction in CHD risk ( '42'- 45 This determination was based on evidence obtained from several studies. Two were large prospective studies designed to assess differential mortality among adults classified according to their smoking history. Both reported that CIID mortality rates of former cigarette smokers were well below rates of current smokers especially among younger .groups @ig. 21) 46.- 48, 54,)., The differential CIM mortality between former and current smokers was greater when the group of former smokers was restricted to those who stopped smoking. for reasons other than doctor's orders. Similar findin-s were ob- served in alongitudinal study of mortality among British physicians and in the Western Collaborative Group'Study (Table 12) 44, 90, 91). In 13 the latter it was f6und that- the C-.-ID incidence rate for m@Ldc',Ie-aged ex-smol@ers was into,-mediate between rates 'or men @no never smoked and men who were heavy cigarette smokers at entry. This finding was recorded @,.fter ad@usting f6r several Concomitant risk factors (e.g.,'serum cholesterol. blood pressure, physical activity). Further, the combined experience of. adult males followed prospectively -adjust, by the .,..studies cooperating in the Pooling Project showed that the ace incidence rate of severe forms of CHD ainon- male ex-smoker-s was ab6ut as as that observed for males who had never smoked, and was -much'lower t,,@ the rate for men (6, 6a-k). @Again, the findings were independent of serum cholesterol and blood pressure. The consistent findin-s of all these studies provide highly suggestive evidence in support of the concept that cessation of cigarette smoking is of value in the effort to prevent CHD. treatment for hypertension: Drug treatment for patients with diastol@L blood pressures averagin- from 115 to 129 mm. Hg has produced marked reductions 3.n morbidity from hypertensive complications (Table 13) 77 Recently an important report was published on the Veterans Adminj4-stration Cooperative Study of drug therapy for male hypertensive patients diastolic blood pressures averaging between 90 and 114 mm. Hg (so-called '@ild" hyper- tension) 78 Three hundred eighty such hypertensive men were randomly assigned to either active antihypertensive agents or placebos and followed for periods of one to 5.5 years (average 3.3 years). F@ifty-six of the placebo .treated patients aeveloped.morbid events, as contrasted with 22 of the actively treated patients. Life-table analysis indicated that the estimated risk of developing a mordid event over a five year period was reduced from 55 to 18 per cent by treatment (Fig. 22) (78). Major nonfatal and Latal cardiovascular events (terminating morbid events) occurred in 35 p'-ib' the control group as a6 nts of', compared to 9 patients in the treated group. Nineteen deaths related to hyper- 14 tension or atlieroscicro@is occurred in the control group &-,Id 8 i' r, Z:Llc act-r In addition to the morbid events 2 20 patients- all in the control group-d'evelopcd persistent elevation of diastolic blood pressure to 125 or greater. The beef ficial effect of treatment wA',T@more evident in the patients with higher initial blood pressures than in those with lower levels a6 entry.' Treatment apparently was most effective in the prevention of congestive heart failure and stroke,, and least effective in preventing clinical manifestations of seve ..;e.-coronary atherosclerosis. The limited size of the study-precluded a defi-,iiti- .assessment of ability to prevent premature CHD by drug treatment of hypertension. However, the data currently available sup@ort the judgment that effective Ion,,-term therapy for hypertension may help to-prevent CHD and other atherosclerotic diseases. Control of ultiT)le risk factors: Only one investigation has attempted to explore the possibility of prevention by control of multiple risk factors hyperlipidemia, obesity, hypertension, cigarette smoking and sedentary living. This Chicago Coronary Prevention Evaluation Program has used diets low in saturated fat and cholesterol, and moderate in calories, total fat, polyunsaturated fat 31 carbohydrate and salt (29). It has avoided recommending diets high in polyun- saturated fat. It has encouraged cigarette smokers to abandon this habit and urged sedentary men to take up regular, frequent moderate exercise to enhance cardiopulmonary fitness. Its participants are 519 coronary-prone men originally age 40-59. They are being compared with over 3.,200 matched men from the U.S'. national cooperative Pooling Project (6,'6a-k). This study, still in progress, has reported encouraging effects on,C',M and total mortality (Fig. 23) (88). Like the other "first generation" field trials described above, the investigation is limited by relatively small sample size as well as lack of a randomly assigned control group. Therefore, its findings on the possibility of preventing premature death in high-risk middle-aged -,,nales can be viewed only as suggestive (88,, 89). Converging lines oc @bideniol clinical and experimental o--ical evidence, both animal and human, support the iud@nent that the rcla-tion- ship between the risk factors, particularly the major risk factors 4.-.e. hypercholesteroloniia Cigarette smol-inz, hypertension and the develop- ment of coro-@iarv heart disease is causal. This should not E;e interpreted as implying that the evidence on this matter is con- elusive.. Nevertheless, the data strongly indicate that to a considerable degree coronary heart.disease in the United States, particularly in the under 60 age group, results principally from the impact of these three widely prevalent risk factors. This critically important con- elusion rests on the following foundations: Confirmatory data are available. from many sources on the epidemiologic associations; these associations persist when confounding variables are taken into account; the associations are strong and consistent; they are in accord with findings from other research disciplines and are biologically plausible in terms of reasonable pathogenetic mechanisms and concepts of multi- factor.@.etiology relating apparent cause and disease. Alternative hypotheses to account for the associations do not fit the majority of observations to date. The research findin,,,s on risk factors strongly indicate the possibility of effective primary prevention of atherosclerotic disease, particularly premature coronary heart disease (Tables 14-16).(76r 92). 16 III. RECOYiYiEl\'DATIONS FOR PRDIIRY PREV'-7',\TIO@N. A. The Cor@-,i,'-ssion recommends that a strategy 2f- -,iar 2f ature dtherosclcrotic diseases be ar-loptcd as long-term national 0licy -@or Lhe United States and to i,-np!Omc',It h@a t. ec!Llate resources of monev and r,,,annower be co. @itted to cco,- ..T)Iish: .... (,Ilan@es in diet to 2Leve or on-,rol hvpe-rlipidemia, besitl -n-L lw hypertension and diabetes .... Flimination of ci5zarett6 smokin(, ..*.Ph c control of elevated blood Dressure. B. Th-c 0 lissiOn eco-mends that a T)ecial Committee be established at a level 2f the Federal Government to develop oordina-Led -Dlan,,3 for large-scale) lon@-term trials to determine the effect of various inter- ve .:Ventions, diet modification on the rates of ature atherosclerotic 3-seases in the United States. The Commission recognizes that differences of opinion exist with regard to the likely beneficial effect of various types of change, particularly fat modification of the -diet, on premature CHD in the United States. The public health importance of CHD makes it mandatory to conduct such trials' 76, 94, 95). The Commission further recognizes that even if planning were to start immediately, the American public would probably have to wait at least 10 years for results of these studies. At times urgent public health decisions must be made on the basis of incomplete evidence. Therefore, the Commission recommends that actions with regard to th e reasonable and safe changes described below be p'ro'mptly implemented. C. The Commission recommends the followin@ modifications' of diet for the oral ,ublic, and particularly :for.individuals with Trari-ed increase 17 in risk of Premature atherosclerotic disease. 1. Caloric iTita7@e be aditi,,ted to achieve aiid T-@aintain correction of obesity is known to be frequently associated with sig@@icant control of certain CHD ..?:isk factors, p.g., fall in blood pressure of some hyper- tensive patients, decrease in blood glucose levels in some pa' tien'@-s with maturity-onset diabetes, decline in elevated serum triglyceride levels. It is generally agreed that this measure is a reasonable and-' safe aspect of any prophylactic regimen. 2. A reduction of dietary cholesterol to less than 300 per @a The average daily diet in the United States contains approximately 600 mg. of cholesterol. Substantial reduction in amount of cholesterol in the diet haLs been found to lower con- centration of cholesterol in the serum of most people. Since cholesterol is.present in many protein sources of high biological quality, careful planning is necessary to lower intake of cholesterol 'without impairing intake of protein. 3. A substantial reduction of tar saturated fats. This change will lower concentration of cholesterol in the serum of most people. 'fiie ideal quantity of fat needed in the diet is not known but moderation in intake is considered desirable, e.g., less than 35 per cent of total-calories from all fats. Intalce of less than 10 per cent of total-calories from saturated fats is of critical importance for attai=ent of optimal serum cholesterol evels for most people. Unsaturated fats may be used in moderation to replace a portion of the saturated fats, i.e.,.IO percent of calories from mono- and'up to'10 'percent from polyunsatura.ted fats. With'proper control of saturated fat, cholesterol and calorie intake,, as reco,@,.e-,ided above, ingestion Of large @,ounts o@ polyunsaturated @-ats'-- i.e., 10 per cent or more of total calories -- -is generally not necessary for control of serum lipid levels. International data indicate that populations with low serum lipid levels and low CHD mortality rates habitually consu,,.e diets low in saturated fat and cholesterol, and low or moderate in total fat and poly- unsaturated fat -- not high in the latter (5, 40 With these dietary principles, requirements for optimal nutrition can be met for all sectors of the population, including infants, children, adolescents, pregnant and lactating women, and older persons. Changes in the environment to aid the American people to improve their diet should be a major aspect of this effort at prevention. Recent research has shown that it is entirely possible to prepare foods commercially in ways that will contribute sub- stantially to the control of hyperlipidemia. In the National Diet- Ileart Study, many foods were prepared with sizeable reductions in content of total fat, saturated fat, cholesterol and calories 76 This was done with da-,ry and meat products, baked goods, frozen desserts and other foodstuffs. It was demonstrated that modified foods can be made in forms that are highly acceptable to the consumer. The Commission therefore'recoT-,:nerds that the food industry be encouraged hy the medical Drofession and the s. zovernment and @upported hy the eral lic to make available leaner meats -and essed meats., dairy DrOdUCtS, Lrozen desserts and baked goods reduced in _saturated fats, cholesterol and calories, and 19 'b. edur-tio-n in s@-,tura-Lcd fat and cl-,olest cl,,oieslcrol contort of (fairy Industry i@,d hould LeViCI,7 @nd establish licic!s (3-ncludin<, T)Olicies) thit will encoura@e d of loN,7-fat, lo-,.7-cliolesterol mil',,,.--nd. milk ucts, and use of coxqs Droducin5Z large amounts of hi@,li tein, low fat milk. l@TF@iolesale pricing of d airy products .,is still based on butter fat content, a practice persisting from the days when measurement of butter fat was use'd to detect skimming or watering of milk. ... The dairy hould be helped and encouraged to elo techniques for redu cin saturated fat and cholesterol @n beeses of all varieties. 'Total fluid milk consumption in the United States is decreasing while consumption of cheese is steadily increasing. At current levels of consumption significant control of hyperlipidemia seems unlikely unless composition of cheeses can be altered. The National Diet-il,eart Study demonstrated that limited progress has been made in this area, and further progress certainly is possible. Industry should be stimulated to develop creamers low in total fats. saturated fats @nd cholesterol. ,an@es in lin Ind advert of Lream substitutes are ceded) so that their actual fat composition is clear. The so-called non-dairy-fat creamers currently on the market present a special problem. These products are characterized by a high content of coconut oil and/or hydrogenated vegetable oil and therefore of saturated fat (96)" Coconut oil is one of the most potent agents for elevating serum cholesterol level. Labels that 21 read "made with vegetable oil" ive an erroneous c a t i on Lhat the product is to be preferred over one.co-,itaining dairy fat. Reduction of-saturated fat, cholesterol and caloric co-Litc-It of baked goods. As the National Diet-Heart Stucy Demonstrated, nutritionally excellent baked @oods ,Of' all itypes can be prepared corwercially in completely acceptable forms with reduced saturated fat, cholesterol and calorie content. Wide- ead. of these fat modified products should be encoura5zcd. d. Promotion of fats and oils low in saturated fats and cholesterol for table spreads, shorte,-iin cooking and salad dressings, etc. In some areas of the country,state and/or local laws prohibit the use of butter substitutes in restaurants and institutions. These laws should be repealed. e. Reduction of yolle- consumption. The yolk of the egg is-the. single highest source of cholesterol in the average American diet, as well as a source of considerable saturated fat. In-estion of two eggs a day in visible and/or.invisible form (i.e., in prepared foods) will seriously hamper dietary programs aimed at reducing serum cholesterol. Consequentlv the public should be encouraged to avoid consumption, and the food industry should be aded to minimize-egg yolk content of commercially ared foods. Food manufacturers have rP-cently developed low' cholesterol an4i'low saturated fat egg substitutes which may be used successfully in quantity cookery and for scrambled eggs, omelettes, etc. Such developments should be encouraged. 22 f. Iloder@ization of regulation on la',Del i,-!z of foods. In December 1959 the Food and Drug Administration introduced into th' e Federal Register the statement "The role of cholesterol in heart and artery diseases has not been established 97 Consequently,. it ruled that adver'CAsing claiming' that the consumption of a food p'roduct night protect ayainst di@qea:ses of the heart and arteries was false and misleading. The Federal Register in Yay, 1965 published a proposal favorable to the labeling of edible fats.. This was supported by the American Heart Association and the American Diabetes Association. In February 1966. however, the FDA rejected the recommendation to label edible fats and oils, but endorsed a study of this problem to be conducted by the Council on Food.s and Nutrition of the American Medical Association. The Council completed its report and transmitted it to the FDA, The report favored such labeling but the FDA took no action. The FDA's regulation with respect to labeling of foods n54 is should be reviewed and updated. A new approach to labeli needed to allow the consu-.ner easily to identify nutrient content the amount and type of fat and cholesterol) -in all foods, including co.,=,,erciall ared -,nixed dishes, and low in s@a@ll-urated to encourage the manufacture Of utritious ucts fats and cholesterol. Correspondingly rules and regulations of the USDA, state and local cies on foodstuff definition. adulteration, etc., should be modernized to rmit and encourage production, advertising and ... .... . ... .... The sale of ucts Loi-7 in saturated fats and cholesterol @e.g., 23 processed neats), made x-7i,h riodp-rat amounts of uric3a- instead of rare riouiitq of saturated fats. 9* Improvement in school luncii, food stann. other ram,-, and -,Iinistc--ed utri-ion Armed Forces letcran-- Administration_facilities). Pc>licies, regulations, practices and educational aspects of these programs should be revised.to encourage improved eating habits including consumption of low saturated fat, low cholesterol diets am6ng children teenagers, young adults and low income groups 98 h.,. Deve ent of a cor,,,Drehens4ve and sustained Dublic and s-@ional nutrition duca--ion Drooram. To effect the' required changes in dietary habits,'it is -essential that the entire community be actively involved through a comprehensive and sustained public and professional education program. This will d.eepen understanding and appreciation of the need for primary prevention and inform the public and health professions on ways of selecting and preparing foods consistent with sound nutritional practices. Special empha7sis must be directed toward developing effective instructional programs on nutrition in the educational curricula at all levels. For this pur should be pose, particular attention given to the institutions training health professionals with expertise in nutrition.-- e.g., college and university home economics departments, hospital dietitian instruction programs,, schools of medicine, dentistry and nursing, and teachers',colleges. These sources should:devel@op,.educational programs based on modern concepts of sound -nutrition. Succeeding generations s@ould'have the Elementary school. advantage of this knowledge beginning in e 24 Food manufacturers have an excellent opportunity to provide public education throu"IT advertising. They should be encouraged to call attention in their advertising to the type and amount of fat and the cholesterol content of their products. There is a great need for extensive and continuous dissemination by the news media of information on diet, as well as other risk factors. Public, service communications in -this area should be substantially strengthened and broadened. With proper education, information and the availability of fat modified foods, it will be possible for most Americans to make desirable changes in their diets without major dislocation of personal eating habits. Americans should be encouraaed.to modify habits wi-th regard to all five major sources of fat in the U.S. diet meats, dairy cts, baked goods, eggs, table and cooking fats. Specifically a superior pattern of nutrient intake can be achieved by altering habits along the followin- lines. Use lean cuts of beef, lamb, pork and veal, cooked to dispose of saturated fat and eaten in moderate portion sizes;' too. Use lean meat of poultry and fish; Use fat-modified* processed'meat products (frank- furters, sausage, sal i, etc.).; too* Use organ meats (e.g., liver) and shellfish in moderation since they are higher in cholesterol than muscl e of red meat, chicken and fish; Avoid fat cuts of meat, addition of saturated fat in cooking meat, large meat portions and processed meats high in saturated fat; *Throughout this set of.guide.lines fat rocil'-fied refers Lo products Use low fat and fat Modified dairy products; Avoid high saturated fat dairy products; Use fat modified baked goods (pies, cookies, cakes, sweet rolls, doughnuts, crullers); Avoid baked goods high in saturated fat a-,id cholesterol; Use salad and cooking oils, new soft margarines and shortenings low in saturated fat; Avoid butter, margarine and shortenings high in saturated .'at: Avoid candies hi-h in saturated fat; !Avoid egg yolk, bacon, lard, suet; Use -grains, fruits, vegetables, legumes D. The C@oTmnission reco,=.@ends tl-i a t T)r4-oritv be en to the elimination of cigarette smokinsz as a na.t.4.onal habit. 1. Efforts should be made to reduce smolrIl' among young people by strict restraints on advertising and the sale of cigarettes. All advertising of tobacco in the mass media (including television, radio, newspapers and magazines should 'De discontinued. Short oj' this all advertising should carry an ho--iest, frank, highl), visible 'warning for potential consumers. 2. The mass media education Drograri or.-,phasizing the health hazards of should be continued indefinit ly to redress. the imbalance created decades of rette advertising. 3. Education r--T@-s on the risks of smoking should be .. ........ strengthened and extended throughout the school system be@-irning N-7ith the' early mar des.. Parents,.L-eachers) health professionals 26 and other adults in positions o' responsibility (e.g., television entertainers and sports personalities) should be made aware of the se@ious adverse influence of their own smoking habit as a poor example for children who may become lifelong cigarette smokers. It is noteworthy that physicians have been particularly successful in giving up cigarette smoking and are in a unique position to exe!-,t great influence in helpinc, their patients stop smoking. 4. vendin@ machines should be removed from all medical J'.acilities and Public buildin@s or, prcferabl,7, banned altogether. .5. The Prohibition agai-.ist smoking in large meetings and mass transit facilities should be-vigorouslv enforced. 6. Revenues from progressive increases in taxes on tobacco should be ear-marked for smoking control programs and the care of ent,- with diseases associated with smoking. 7. Cu rrent ar ge subsidies by -government for zroNqing and exporting tobacco should be critically revie@.,@ed with the objective 2-f making economic supports for a-.riculture consonant with national@ health _goals. 8. Planning hy appropriate social science exoerts should go forward for the orderlv Dhase out of the tobacco industry without major economic dislocation of Uiose @.7hose livelihood is involved. E. The Commission recommends a maior national effort to detect and control bv-Dertension. Recent studies have shown that the prevalence of elevated blood pressure is generally high inthe United States, 27 especially in the iNegro population (Table 17 99 Niaiiy hyper- tonsives have noh been identified; many others known to have the disease are not receivin- adequate therapy. Pro-ra,-,,s are urgently needed to.identify liypertq@sives in the co,=,unity and assure their subsequent treatment. The recently published positi ve results fro-,,i the Veterans Administration field trial of dru@ therapy for so-called limild" hypertension underscore the'potential significance of such programs 79 F .The Commission rcco@.ends that con-runitv -i c-@,,i s b e-ind nded for the detection and trcat-ient of De,-sons of all nPCS' who are very susceptible to premature atherosclerotic diseases due to co,-ibina- tions of the. major risk factors. This recommendation is premised on extensive experience demonstrating that effective community programs.for prevention ofdise'ase generally combine measures addressed to the entire population with concerted efforts@for the detection and care of high'risk individuals. All available evidence indicates that this well-established principle applies to the prevention of the atherosclerotic diseases.- On the basis of recent experience detection pro-rains are likely to identify a very large proportion of the population -- e.g., about 20 or 30 per cent of middle-aged adults -- as be'in- at unusually high risk. For such individuals, co,@-,iunity services should be provided to assist their physicians in long-term management. Such programs will .require the training and use of large numbers of allied health pro- fessionals, as well as physicians. *Detailed proposals concerning these co,-,i-,,u-,iity services will be presented in subsequent reports of the Cor--,iission. 28 G 'ni eCommission pr@scnts tlc Eo'@lo,,,in@ observat4Lons o,., trcat,@op,,@- cf hyperlipidemia and on c-xercise progra,-,is, are their possi@,12 role 4@n the preventive effort: Drugs for the treatm@'E of hyperlipidcria have been developed in recent years. For example, several years. of exper,,Ience.with cliol@estyrar,-,-Ln@, -clo.@2'.- bratel dextrothyroxine and nicotine adid have demonstrated that they will 'reduce cholesterol and triglyceride levels in the blood of many patients especially if they are abnormally high. Viiat is yet to be determined 'IS whether the biochemical action of these or similar drugs will exert any favor- able'effect on the course of the atherosclerotic diseases and whether long term continued use of these substances produces significant deleterious effects. Clinical indications for the prescription of these drugs are now being defined. For example, they are possibly indicated for specific types of patients with marked hype rlipidemia incapable of being normalized by diet alone. In this situation the risk of progression of atherosclerotic disease may outwei.ah any as yet unrecognized hazards of long-term medication. There is a need for fur-' ther development and evaluation of relatively nontoxic drugs for the lowering of elevated blood lipids. Regular exercise, particularly those forms of endurance exercise which enhance cardiovascular fitness may have a role.to play in the prevention of atherosclerotic diseases. It is impo rtant to emphasize, however., that exer- cise is not free of danger both to the -,nusculoskeletal and the cardiovas- cular systems. This is particularly true for middle-aged individuals-. especially coronary-prone persons-who suddenly take up vigorous exercise after years of minimal physical activity. Physicians and other professionals need aid in guiding a concerned public to avoid these problems. 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American Cancer Society Study of One',%iillio,-i '@ien' and 1-@'omen Non- Cigarettes S@i-,oked Daily Age and Spx Smokers Under 10 10-19 20-39 40.+.- Avien i 45 to-54 ---------- 1'.0 2.4- 3.1 3,1 3.4 ;55,to 64 ---------- 1.0 1.5 1.9 2.0 '2.1 65 to 74 -------- @- 1.0 1.3 1.6 1.6 to 84-@ -------- J,o 1.2 1.4 ------ Women; 45 to 54 ---------- 1.0 0.9 2.0 2.7 ------ 55'to 1.0 1,3 116 2,0 ------ 65 to 74-7T",7777.7- I,o 1.4 1.9 ------ 75 to 847T@777T,-- 1,0 ----- --------- ----- ----- EXpected deaths were less than 10. 0C) U) 0 (N ON co Lr) 01) I kD Li) ID I t > CN LI) r) r3 e (N C,4 ON eq 14 CN r-4 in CN C,4 r- Cl) CO :4 in 00 r, (N r- 0 C-4 CN0 C,4 (3) ko 00 C,4 C,4 C,4 tD 0 rq r,4 -i 0 U) C'i _q C) I tD C) N co o co (N 0 0 1)@ 0 r-A U) in C,4 r- r) r- 0) ko Le) U) C,4 IY, (n in CO m r- Lr) (n Lf) C) Le) o ,o kD Cl) C.) I cn r- -4 r-i r- u) (N C' 1 03 Li CN @o C\l C) 4-) 0 co 0 0 r- 0 r- 0 C)0 0 0 CD C) r-I kD LIr) CNI @ CC) 0C) 0 0 0 0 0 0 > 0r-I -i %.O -4 4J C) U) (,j r- iL LO 0 rri >1 Lr) 00 'IO co 'm (3) (n C,4 r- r-I kD C\l Ul) r- m r-0 r_ 0oi M r- r-A Lo (N Lr) I 0 .1, U) I I H U-), -7 Cl) m CT I C)0 -4 CN E-f U) 0 4JI 1 4-) >4 0 44 (:) (n -E-4 4i 0 in r- co 03 re) to C:) ai C,4 co 00 t- 4i rl in -i r- " Lo Lr) o-% ,o tD C) C,4 >1 LI C) Ln ri 0 CN kD CIA U') H in cN - . . . . A 0 rz5 -4 cq I I I Cl) CN -4 (n C\l CN :f) C.) CN .,4 Er, 0 L14 0 cr% o ,o CC) 0) m a) (1)N co r- cn OD VI r- CO r) (N -T r- kO Lr) li co IT 0 in r, 0) 4-3 0 ol in r-4 r-I >, r-4 I . rq CIT 9 (N (N 4J r-i fu 0 $4 :> Q C) 0 o r- 00 (3) -0 .0) CO 4 in @ t.0 ru 0 0 kD r, - @ -4 ko Lr) r-4 M r-i 0 Q) _r -i V ol 0) cq r, U) I -4 14 Iq 4 i r-I 4J tn CO r, o o m (3) Co 0) 0C:)0 0 0 0 U) Lr) ro Li) tD r, 00 0 0 0 0 0 0 0 -4 tD.r- cq in :i I r-i r-i r-f r-i r-( r-i r-i 0 r. .,A 4i ru t I t t Iv I. 11 E/ I (f) U) in cn ri) to ul U) U) (r) (A tf) (n (f) (f) (n 4-i $4 p $4 @4 p -,4 (o cu (a fu O-) a) C) (U (,j C) a) >1 >4 >1 >1 >3 >1 >, >1 >1 >4 >1 >I >I >I 4-) 0) (n m (n CN (:Y) (3) (n (INM 0) 0 0) 0) C) 0) @i in kg En @r) N (f) v Li) tD C) I I I t t' (,, r, Q) 1, GI r t ei (1) 0 0 0 -i 0 0 0 0 In 00 0 0 r-i 0 0 0 0 4-) -4 Li) %,O r- rj if) %D r- ci " LC) kD, r- -4, Ln ko aj in ft4 Table 8 Prevalence of Coronary Ilc@art Disease among Diabetics and Controls by 'Presence or Absence of Ilyperteiasio-.i (56) Diagnostic Status O. of Coronary Ileart P Value -etcs Hypertension ab Persons Disease Chi Square Test All Diabetics 662 122 184,@ <0.001 Controls 662 65 98 Hypertensive Diabetics 244 76 311 <0.001 Controls 158 25 158 Not hypertensive Diabetics 418 46 110 >0.10 Controls 504 40 79 *Number of persons. Rate per 1.9000. "iw LE 9 14ti@er aLnd li-oportion i,cr 1,000 of @-r,-ons 17 Years o@ ,-age and D;cr in ilo,,)ulation, by cigarette tr-coi-d,nq to E.,y zinc3 tl:,@i-ted CLrrt,-it -@t4 @r,. znc' IL@'. I L r 0 L CigarettL, S,-,iokinq Statu,, -- FAte Per '.,OOO Sex and Age Date Persons in ToLal,, Pre,;entl F o,,:,-, c r tNcvt@r U.-,' -, r. w: Thous@indc n srioker s,-,)k e d C-@L:: BCriH SE@RS Total, 1 years and qver----- June 1966, 124,500 1,000 396 115 464 25 Aug., 1967 126,579 1,000 3911 123 462 25 Aug. 1968 128,556 1,000 377 132 469 23 17-24 yealrs --------------------- June 1966 22,711 1,000 376 44 557 '23 Aug. 1967 23,377 1,000 370. 49 556 24 Aug. 1966 23,962 1,000 346 58 573 21 25-44 years --------------------- June 1966 45,132 1,000 496 117 367 -20 Aug. 1967 45,488 1,000 465 126 369 20 Aug. 1968 45,985 1,000 471 136 375 17 45:-64 years -------------- June 1966 38,960 1,000 402 145 424 30 Aug. 1967 39,6,9 1,000 400 152 420 26 Aug. 1968 40,227 11000 385 161 427 27 6.5 years. and over --------------- June 1966 17,697 1,000 153 138 680 29 Aug. 1967 18,064 11000 160 144 665 31 Aug. 1968 18,381 1,000 159 152 659 29 Total, 17 years and over ------ June 1966 58,4r,9 11000 466 172 314 28 Aug. 1967 59,246 1,000 478 182 314 26 Aug. 1968 60,073 1,000 459 192 32G 23 17-24 years ---------------------- June 1966 10,529 1 1,000 444 46 483 27 Aug. 1967 10,739 1,000 438 52 483 27 Aug. 1968 10,987 1,000 413 65 500 22 25-44 June 1966 21f536 1,000 579 160 239 22 Aug. 1967 21,733 1,000 563 169 249 Aug. 1968 21,987 1,000 547 178 258 17 45-64 years ---------- ---------- June 1966 18,688 1,000 501 219 248 33 Aug. 19,57 18,956 1,000 496- 231 24'. 29 Aug. 1968 19,IF,9 @,000 473 240 260 27 65. years '-and, overz: -------------- June 19@r, 7,717 1,000 246 267 454 32 Aug. 1967 7,821. 1,000 255 278 434 33 Aug. 1968 7,910 1,000 245 1 288 434 33 Total, 17 years and over ------ June 1966 66,031 1,000 316 65 597 22 Aug. 1967 67,330 1,000 314 70 593 23 Aug. 1968 68,483- 1,000 305 79 594 22 17-24 years --------------------- Jure 1966 12,182 i,ooo 316 42 622 20 Aug. 1967 12,638 1,000 312 47 621 20 Aug. 1968 12,975 1,000 294 53 634 19 25-44 years --------------------- June 1966 23,596 1,000 421 79 483 17 Aug. 1967 23,755 1,000 413 88 480 19 Aug. 1968 23,998 1,000 402 98 482 17 45-64 years ----------- June 1966 20,272 11000 311 76 587 26 Aug. 1967 20,694 1,000 313 79 581 27 Aug. 1968 21,039 1,000 305 88 579 27 65 years and over --------------- June 1966 91960 1,000 81 3a 855 26' Aug. 1967 10,243 11000 87 42 842 29 Aug. 1968 [ 10,471 1,000 95 49 629 27 NOTE- For offi6ial population estimates for more general use, see U.S. Bureau of the Corsus reports on the civilian population of tire United States in current Po,)Ulation Fc:)ortst Series P-20, P-25 and P-60. TABLR, 10 Status, by Age and Sex, 1-naites 'Cigarette Smoking Chicago Heart Association Detection Project 1967 - 1969 A@,e-Adjusted Rate Per 1,000* Cigarette 262 ',,en 958 Woiren .2,137 @',en 1,249 I-,Iomcn Smoking Status e-25-44 Age 25-44 Age 45-64 Age 45-64 Never Smoked 261.5 369.6 245.0 511.3 Ex-Smokers 261.2 171.9 340.7 147.2 <10 Per Day 71.8 10916 63.8 119.6 lo Per Day 405.5 348.9 350.5 221.9 Ex-Smokers x 1,000 353.7 272.7 451.3 301.2 Ever Smoked. *All rates-age-adjusted by 'L-ive year age groups to U.S. white population 1960.' Tible 11 Regression of Coronary Atlileroscle--osis with Cessation of Atliero<,eiaic Diet, @iale Rhesus \io-,ikeys (83) droup ',N'utritional LLu,.iinal Narrowing Regimen @lain Coronary Left Arterior Le4't---- Disf--a'L Left Right Des cending Circu,-ni'lex Co-@iti-,iuat-Lo.-, 'High Egg Yolk Fat, High Cholesterol '17 iionths 60 8 56 ±.7 53 ±,8 57 9 65 + 10 2 'High Eg- Yolk Fat, L 'High Cholesterol -- 17 I-leeks; Low Pat, Low Cholesterol 17 4 14 + 3 21 4 22 + 6 15 5 40 Yionths 3 High Egg Yolk Fat High Cnolesterol 17 lqeeks; High Corn Oil Fat, Low Cholesterol 40 L@lQnths 25 5 26 3 20 5 23 6 13 5 Values are means ±'s@dard errors* Table 12 Incidence of New Coronary Ilcart Disease by Srooliiig Category:. 'L'Y Weste-n-i Collaborative Group Study, i@ialc-@s 30-49 Years of A-e at Ert C> 1/2 Years Average Obsc-rvatioi-i Data (44.,90) Rate per 10.,OOO Population Smoking Category Number Adjusted for Not of @l@eii Concomitant Adjusted Variables .3 29 Never smoked 540 Former cigarette smokers 241 67 92 Pipe and cigar only 406 27 16 1-15 cigarettes 212 .51 52 16-25 cigarettes 436 89 92 26 cigarettes a-,id over 425 .98 104 Tible 13 Effects of Trcatmei-it on l,lor!)idity 'L.fortality in liyporteiision -- @iale Pati(-@nts with DiastoLic "Ol.o'od Prc!ssures Avera-iilg 115 129 rimi. li- at Entry -- %let:cr,-L@ns A@rii-,iistrat:io-,i Cooperative Study on Aiitiliyperteiisi2ve A-ents (77) Type of l@@nber of Events Event Placebo Hydroclilorothi.azide Rese'rpiiic + hydralailii'lc, 70 ',Ilen Deaths 4 0 Class A events 10 0 Subtotal 14 Other treatment failures 7 1 Total terninatina events 21 Class B events (noiitermiiiatin-) 6 1 Total 27 2 Average period o@' observation: 15.7 months for the placebo group,, 20.7 months -for the active-drup group. .Of the four'deaths, two were attributed to dissecting a,-.ieurysm., one to ruptured abdominal aortic aneurysm and one was a sudd6-.-i death. Class A (terminating) morbid even-Ls: hypertensive complications as defined in the protocol which required treatment with k-@io-,,n, active acents and permanent removal from protocol assigned therapy, -.:Lncluding:, fundoscopac evidence of grade 3 or 4 hypertensive retinopatlly; doubli-,i-- of blood urea nitro-en to levels 0 C) above 60 mg./dl.; dissectin- aortic aneurysm; cerebrovascular hemorrhage (as opposed to thrombosis); subaraciano-'@d hemorrhage; congestive heart failure persistin- despite di-italis and mercurial diuretics; elevation of diastolic blood pressure to 140 rare. Hg or higher on three repeated visits and average rehospitalization diastolic pressure to 130 I'Lc., or higher. Class'B (nonterminating) morbid events: as opposed to class A events, were those'. which did not require permanent disconl.-inuation of protocol treatments. Patients with developing B events could be treated with knoi,7n a-,itihyperL-ensive agents for as long as six months, after which protocol trea@,..e-@it had to be reinstituted. Class B events included orc.,a-iiic ccrm,D14.cations associated with atherosclerosis-,.. such ,as cercbrovascular thrombosis (as contrasted - to hemorrhage which was considered a class. A event:) or myocardial iiifarctio-@i.' Con-.estive heart failure watch responded to routine tlie-cal)y with digitalis or r,,,ercurials and did not require-aiitihy,@)crtensivC agents also was classified as a B event. POT@"\'T""-' I@@"-)-@'CT OF OF CORONAN HEART DISRASE (TABLES 14,15,16) Because.of the high incidence and nor.L- ality from clinical coronary heart disease, the.impact of a program of,primary prevention'may be substantial. i%fost coronary heart disease deaths occur within the first few hours after the onset of the clinical event,, before adequate medical care is available.* In theory, therefore,- -the majority of these deaths can be prevented only by preventing the occurrence of the initial event. The impact of a pro-ram of primary prevention depends upon three variables: 1. The magnitude of the disease in the community as measured by incidence, prevalence, or mortality. 2. The potential effectiveness of the program in reducing the number of events, 3. The percentage of the opulat ion at risk that will p accept the program. The estimated incidence of clinical coronary heart disease per year is 4/1 000 at age 35-44, 10/1 000 at age 45-54, and 20/1 000 age 55-64 for white men. Approxiriately 20 per cent of the new events will result in deaths and about two-thirds of the deaths will be sudden, i.e., occurring within the first few hours after the event. Incidence data for the black population are not available at present but are probably similar to these for whites. *Studies indicate that from 60-70% of coronary heart disease deaths occur outside the hospital. The median time of survival fro-,a onset of attack to death for these patients is about 25 minutes.- B&sed on current United States population esti-,u'ates, the incidence and number of deaths from an initial coronary event for white males a,-e 35-64 is shown in Table 11. The estimated ir@ipact'oi'- a primary prevention program is showi in Table 12. These projections are based on varyinc, percentages of potential efficacy and the percentage of the population that is included. Note that even if the effectiveness of primary prevention is small ..@-(10%) but is available to a ent of the population the impact 0 in'terms of reduction of mortality a-Lid morbidity will be substantial. Thus, the potential for primary prevention of coronary heart disease when based on a community effort as recommended in this report is'very. great. Table 14 Estimated Number of New Cases and Deaths frcrn an Initial Coronary Event for White @,'ales (92) Age Population Number of Cases Number of Deaths 35-44 10 000 000 40 000 8 ,ooo 45-54 io,,Ooo.,Goo ioo;ooo 20;ooo 55-64 8 000 000. 32 000 .1000 160; TOTZ@L 28;000;000 300JO00 60)000 Deaths following initial event only. en C:) C) 0 4j:> 1 144 14-41 (1)14 C) 4.) C) > Cl) -Li> 4-i \.O C) oi LO > 4i (01 (O C:) LH Cl) WC) U) C) U-4 44 C C) 44 4i Cl) Lf) C) 0f4 ei CY) 0 ;4 4i C) C/) cu ci 4J PQ C) r, a -a 4-1 rn C) C) (ij Lt) ri > co C.) -w @ p C) LO cn la U) P4 C)> ci ci CN 10 Fq cq C) 4-i . I 0 C,4 oi u 0 .,4: cu -4 c,, 4-J :J .14 C) C4 4i P4 6-) ri)0 4i Ucl cu 0 ;> 0 C:> C:) (IJ cr) C) 4.) (I @ 0 C) u P-1 0 cu U) to 4i 4i 4-J ci > ra ci LH -4 0P4 $4 $4 Q) ZD C) P-4 @a; G = Cor-4=ul Gre-ece; K Crete,, G::eec.- (4-"). on Epidemiology of Cardiovascu-"-az J:.Sease I?ic,ure 6 Irte@,,at-Lonal cooperative study @',.O-59 sever, countries; average seat ce@-t: oz total c .orias =I-GI. sazura@-c@ fatty acids 4-r. the -O-a4-L-,st: the s a -z cholesterol values of cohorts; for -der,4 -L cohorts see le-end for F-;-@ure 5 (40). on Epidemiology o-@ Cardiovascular -Figure 7 --. '-ri-,te@,iatioral. coo-,oc::a@live study or a-e 40--@19 :L-.i seven countries; a-e-stan--'a-zd-'-zed @-ye,,r incidence rates @Gr fatal. Cl.1,D (u-D-Dar .44-gu.-e) and for all myocardial (nonfatal + @zatal) .7ar amoi- me, --Lz::ee at- eztzy, plotted against perce,-,to.-a of total cal-o--ies -oroN74-Wle@ by fatty acids 4--,l the d4-et;' 4-c a ton of co@oi-t:s@ see leaned for @-.-L -,u.-c 5 (40)@ on Epidemiology oz Ca--d4ovcscul@r Figure 8 cooperative study / men or4--4-nally a-e 40-59 J.-,a -:es; a-e-sta.-.@ardized 5-ye--r incidence rates for @r-ta7 seven cou.,tr L CIM u-o ..?er -.-i-u::e) &Fe d for z,.s. zc,-. -zicl-ure) a7.on- 'ree at entry, plotta' + :Eatal) (lo%,,arL CF@D L aga st. med-a-.i serum cholesterol concentrations; for -orts, see for 5 (40) of the co', 'Figure I 1, East.Orar,-e New Jersey'Veterars Administratio-,i Hosp-Lt:a',- study; degree of coronary atherosclerosis at autopsy, r,-.en a-e 4@'-@'9 at men who had never s-.okc-d re-ularly -"@ose w L. lo had br--e.-4 curza@.t cigarette sr-o'"-ers prior to dcai:h (51,54). -Figure 13 study; blood glucose level one hour after 100 oral load., blood pressure, Serum cholesterol a-,id rela',:-@ve O.C coronary heart disease in i.-,e-,i (upper craph) and w@.e,-, (!-cx,7er A. Figure 14 @L 'Lle study; casual blood su-ar and r4 c;p 0 s'"- of -.ajor "est:a':.-o-s oz men and wo.-..C- a@a @0-'2 a" d 0 12 year zollow-up data (59). @07 Da;: 1.74 3wa:: (.77, 7@@" u:: e O' :,,arc t: 4 C),. C) t..e u C. o,-, a-a years c, v c:: to s 'ar,r st:":2y; P4 _U- S S -;:.a - C @_oleS Vat:C:: D3.. on le@- --Vas 0 @7 o-@t:ed as ---@va ccc.,put:cd by rates t@e o%tcrl--3 N,7ise Occurs @arc error -s a c -Z; C, - @r. Y, -a@- at some s @z- 31 - -- c or.-,D C a 0 s @ezers to a,-,y or -Doss--:) Oz .2 t-Y e:.z o;@-. by a-a N,7as t:x.@,o -rou@'s C-.- zc7u@ Size; tl,,e cut DC,4-7.t I.,@as 6-::, .:@: yoa-zs Va@L,@as ra::Zz c o,-z2 a r SO,-,S OZ e@-,Z@-re CUI'%Ias C c r o a-. a---. The graph on sudde.-i deatl-. due to C.-iD o.- overt), Z7,-, d e cerebral @@0- by a-a' at: e,-.-"Zy ar.@, se-zun C"-.0 (85). @--,gure L9 St-,:zly; 4-nc4lc--Ce o@ a7Dle to C-,iD 71-.erl a-a at e--try, F@,cTure 20 LN&i.7 vor-4 C- 0 study; active vc a-e 40-59 at ertzy, -free cl z@ca- C,@,D (87' se@se r,,or-::a!4 -'-y r- -es o@ u P- 2 S. veterans study; coro@,ary 'ear "LA Or,- sr,-, o'@ e r S; of 20:-@19 -,a.- '"ay, a@-4@ ex@s.-.o.cers o@.20-'D9 @@5-I.-4 ex-@,.e@@rs S-,O-D-Ded. J@o::-reasc,@-,s o t; "-. e, d yaaL-. (48, @4) uz re- are per F-@',,ure 22 Veterans Stu,--'y or, 4nc-da,-,ce o@ 5-year Ager,@s; est:-.,acad c or pa@4od as ca cuic.,cad by a t- o events -.orb4d averts (lower Nq )d'aS- @014C blood Pressure a- al- .t;- y Fi-ura 23 Corora::y C> a@e-a-Aus-Led o@ c ur.-. u a-c 40-.z:)9 a4- an Z::y, ,o ::o 4 C;C: Z '97'; o- -e. t:ot:@l co-o::t o@ data as of a-- c @E:? study, ,d77 1.7c:ra c or.:: 142 ware dro@ou-s @s o@ '-970; c, ::o -IC 2, 6 -2 a c C. -Y @-yca:: a-,-, ll,'ig. 2 y @JO-59 a o ro cc scr-, c@o-iastcrol -"avc, lo-ycar a-e-zdjustcd rates --,r 1 ":O::: any r""-,.4jor coro--@@- Li a"4y a-.it z co-orla::y C- stidd,,i-, death to -alcs c.-c at: y; all- rates L-c-a,,us-@ed iy C.-,a s @o White -,,ale DO.DU,7atio- 1960 ( 6 9 coc)- .)Crac-ivo- poc,!--,I- pro4cc-::; d4--stolic bi -Goa .Drcssdre lc;vc--, 1. entry and 10-ye-,@- es -Dcr C)OO Z-or: a-,ay rc, .@c,:: sudk-"eii de,-,th any coro.-Lary d c c. .7 ( c, @--) c :: ,- r s t o all causes ; coron--y event late! ',\,I @ I 4-P, due to 0 - a-c--adiuste-"7 by 1-0-yea- 'a@a U.S. 960 (6 6a-k). Fi-. 10 P::O-cct; io-@ ra':cs -,oe2: I 0 "i 0 "C. C"a year -a@ -,y maior co::ora:.y cven e@l.-h a-,iy coro@,ary iro- ca-@ses; all @y major coro@@@::y evon-- en C- 'Lo S. as a C ze .iO-59 at entry; a-,! by .G-year a-e -ro,,I-os to U. PO-?U!Zt@-o-@i 1960; t'@le ul.),Daz two "lie data DI, st-@-us and tl-Le !-O-Ycjr 1 0-0 ir::es@ecti%,c o@ Gz,- @a'.sk -@a'ctors; the ti.,-o -ra-):"s -o--,asc.-Lz Close, rates @Lb:: at: entry s t: a o -,; scor@-,:rol o-@ s!@cr-@, @LDr the t',ie fo' -Do-, .Y @ -r@":s are. -,;sed:' cig,-nra@.-@e (S) -- any @se 'ni: e,.it:ry., ser-@.. 250 blood praSSU@-a (_71 > go F'I-. J'2 coo-Dcra--4-ve Poo-, y? tc-r,@sio,-ij C-,,arotte S- ".ok4- a7,c 'DOr l,'uu"u zo:::- io.- coror,@ry ev@,tp suc@c.-@-L any co::@. ary dc-t,. oil SCS.'.; ,,a4o- Co- @0- .,Zr,j C.Van@ u j Inc@',ICCS nor@@@@L-al @z-: L. C. 1 s u d C.-, d c h. to O'@: -Z) U. S te -,a es 'a a @j - 59 -a@. CT,-@--Y; z:!.,6 rates n-c-,adj4u--t,cd @y li@-ycar a-a groUT)S to the U.S, t a -,,ale oc,.Du@ _p@4 0- CZ 190 T@.ALE fo.000 e.ooo IO.Ooo O.Ooo ro,ooo 0,000 41000 -4,Ooo 2,000 2,000 I.Ooo 11000 800 ......... coo 600 600 eyoo rs --too O..", 5-5- 64 4 5-54 years 2.00 200 too Go 100 00 Go 35-44 yoorg C6 GO 40 Orr, 40 20 20 to fit 10 6 4 2 to tvoo itorio to of (,I W@I!TE k@ H.) T F A L io,ooo 10,000 n,ooo 0,000 6,000 nd oi,4,r G,000 C5 yearr, an@' over 4,000 ....... 4,000 76-04 years 75-84 yaort, 21000 t 2,000 65-74 yoors 11000 11000 000 kttlitt@, ...... Goo r F. 600 .55-6.4yours 600 400 400 .......... 2 4 200 200 C> 0 too 100 0 0 o ro 40 40 20 20 Z5-44 10 20-34 yoors 4 25-34y*oet "O"Iogg@ I I11-1 IILLIII! III] I 1940 1950 1960 LI < Cl) LL L!j U) FLO LI) lz CIO LQ LL LI) CL ui LO La 'IO tn Lo cl@ LO v-1 44oic AORTA CORONARY AiTEf@IES Rolto Rotio Now Ociton(, Whiff, 1.2 5 2.2 3 Osio 1.0 4 1. 38 Durban Indian 0 9'3 1. Now 0(loont Negro 0 1.05 Monilo 1.13 2.62 Carocol Whito 1.15 1.85 Sio Paulo %'into 1.06 1.58 Puerto Rico write o.6 1.32 Jamaica N@gro 1.22 1.10 Cali 0.76 1.54 Puerto Rico N(dgro 0.75 1.61 L i m a 0.05 1.22 Costo Ricc, 10.82 1. 54 Santiago 0.83 i.86 mqxico 1.12 1.36 SZO Paulo Negro 0.02 0.86 bogoto" 0.67 1.05 0. 7@ Durban Bantu 1.19 0 10 20 0 10 20 PERCRNT SURFACE INVOLVED Males Fomoles I 0 .00 LO ci V@C] co LLJ cj @-l'V C,4 ff (D co C)i 0 cli cn tu E 0 w 0 0 It CJ. aQ: w D 'OD c2 cli co 0 cli oot J-,d SIZ)dVj -'41 'SHiV30 CIlo O(X Si-sv.) (I @l:) I iv ,VI, Lf) Lf) Lt4 rj fo L!j c@o w Ln Lu LO co VI Q3 CL CL vi L!i iu Fit Lil Cl Li CL. clr\ r 7.': LT LLJ ul LU ti C'f) Q-Q CD (:o CL u-1 4 CZ LL CZ LLI LU CL, Lo Lli w CL" ui Lij LL) Lii Al Yu 112- cq V) C-11 Lr) LU < tn LU L!l Q tn (i) LLI LU 77 Ul LU LI) LU LU CL tu LL @o Lu LU z Lu co co co CZ Lu LU (n :z c, CD co LU LU C4 LU LU z CL. LU LU till 21 0 C, LU lu ui C4 -1 LU LL LL CL 0 tL cr Lo 0 LU Lli L!i I= a. c co co Al CID v ui + ce VI LLj Ln CL in (A r-) co C,4 o3 C3 Lu LA Ij co uj cD vN c SIN31IVd 10 IN30 @3d Lu v) vi c-i tA m cr_ 'n I uj ca cn LLI v) cD cN @3d C,4 ra AA s@ '[lye :n jN3@ @?'d 00 F-4 r-4 VI E-4 2. D. b 90 70 60 50 z Li 40 LU CL 30 20 2@l 10 1966 '19,55 19 s IVi A L F E N-'. A Curro-,,, s,-,i o Fo r G2 ,ilk 100 FlrURE I TOI) left: Baselilic atilcrosclcrosis. itilli;@ial occlilsioll by CIICI'Oclc7llllciit of i@i,illia &7iotoi;lg set;cr(il of the f@tt,res fall,,(,: cel'Ill le., r 7n(ict, fibrous anc,7 c I X 100. A'o A do(viisti-c!ill,2 sect,, l@ irolz, t Bas 06 0 le e,?,U %,hoicil ill to,) left after st(lillilig for Itit. A ;-elitivel-i ft.,t-irce CC)II(I; of the ltl?lleli. Olit III(, r(..%t of ,le iiililtt(z illixitires 0 c(!Ily arc father rllliull" , al?loftiits of ilititiial s-carriij,,. Oil-lt,(I-o, X @)o- li'fL: ]3a.@-clit@e '(,rosclez-osis. Lar@,,!.', fil(isvc-s of (IC(-Ilttl(ir ?izatei-ial or(, scz,ii at the after ti,irel oi the ititi?)ia. lfc",latorull:ii aizcl cosi2i, X 70. Alici(lic e l(li"l r ai,,Ic,,)U a ic(lial arraiigeiyic,iit of the otilc,i- fibi,otiv %triicitir(., of the iii,,it)ta oric,iity if iiiivezl I)o;)Iilellit)it of cc,llv, th(' 711irltIle ;)oriii);i ititiiiial l@,,vioti is occiilii(,il !,,I a circtililfel-c,litial --btoits coll(ii-, laid ill@, iiiiierillost 1)ortiott shows C(,Iiiileir litil)er7)[a,si(i. This for;i@ of irteiisc arci-,:t'is iiiaU be sce:i li-c,qitc-ittly as a rcs,)oiisc to the The poilioti of bt-,,,c;, @,cr:l s7,,oiciz at t)ic l@-ft@ liny a ac(,,,'Iiil@ir ortioit in the iittiiiial ilcit@,aioxuliii (tied cosiii, X 110. I'loccoiii ]CIE; Rc,,i-essioii atlei-o- sclerosis, Visible iiiiinial lipid (b,ack-) is sinal.7 wile.iii ar, unusually lai@gc residual iiiavs of fil)rotis C;rcrilatioti riojearcli, Vcl. XXV,'[, jiilv 197() tict.'hZ5@ION,OF CO,',,ONARY L Z.-% C) FiGu;zF 17 Tol? left: li(,gr ' csyioii utliel-oyc.lel.osiv. i'Vigilic?).Olls slllclll @lal)s t)cctzr itt cii !-SC i??tart iiitcr:ial elastic Rcsi(it@al i7ic4lial (Ic'?,tlgc is I)rcyc,@it at to;? X 100. 'o) Rcgrcssiot,i 7't'le ilitillia dal-k (,'?I(l t7iC ??ICCI,'17 P,,Ilc (stlioc)tlt 2,111,SCltl.) 'itit 11' rlU itt,'t,,ci arcltit,,ct,,irc!. I'ait (,ioso,i, x 90. @otL4)lr, left: CI'eroscl I(, C(i Grc)siv,. 'Tlie iizlillltl cOi@vists lately ol coli2jectit;<, iivS,IC. Ilcircloxyl-'tt aiid cosiii, x 90.",IOEEOIII 'R Cgrcssioii all@@,roscleroyis. Utitistitill, srilcill of it,,, I?lal tliickc,z)in,, occur, the lar,, st u/ tcliicli is @it 1;40 bottom of III(? scctiol". llcil)(lioxUlir@ aticl eosiii, X 1120. c il\,C tile Oie was tl)@@l- 9l'o )II or C-" 'llilot b(@ tiol, of fc\N-er lcs,.,CI-js ierc)sclerosis, access-'!)le si;ice the C Oss@tioilil'L area oL' tile "N,el.c secret 'lI RrteriCS Of 'tllis -roup \vls labor ',',-,an i,,i tile w: SC c ii'lie,-osclerosis. Tl-,is rcai-ession ai-iinioals, ii',tliou@'ll ti'@c@egi-essioli separ-a,,ei'),. A secord O' nionke),s- \vei-e more tliin 3 Acres t to tlic gross appeiiranco o@ t' t54ier I criiins I iie iutol)sy. tilloi)cne(I Ai-,tac'L -iri-oNN,iiig of ti)c i oLil) 1 Iizici I)ca(lo(l, i\,orv-co,o,:ed iirtc;--,'Cs, recession -i-oti-i)s 'i-@,td si-.iooiiaor, The Decreased )I. the coroiiai r %,,is iccoii-ipiii)jcdby sc\,cral t'eatti,@-es II-' reginieiis N Will@'s. 'fi'ic' tliircl, that \N, K(,Cl for -,t the el-, (I c,'L' a -Illci to iis, tiystlc. su(lall n, x 90. 1,octoiii R(?g?-css,oii The rcs tio i;t nir !or. is i-icli it; colle.,@cti (dark-), atid colitigeii %cars are secit also in i lic itic,(Iia. Vart Gicson, X 90. Cifulal;om Rojedrch, Vol. XXVII, July 1970 S7'RA-,ItiED &Y ArZ 40 30 CAI'. P=0.04 20 0 O@ '."6 0 STRATIFIED 6Y INITIAL SERUM CHOLE'@TEROL CrN. so H I r, H cR p=0.04 4C) COIN 30 p=0.06 20 LAJ 10 U.i 0 60 STRATIFIED BY T CON.! LU PIZE-EXISTING COMPLICATIONS > so WITH j p=O.Ol 40 2 0. W!IHOUT EXP. f p=0.03 0. 50 T CON.'L 40. ALL CASES p=0.02 30. 20, lo. 0. .2 3 4 6 7 YEARS IN STUZ)Y El Lu ui LU Vi wi LU LIP L,J LV C4 7) LU co C-4 co co 10 LU Cl- \ - I , :'.-'4j; L'i 40 LU LU C4 v n I .1. :D - Z) ?. r; I 1, - - 2 I I .I . .1 I r ut tu LL .s i I F U) LU LL, LU LIJ CD FL- c;i cn Ca C%l C%i CD L:-J r-4 I CD CD CY'N l@ References Coronary 1',C.Irt DiscaL,(,- in Adults, linitoo st:ntes. 1960-196?. Data from the ,il lical 's, Nation, Viza I ai,,d i7ca'LLi,, St:,a,,:,@ .ics. Sc@rics 11, 10@ U.S. Dcj)artmciit of I'caltli I , EducitiO',l Public 'Ilealtli Sc!r-vice -igton Wabhii D,,C.., 1965. 2i* Vital Statistics of the U.I i'cd States, 1967 Vol. 2, Parts A and B., @lorLIlity, U@S@ Dcpartr,-,cn'L: oi@ llealtl&-il -IducaL:ion and Welfare Public Health Service 14ashington., D.C. 1969. 3@ Moriyoma, Stamier, J. aiid Krue,-Or., D.E. The %',ajor Cardioviscul.ar Diseases'-- An Ei)i.dc-@niologic-Aralysis, Amer. Public II---altii t@ssoc.., iNci-7 York N.Y. in press. 43, Ifortality Statistics., Cardiovascular Diseases, Annual St-.atistics 1955-1964 i by Sex aiid Age. Epidemiological and Vital Statistics Report; World Health Or-anization @0, 539., 1967. 5@ Stamler Stamler -zelle .Y J0.9 , R. and She, R. Regional Differences in Nlortality., Prevalc,-ice and Incidence of IschFemic Heart Disease. Snellen IT .1 H.A.., Ed.,, -@oerliaave Course oi isch@ie,.i-Lc- -eart Disease, 1969. Leiden, the N@etherla,-,ds, in press. 6@ Data from the Pooling Project, Council on Epidemiology, American Heart Association -- a national cooperative proj4cct for pooling data J',-oi-,i the Albany civil servant., Chicago Peoples Gas Compa,@-iy,, Cliici-o Western Electric Company, Framin-ham co,,@,unity, Los. Angeles civil servant, @.Li-,inea-oolis-St:. Paul business men, a,,id other prosnactive eDidc--riio'Logic studies o-l- adult cardiovascular disease in the U,-ii@ed States. The folloiqi-,i- are represerl@a- tive references on the individual studies and on the results of the Poo',-3'.n'c' Project presented to date: 6J a, Doyle., J.T. Risk Factors in Coronary Heart Disease. New York State J. Nled. 3 1317 -1963. 6@ 6. b. Stamler, J. Cardiovascular Diseases in the U-Li-i-ted States. Amer. j. Cardiol. 10 319 1962. 60 c.. Paul O., Lepper, Phela-,i., W.H.@ Dupertuis, G.Wo. iNlacMillan, A,, @IcKcaii,, 11, and Park, HO A Longitudinal Study of Coronary Heart Disease. Circulation, 28., 20 1963. 6* d. Dax,7ber T.R., Kannel, '@@I.B. and @,Lc.\amarl, P.I%I. The Prediction of Coronary ',-,cart Disease. Trans. Assoc. Life Insur. ',Ii'Cd. Dir. 47., 70.7 1964. 60 co J." and The li-Ltcrr(-@l,ati-onsl.,,ip ol@7 Scrur@i llyl)ortcnsion, I-,id Risk of Coronary Discac;c. RC-.Suli--f, of tire l@irst: Tc,-i Years Follo@,7-u,,) @-iie Los /Circles llcirt Stud3,, J. Cliron, Dis., 17., 1964. 6. f- . Keys,, A. Taylor., II.L., Blac'L\-burn., BrozeL-,., J.., Andcrso,-i: J.T,, --,Id Simonson E. Coronary Ileart Disease Njlinnesota Business and Professional Polloi7ed rirL-teen Years. #,Circulation., 2@ 381', 1963. g @,oore, F.E. Some Preliminary Findings from the Pooling Project of the Council on Epidemiolo-y., America,-Li Heart Associition. Paper Presented ,.t the Coi,,@r-cre-@ICC on Cardiovascular Disease Epidc-,niolo-y. Council on Epid=:LQlogy., Ariier.-Lca-li Heart Association LNiarcii 3-4 @,i Orleans, La. 1969,,N 6 h. Doyle@ J.T. and Kincli., S.11. Coronary Heart Disease in the TJnited States: Some Preliminary F i-Lidings from the Poolii-i- Project; 0-ic- the Council@ on EpiOcniolo-y of the l@-n c r i c a-,I Heart Association. Presented at the 42rd Scientific Sessions, American Ilezirt Association, Nov. 14, 1969. 6@ i. Epstein, F.H. and iNiloore., F.E. Progress Report to the National Heart institute on the National Cooperat-Lve Pooling Project 1968, 6@ Jo Paul@ 0. The Risks of llild Hypertension: A Ten Year Report. Pooling Project Council on Epido-n4Lolo-y. American Heart Association. Paper presented to the VI World Coii--ess of Cardiology, London., E-,I-Iar@d September., 1970. Brit. Heart J.., in press. 6. kd Doyle; JQ'T, and K'a-,inel, WoBo Coronary Risk, Factors: 10 Year Findin-s in 7'1+4-6 Americans. Pooli-,ic, Project; CD .3 0 Council on Ep@Ldcrriolo-y., Anerican Heart Associatio-,i.' 'Paper presented to the VI World Con-ress of Cardiolo-y., London,, Englard, L> Septeml,)er,, 1970. Brit, Heart J, in press. 70, Kuller L. Sudden Death in Arterioscleroti@ Heart Disbase--The Case for Preventive @ledicire. Amer. J. Cardiol., 24, 617: 1969. 8. Gubner., R. Ifortality Ratios in Coronary Heart Diseasa,, in Councils for Arteriosclerosis., -)il-'tation L Iew York Cl'inical Cardiology and Re',iaL L , t%,-,,crican Heart Association., N Sept. 15@ 1967, Conference on Coron',@rv Artc,.rv Disease. 'cd. Dir. er. 0 Trans, Assoc, Li@c Insur. Ni 51@ 2'@".., 19'7. 9,- Coronary Drug Project Research Group. Control of 4. Pro-ress in Drug Trials of Secondary Prcventioi@ Nqitti Par'Licular 'L'@C.'Lcrcoco. Lo Llic Coroniry Drug Proiccl$-. i-,i Joncs A@.oJ*y @"do; Atherosclerosis, Second Tntcrnat4o-,ial SN-,-n@osi@., Springer-Verlag2 Nei,7 York., NeYe. in presso 10. Adains, Llo@,d-Lti;,,c Loiido-Li En,,!.-tncl 1967. 11. Allen, E., Barl@er, r,. and 1,Lines, E.A.,, Jr. -Perii)licral Vnsciilar Diseire., ')rd J@"dit;io-ii., Saunders., Pliiladelpl,iial 1962. 12. BILuiienthal, II.T., Editor, CoN.,,(Iry's Arteriosclerosis., 2iid Edition Cila;:Ics C. Tllc,-,nls,, Sprin,-,Jlield, Ill.., 130 Brest:,, A.iN. and 'Llioyer,, J.11.,, Editors. Atlicrosclcrot4Lc Vascttl,-@r I)isccse, Appletoii-Cc-@iitu;:, -Cro-L:ts N@,7 Yori@., INI.Y.., 1967. 14,, Chalmers, D.G. and Gresham, G.A.., Editors. Biolo@,icil As,@ects of Occlus-;.ve @lisc.L,.I,-,r D4-scase. Carabridge University Press., Ca,7,Drid-c. En-la-iid, 1964. II.' Constantinides., P. Eyincrimo-iital ttlicl-osclcrosis, Elsevier, Aristerdam, Netherlands, 1965. 1610 FricdiL-.an, @l. Patliogenc,.sis of Coronary Arten, Disease, YcGraw-Hill Book Co.., '.LN' ei%T York, N..Oyol 1969. 17@@. Jones, A.LI.., Editor. llodci-n Trends in Cardiologv But:ten,7orL",is Lo-Lido-.i '1969. la. Jones., R.J., Editor. Evolution o' Atl,,crosclerotic Placue .L -- , University of Chica@o Press., Cliicago; Ill.; 1963. 190 Jones R.J., Editor. Atherosclerosis. Second International Sy,-,.posium, Spri-Li-er-Verla-., New York,, N-Y, 0 in press. 20. Likoff: lq. and ',,'@oyer., J.H., Editors. Corona2a Ilea.-t Disc-ns Grune and Stratton, New York, N.Y*,. 1963a 2 l@! @lann, GaVo. Ec!iL@oro S)-mi@osiLu-n on Ati-terosclerosis. Amer, J. 'L4ed., 46, 655 1969. 22, llcGill., II.C.,, Jr., Editor. Geogral)liic Patliolo@v o' Al-herosclo--. W41lia- ,IS and Wilkins., Bzltiniore,, @ld..,, 1968. 23.. @lillikan.. C.11., Sicl,,ert., R.C. and 1.@'hisnant,, J.P.., Editors. Cerebral Vascular Diseases., Fifth Co,.ifercnce, Gru-,ic and Stratton, New York., N.Y.; 196'00 .2 Ifiras ., C.Jt, Ilo@.iard, A.N. and Paolett-i., R., Editors. Pro,,Iress in BiochcT-,i-cal Ar.1v@-nces in Atl,,crosclcros-i--o S. Kargcr., Basel/;%'cw York., !9u-b. 25. raab,, W. I .1 i Prevention of lscl,.cmic lTc,-irt Discn.-c., Charles C, ThoTriasv Springfield, 111.@ 19'0'Uo 2@6. l@o 1) c-@ i: t: Jrc. SLra-,:,E,, Ro; Ed-ztors, L.Iler0sclerosis, New Yor'L'-, N.Y.: 1965,, 27* Sandler and Bourlic, G,.E@) Editors. Atherosclerosis and Its, Ori@iii, Acad@,.zLc press New York., N-Y.., 1963. 2,)'. sciie' ttler'. FOG'. and Boy'd. C.S.., Editors. Athororclcros-'c Elsevier @rst:erda,-,, 1969, 29. Stinilcr, J. Lectures On Prc-,,rentiNre Cardioloal@; Grui-ic and Stritton, 'New Yorlic.7 NOYO., 1967. .3 0 St;ranrliicss., D*Eo.5 Jro Toole, J.F. and Patel., A.'i\'o. Editors,, Cerebrol,7aScula@- Disorders, Book Co,,, New York,, N.Y., 1967. 32 Toole@ JOPO., Siel-ort, R.C. and 1,@Iiiisnant, T.Po., Editors. Cerebral 17,lscular Diseases, Si-@tli Co@-i-@@erencc, Gru-Lie and Stratton., New York, N.Yo L!)Ob, 331 Atherosclerosis: Recent Advances. Ann. New York Acad. Sci., 149, Arto,2., pp.585-1068., Nov. 21., 1968. 34, New York Heart: Association Conference on Coronary Heart Disease: Preventive and Therapeutic Aspects. Bull. I\I,Y. Acad. ',Llfcd., -@4, NO. 8, Aug., 1968. 35 The President's Cor,-mission on Heart Disease, Cancer a,-dStrokc. Report to the President. A Natioial P--oszram to Conitior lic@nrt Disease. C,,ince,- and S Dec. and Fe7D. 9@65. C.Ho@ Editors. 36. Andrus., E.C. and @lazx The Heart and Circulation -- Seco,-.d Con-L=ere-.ice on C@rdiovascular Diseases, Vols. -L aL-d !T. Federation o@L ,%i-.icrican Societies zor Experimental Biology., lqasiiingtoli.,- D.C.,, 1965. 370@ ..2nd Edition (Revised), Arerica-Li Heart ii Heart Association NcN,7 York., N.Yo., 1968. 380' Prodricl@on; DoSq., L@; R.I. a-,id Lees., R.Sc FaL' Transport in Lipoproteins--An Inte-rated Approach to @lechanisris and Disorders. New El-Lgl . J, 'Led.,, 2,'6. 34@ 94., 148 2 15 and 273; 1967. 39. Keys,, A.., - Aravanis; C. @Blackburn, vanbuclicm, r@.S.Po,, Buzina, R.., Djordjcvic, B.S., Dont'n.s. i'@.S., Fidanza., P., Karvonen Kimura., N., Lekos, D,., ,I., Puddu, \'. and Taylor.1 @I.L. Epidcr,iiological Studies Related to Cor@,ary Heart Disease: Characteristics of been Agecl L'iO-59 in Seven Countries. Acta IIcd. Scaiid., Suppl. 4u'Op 1966. 4o. Yeys, A. Editor. Coronary Ilcart Disease in Seven Countries. Circulation 1970. It 1., Suppl. l@ T, 41,, Ilciiilc, R.A., I,C%'Y, D.S, and Corl'Ln., Lipid l@n-ioZra,@Iiically --Do,@Lu,,ici-itcd Co):(.)iizzry Artery D4-,-zcase. Aiiicr. J. Cirdiol.; 178.1 1969. 42@ Si,,iol@iii@ nncl llcal',-Il: Report O@L tile Advisory COT,@iitt:cc to the Sur-co-,i General L, of tile Public liciltli sel-Nr:,L,- education ---,id I,,Ielf@ire cc L I ., U.S. Depirti,.i@-it o' @lealuli, Public Ilealtli Ser-vice P'ul)licition ,No. 110-'), Supc,.-ir.Lei-id'@-it of DociL-nciics, U.S. Government Priiitiii- O.L'ficc, lqas",Aingto-,i., D.C.., .19'01@@ 0 439"' The 1-1@ciltli C-o-,nf-,c,(-,uciices of !Tcaltli Ser-v,4-cc 1967. U.S'. of Lducation and Pu@Dlic lica'j'tii Serv-@ce Publicatic-ii No. 169' 1967. D.C.; 440, The Ile-qltli Cont,,enucnces o:F Smok-".niz--1968 SunDlamcnt to the 3.90'7 Public TIcL-ltli -\rice c- 1 -J'- a r a Ser ]Zcvic,, U.S.. Dcpar @it: o@ liczlltii., Education aid I It 1968 Supplement to Public Ilcaltli Se,-vice Publication 1696 45 Tlio- Ilealtli Consc(,uc-,iccs of Si-nol-,inc-1--19'9 to the 1967 Pu' lic Service U.S. Department of li@caltL!i., 2ducation and I-Ic-l-Fare Public '[',earth Service Publication No. 1969-2 1969a I-.7asi-iington, D.C., 46. Haimnond., E.C. Sniokinc, in Relation to the Death Rates of -O.-ic I-lillion ',&fell and c' liac@nszel roncl@ lq.., Ed., EDide-aioloRical Ai)n --.,-es to tl,.c Stti@i-\, o' Circer and Other Diseases, l@ational Cancer !,-istitui:e @ionogral.3h ,\-O. 19., pp. 127-204-1 U.S. ublic Service., FcLhesda., iN!d.., Jan. .1966. 47, Ilannond E.C. and Garfinkel Lo Coronary Ileart Disease Stroke and Aortic Aneurysm--racL-ors in the Etiolo- CY Arch. Environ, Health., 19., 167@ 19019. 48. 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