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C FRAZIER, TODD M.--Asslstant director, Harvard Center for Community Health and Medical Care, Earvard School of Public Health, Boston, Mass. }LASS, GEORGE M., M.D.--Chairman, Division of Pathology, Presbyterlan-St. Luke's Hospital, Chicago, Ill. HIGGINS~ IAN T. T., M.D., M.R.C.P.~Professor, Department of Epidemiology, University of Michigan, School of Public Health, Ann Arbor, Mich. HOFFMANN, DIETEIOI, Ph. D.--Associate memher, Environmental Carcinogenesis, Nloan-Kettering Institute for Danc~r Research, New York, N.Y. KELLER, ANDREW Z., D.M.D., M.P.H.--Chlef, Research in Geographic Epi- demiology ~eseerch Service, Veterans kdmlnist~a~ion Central Office, Depar~enL of Medicine and Surgery, Waghington, D.C. *KERSI[BAUqM, ~LpRED, M.D.--Asslsta~t Chief, Division of Cardiology, Philadelphla General Hospital, Philadelphia, Pa. (Dr. Kershbaum, who contributed to this and prevlo1~ report~ died suddenly in March 1969 .) KOTIN. PAUL, M.D.--Director, National Institute of Environmental llealth Sciences, Research Triangle Park, N.C. KRL~OLZ, RICILARD A., M.D.--Director, Institute of Respiratory Diseases, Kettering Medical Center, Kettering~ CaiN. LEUCHTENBERGER, CECZLE, Ph* D.--Head, Department of Cytochemistry Swiss Institute for Experimental Cancer Research, Laus~ne, Switzerland. LEUC}[TENBERGER, RUDOLF, M.D.--Professor, Swiss Institute for Experimental Can~er R~search~ Lausanrve, Swltzerland~ LIREOW, AVhHILL A., M.D.--Professor and chairman, Department of Pathology, Eniversizy of California, San Diego, La Jolle, Calif. LILLIE~:FELD, A~KAHAM, M.D.--Professor and chairman, Department of Chronic Diseases, Johns Hopkins School of Hygiene and Public Health, Baltlmore, Md. LYON, HARV~X W., D.D.S., Ph. D.--Secretary, Co,ell on Dental Research, American Dental Association, Chicago, Ill. *Deceased t¢

~Lac}~HON, BRIAND, M.D.--Professor of epide~aiology, Harvard University SehoDl of Public Health, Boston, Mass. McLEA~N, ROSS, M.D.--Professor of medicine (pulmonary disease), Emory Uni- versity, School of Medicine, Atlanta, Oa. MITCI{ELL. ROGER S,, M.Do--Ddrector. Webb-Waring Institute for Medical Research, U~iversity of Colorado ~ledical Center, Denver, Colo. MURPHY~ EDMOND A., M.D., Sc. D.--Associate professor of medicine, The Johns Hopkins Hospital, Baltimore, Md. PAFFENBARGER, RALPH S., JR., M.D.--~*lef, Bureau of Adult Health and Chronic Diseases, Department of Public Realth, Berkeley, Calif.¸ PRTERSON, WILLIAM F., M+D.--Chief, Obstetrics and Gynecology Service, USAF Hospital Andrews, ~}[CB, Andrews Air Force Base, Washington, D,C. PETIt. T~O~K~S L., M.D.--Assistant professor of medicine. University of Colorado ~ddc~l Center, Denver, Colo. ROO|kMIB. PAUL C.~ M,D.--Heart Disease and Stroke COntrol Program. Health Services and Mental Health Administration, R.S.P.H.S., Arlington, Va. ROSS, WILLIAM L., M.D.--Calef, Cancer Control Program, HealS5 Services and Mental Health Administration, D.S.P.H.B., Arlington, Vao SAFFIOTTI, UMBERI'O, M.D.--Associate scientific director for carcino- genesis, etiology, National Cancer Institute, National Institutes of Health, gethesda, Md. SCKA~{TER, JOSEPH--Statistician, Adult Heart Activities, Heart Disease ~d Stroke Control Programj ~ealth Service~ and M~ntal Health Administration, U.S.P.H.S., Arlington, Va. SCHL.~L&N, LEONARD H., M.D.--Professor of epidemlology. University of Minnesota. School of Public Health. Minneapolis. Minn. SRI~IN, }dCHAEL B., }i.D.--Director, Regional Medical Programs, University of California at San Diego, La Jolla, Calif. SIL%~Z~v~LN, SOL~ JR., D.D.S .--Professor of oral biology. School of Dentistry, L~iversity of California, Sa~ Francisco, Calif. ~O

SP/'fl{, LOWELL C., D.D.S.-~hief. Preventlve Servicms Section, Go~z~unity Programs Branch, Division of Dental llealth, U.S.P.~.S. ~ 8ethesda, Md. ST~ER, JEREMIAH, M.D.--Executlve director, Chlcago Health Research Foundation, Chicago, IIi. STEDMAN, RUSSELL L., D. So.--Head, Smoke Investigations, Tobacco Labora- tory, U.S. Department of Agriculture, Philadelphia~ Pa. TIECKR, RICILARD W., D.D.S.--Director, Research Institute, American Dental Association, Chicago, Ill. TOBIN, C~LiELRS E., Ph. D.--Professor of human hlology, U~iver~ity of Colorado School of Dentlstry~ Denver, Colo. TYLER, WALTER S.~ D.VoM., Ph. D.-~Professor and chairman, Department of Anatomy, School of Veterinary Medicine, Universlty of California, Davis, Callf. UNDERWOOD~ PAUL, M.D.--Assistant professor of obstetric.g and gynecology, Department of Obstetrics a~d Gynecology, U~ivers±~y of South Carolina Medical School, Charleston, S.C. V~ DUUREN, BENJA~N L., M.D.--D~ssoclate professor, N~ York University Medical Center, Instltute of Enviror~ental ~ealth, New York, N.Y. WEIR, JOhq~ M°--Director~ Bureau of Den~al Realth Education, Amerlcan Dental Assoclatlon, Chicago, Ill. WYNDER~ EP/~E~Y Lo, M.D.--Associate member, Sloan-Kett~rlng Instltut~ fo~ Cancer Research, New Yo~ N.Y. The following professional staf~ of the Rational Clearinghouse for Smoking and Health contributed to the preparation of this report: Lolls Nemser, M.D., David V° Sharpe, M.D,, Dorothy E. Green~ Ph.D., Richard Elsi~ger~ RoSert S. Hutchin~s, Emil Corwln and Richard W. White. S~ec1~i ~ilanks are due Jen~i~ M. Jer~in~s, ~M~idred ~. P~Itehle a~d Donald ~. Shopland° #¢

SMOKING AND CARDIOVASCULAR DIS~%SE3 SU~RY Cozonaz~] heart disease (C~D) among men in the Western world is an epidemic whi~ Guts short the lives of many in their prime productive years. The evidence linking smoking and CHD has been re?orted not ouly from s£udies in the U~ited gtates~ but also from ~uch diverse a~as as west Germa=y, the U.S.S.g., Fr~ace, Israel, Italy and the British ~sles. The 1968 Supplement (27) stated: Because of the increaslng convergence of epldemlologlcal and physiolo~laal findings relating cigarette smoking to coronary heart disease, i£ is concluded that eigarett~ smokln~ ca~ con- tribute to ~he development of cardlovascul~r disease ~d particularly to death f~'o-a eor~nu~I heart disease. The convergence of autopsy da~a and experimental data presented in ~hls and previous reports suggests tha~ cdgaret~e smoklng promotes atheroselerosls~ including thac of the coronary arteries. The results of phys~ologlcal research and the finding of diminished rlsk of CHD in those who have s~opped smoking indicate ~ha~ there is also a T~re imedla~e ~chanism operative° The mechanisms which mi~h~ be responsible for the promotion of myocardial infarction and fatal cardiac arrhy~hmias by cigarette smokin~ were ex- tensively reviewed in the 1968 Supplement (27)° gzlefly stated, nutrient supply ~o the myocardi~ in ~e~eral and, perhaps more impor~m~ly, to focal ischemic areas of ~he myocardim~ may be seriously compromised by a comblna- ~ion of effects caused by smoking, and the deprived myocardlum may become infarcted or develop an arrhy~hmia. These effects include diminution of ~j G~

blood flow through atheroscleroti= coronary vessels and dimiBution of available oxygen for tissue use resul£1ng from the binding of carbon monoxide to hemoglobin in the place of oxygen and possibly, although presently speculative, the poisoning of respiratory enzymes by hydrogen cyanide. Cigarette smoking has been shown to be an important risk factor in the development of ClID. It is important bo~h by itself amd in the pres- ence of other significant risk fa~tors. In combination with certain other risk factors~ the Joint effects appear to be even greater ~ha= those accounted for by these risk factors independently. EPIDEMIOLOGIC~L STUDIES Hammond, et al. (ll) have presented new data on mortality from C~D, stroke ~d nonsyphilltie aortle aneurysm among more ~han 800,000 ~n and women who were between the ages of 40 aad 79 in 19S9. The authors were attempting to evaluate the significance of mul~iple factors (s~x, age. diabetes, higil blood pressure, body weight, change in weight, exercise1 cigarette smokisg, sleep a~d nervous tension) in the variations in death rates from Khese three diseases. It should he noted ~hat this informa- tion consls~ed of self-reports obtalned by ques~ior~naire and were not obKained from medical exami~atlon. Causes of death were based on death e~rKificate reports. As illustraKed in table i, coronary hear= disease death rates ~d ~or=ali~y ratios increased wiKh increased cigarette smoking for men in all

Table 1.-- ,e ~h rates and mortality ratios for coronary heart disease and stroke, by a~ount of cigarette smokins~ sex~ and a{~e Sex an~l age Males 40-49 years 50-59 60-69 70-79 Females 40-49 years 50-59 60-69 70-79 Males 40-49 years 50-59 60-69 70-79 Females k0-49 years 50-59 60-69 " 70-79 ~ever ~ Dk~d Corona~y hcart disease _ Re~"glarg]~ smoked cigarettes_ c J g~rettes 67 263 711 1,720 13 59 268 979 Number s~oked d ~il : Deat~ Z09 176 256 375 409 548 616 718 961 1,184 1,241 1,166 1,970 2,43l 2,573 2,5~8 17 27 47 43 68 140 158 220 279i 479 558 542 740 963 .,243 Mortalii 1.63 2.63 3.82 5.60 1.561 2.o8 2.34 2.73 1.351 1.67 1.75 1.64 1.15 I.~i 1.50 1.48 1.31 2,08 3.62 3.31 1.15 2.37 2.68 3.73 1.04 1.79 2.08 2.02 0.76 0.98 1.27 ~eYer smoked Sex and age cigarettes FemaLes 40-49 years 50-59 60-69 70-79 Ratios I/ 1.00 1.O0 1.00 1,OO lO 27 llO 487 1.O0 1.00 1.00 1,00 Stroke ~e~ularly smoked eisarettes Number smoked or /aor~ 1.00 1.00 1.00 1.00 Females 40-49 years 50-59 60-69 70-79 i/ The mort&lity ratio is the observed rate divided by the expected rate. SOURCE: Ha~aond, E. C., et al. (ii). 57 95 5.70 3.52 IIII

age groups and for womeu under the age of 70. Although the mortality ~atlos were hlgILer in the yo~g~ age group61 the differences in death rates b~tween nonsmokers and heavy smokers became progressively higher with Inc~easing ag~° Although C~D rates we~ higher for thos~ who were I0 pea- cent or more above the average weight for their height-age-sex g~oup~ and for those who reported gavlng hlgh blood pressure, the trend is clear that the effect of smoklng persists and Is appreciable, even when these other ~actors are held constant (table 2). ~a~ondj et al. also s~udled CHD mortality ~mong men who were ex- Bmokers of c±garett~. The de~th rates f~om CHD wer~ lower a~ong the e~- smokers than among those still smoking at ~he beglnu£ng of the study, the size of the dlfferenc~ being larger the longer they had been off smoking (table 3). Some people s~op smoking because of illness or symptoms and ~hese people would be expected ~o have high¢~ ~-ath ~a~es t~an those who stop for o~r reasons. E~rly deaths among ~hos~ with pre-existing disease may account, at leas~ ~n par~, for the high death r~tes from C~ a~ong ex~s~okers ~ th~ ~ly years of abstention° Mortality ratios fo~ stroke w~re higher among ~igar~t~ smo~r~ w±~h the exception of those over 70 years of age. Male ex-c£garette smokers had m~rtality ra~ios ~or stroke approximately equal to those of non- G~

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T~ble 3.--Observed and expected number of deaths and mortality ratios for ex-eigarette smokers with history of s~oking only cigarettes, by number of years sluee last cigarette smoking and for current cl~are~ s~okers~ coron~ heart dlse~se and stroke; compared to persons who never smoked regularly, in men ~ged h0-79 ___TY~ of smoker Ex-sigaz~t 5e smokers (Fonu<r smokers of 1-19 cigalettes a day): Stoppe~l: Less than 1 year 1-4 years 5-9 i0-19 " 20 or more years Total Curre~ cigsmette smokers Never smoked regularly Ex-cigarette smokers (Former smokers of 20 or more c~garettes a day): Stopped: Less than 1 year i-~ years 5-9 i0-19 " RO or more years Total Current cigarette smokers Never ~moked regularly Coron~z heart disease Observed 29 57 55 52 70 263 1,o63 1,841 Expected Ratio 17.9 1.62 46.6 1.22 h].7 1.26 5~.i 0.96 64.7 1.08 226.9 ±.16 559.5 1.90 1,8~i.0 l.OO 38.6 1.61 i01,9 1.51 116.5 1.16 106.1 1.25 76.~ 1.05 ~39.7 1.28 1,104.7 2.55 1,841.0 1.00 StrOke ~ected 57 56.9 2O7 134.5 501 501.0 9h lOl.l 440 234.7 501 5Ol.O SOURCE: Hammond, E. C., et al. (ii). 62 154 135 133 80 564 2,822 1,841 Observed Ratio / 1.00 1.5h l .O0 0.93 1.87 1.00 I !

( A clear increase in mortality from nonsyphilltlc aortic aneurysms with increasing cigarette smoking among men aged 50-69 is seen in table 4. The mortality ratio for heavy smokers was 8.00. Table 4.--Aortic aueurysm death rates and mortality ratios for m~n aged 50-69, clasaified by cigarette smoking habits [Rates per 1,000 population] Never smoked Measure regularly Death rate 13 Mortality ratio 1.00 2.62 Current smokers, by daily cigarette consumption 1-9 i0-19 20-39 40 or ~re 34 50 59 104 3.85 4.54 g.O0 SOURCE: Hammond~ E. C., et al. (ii). Han~mond, et al. 8tare: "Death ra~es from the three diseases varied consideraSly with rela- Give weight, amount of exercise, amount of cigarette smoking and hours of sleep per night, guhjects who were obese~ took little or ~o exercise, smoked many cigarettes a day or slept nine or more hours per night had high death rates. Those wi~h a combination of th~se factors have espe- cially high death rates from the three disease6." "Death rates from C~D and stroke were l~er in ex-cigere~ smokers than in men wi~o were currently smoking cigarettes at the ~ime ~hey ~n- rolled in the study. ~ne death rates of male ex-cigerette smokers who had not smoked for ten to ~wen~y years were no higher or only slightly higher the% the deaLh rates of men who had never smoked reKularly." ~J