TaBLe 3.—Sudden death from coronary (Mortality ratios—actual number Author year, Number end Date Follow-up Numbe: country, typeof collection years “of , reference Population deaths Pooling 7,427 white Medical 10 145 Project, males 30-59 examination American Heart years of age and Association, atentry. follow-up. 1970, U.S.A. (88). TasLe 4.—Coronary heart disease (Risk ratios—actual number of CHD (SM = Smokers NS = Nonsmokers PROSPECTIVE STUDIES Author, year, Number and a Follow- Number of country, eo collection ap incidents Ci ettes/d. reference population years ee Doyle 2,282 males Detailed 10 243 myo- NS ............ 1.00 (52) etal, Framingham, medica] cardial All amokers ....2.36(191) . 1964, 30-62 years examina- infare- <20 -1.98 (44) USA. of age. tion and ‘tions and 20 2... 2.05 (64) (84). 1,913 males follow-up. CHD >20 3.04 (83) Albany, deaths, 39-55 years of age. Stamler 1,329 CHD- Interview 4 46 CHD NS 2.2.22... 1.00 (2) etal, free male and examin- <10 cigarettes. 2.92 (6) 1966, employees of ation with <5 cigars... } ° U.S.A. Peoples Gas cUnic <5 pipes..... (177). Company follow-up. 10-19 cigarettes.3.67 (8) 40-59 years >20 cigarettes. 3.83 (29) of age. > 5 cigars.... > & pipes..... Epetein, 6,565 male Initial 4 96 male, Males 1967, and female medical 92 female _ 40-59 UB.A. residents examina- CHD in- NS ...es eee eee 1.00 (1) (e@1), of Tecumseh, tion and eluding EX .... -.-6.63 (10) Mich. repeat deaths, Cigarettes .....5.20 (36) follow-up angina, and Females examina- myocardial NS aoa dO (22) tions. infarctions, EX .......... ~-0.89 (3) Cigarettes .....1.02 (14) 3 Unless otherwise specified, disparities between the total number of mant!- festations and the sum of the Individua] smoking categories are due to the exclusion of cither occasional, misceDaneous, mixed, or ex-smokers, 26 heart disease related to smoking of deaths shown [n parentheses) Comment Cigarettes/day Never smoked ........... 1.00 (15) S10 oo... eee -1.90 (23) 20 eee cee ee 90 (50) P20 Loe eee eee 8,36 (44) See table 1 for description of Pooling Project. morbidity as related to smoking manifestations shown in Parentheses)! EX = Ex-amokers} PROSPECTIVE STUDIES—Continued Pipes, cigars Comments Data include CHD deaths, only on males 40-49 years of age and free of CHD on entry. NS includes pipes, cigars, and ex-smokers. NS includes ex-smokers. Includes all CHD. Males—Continued Males Reexamination 60 and over 40-59 of patients 1.00 (7) SM +++ -1.80(2) was spread L27(11) 60 and over over 114-6-year 1.96(23) SM... .0.86 (6) period, but Pemales—Continued data are re- 1.00(47) ported in 1.41 (6) terms of 0.42 (2) 4-year inci- dence rates. Actual number of CHD inci- dents derived from data on incidence and total in smok- ing class, 27 TABLE 4.—Coronary heart disease (Risk ratios—actual number of CHD (SM = Smokers PROSPECTIVE STUDIES NS = Nonamokers Apthor, Number and Data Follow- Number of country, = typeof collection up incidents Cigarettes/day reference population years Jenkins, 3,182 males Initial ayy 104 myo- NS oo... 6222100 (22) etal, 39-59 years medical cardial EX oe. 2.47 (15) 1968, of age at examina- infarctlons. Current .. --2.78 (68) U.S.A. entry. tion and O-l5/day .. ~$1.39 (45) (90). follow-up 16 2.00221 3.08 (89) by repeat examina- tions. Kannel, 5,127 males Medical 12 228 myo- Myocardial Infarction etal, and females examination cardial Males 1968, 80-59 years and follow- infarc- NS wo... pa eneee 1.00 (21) U.S.A. of age. up. tions. All SM ........1.61(153) (94). 280 CHD. Heavy SM ....1.85 (59) Risk of CHD (overall) Males NS .. ++--1.00 (61) 1-10 .. --1.34 (25) 11-20 ........2. 1.80 (90) 20 2.00... 2.41 (76) Shapiro 110,000 male Baseline med- 3 Total Males etal, and female feal inter- unspecl- NS ............ 1.00 1869, eDrollees view and fled. All current ....2.14 U.S.A. of Heakh examination cigarettes (p<0.01) (178), Insurance and regular <20 Lee. 1.50 Plan of follow-up. 20 ........0., 233} Greater >40 0 22. 8.96 New York CHIP) 25-64 years of age. Keys 9,186 males Interviews 5 65 deaths. NS, EX 1970 in & coun- and regu- 80 myocar- (SM <20) ...1.00(306) Yugo- tries 40-59 lar follow- dial in- AU current alavia yearsof up examina- farctions. (20). 2.2. ..1.81(108) Pintand age at entry. tion by 128 angina Italy local pectoris. Nether- physicians 155 other lands _ Greece £428 total. (112). * Unless otherwise specified featations and the som of exclusion of either occasi 28 » disparities between the total number of mani- the individual amoking categories are due to the onal, miacellaneous, mixed, or ex-smokers, morbidity as related to smoking (cont.) manifestations shown in parentheses)! EX = Ex-smokers] PROSPECTIVE STUDIES—Continued Pipes, cigars Age variatfon Comments tinecludes non- (p<0.001) _ $9-h9 50-59 smokers and NS8......1.00 (4) 1.00 (6) ex-smokers. (p<0.001) Current 4.23(85) 2.28(83) NS inchuides (comparing former pipe O15 and 16+) and cigar smokers. Myocardial infarction-—Continued Females 1.00(31) 1.71 (23) Risk of CHD (overall)—Continued Females 1.00 (89) 0.86 (18) 1.29 (18) 0.93 (3) Females Males only Males Females Total myo- 1.00 NS ......1.00 S5-44 45-54 55-64 35-44 45-54 55-64 cardial in- 2.00 SM ......1.82 1.00 1,00 1.00 1.00 1.00 1.00 farction in- (p>0.01) (p<0.08) 2.47 3.06 1.69 2.26 2.87 1,80 cludes those 0.52 2.16 1.82 dead within wat 3.04 $29 1.81 126 281 1.65 48 hours. 5.92 10.09 7.69 5.80 20.26 11.79 4.07 NS include ex-smokers. Includes all CHD incidence includiag EKG diagnoses. Covers all countries in- vestigated except U.S.A. t Difference between total CHD and the sum of smoking groups is due to difference in figures presented by ‘authors. 29 TABLE 4.—Coronary heart disease (Risk ratios—actual number of CHD [SM = Smokers NS = Nonsmokers PROSPECTIVE STUDIES Author, year, Number and Data Follow- Number of country, tyne of collection up incidents Cigarettes/day reference population years Taylor, 2,571 male Interviews 6 46 deatha. NS and EX ....3.00 (62) etal. railroad and regu- 33 myocar- All current ....1.77(150) 1970 emphyees lar follow- dial-in- U.S.A. 40-59 up examina- farctions. (183). years of tion. 78 angina age at pectoris. entry. 66 other CHD, 212 total. Dayton 422 male U.S. Interviews upto8 27 sudden <0 2-2 ese... 1.00 (26) etal, veterans par- and routine deaths. 10-20 ..........1.04 (22) 1970, ticipatiog as follow-up 44 definite >20 ..........-).17 (13) U.S.A. controls in a examina- Myocardial (48,49). clinical trial of tions, infarctions. adiet high in unsatu- rated fat. Dunn 13,148 male Data only uptol4 Totalun- etal, patients in on new specified. 1970 Periodic heatth incidents U.S.A. examination extracted (55). clinics. from clinic records. Pooling 1,427 white Medical 10 538 Project, males 30-59 examination Includes Never emoked ..1,00 (63) American years of and follow- fatal and <10 .. 165 (72) Heart age atentry. up. nonfatal 20. - -2.08 (205) Association myocardial >20 ....----40. 3.28 (164) 1970, infarction U.S.A. and audden (an). death. Pauletal, 1,989 Western Sereening 1963, _Electrie Co. examination Coronary U.S.A. male workers and eases (£7) (148). participating history. 23° in a prospec- 2 tive stody 9 for 4% years. 6 47 3 9 3 Uniess otherwise specified, disparities between the total number of mani- festations and the sum of the individual smoking categories are due to the exclusion of either occasional, miscellaneous, mixed, or ex-smokers. 30 morbidity as related to smoking (cont.) manifestations shown in parentheses)? : EX = Ex-smokers} - ' PROSPECTIVE STUDIES—Continued want ak - = Soke ae “Age variation . 3 “ Comments " Pipes , cigars vy {> ANI CHD oP including EKG diagnoses. - aoe a A abe? fst CoP Aha ONG SK 2 OO edaelyo Gt lt Nodataon Catgio Stans oom Bt nel Perinat: by cane . Stas ee bitty 4 parotaad group. wa e yy te i coeds - Clb dont : coast ; . tee tts 20-39. $0-49 50-59 t Includes oe ‘ ee how oe - NS, EX, and wot ae » SM 1.00(25) 1.00(125) 1,00(157) <20 cigarettes ‘ . . tHigh ert. th day. one ‘ - : SM 2.17(10) 0.90 (31) 1.41 (53) $220 ciga- r ty, cee ey ate ee be a. rettes/day. ; “ oe cee eee ns Includes all fag moma uo o CHD but 2 pon oe Sigcre JD. exeludes : . diese} foe Te death, ~ ‘ oo " ~ “ ‘ No data avail- bbe cla te ER vk to ae able comparing ~ 7 wry toe rey ba ai . . smokers and . , nonsmokers. “+ 1.00(53) 1.25 (54) 88 developed ’ elinica) - coronary | ° disease, a 47 angine 7 pectoris, 28 myocardial - . a infarction, ct Veni ue a7) t. 13 deaths CHD, ae Dt, studies have shown an increased risk of this manifestation among smokers, others have not (see table 5). From these longitudinal studies, it has become increasingly clear that cigarette smoking is one of several risk factors for CHD and that it exerts both an independent effect and an effect in conjunc- tion with the other risk factors. The basic concept may he ex- pressed as follows: The more risk factors a given individual has, the greater the chance of his developing CHD. The importance of the constellation of coronary risk factors which include cigarette smoking, high blood pressure, and high serum cholesterol in pre- , dicting the risk for CHD is illustrated in figures 1 through 3. Other risk factors are included in certain of these figures and are dis- cussed below. Knowledge of the effects of cigarette smoke on the cardiovascu- lar system has developed concurrently with the knowledge derived from the epidemiological studies. Nicotine, as well as cigarette smoke, has been shown to increase heart rate, stroke volume, and blood pressure, all most probably secondary to the promotion of catecholamine release from the adrenal gland and other chromaffin tissue. This release of catecholamines is also considered to be the cause of the rise in serum free fatty acids observed upon the in- halation of cigarette smoke. Studies concerning the effect of nico- tine on cardiac rhythm have also suggested that smoking might contribute to sudden death from ventricular fibrillation. In addition, research efforts have also been directed toward the effects of smoking on blood clotting and thrombosis; since many eases of sudden death and myocardial infarction are associated with thrombosis in a diseased coronary artery branch. Cigarette smoking may be associated with increased platelet aggregation in vitro and thus might play a role in the development of such throm- bi or platelet plugs in vivo, oO Other mechanisms have been investigated. Because cigarette smoking has been shown in some studies to be related to the prev- alence of angina pectoris as well as to the incidence of myocardial infarction, it has been suggested that smoking enhances the de- velopment of atherosclerotic lesions. Autopsy and experimental ' Btudies have shown that cigarette smoking plays a role in athero- - enesis. The administration of nicotine has been observed to in- crease the severity of cholesterol-induced atherosclerotic lesions in experimental animals. Attention is presently being given to carbon monoxide, which is present in cigarette smoke in such concentra- tions as to cause carboxyhemoglobin concentrations in the blood of smokers as high as 10 percent. Based on research in animals, it is reasonable to conclude that the atherosclerotic Process may be enhanced, in part, by the relative arterial hypoxemia in cigarette 32 ana ts TABLE 5.—Coronary heart disease morbidity as related to smoking—angina pectoris—prospective studies Kore Moe . : (Risk ratlos—actual number of CHD manifestations shown in parentheses)! te co Moy Vos: 7 [SM = Smokers NS = Nonsmokers} te nee Author, . . year, Number and .\ Data -, Follow-up Number Cigars - ” wy +) country, ° typeof *. collection > years of Cigarettes/day . and pipes wy a Age variation me Commenta | reference Population —“ ‘incidents —° : Ft : Ce Doyle 2,282 males, Detalled 10 BL ONS eee e eae 1.00 (80) el . cn NS include ex. etal., Framingham, - medical Ao, AM vice ce cee ceaee _e Oo(S1) 7 03 ” smokers and 1964, "80-82 years SS examinations Lek 80 sees even ees oLDT (IB) | a. ws SEs pipe and "OR USAN of age. wand) nah 20 ev eeeeseveees 0.09(18) ° Peet Re ORL ! elgar 5, (8S). 1,018 males, follow-up. % PLD cece cece eevee oDIB(1B) _- poe M ea Lr emokers. | 3 Albany, ‘.. m 7 : or i * ; o =f 39-55 years | a _ a we : Vorpou ; . of age, wr re ey ts Py : pee te eG mel . ron my ~"Jenkine 3,182 males Initial medical = 44g Be NS eee B00 (8), - NS Include : etal, .. aged $9-59 ©: examination - ’ All current , t-- former pipe 35 1968, atentry, 3 te and follow. - cigarettes .......1.44(16) | - 3 and cigar te USAS “. up by repeat» ©. csi PIE eee OSM) BS. < wmokers, 4 HOV. Fee \ examina- r wo 7 a eh Te NE tion, a ‘Kannel — 5,127 males _ Medical 12 - 107 Males , en andfemales -: examination =, 3: > NS tepeeeeee eens T00(16) . . ok woe! le " years of age ) and follow. - cote) we Heavy SM, >20 : : aw . 30-59 = : ’ cigarettes ........2.06(17) - ty 3 : - : - Females re : “4 i oe, vs NS cseeeeserereeee00(68) eS * 4 seh ME * Cigarette SM ....,.0.66(16) 7 02 . pee ie ; -Bhaplre 110,000 male Baseline er | Total Males Females Males . ., Males t(p<0.01) etal.) and female ia medieal ; \ Unepees NS .....46,.1,00 1.00 NS. ..1,00 Sk, Ba oe Uhh 45-84 88-84 (0 <0.05) iS rN “interview tice ae “s ffied Current a 7 SMELL. Ns uv aede lave i100 5 1.00 + 1.00 NS Include 5 New York City’: and examina. ee . Clgarettes {191 00-120 | Current clarettes 7.3.40 51.87 2.06 ex-amokers. v: HIP 85-64 ton and kg SMO eee BA 1200 KAO seeceeveepee e238 IMO LBA pox veare ofage regular os * 4d ee} 320°, >40 chenee tsi 1610. 15258 6.15 oe Lo —_ follow-up,” . ‘ “oy ” Females’ e . gel Poa I. a . : ae NS: beecuechech. “41.00 1.00 1.00" " wor ing nt SA AE ee - . mony ee = Current siearettee 1.88 C167 0.97 |: vom POSE Dee on Pos oe SAD eevee ee eee VelOT LOS 7 1L04- : ' PhO eecceerenee es — 412 ~ Unless otherwise specified, disparities between the. total number of . to the exclualon of either occasional, miscellaneous, mixed, or ex-amokers. “ .' Waanifestations and the sum of the Individual smoking categories are due smokers caused by the increased carboxyhemoglobin level. With respect to the acute event of myocardial infarction, atten- tion has been focused on the role of nicotine. Nicotine stimulates the myocardium, increasing its oxygen demand. Other experiments have demonstrated that in the face of diminished coronary flow ‘(due to partial occlusion from severe atherosclerosis in man or to partial mechanical obstruction in the animal), nicotine does not lead to an increase in coronary blood flow as seen in the normal individual. These effects exaggerate the oxygen deficit when the supply of oxygen has already been decreased by the presence of carboxyhemoglobin. Thus, a marked imbalance between oxygen demand (which has been increased) and oxygen supply (which has been decreased) is created by the inhalation of CO and nico- tine. This imbalance may contribute to acute coronary insufficiency and myocardial infarction. — EPIDEMIOLOGICAL STUDIES Numerous epidemiological studies, both retrospective and pros- pective, have been carried out in various countries in order to iden- tify the risk factors associated with the development of coronary heart disease (CHD). Many of these studies have included smok- ing as one of the variables investigated. Tables 2 to 4 present the major findings. | CORONARY HEART DISEASE MORTALITY Table 2 lists the various prospective studies concerning the rela- tion of CHD mortality and smoking. These studies demonstrate the dose-related effect of cigarette smoking on the risk of developing CHD. For example, the Dorn Study of U.S. Veterans as reported by Kahn (93) reveals progressively increasing mortality ratios, from 1.39 for those smoking 1 to 9 cigarettes per day to 2.00 for those smoking more than 39 cigarettes per day. Although the data are not detailed in the accompanying tables, several of these stud- ies have also shown that increased rates of CHD mortality are associated with increased cigarette dosage, as measured by the degree of inhalation and the age at which smoking began. Although not as striking, the data for females reveal the same trends. : In most studies, the smokers’ increased risk of dying from CHD appears to be limited mainly to those who smoke cigarettes. Some studies that have investigated other forms of smoking have shown much smaller increases in risk for pipe and cigar smokers when compared to nonsmokers. However, the recent study by Shapiro, et al. (172) of a large population enrolled in the Health Insurance Plan (HIP) of New York City showed a significantly increased 34. risk for the development of myocardial infarction and rapidly fatal myocardial infarction for a group consisting of both pipe and cigar smokers. _ Table 3 details the findings of the American Heart Association Pooling Project on sudden death. The Pooling Project, a national cooperative project of the AHA Council on Epidemiology, is de scribed in table 1 (88). Cigarette smokers in the 30 to 59 year age group incurred a risk of sudden death from CHD substantially greater than that of nonsmokers. Pipe and cigar smokers were observed to show a risk slightly greater than that of nonsmokers (table 3)... . The relative risk of CHD mortality is greatest among cigarette smokers (as well as among those with other risk factors) in the younger age groups and decreases among the elderly. In table 2, Hammond and Horn found that for those smoking more than one pack per day, the risk is 2.51 in the 50 to 54 year age group and 1.56 in the 65 to 69 year age group. Although the relative risk for CHD among smokers decreases in the older age groups, the actual number of excess deaths among smokers continues to climb since the differences in death rates between smokers and nonsmok- “ers continue to rise. Coronary HEART DISEASE MorBipiry Tables 4 and 5 list the prospective studies carried on in a num- ber of countries to identify the risk of CHD morbidity incurred by smoking. Here, CHD morbidity includes myocardial infarction as well as angina pectoris. Certain studies, notably those of Doyle, et al. (54), Keys, et al. (711), and Taylor, et al. (188) include a number of CHD deaths in their data that could not be separated out ‘using the information provided in their respective reports. As noted in the discussion on CHD mortality, the CHD risk ratio increases significantly as the number of cigarettes smoked per day increases. Similarly, the HIP data of Shapiro, et al. (172) show that the elevated morbidity ratios declined with increasing age as has been shown for mortality ratios. — A recent monograph edited by Keys (111) dealt with the 5-year CHD incidence in males age 40 to 59 from seven countries. As Summarized in table 4, cigarette smoking was found to be associ- ated with an increased incidence of CHD in the U.S. railroad worker population, 2,571 individuals (183). None of the differences in ratio between smokers and nonsmokers was statistically signifi- cant for the 13 other population samples which varied in size from 505 to 982 individuals, from the five other countries. (Smoking was not considered in the two Japanese populations.) When more cases 35 become available to provide greater statistical stability to the rates, this intercultural comparison should prove illuminating. The results of those studies which have separated out angina pectoris as a manifestation of CHD are presented in table 5. Doyle, et al. (54) found no relationship between this manifestation of CHD and cigarette smoking. Both Jenkins, et al. (90) and Kannel, et al. (94) observed increased risk ratios among male cigarette smokers although these’ differences were not statistically signifi- cant. More recently, Shapiro, et al. (172) found a significantly increased risk for angina among their male cigarette smokers as well as increasing risk ratios with increasing dosage among both males and females, particularly in the ‘younger age groups. A variety of hypothetical explanations have been advanced to account for this seeming contradiction. Among these are the relatively small number of cases, the difficulties associated with the definitive diagnosis of the syndrome, and differences in the methods of clas- sifying those cases of angina pectoris which are followed by mvo- cardial infarction. RETROSPECTIVE STUDIES Table A6 presents data from the various retrospective studies of CHD prevalence. Most of these are case-control studies and show an increased percentage of smokers among those with clinical CHD when compared with a selected control population, usually without apparent CHD. Two of these studies include data on mortality. THE INTERACTION OF CIGARETTE SMOKING AND OTHER CHD Risk FActTors ‘The preceding section has reviewed the epidemiologic evidence which supports the judgment that cigarette smoking is a signifi- cant risk factor in the development of CHD. Many of the studies discussed above have identified a number of biochemical, physio- logical, and environmental factors, other than cigarette smoking, which also increase the risk of developing CHD. These risk factors include elevated serum lipids ( particularly serum cholesterol) and hypertension, which, with cigarette smoking, are considered to be of greatest importance. Other factors are obesity, physical inac- tivity, elevated resting heart rate, diabetes (as well as asympto- matic hyperglycemia), electrocardiographic ‘abnormalities, and a positive family history of premature CHD (88). A number of these studies have also found that these factors, when present in the same individual, exert a combined effect on the risk of developing CHD. Figures 1 through 8 depict this inter- action of risk factors. As may be noted in Figures 1 and 2, the 36 additional factor of smoking greatly increases the risk of develop- ing CHD among those people already at high risk because of other factors. Furthermore, these studies have shown that the effect of smok- ing on the risk of developing CHD is statistically independent of the other risk factors. That is, when the effect of the other factors is statistically controlled, smoking continues to exert a significant effect on increasing the risk of developing and dying from CHD. Smoking and Serum Lipids The interaction of smoking and serum lipid levels in the develop- ment of CHD should be considered in the light of information con- cerning the relationship of smoking to serum lipid levels. Table AT presents studies which deal with the association between smoking and lipids, notably cholestervl, triglycerides, and lipoproteins (con- cerned with lipid transport). While some of the studies have indi- cated that smokers show increased serum levels of these lipid con- stituents, others have not. The populations investigated and the methods of the various studies show significant variation. This lack of comparability makes interpretation of the findings difficult. It is clear, however, that in the presence of high serum choles- terol, cigarette smoking increases the risk of. CHD. Figure 4 de- picts the data from the Chicago Peoples Gas, Light and Coke Com- pany study which show that smoking greatly increases the risk of CHD in each of the cholesterol groups. Smoking and Hypertension Some epidemiological studies have indicated that smokers tend to have lower mean systolic and/or diastolic blood pressures than nonsmokers, while other studies have not found this to be the case. (table A&). Reid, et al. (155), in a study of 1,300 British and American postal workers, found that the blood pressure difference between the smoking and nonsmoking groups was eliminated after. controlling for body weight. Tables 9 through 11, derived from the study by Borhani, et al. (27), demonstrate the following associations: That for both smok- ers and nonsmokers, the risk of dying from CHD increases with increasing diastolic or systolic pressure, and that the risk of mor- tality from CHD is higher among smokers than among nonsmokers in each blood pressure group. Cigarette smoking, therefore, has been shown to elevate CHD mortality independently both of its effect on blood pressure and of the effect of hypertension on CHD. Smoking and Physical Inactivity The recent study by Shapiro, et al. (172) of more than 110,000 37 TABLE 9.—Death rates from coronary heart disease, by systolic blood j pressure: a ILWU mortality study 1951-61 x on those 4 “(Coronary heart disease as classified under ISC Code 426) . . Smokers Nousmokers rage My de bo. 7 “ "12 Bystolle blood = Person-years Death - Person-years Death ~ -.* Age group 7 } Pressure in 1951 0 of obeervation rate? of chservation rete? M656 eeepc 170 ret) » 180-149 160-169 >170 :~ 3 p<0.026. #p<0.01 - ? TABLE 10. “Death rates from coronary heart disease, by diastolic blood pressure: ILWU mortality study, 1951-61 eee he oe, (Coronary heart disease as classified under ISC Code ¢20) a ease 4. Smokers : Nonsztwokers : . Diastolic blood Person-years Death Person-years Death ‘ pressure in 1861 of observation rate) of observation rated <80 (4h + «4,627 vals 26 (re | 80-89 ye, 221B a1 _ 2947 gs so 99 BR BR OT 32 D100 of dag cist gs vo 2020 2 er fT) 100 ope 869 oa 163 7 S54 . wet 3 Rate per 10,000 person-years of observation. 2 p<0.05. 2 p<0.01. —— a + Source: Borbani, N.O., etal. (27). ave . letn, ote FA le they aig TABLE rH —Death rates from ‘coronary heart disease, among hypertensives ond nonhypertensives: ILWU mortality study, 1951-61 2 . . (Coronary heart disease as classified under ISC Code 420) : oe vp Bes . Smokers . . Nonsmeokers T4nie eee cee peter: Blood pressure * Person-years ” Death Pereon-years Age group status? _ (Le of observation ‘rate? - of observation Hypertensives -.-- Nonhypertensives . Hypertensives ..- Nonbypertensives 1 According to the WHO recommendation, the following cut-off points are recommended for the Sefinition of hypertension: ° (1) Normotension—below 140/60 mm. Hg. * (2) Hypertension—aystolic blood pressure 160 mm. He. or over, or diastolic 95 ram. Hg. or over, or both. - (3) Borderline—the residual category. In this analbsis, Normotensives and Borderiincs were combined and the population | was ercuped into ‘Nonhypertensires" a and 3) and “Hrpertensives’ q). ae _ oe . to, 3 Rate per 10,000 person-years ¢ of obeervatioa. . ein tea : oS , - ay 5 p<0.01. : . ons iBe asset toe : od rs a “3 pn Souacz: Borhanl, N. O., et al (27). . . " lene 4. ‘Ne hmebe we £0 AS sie ist fo "Ss: gadZ 3 wed ybite.s ae 2st est 2 38 INCIDENCE PER 1,000 MEN 30-—- 70-— ALL NON NON NON SMOKERS SMOKERS SMOKERS SMOKERS SMOKERS SMOKERS <225 225-274 2754 225 225-274 2754+ CHD 46° 1 5 2 3 16 12 K 1329° 187 235 7 336 317 151 AGE 49 49 50 51 50 49 50 SYSTOLIC = 134 133 136 139 131 133 135 PRESSURE . WEIGHT 1.16 1.19 1.21 Lig Li 115 Ly RATIO Ficure 4—-Relationship between smoking status and serum cholesterol level at initial examination, and incidence of clinical coronary heart disease in men originally age 40-59, free of definite CHD, and followed subsequently without systematic intervention, Peoples Gas Light and Coke Company study, 1958-1962. *For 34 men, no information on smoking status was available; one of these men had a coronary episode. Source: Stamler, J., et al. (177)- persons participating in the Health Insurance Plan of New York City has further identified and elaborated upon the interaction of the various risk factors. Physical inactivity, both in employment and during leisure time, was found to be a potent risk factor for _the development of CHD, particularly for rapidly fatal myocardial infarction. Figure 5 depicts the effect which smoking exerts on CHD In combination with physical inactivity. Of note, also, is the observa- tion that within each activity grouping, smoking greatly increases tne risk of myocardial infarction, thus exerting an independent ect. Smoking and Obesity The analysis by Truett, et al. (190) of the risk factor data from the Framingham study revealed that weight, while a significant risk factor, had a considerably smaller effect on CHD incidence than serum cholesterol, cigarette smoking, or elevated blood pres- sure. The results concerning the interaction of smoking and obesity from the San Francisco longshoremen study are shown in table 12. 39 10.89 U0 ¢ 10.0 - 9.0 - Not b> wi n Bo 48 hes. 5.72 g ($7) 70 F NONCIQARETTE SMOKERS i 6.33 2 gol 5.78 7 60 bk i 3.76 § 4.0} (47) 4.48 3.03 . 166, 77 peed _ within 48 brs, ey 20 - 7 2.34 (218) 2.57 oF 1.30 en a 7 0.0L Least More Least More active active active active Note: Both for clgerstta smokers and noncigerette smokers differences betwaen rates among the feat more active men are statistically significant for totel Mi and rapidly fatet Mis at the 0.99 confidence « For other Mis the difference is statistically significant onty for the nonsmokers (confidence level 0.95). Ficurr 5—Average annual incidence of first myocardial infarction among men in relation to overall physical activity class and smoking habits (age-ad- justed rates per 1,000) (Actual number of deatha or myocardial Infarctions area represented by figures in parentheses) Source: Shapiro, 8., et al. (172). This table shows that cigarette smokers in the 65 to 64 year age Sroup were observed to have higher CHD death rates than non- smokers in all welght categories. Similar findings, although not in all weight groups, were observed for the 45 to 54 year age group. Cigarette smoking is thus shown to be a CHD risk factor indepen- dent of body weight. 40 TABLE 12.—Death rates from coronary heart disease among men unthout abnormalities related to cardiopulmonary diseases by weight classification in 1951: ILWU mortality stuly, 1951-61 (Coronary heart disease as classified under ISC Code 420) Smokers Nonsmokers Weight Person-years . Death Person-years Death Age group classification ! of observation rate = of observation rate? 45-84 2. Not overweight _ 388 21 279 1 Slightly overweight 962 28 1,096 0 Moderately overweight 1,383 28 1,574 28 Markedly overweight 1,055 22 1,797 o 53-44 -..-..... Not overweight 222 43 247 e Slightly overweight 536 15 “606 36 Moderately overweight 855 103 1,320 711 Markedly overweight 735 88 1,653 112 *The four classes are defined in the text. 7 Rate per 10,000 person-years of observation. 3p<0.01. Source: Borhani, N. O., et al. (27). TABLE 13.—Death rates from coronary heart disease, by electrocardiographic findings in 1951: ILWU mortality study, 1951-61 (Caronary heart disease as classified under TSC Code 420) Smokers Nonamokers Electrocardiographic Person-years Death Person-years Death Age group findings in 1951 of observation rate? of observation rate? 45-84 ......... Abnormal wen cece eee eee 586 102 1,020 39 Normal ............... _ 4,454 38 6,134 “15 55-64 22.2... Abnormal ............. 683 223 1,143 96 Normal ............... 3,031 86 6,478 731 1 Rate per 10,000 Person-years of observation, 7p<0_005. Source: Borhani, N. O., et al (27). TABLE 14.—1958 status with respect to heart rate, blood pressure, cigarette smoking, and 10-year mortality rates, by cause (1,829 men originally age 40-59 and free of definite coronary heart disease) Peoples Gas Co. Study, 1958-68 1958 risk factor status Ten-year mortality, 1958-68 Heart Cigarette Diastolic Number All causes . CHD” rate smoking pressure of men Number Rate Number Rate NH NH NH 378 20 148.3 5 112.0 H NH NE - 46 6 114.9 8 70.8 NH NH H 107 “4 118.3 6 “51.8 H NH H 30 8 221.6 3 52.0 NH H NH 491 87 116.8 19 38.9 H HR NH 127 22 VLI 8 62.3 NH H H 103 22 190.4 6 55.0 H H H 44 1s 265.4 ‘6 949 All 1,325 162 118.2 65 39.4 * Rate per thousand. All rates are age-adjusted by S-year age groups to U.S. male popalation, 1960.. High (H): Heart rate 280; 210 elgarettes per dey: diastolic blood pressure 290 mm. Hg. NH is not high, ie., below specified cutting points. 3 No smoking data available on 4 of the 1,329 men, Source: Berkson, D. M., et al. (£3). 41 TABLE 15.—The effect of the cessation of cigarette smoking on the incidence of CHD (Incidence ratios—actual number of cases or events are shown in parentheses) Author, year, country, Results Comments reference AU myocardial AU CHD events infarction Jenkins Never smoked eee eee eens 1.00(80) 1.00(21} etal, Current 1968 elgarette amokers ....... -2.36 (84) 2.78 (68) U.S_A. Former (90). cigarette smokers ....... -2.18 (19) 2.47 (15) Death from CHD Smoked >#0 Smoked 1-19 cigarettes/day cigarettes/day Hammond Never and Garfinkel, smoked regularly ...... 1.00 (1,841) 1.00(1,841) Male data only 1969, Current US.A. cigarette amokers .......1.90(1,063) 2.55 (2,822) (78). Stopped pack/day .. -- -1.65(34) 1.65 (72) for description Association TE pack/day ........22.2..1.70(86) 2.08 (205) of Pooling 1970, > pack/day ..............3.00(68) 3.28 (154) Project. U.S.A. Ex-mokers ......2.....004 0,80(19) 1.25 (51) (88). TABLE 16.—Annual probability of death from coronary heart disease, in current and discontinued smokers, by age, mazimum amount smoked, and age started smoking Age started smoking 15-18 20-24 Discontinued Discontinued Maximum daily Current for five or Current for five or Age ber of cign- smokers more years amokers more years nrettes smoked (Probability X10 *) BEA . ° 501 — 501 _— 10-20 798 BEE 811 551 21-39 969 766 872 698 €5-T4) 2... wees o 1,015 —_—_ 1,018 — 10-20 1,801 1,169 1,478 1,218 21-39 1,710 1334 1,578 1,098 * For are group 65-74, probabilities for discontinued smokers are for 10 or more years of dis continuence since data for the 5-0 year discontinuance group are not given. Source: Cornfield, J., Mitebell, 8. (48). Based on data derived from Kahn, H. A. (#5). 42 Smoking and Electrecardiographic Abnormalities Electrocardiographic (ECG) abnormalities such as T-wave and ST-segment changes as well as a number of arrhythmias are use- ful indicators of CHD and may, therefore, be predictive of the development of clinically over’ CHD manifestations. The results summarized in table 13, from the prospective study by Borhani, et al. (27), reflect the joint predictive value of smoking and ECG abnormalities on the death rate from CHD. Smoking and Heart Rate Recent analysis by Berkson, et al. (23) of the data derived from the Chicago Peoples Gas, Light and Coke Company study of middle-aged men revealed that resting heart rates of 80 or greater were associated with an increase in the risk of death from CHD. These authors found that this association was independent of the other major coronary risk factors. Table 14 presents the interaction between smoking, blood pres- sure, and elevated heart rate in increasing the risk of CHD mor- tality. This study shows that cigarette smoking increases CHD risk in the presence of elevated heart rate as well as in its absence. THE EFFECT OF CESSATION OF CIGARETTE SMOKING ON CORONARY HEART DISEASE A number of epidemiological studies have been concerned with the CHD incidence and mortality among ex-cigarette smokers as compared with current smokers (51, 76, 88, 90, 98, 172). These studies are listed in table 15. Table 16 presents the data derived by Cornfield and Mitchell (45) from the Dorn Study of U.S. Veterans (93). Ex-cigarette smokers show a reduced risk of both myocardial infarction and death from CHD relative to that of continuing ciga- rette smokers. The Pooling Project (88) and the Western Collab- orative Study Group (192) which adjusted for the other risk fac- tors of elevated serum cholesterol and blood pressure observed this relationship. Hammond and Garfinkel (76) noted that cessation of smoking is accompanied by a relative decrease in risk of death from CHD within 1 year after stopping. This decreased risk of CHD among ex-smokers further strength- ens the relationship between smoking and CHD. It must be noted, however, that the group of ex-smokers is composed of individuals who have stopped smoking for a variety of reasons. Those who stop because of ill health and the presence of symptoms are gen- erally at high risk and can bias the group results in one direction; 43 those healthy persons who stop as part of a general concern about their health and may adopt a number of self-protective health prac- tices are generally at low risk and can bias the group results in the other direction. Therefore, ex-smokers as a group are not fully representative of the entire population of smokers and may have limited value in predicting what would happen if large numbers of cigarette smokers stopped smoking purely for self-protection. Cer- tain incidence studies, such as the Pooling Project (88), were initi- ated with only clinically healthy individuals. The data from such studies, as well as those from the British physicians study, contain ex-smoker data less influenced by these biases. Fletcher and Horn (68) have recently presented data derived from the British physicians study of Doll and Hill. Over the past 10-15 years, cigarette smoking rates among British physicians have declined significantly in comparison with those of the general British population. The information presented by these authors concerning all cardiovascular diseases showed that for individuals between the ages of 35 and 64, the age-adjusted death rate for CHD declined by 6 percent among physicians and rose by 10 percent among the male population of England and Wales during the period from 1953-57 to 1961-65, THE CONSTITUTIONAL HYPOTHESIS The effect of smoking on the incidence of CHD has been found to be independent of the influence of the other CHD risk factors. When such risk factors ag high serum cholesterol (177), increased blood pressure (27), elevated resting heart rate (23), physical in- activity (172), obesity (27), and electrocardiographic abnormali- ties (27) have been controlled, cigarette smokers still show higher rates of CHD than nonsmokers. It has been suggested by some (89, 1 70) that the relationship between cigarette smoking and CHD has a constitutional basis. That is people with certain constitutional make-ups are more likely to develop CHD, and the same people are more likely to smoke cigarettes. This hypothesis maintains that the relationship between cigarette smoking and CHD is thus largely fortuitous and that the significant relationships are between the genetic make-up of the individual and CHD and between the genetic make-up of the indi- vidual and hia becoming a cigarette smoker. Two sets of epidemio- logic data bear on this hypothesis. It has been maintained that People with a certain temperament are more likely to smoke and also more likely to develop CHD. These characteristics have been demonstrated for those with the 44 Type A behavior pattern of Rosenmann, et al. (159) which is characterized by competitiveness, excessive drive, and an enhanced sense of time urgency. The prospective study organized by the Western Collaborative Group indicates that individuals who ex- hibit this type of personality are more likely to have or develop CHD than those without it (Type B), whether or not they smoke. When the incidence rates of CHD are analyzed with respect to smoking and personality types (tables A17, A18), it is noted that in both Type A and Type B individuals the incidence of CHD is greater among cigarette smokers than among nonsmokers. This research indicates that both personality type, as measured in these studies, and cigarette smoking contribute independently as risk factors to the development of CHD. To what extent such behavior patterns are determined constitutionally or represent acquired characteristics is still open to question. The other type of research designed to study the genetic hypoth- esis has made use of data from registries of twins. Cederlof, et al. (37, 38, 39, 40) have utilized the Twin Registries of Sweden and the Veterans Follow-Up Agency of the U.S. National Academy of Sciences-National Research Council to investigate the relative contributions of heredity and smoking to cardiovascular and bron- chopulmonary symptom prevalence. Data obtained by mailed ques- tionnaires were analyzed for the following characteristics: zy- gosity of the same-sex twin pair, urban-rural residence differences, smoking concordance, and history of various symptoms. Compari- sons were made between smoking discordant monozygotic (iden- tical) pairs and smoking discordant dizygotic (fraternal) pairs, and between unmatched twin pairs and matched twin pairs. Smok- ing discordance has been defined somewhat differently in various reports but, in general, describes twin pairs in which the smoking’ habits differ between the two members of the same twin pai: Analyzing the data obtained from 9,319 Swedish twin pairs (72.3 percent of the possible respondents), Cederlof, et al. ($9) found that respiratory symptoms were more common among smok- ers in both the unmatched and matched smoking discordant twin pair groups. The authors analyzed the data in two distinct man-' ners. Group A analysis, which did not control for genetic factors utilized two groups; the first composed of all the firstborn, and the second of those listed second on the birth certificates. Group B analysis utilized MZ and DZ twin pairs which were discordant for smoking, thereby controlling genetic factors. “Angina pectoris,” a8 defined by a certain pattern of responses to the questionnaire, was found to be more prevalent among smokers in Group A, but this” @ifference was not present when the data from Group B were an- alyzed. Males in the first group exhibited a “hypermorbidity ratio” 45 of 1.6, while those in the second group were found to have one of approximately 1.1. The authors concluded that this difference be- tween the two groups provides better support for the importance of constitutional factors as against the importance of cigarette smoking in the development of angina pectoris. A similar study was done using the responses of 4,379 U.S. Vet- eran twin pairs (approximately 60 percent of estimated available total) who completed the mailed questionnaires (88). Cederlof, et al. found a significantly increased prevalence of chest pain and “angina pectoris” among smokers when Group A’ was analyzed. Analysis of the smoking-discordant matched twin pairs (Group B) revealed no association between smoking and cardiovascular symp- toms among the monozygotic pairs. The dizygotic pair data did show a slight association. The authors concluded that this lack of association among the monozygotes and its presence among the dizygotes and unmatched pairs strengthens the case for a constitu- tional hypothesis. A major problem in these studies is the small number of cases available and, therefore, the statistical instability of the results. In the Swedish study, among the 274 monozygotes, only 19 smokers and 16 nonsmokers were classified as having angina pectoris while among the 733 dizygotes, 25 smokers and 25 nonsmokers were so classified. In neither group was the difference between the prev- alence ratios found in the Group A analysis and that in the Group B analysis of statistical significance. Analysis of the data on women shows a similar lack of significance. Similar criticisms may be made of the study which utilized the U.S. Veteran Twin Registry. In that study, the authors observed that the difference in the prevalence of angina pectoris between the low-cigarette-exposure and high-cigarette-exposure dizygotic groups was not present among the monozygotes. The authors ques- tioned whether the excess morbidity associated with cigarette smoking found in the dizygotic group was causal as it was not pos- sible to reproduce the association when studying monozygotic smoking-discordant twin pairs. As noted above, the numbers in this study are also gmail so that the differences in rates do not approach statistical significance. _ Libblin (188) has questioned the value of a mailed questionnaire to diagnose heart disease. The questionnaire as originally con- structed was used and validated by interview technique alone (157, 158). Cederlof, et al. (40) conducted a study to determine the validity of this questionnaire as a mailed instrument by personally interviewing and examining 170 of the twin pairs who had replied. Of the eight males who were diagnosed as having “angina pectoris” by the questionnaire. four were found to be free of symptoms on 46 clinical examination, while among 204 responding negatively, two were found to have angina by clinical criteria. None of the 11 women who were diagnosed as positive by questionnaire was found to be clinically affected, and of the 136 reporting as negative, three had symptoms of angina pectoris. Other major difficulties associated with these studies include the problems of using prevalence data in the investigation of a disease (CHD) from which a significant number of those affected die shortly after the onset of symptoms, the inclusion of ex-smokers in the smoking population, and the low numbers of heavy cigarette smokers in the Swedish population. In general, the problems of using twin registries to study the etiology of cardiovascular disease with mortality and morbidity ratios in the neighborhood of 2 to 1 are much more difficult than in studying the etiology of bronchopulmonary disease in which the relationships are of the order of magnitude of 4 to 1. More recently, Friberg, et al. (69) reported on mortality data from the Swedish Twin Registry. The authors suggested that part of the increased mortality observed among smokers when com- pared with nonsmokers was not due to smoking per se but to fac- tors associated with smoking. The very small numbers of total deaths presently available (47 deaths among 706 dizygotic pairs and 13 deaths among 246 monozygotic pairs) do not provide a sta- tistically stable base for deriving any conclusions at the present time. Hauge, et al. (81) have recently reported on the influence of smoking on the morbidity and mortality observed in the Danish Twin Register. Among 762 monozygotic and same-sexed dizygotic twin pairs, angina pectoris was found to be significantly more fre- quent in those cotwins with a higher consumption of tobacco than m those with a lower or no consumption. A similar tendency was observed for myocardial infarctions but was not of statistical significance. _ Seltzer, who has been a proponent of the constitutional hypothe- #18, In a recent review of some of the experimental, clinical, and “Pathological data relating smoking and CHD, concluded that the evidencé from these areas has not “reasonably substantiated” the “hypothesis” of the acute effect of cigarette smoking on the coro- nary circulation, nor has the chronic effect of cigarette smoking on the cardiovascular system been shown to be a “clear” and con- sistent one (170). His views are contrary to those of most re- searchers in this field. Although the data from the twin studies are inconclusive with regard to a role for genetic factors in heart disease, it would be surprising if genetic factors did not play such a role. It is open to 47 question whether findings from twin Studies can be used to distin- guish between the hypothesis that genetic factors govern the level of host susceptibility or resistance to the effects of an exogenous influence such as cigarette smoking and the hypothesis that genetic factors “cause” both heart disease and smoking. AUTOPSY STUDIES RELATING SMOKING, ATHEROSCLEROSIS, AND SUDDEN CHD DEATH A number of researchers have investigated the cigarette smoking habits and the cardiovascular pathology of those individuals dying suddenly from CHD and of large populations of individuals with and without histories of overt CHD. Spain and Bradess (175) recently analyzed the smoking habits of 189 individuals who died suddenly and unexpectedly, apparently from the first acute clinical episodes of CHD. The authors noted a close correlation of a history of cigarette smoking with this type of sudden death and also with shorter survival times following the acute episode. This association was strongest in those persons under 50 years of age. The authors also observed that those Surviving very short pe- riods of time showed a notable lack of intracoronary artery throm- bi at autopsy and that the frequency of thrombi present increased with increasing survival time. They suggested that thrombi found at autopsy may be the result rather than the cause of certain instances of myocardial infarction, Particularly of lesions showing subendocardial necrosis. This finding is of significance in the study of the effect of smoking on myocardial metabolism and oxygen supply and demand rather than on thrombus or platelet plug formation. While the autopsy study of Spain and Bradess (175) concerned sudden death among smokers, other autopsy studies from various dilov, ét al, (73), Sackett, et al. (165 ), and Strong, et al. (182) found that aortic and coronary atherosclerosis were more common and more severe among smokers than among nonsmokers. Auerbach, et al. (12) noted that this relationship persisted when the cases Were matched for both age and cause of death or when the follow- ing cases were excluded ; Men with a history of diabetes ; men who had died of any type of heart disease; and men whose hearts weighed 400 grams, or more. Sackett, et al. (165) found that the 48 64 TABLE 19.—Autopsy studies of atherosclerosis (Figures {n parentheses are number of individuals In that smoking category)! NS = nonsmokers} (SM = smokers Cigarettes per day Conclusions Comments Severity of aortic ecleroes Above average Average NB ovissecerees 9.9 (161) 60.2 S20 ceceeenees 1926152) 63.2 20-30 ..ccceuns 26.4(288) 62.5 80 cee neue f26.1 (199) 61.8 Below average 29.8 17.8 Mi $13.6 The authors conclude that in 60 percent of cases, the degree of asclerosls at autopsy was commen- surate with age of patient, regardless of smoking habita, In the remaining 40 percent there {fs ev!- dence that cigarette smoking may be asso- elated with an abovee average degree of sortie sclerosis, Smoking data unavailable for 120 cases, Each aorta specimen given an “atherosclerotic age” by comparison with a standard, If “athero- sclerotic age’ was found to be 10 years more than real age, the sorta was sald to show above. average aclercals, tp<0.001 comparing 9.9 with 26.1 and 29.8 with 18.6, Author, year, Autopay Data country, population collection reference Witens 989 consecutive Routine clinical and Plair, male autopsies records of 1962, at New York previous and USA, City VA present (88). hospitals. admiastons. Averbach, 1,872 autopsies Interview with etal, of male next of kin, 1986, patients in” U.B.AY, Orange, New (12), Jersey, VA hospital for whom smoking . habit data were _ available and who d{d not have overt CHD at death, Degree of coronary artery atherosclerosis (overall age- The authors conclude that adjusted results) No athero- : _acleroria’ = SUght NS veeeee e668 (68) --5e 57.8 Current elgarette <20 0.64 2.6(189) 80.9 20-89. 4.0.8 (299) 19.7 40 04605 .0.6 (144) 18.1 1 Unless otherwise specified, disparities between the total number of in- dividuala and the sum of the individual amoking categories are due to the exclusion of either occasional, talacellaneous, mixed, or ex-amokers, ‘Moderate Advanced | 21.8 87.8 ant 35.4 15.8 20.2” 87.4 45.9 + the percentage of men with an advanced degree of coronary atherosclerosls was higher among elga- ~ rette smokers than among nonsmokers and that the percentage Increased with amount of cigarette | smoking. This relation- ship persisted even when cases were matched for age and cause of death. os TABLE 19.—Autopsy studies of atherosclerosis (cont.) (Migores {n parentheses are number of individuals in that smoking category)? (SM = smokers NBS = nonsmokers) deathe 1956-1064 exclusive of 81 male pipe and clgar smoker and 65 income plete files. ‘Unless otherwise specified, disparities between the total number of Ine dividuals and the gum of the Individual smoking categories are due to the exclusion of either occasional, miscellaneous, mixed, or ex-amokers. Aothor, year, Autopsy Data ~ ; gentry, population | collection Cigarettes per day Conchusions Comments Avtandiloy, 259 male and Not specified, Comparative eise of mean area of atherosclerottc legtiona The author concludes that Causes of death 96-athero- 1965, 141 female but there were: in inner coat of coronary arteries, the worst changes were sclerotic, 102-accldental, Ruaala autopsles. 180 SM and Right coronary artery Left coronary artery « found In the left and 202-varlous diseases. (18). 220 NS, SM NS right coronary arteries {T-test for significance 30=39 ... $15.5 (80) 1.3 (82) with less severe changes of difference between 40-49 .. $28.6(94) ° 13.6(27) in elreumflex artery means js significant 50-50 .. £86.3(89) 14.8 (89) and aorts. at p<0.05 level, 60-69 .. $81.91 32) 23.8 (86) 10-78 ., 41.9(18) 31.7 (86) Sackett, 893 total, Patient The resulta concerning aortic atheroaclerosis are given in The authors conclude that eal, | including 483 interview on form of figure presentation of ridit-analysis. among males, “.., @ 1963, male and 450 admission. large increase In the U.B.A. female (white) severity of aortic athero- (188), patients autop- sclerosis occurred in the nied at Roswell groups uslng either clea. Park Memorial rettes only or both clga- Hospital. rettes and alcohol aa Represents all compared with the group ualng neither clgarettes nor alcohol... there was only a small and statistically insignificant difference between the group using cigarettes alone and the group using both cigarettes and alcohol,. ooo The severity of aortic atheroscleroels increased with Increasing use of cigarettes, when measured both by In« tenalty and by duration of amoking.